The ribosome is a macromolecular complex composed of RNA and proteins that interact through an integrated and interconnected network to preserve its ancient core activities. In this review, we emphasize the pivotal role played by RNA-binding proteins as a driving force in the evolution of the current form of the ribosome, underscoring their importance in ensuring accurate protein synthesis. This category of proteins includes both ribosomal proteins and ribosome biogenesis factors. Impairment of their RNA-binding activity can also lead to ribosomopathies, a group of disorders characterized by defects in ribosome biogenesis that are detrimental to protein synthesis and cellular homeostasis. A comprehensive understanding of these intricate processes is essential for elucidating the mechanisms underlying the resulting diseases and advancing potential therapeutic interventions.

In the intricate dance between viruses and host cells, RNA-binding proteins (RBPs) serve as crucial orchestrators of gene expression and cellular processes. We will delve into the riveting realm of viral hijacking, where viruses deftly exploit host RBPs to manipulate cellular machinery for their replication and pathogenesis. Through a masterstroke of molecular subterfuge, viruses co-opt RBPs involved in various facets of RNA metabolism - from transcription to degradation - to promote viral gene expression and evade host immune defenses. This manipulation leads to global alterations in cellular RNA metabolism, impacting essential host genes vital for immune responses and homeostasis.Unveiling this clandestine alliance between viruses and RBPs is not just a scientific pursuit, but a critical imperative for devising innovative antiviral strategies to disrupt these interactions. By unraveling the intricate interplay between viral proteins and host RBPs throughout the viral life cycle - from entry to assembly - researchers aim to identify vulnerabilities that can be targeted for therapeutic intervention. Strategies such as disrupting viral protein-RBP interactions hold promise for inhibiting viral replication and curbing pathogenesis, offering a beacon of hope in the battle against viral infections.Our manuscript elucidates the indispensable roles played by RBPs in viral replication, translation, and pathogenesis, shedding light on the molecular mechanisms driving viral success. Delving deeper, it explores how viruses intricately entwine with host RBPs, manipulating cellular signaling pathways to create a hospitable environment for viral spread. By dissecting these manipulative tactics, researchers uncover new targets for antiviral therapy, envisioning a future where tailored interventions disrupt viral-host RBP interactions with precision and efficacy.As the narrative unfolds, the therapeutic implications of targeting RBPs or their interactions with viral proteins emerge as a promising frontier in the fight against viral infections. From small molecule inhibitors to RNA-based therapeutics, innovative approaches are on the horizon, offering new avenues for combatting viral diseases. We set the stage for future research, beckoning researchers to delve deeper into the molecular intricacies of viral hijacking of RBPs and charting a course towards novel therapeutic interventions that promise to reshape the landscape of antiviral therapy.\Ultimately, it beckons the scientific community to embark on a voyage of discovery, unraveling the secrets of viral hijacking of RBPs and paving the way for transformative advances in antiviral therapeutics. The stage is set for a new chapter in the battle against viral infections, where knowledge becomes the sword and innovation the shield against the pernicious machinations of viral pathogens.

Heartland virus (HRTV) is an emerging tick-borne bandavirus that is capable of causing severe disease characterized by acute thrombocytopenia and lymphopenia. The virus is endemic to the eastern United States, and is carried by the Lone Star tick (Amblyomma americanum). Since its discovery in 2009, at least 60 human infections have been recorded across this area, with an overall 5-10\% estimated mortality rate. All infections reported thus far have occurred following a known tick bite or exposure to tick-infested areas, but the possibility of nosocomial transmission has not been ruled out. Despite relatively high rates of seroprevalence among certain wildlife species such as white-tailed deer, the reservoir species for HRTV remains unknown, as the virus has never been isolated from any mammalian wildlife species. Furthermore, how the virus is transmitted to its vector species in nature remains unknown, though laboratory studies have confirmed both horizontal and vertical transmission of HRTV in A. americanum. In addition, the recent 2017 introduction of the Asian longhorned tick (Haemaphysalis longicornis) to the US has raised concerns about possible spillover of HRTV into a new tick species that has been confirmed to be a competent vector for HRTV in the laboratory. Thus, an increased awareness of its clinical presentation is needed, and further research is urgently required to establish the natural transmission cycle and develop new countermeasures for this novel zoonotic pathogen

Untranslated regions (UTRs) of flaviviruses contain a large number of RNA structural elements involved in mediating the viral life cycle, including cyclisation, replication, and encapsidation. Here we report on a comparative genomics approach to characterize evolutionarily conserved RNAs in the 3'UTR of tick-borne, insect-specific and no-known-vector flaviviruses in silico. Our data support the wide distribution of previously experimentally characterized exoribonuclease resistant RNAs xrRNAs within tick-borne and no-known-vector flaviviruses and provide evidence for the existence of a cascade of duplicated RNA structures within insect-specific flaviviruses. On a broader scale, our findings indicate that viral 3'UTRs represent a flexible scaffold for evolution to come up with novel xrRNAs

Mosquitoes are responsible for the transmission of numerous pathogens, including Plasmodium parasites, arboviruses and filarial worms. They pose a significant risk to public health with over 200 million cases of malaria per annum and approximately four billion people at risk of arthropod-borne viruses (arboviruses). Mosquito populations are geographically expanding into temperate regions and their distribution is predicted to continue increasing. Mosquito symbionts, including fungi, bacteria and viruses, have desirable traits for mosquito disease control including spreading horizontally and vertically through mosquito populations and potentially colonising multiple important vector species. Paratransgenesis, genetic modification of mosquito symbionts with effectors to target the pathogen rather than the vector, is a promising strategy to prevent the spread of mosquito-borne diseases. A variety of effectors can be expressed but venom toxins are excellent effector candidates because they are target specific, potent, and, stable. However, the only toxins to be explored in mosquito paratransgenesis to date are Scorpine and mutated phospholipase A2. To enhance the scope, effectiveness, and durability of paratransgenesis, an expanded arsenal of effectors is required. This review discusses other potential toxins effectors for future paratransgenesis studies based on prior in vitro and in vivo antiparasitic and antiviral studies and highlights the need for further research and investment in this area. In terms of mosquito-borne diseases, paratransgenesis strategies have been developed to target Plasmodium. We postulate the potential to apply this principle to target arboviruses using antiviral toxin effectors.

The complexity of RNA cannot be fully expressed with the canonical A, C, G, and U alphabet. To date, over 140 distinct chemical modifications to RNA have been discovered. RNA modifications can profoundly impact the cellular outcomes of messenger RNAs (mRNAs), transfer and ribosomal RNAs, and noncoding RNAs. Additionally, aberrant RNA modifications are associated with human disease. RNA modifications are a rising topic within the fields of biochemistry and molecular biology. This review aims to provide budding scientists with an appreciation for the significance of RNA modifications, alongside the skills required to identify and fluently discuss fundamental RNA-protein interactions. The Pumilio RNA-binding protein and YT521-B homology (YTH) family of modified RNA-binding proteins serve as examples to highlight the fundamental biochemical interactions that underlie the specific recognition of both unmodified and modified ribonucleotides, respectively.

Recognizing the need to enhance immune cells' ability to target and eliminate tumor cells by focusing on tumor-associated antigens is crucial for the success of immunotherapy. Numerous cell-based therapies, such as CAR-T cell therapy, tumor-infiltrating lymphocyte (TIL) therapy, CAR-NK cell therapy, and T-cell receptor (TCR)-based therapies, are currently undergoing clinical and pre-clinical evaluation across various cancer types. However, a significant challenge lies in managing the inflammatory responses that are harmful to cancer patients. To overcome this, developing advanced strategies to target tumor cells precisely while preserving immune balance in cancer patients is imperative. One promising approach involves using modified tumor-associated macrophages (TAMs), which constitute approximately 50% of the tumor microenvironment (TME) and play a pivotal role in tumor progression. CAR-Macrophage (CAR-M) therapy is an emerging potential asset of immunotherapy for a wide range of tumors.

(1)Background: Fascioliasis is considered a neglected tropical disease affecting an estimated 17 million people in more than 70 countries worldwide. The highest prevalence of human fascioliasis is found in regions where livestock farming and consumption of raw or undercooked freshwater plants are common, such as parts of Africa, Asia, Europe, and Latin America. It is responsible for over 90,000 disability-adjusted years of life due to associated abdominal complications. We conducted a study to investigate the prevalence of human fascioliasis through a systematic review and meta-analysis of all available literature in Sun-Saharan Africa.(2). Methods: We screened a total of 126 publications using pubmed online search engine databases; Web of Science and CAB for articles published within a 20-year period between 2000 and 2022. We used a comprehensive search method using a combination of terms, parasite and disease names. The initial search resulted in a screening of articles by title, abstracts and full texts. The relevant information on the prevalence of human fascioliasis in Africa was extracted. Of the 126 publications, 33 articles were selected for meta-analysis. The essential information required was extracted from these documents and determined through statistical analysis in Microsoft Excel for calculating the prevalence of human fascioliasis in sub-Saharan Africa. The variance of each study was assessed using a bimodal distribution and heterogeneity assessment using a I2 index. Analysis was performed using random effects models.(3)Results: A total of 271 articles were searched through the database search and 33 articles were eligible studies that provided qualitative information on the prevalence of human fascioliasis in Africa. These make up 12.17% (n=33). The pooled prevalence estimates for human fascioliasis are 0.032% (IVhet PPE: 0.032% (95%CI 1.4-6.53). The highest prevalence rate was observed in Egypt with a prevalence of 100%. The prevalence of human fascioliasis is very high in some sub-Saharan countries, partly due to neglect of diagnostics, demonstrating the bias of available information for decision-making in human fascioliasis across Africa, given the spatial presence, scarcity and incompleteness are region.(4)Conclusions: The prevalence of Human fascioliasis is very high in some Sub-Saharan Countries partly due to neglect in diagnostics. This presents how highly focal with spatial occurrences, scarcity and patchy the available information for decision making is on Human fascioliasis across the Sub-Saharan African region.

Tularemia is a zoonotic disease caused by {\it Francisella tularensis} bacteria, a gram-negative coccobacillus-shaped bacterium. There are multiple transmission routes of the infection to humans such as consumption of contaminated food or water, handling of infected animals or bites from {\it haematophagous} arthropods (such as ticks, deer flies, or mosquitoes). In this study we focus on transmission via the bites of ticks and developed a deterministic model of ordinary and impulsive differential equations to gain insight in the differential effect of prescribed fire on {\it Demacenta variablis} and {\it Amblyomma americanum} ticks and the prevalence of tularemina. We found that prescribed fire differentially reduce the number of the two ticks with {\it A. americanum} reduced the least compare to {\it D. variablis} subsequently leading to differential increase of tularemia new infected cases in humans and rodents. Our result further indicates that the spatial arrangement of burn against unburn areas may not matter as either arrangement led to fewer ticks and reduction in tularemia transmission when prescribed fire was implemented. The results of this study provide important new understandings of the intricate effect of prescribed fire on tick species, and the dynamics of the tick-borne disease, tularemia disease in this study.

In this study, we investigated the features of co-infection with SARS-CoV-2 and nonpathogenic strain LEV8 of coxsackievirus A7 or enterovirus A71 for Vero E6 cells and Syrian hamsters. The investigation of co-infection with SARS-СoV-2 and LEV-8 or EV-A71 in the cell model was shown that a competitive inhibitory effect for these viruses were especially significant against SARS-CoV-2. Pre-infection with enteroviruses in animals caused more than a 100-fold decrease in the levels of SARS-CoV-2 virus replication in the respiratory tracts and more rapid clearance of the lower respiratory tract from infectious SARS-CoV-2. Co-infection with SARS-CoV-2 and LEV-8 or EV-A71 also reduced the severity of clinical manifestations of the SARS-CoV-2 infection for animals. Additionally, the histological data illustrated that co-infection with nonpathogenic coxsackievirus decreased the level of pathological changes by SARS-CoV-2 in the lungs. Research into the chemokine/cytokine profile demonstrated that the studied enteroviruses efficiently triggered this part of antiviral immune response, which can be associated with significant inhibition of SARS-CoV-2 infection. These results demonstrate that there exists a strong viral interference between the studied nonpathogenic strain of coxsackievirus A7 or enteroviruses A71 and SARS-CoV-2 pathogenic for humans in vitro and in vivo.

Malaria parasites increase their host erythrocyte’s permeability to obtain essential nutrients from plasma and facilitate intracellular growth. In the human P. falciparum pathogen, this increase is mediated by the plasmodial surface anion channel (PSAC) and has been linked to CLAG3, as encoded by one member of the conserved clag multigene family. Whether paralogs encoded by other clag genes also contribute to PSAC formation or serve unrelated roles remains unknown. Here, we generated transfectant lines carrying epitope-tagged versions of each CLAG. Each paralog colocalized with CLAG3, with concordant trafficking via merozoite rhoptries to the host erythrocyte membrane of newly-invaded erythrocytes. Each also exists within infected cells in at least two forms: an alkaline-extractable soluble form and a form integral to the host membrane. Like CLAG3, CLAG2 has a variant region cleaved by extracellular protease but CLAG8 and CLAG9 are protease-resistant. Paralog knockout lines, generated through CRISPR/Cas9 transfection, exhibited uncompromised growth in PGIM, a modified medium with more physiological nutrient levels; this finding is in marked contrast to a recently reported CLAG3 knockout parasite. CLAG2 and CLAG8 knockout lines exhibited compensatory increases in transcription of remaining clags and associated rhoph genes, yielding increased PSAC-mediated uptake to specific solutes. We also report distinct transport properties of these knockout lines, suggesting partially overlapping roles of CLAG paralogs in PSAC activity. We propose that the nutrient channel pore is formed by a higher order assembly of CLAG proteins at the host membrane.

Background: Recent developments in our understanding of the interactions between long non-coding RNA (lncRNA) and cellular components have improved treatment approaches for various human diseases including cancer, vascular diseases, and neurological diseases. Although investigation of specific lncRNAs revealed their role in the metabolism of cellular RNA, our understanding of their contribution to post-transcriptional regulation is relatively limited. In this study, we explore the role of lncRNAs in modulating alternative splicing and their impact on downstream protein-RNA interaction networks. Results: Analysis of alternative splicing events across 39 lncRNA wildtype and knockout RNA-sequencing datasets from three human cell lines: HeLa (Cervical Cancer), K562 (Myeloid Leukemia), and U87 (Glioblastoma), resulted in high confidence (fdr < 0.01) identification of 4432 skipped exon events and 2474 retained intron events, implicating 759 genes to be impacted at post-transcriptional level due to the loss of lncRNAs. We observed that a majority of the alternatively spliced genes in a lncRNA knockout were specific to the cell type, in agreement with the finding that genes affected by alternative splicing also displayed enriched functions in a cell type specific manner. To understand the mechanism behind this cell-type specific alternative splicing patterns, we analyzed RNA binding protein (RBP)-RNA interaction profiles across the spliced regions. Conclusions: Despite limited RBP binding data across cell lines, alternatively spliced events detected in lncRNA perturbation experiments were associated with RBPs binding in proximal intron-exon junctions, in a cell type specific manner. The cellular functions affected by alternative splicing were also affected in a cell type specific manner. Based on the RBP binding profiles in HeLa and K562 cells, we hypothesize that several lncRNAs are likely to exhibit a sponge effect in disease contexts, resulting in the functional disruption of RBPs due to altered titration of the RBPs from their target loci. We propose that such lncRNA sponges can extensively rewire the post-transcriptional gene regulatory networks by altering the protein-RNA interaction landscape in a cell-type specific manner.

Cytokines play a substantial role in the pathophysiology of infectious diseases. Consequently, genetic polymorphisms in cytokine genes can have profound effect on the susceptibility to or protection from infections and also influence the clinical manifestations, disease severity as well as outcome. The objective of this brief narrative review is to provide an update on the recent research findings on the role of genetic polymorphisms of IL-18, a recently discovered cytokine on certain infectious diseases of public health relevance. The current review suggests there is a significant impact of IL-18 polymorphisms on different infectious diseases. The presence of G and T alleles at position -656 is suggested to have a probable protective effect against VL. The −137G/−607C (GC) and −137C/−607C (CC) haplotypes in the promoter region are associated with increased susceptibility to severe malarial anemia. SNPs rs544354 and rs574429 (GC) are linked to a higher risk of P. falciparum infection and increased parasitemia. The -137 C/C genotype and -137 G allele (with G/G genotype) are associated with faster progression to AIDS. In contrast, the IL-18 genotype does not seem to affect overall HIV susceptibility but influences disease progression. The G and GG genotypes at position -137 and allele A at position -607 are likely associated with protection against HBV infection. Conversely, the C allele at position -137 is linked to increased susceptibility to HBV infections. The GG genotype of IL-18 -137 G > C variant is associated with increased susceptibility to pulmonary tuberculosis (PTB). The AC genotype of IL-18 -607A>C has been linked to PTB susceptibility, particularly in patients with co-morbid diabetes mellitus. SNPs −137G/C, 113T/G, and +127C/T are associated with susceptibility to H. pylori infection, indicating that these genetic variants may influence the risk of H. pylori-related diseases. There are conflicting results in studies conducted in different populations (e.g., genetic polymorphism, studies conducted in India and China against HBV infection) highlighting the need for further research with larger sample sizes to resolve discrepancies. Due to the variability in findings, extensive studies in diverse populations are needed to better understand the impact of IL-18 polymorphisms.

As recent history has shown, changing climate not only threatens to increase the spread of known disease, but also the emergence of new and dangerous phenotypes. This occurred most recently with West Nile virus: a virus previously known for mild febrile illness rapidly emerged to become a major cause of mortality and long-term disability throughout the world. As we move forward, into increasingly uncertain times, public health research must begin to incorporate a broader understanding of the determinants of disease emergence – what, how, why, and when. The increasing mainstream availability of high-quality open data and high-powered analytical methods presents promising new opportunities. Up to now, quantitative models of disease outbreak risk have been largely based on just a few key drivers, namely climate and large-scale climatic effects. Such limited assessments, however, often overlook key interacting processes and downstream determinants more likely to drive local manifestation of disease. Such pivotal determinants may include local host abundance, human behavioral variability, and population susceptibility dynamics. The results of such analyses can therefore be misleading in cases where necessary downstream requirements are not fulfilled. It is therefore important to develop models that include climate and higher-level climatic effects alongside the downstream non-climatic factors that ultimately determine individual disease manifestation. Today, few models attempt to comprehensively address such dynamics: up until very recently, the technology simply hasn’t been available. Herein, we present an updated overview of current perspectives on the varying drivers and levels of interactions that drive disease spread. We review the predominant analytical paradigms, discuss their strengths and weaknesses, and highlight promising new analytical solutions. Our focus is on the prediction of arboviruses, particularly West Nile virus, as these diseases represent the pinnacle of epidemiological complexity – solution to which would serve as an effective “gatekeeper”. We present the current state-of-the-art with respect to known drivers of arbovirus outbreak risk and severity, differentially highlighting the impact of climate and non-climatic drivers. The reality of multiple classes of drivers interacting at different geospatial and temporal scales requires advanced new methodologies. We therefore close out by presenting and discussing some promising new applications of AI. Given the reality of accelerating disease risks due to climate change, public health and other related fields must begin the process of updating their research programs to incorporate these much needed, new capabilities.

We remind about the dogma initially established with the nucleic acid double helix, i.e. the DNA structure as the primary source of life. However, we bring into the discussion those additional processes that were crucial to enable life and cell evolution. Studying chemosensory proteins (CSPs) and odor binding proteins (OBPs) of insects, we have found a high level of pinpoint mutations on the RNA and peptide sequences. Many of these mutations are found to be tissue-specific and induce subtle changes in the protein structure, leading to a new theory of cell multifunction and life evolution. Here, attention is given to RNA and peptide mutations in small soluble protein families known for carrying lipids and fatty acids as fuel for moth cells. A new phylogenetic analysis of mutations is presented and provides even more support to the pioneer work, i.e. the finding that mutations in binding proteins have spread through moths and various groups of insects. Then, focus is given to specific mechanisms of mutations that are not random, change α-helical profilings and bring new functions at the protein level. In conclusion, RNA and peptide mutations are not seen as representative of a multitude of diseases, but rather as an alternative way by which protocells developed to acquire multifunction and totipotency. This provides a basis for the theory of RNA/peptide mutations for birth and evolution of life on earth’s crust proposed here.

The emergence of existing and novel vector-borne disease pathogens is highly unpredictable because there are so many possible causal factors of sociological, ecological, biological, behavioral and political origin. Traditional data-driven forecasting tools have limited use in circumstances featuring low-probability crises for which trend data is unreliable and non-predictive. Commercial and security sectors have been quick to adopt various forms of wargames to address this gap and provide intelligent insights on possible outcomes in the short, mid and long term future. The lack of commitment and action against vector-borne diseases by governments and local authorities requires a new approach that presents risk in terms of potential actions, possible outcomes and resulting consequences.

In Africa, vector-borne diseases (VBDs) are still a major public health issue especially in cities that gather an increasing human population. Market gardening practices, for example, can favor the transmission of urban malaria, while insufficient water supply and waste management favor the circulation of arboviroses related to Aedes mosquitoes. Urban planning is a major challenge to mitigate vector risks. As a planning strategy, greening is a concept that is increasingly considered as a major element impacting the well-being of inhabitants, but also for the restoration of biodiversity in cities. Nevertheless, the impact of urban green spaces on vector risk remains poorly investigated, as they may serve as refuge for vectors. This is why the diversity of mosquitoes in terms of species and larval habitat, through larval prospections in environmental water collections and human landing catches, is studied here at an intra-urban interface area between a forest and an urban ecosystem in order to assess the vector risk generated by preserving a forest patch in the heart of Libreville, capital of Gabon, central Africa. Out of 104 water containers explored, 94 (90.4%) were artificial, mainly comprising gutters, used tires, and plastic bottles, while 10 (9.6%) were natural, comprising a puddle, streams, and tree holes. The majority of the water collections recovered (73.1%) were found outside of the forested area, natural and artificial ones considered together. A total of 770 mosquitoes belonging to 14 species were collected from water collections. The mosquito community was largely dominated by anthropophilic species like Aedes albopictus (33.5%), Culex quinquefasciatus (30.4%), and Lutzia tigripes (16.5%). The Shannon index of diversity showed that mosquitoes were almost twice less diversified inside the forest (0.7) than outside (1.3). However, both communities were quite similar in terms of common species and relative abundance (Morisita-Horn index = 0.7). Regarding Human landing catches, Aedes albopictus (86.1%) was the most aggressive species, putting people at risk of Aedes-borne viruses. This study uncovered the importance of considering urban forested ecosystems as potential drivers of disease emergence and spread in urban areas, as they might locally boost urban mosquito densities due to poor environmental practices, mainly maintained by humans through poor environmental practices. In Gabon, this study should contribute to guide targeted vector control strategies, especially regarding the implementation of policies for a better environmental management and vector surveillance in urbanized areas.

Starting from December 2019, coronavirus disease 2019 (COVID-19) has emerged as a once-in-a-century pandemic with deadly consequences, which urgently calls for new treatments, cures and supporting apparatuses. Remdesivir was reported by World Health Organization (WHO) as the most promising drug currently available for the treatment of COVID-19. Here, we use molecular dynamics simulations and free energy perturbation methods to study the inhibition mechanism of remdesivir to its target SARS-CoV-2 virus RNA-dependent RNA polymerase (RdRp). In the absence of a crystal structure of the SARS-CoV-2 RdRp, we first construct the homology model of this polymerase based on a previously available structure of SARS-CoV NSP12 RdRp (with a sequence identify of 95.8%). We then build the putative binding mode by aligning the remdesivir + RdRp complex to the ATP bound poliovirus RdRp. The putative binding structure is further optimized with molecular dynamics simulations and demonstrated to be stable, indicating a reasonable binding mode for remdesivir. The relative binding free energy of remdesivir is calculated to be -8.28 ± 0.65 kcal/mol, much stronger than the natural substrate ATP (-4.14 ± 0.89 kcal/mol) which is needed for the polymerization. The ~800-fold improvement in the K_d from remdesivir over ATP indicates an effective replacement of APT in blocking of the RdRp binding pocket. Key residues D618, S549 and R555 are found to be the contributors to the binding affinity of remdesivir. These findings demonstrate that remdesivir can potentially act as a SARS-CoV-2 RNA-chain terminator, effectively stopping its RNA reproduction, with key residues also identified for future lead optimization and/or drug resistance studies.

RNA interference (RNAi) has become a widely utilised method to study gene function, yet despite this, many of the mechanisms surrounding RNAi remain elusive. The core RNAi machinery is relatively well understood, however many of the systemic mechanisms, particularly double stranded RNA (dsRNA) transport, are not. Here, we demonstrate that dsRNA binding proteins in the serum contribute to systemic RNAi, and may be the limiting factor in RNAi capacity for species such as spiny lobsters where gene silencing is not functional. Incubating serum from a variety of species across phyla with dsRNA led to a gel mobility shift in species where systemic RNAi has been observed, with this response being absent in species where systemic RNAi has never been observed. Proteomic analysis suggested lipoproteins may be responsible for this phenomenon, and may transport dsRNA to spread the RNAi signal systemically. Following this, we identified the same gel shift in the slipper lobster Thenus australiensis and subsequently silenced the insulin androgenic gland hormone, marking the first time RNAi has been performed in any lobster species. These results pave the way for inducing RNAi in spiny lobsters, and better understanding the mechanisms of systemic RNAi in Crustacea, as well as across phyla.

Dictyostelium discoideum is gaining increasing attention as a model organism for the study of calcium binding and calmodulin function in basic biological events as well as human diseases. After a short overview of calcium-binding proteins, the structure of Dictyostelium calmodulin and the conformational changes effected by calcium ion binding to its four EF hands is compared to its human counterpart, emphasizing the highly conserved nature of this central regulatory protein. The calcium-dependent and -independent motifs involved in calmodulin binding to target proteins are discussed with examples of the diversity of calmodulin binding proteins that have been studied in this amoebozoan. The methods used to identify and characterize calmodulin binding proteins is covered followed by the ways Dictyostelium is currently being used as a system to study several neurodegenerative diseases and how it could serve as a model for studying calmodulinopathies such as those associated with specific types of heart arrythmia. Because of its rapid developmental cycles, its genetic tractability, and a richly endowed stock center, Dictyostelium is in a position to become a leader in the field of calmodulin research.

There is increasing evidence and recognition that Lyme borreliosis, and other associated tick-borne diseases (LB/TBD) cause mental symptoms. Data was drawn from databases, search engines and clinical experience to review current information on LB/TBD. LB/TBD infections cause immune and metabolic effects that result in a gradually developing spectrum of neuropsychiatric symptoms, usually presenting with significant comorbidity and may include developmental disorders, autism spectrum disorders, schizoaffective disorders, bipolar disorder, depression, anxiety disorders (panic disorder, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder, intrusive symptoms), eating disorders, decreased libido, sleep disorders, addiction, opioid addiction, cognitive impairments, dementia, seizure disorders, suicide, violence, anhedonia, depersonalization, dissociative episodes, derealization and other impairments. Screening assessment followed by a comprehensive psychiatric clinical exam relevant to patient’s complaints and findings with a thorough history, mental status exam, review of systems, neurological exam, physical exam, a knowledgeable interpretation of laboratory findings, pattern recognition and clinical judgment facilitate diagnosis. Psychotropics and antibiotics may help improve functioning and prevent further disease progression. Awareness of the association between LB/TBD and neuropsychiatric impairments and studies of their prevalence in neuropsychiatric conditions can improve understanding of the causes of mental illness and violence and result in more effective prevention, diagnosis and treatment.

Besides common skin pathogens, acute focal lymphadenitis in humans can be caused by a zoonotic pathogen in rare cases. Furthermore, it can develop in absence of any direct or indirect contact with infected animal in cases when the microorganism is transmitted by vector. This clinical entity is rare, and therefore not easily recognized in most regions, yet many zoonotic illnesses are considered emerging or re-emerging nowadays. Focal zoonotic vector-borne lymphadenitis and its numerous causative agents with their variegated clinical manifestations have been described in some case reports and small case series. Therefore, we tried to summarize those data in this narrative overview, with the aim to rise clinical awareness, which could improve clinical outcomes. This overview briefly covers reported pathogens, their vectors and geographic distribution, as well as their main clinical manifestations, diagnostic possibilities and recommended therapy. Vector-borne tularemia, plague, bartonellosis, rickettsioses, borreliosis and Malayan filariasis are mentioned. According to the existing data, when acute focal bacterial vector-borne zoonotic lymphadenitis is suspected, in severe or complicated cases it seems prudent to apply combined aminoglycoside (or quinolone) plus doxycycline as an empirical therapy, pending definite diagnostic results. In this field the „one health approach” and further epidemiological and clinical studies are needed.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, wings, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects and all other arthropods. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. As a means of renaming this protein family, this review article discusses the latest findings (“CSP” is attached to the tail of bigger intracellular proteins) and attempts to compel all the data. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins) and use at least for abbreviations for distinctive animal proteins the common peptide 5-letter code, such as “Bommo-4CSPs”.

Background: Despite its global eradication in 1977, smallpox remains a concern owing to its potential as a biological agent, thereby prompting the ongoing development and utilization of its vaccine. Vaccination with the Vaccinia virus induces immunity against variola virus, the causative agent of smallpox; however, this immunity does not extend to viruses of different genera within the Poxviridae family. In this study, we aimed to assess the efficacy of an enzyme-linked immunosorbent assay (ELISA) method utilizing Vaccinia virus and recombinant A27L antigen for detecting antibodies against smallpox. Methods. Analysis of serum from 20 individuals pre- and post-vaccination with the CJ strain (CJ50300) revealed neutralizing antibodies, which were confirmed using the plaque reduction neutralization test (PRNT). The ELISA method, validated with a PRNT50 cut-off value of &gt;4, exhibited a sensitivity and specificity of &gt;95% and was particularly reactive with the inactivated virus. Furthermore, adherence to the smallpox vaccination policy revealed significant differences in Orthopoxvirus antibody levels among 300 individuals of different age groups. These findings highlight the reliability and efficacy of the ELISA method in detecting post-vaccination antibodies and contribute significantly to diagnostic methods to prepare for potential smallpox resurgence and bioterrorism threats.

Ice-binding proteins (IBPs) have several functions that permit their hosts to thrive in the presence of ice. The ability of IBPs to control ice growth makes them potential additives in various industries ranging from food storage and cryopreservation to anti-icing systems. For IBPs to be used in commercial applications, however, methods are needed to produce sufficient quantities of high-quality proteins. Here, we describe a new method for IBP purification, termed falling water ice purification (FWIP). The method is based on the affinity of IBPs for ice. A crude IBP solution is allowed to flow continuously over the large chilled vertical surface of a commercial ice machine. The temperature of the surface is lowered gradually until ice crystals are produced, to which the IBPs bind but other solutes do not. As in other ice affinity methods, FWIP does not require molecular tags and is suitable for purifying recombinant IBPs as well as IBPs from natural sources. The advantage of FWIP over other ice affinity methods is that it exploits an ice machine designed to produce large volumes of clear ice daily. This system can be easily scaled up and suits the purification of industrial quantities of IBPs. The FWIP method significantly advances the use of IBPs in research and industry.

In March 2013, a novel avian influenza A H7N9 virus was emerged in China, which cause rapidly progressive pneumonia and with a high fatality rate. Serologic studies to evaluate neutralizing antibodies of infected patients and birds are invaluable tools for immunogenicity research of H7N9 and epidemiological investigation. Conventional neutralization assays are laborious and time-consuming which also hampered by biosafety requirement. In this study, We construct and produce pseudovirus bearing the full-length hemagglutinin (HA) of H7N9 virus in the Env-defective, luciferase-expressing HIV-1 backbone. The production of lentiviral pseudovirus was analysed by HA gene specific real-time reverse-transcription PCR, transmission electron microscopy (TEM), and Western Blot assay to prove the nucleic acid replication, the morphology of virus, and the expression of HA protein in pseudovirus. After that pseudovirus based inhibition assay was established to detect neutralizing antibodies of a panel of serum samples. Our results demonstrated that H7N9 pseudovirus which had single-cycle infection was generated. By comparing the neutralization antibody titers, pseudovirus based neutralization test could be recognized as an alternative of conventional microneutralization (MN). Hence, we conclude that it is possible to use pseudovirus inhibition assay to screen sera samples, as well as evaluate vaccine-induced neutralizing antibodies against H7N9 virus.

Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individual’s resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled, re-vaccinated with two doses of Shanchol™ regardless of previous vaccination and followed-up for 90 days. Bloods collected at baseline before re-vaccination, at day 14 prior to second dosing and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60 and 90 across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.

The RNA-binding protein Human antigen R (HuR) regulates stability, translation, and nucleus-to-cytoplasm shuttling of its target mRNAs. The protein has been progressively recognized as a relevant therapeutic target for several pathologies like cancer, neurodegeneration, as well as inflammation. Inhibitors of mRNA binding to HuR might thus be beneficial against a variety of diseases. Here we present the rational identification of structurally novel HuR inhibitors. In particular, by combining chemoinformatics approaches, high throughput virtual screening and RNA–protein pull-down assays, we show that the 4-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)hydrazineyl)benzoate ligand exhibits dose-dependent HuR inhibition in binding experiments. Importantly, the chemical scaffold is new with respect to the so-far known HuR inhibitors, opening up a new avenue for the design of pharmaceutical agents targeting this important protein.

Methylmalonic acidemia (MMA), propionic acidemia (PA), and cobalamin C deficiency (cblC) share a defect in propionic acid metabolism. In addition, cblC is also involved in the process of homocysteine remethylation. These three diseases produce various phenotypes and complex downstream metabolic effects. In this study we used an untargeted metabolomics approach to investigate the biochemical differences and the possible connections with the pathophysiology of each disease. Untargeted urine metabolomic profiles of 21 patients (7 MMA, 7 PA, 7 cblC) were identified through statistical analysis (p&lt;0.05; log2FC &gt;|1|) and then used for the annotation. Annotated features were associated with different metabolic pathways potentially involved in the diseases development. Comparative statistic showed markedly different metabolomic profiles between MMA, PA and cblC, highlighting characteristic species for each disease. The most affected pathways were related to the metabolism of organic acids (MMA, PA, cblC), amino acids (MMA, PA, cblC), glycine and its conjugates (PA), transsulfuration pathway (cblC), oxidative processes (cblC) and neurosteroid hormones (cblC). The untargeted metabolomics study highlighted the presence of significant differences between the three diseases, pointing to the most relevant contrast of cblC profile compared to MMA and PA. Some new biomarkers are proposed for PA, while novel data regarding the alterations of steroid hormone profiles and biomarkers of oxidative stress were obtained for cblC disease. The elevation of neurosteroids in cblC may indicate a potential connection with the development of ocular and neuronal deterioration.

The B169L protein (pB169L) of African swine fever virus (ASFV) is a structural protein with an unidentified function during the virus replication. The sequences of the B169L gene and the downstream B438L gene are separated by short intergenic regions. However, the regulatory mode of the gene transcription remains unknown. Here, we identified two distinct promoter regions and two transcription start sites (TSS) located upstream of the open reading frame (ORF) of B438L. Using the promoter reporter system, we demonstrated that the cis activity of the ORF proximal promoter exhibited significantly higher levels compared with that of the distal promoter located in the B169L gene. Furthermore, transfection with the plasmids with two different promoters for B438L could initiate the transcription and expression of the B438L gene in HEK293T cells, and the cis activity of the ORF proximal promoter also displayed the higher activities compared with the distal promoter. Interestingly, the B438L distal promoter also initiated the transcription of the alternatively spliced B169L mRNA (B169L mRNA2) encoding a truncated pB169L (tpB169L) (amino acids 92–169), and the gene transcription efficiency was increased upon mutation of the initiation codon located upstream of the alternatively spliced B169L gene. Taken together, we demonstrated that the distal promoter of B438L gene initiates the transcription of both the B438L mRNA and B169L mRNA2. Comprehensive analysis of the transcriptional regulatory mode of the B438L gene is beneficial for the understanding of the association of B438L protein and pB169L and the construction of the gene-deleted ASFV.

A defining feature of a productive infection is the co-opting of host cell resources for viral replication. Despite their repertoire of molecular functions, viruses subvert host defenses to take control of cellular factors such as RNA binding proteins (RBPs). RBPs are involved in virtually all steps of mRNA life forming ribonucleoprotein complexes (mRNPs) in a highly ordered and regulated process to control RNA fate and stability in the cell. Thus, the hallmark of this viral takeover is to reshape RNA fate in the cell to modulate host gene expression and evade immune responses. Here we provide an extensive review of work in this area, particularly how the host-viral interplay influences RBP functions to modulate the host cell. Overall, in this review, we highlight the myriad of ways RBPs can regulate RNA stability in either a pro-viral or antiviral manner by gathering novel insights gained from research studies in this field.

Galectins are β-galactosyl-binding proteins that fulfill essential physiological functions. Recently, we introduced galectin-1 (Gal-1) and galectin-3 (Gal-3) as fusion proteins of a His6-tag, a SNAP-tag, and a fluorescent protein. We characterized their binding in ELISA-type assays and their application in cell-surface binding. In the present study, we have constructed further fusion proteins of galectins with fluorescent protein color code. The fusion proteins of Gal-1, Gal-3, and Gal-8 were purified by affinity chromatography. For this, we have prepared glycoprotein affinity resins based on asialofetuin (ASF) and fetuin and combined this in a two-step purification with Immobilized Metal Affinity chromatography (IMAC) to get pure and active galectins. Purified galectin fractions were analyzed by size-exclusion chromatography. The binding characteristics to ASF of solely His6-tagged galectins and galectin fusion proteins were compared. As an example, we demonstrate a 1.6-3-fold increase in binding efficiency for HSYGal-3 (His6-SNAP-yellow fluorescent protein-Gal-3) compared to the HGal-3 (His6-Gal-3). Our results reveal an apparent higher binding efficiency for galectin SNAP-tag fusion proteins compared to His6-tagged galectins which are independent of the purification mode. This is also demonstrated by the binding of galectin fusion proteins to extracellular glycoconjugates laminin, fibronectin, and collagen IV. Our results indicate the probable involvement of the SNAP-tag in apparently higher binding signals, which we discuss in this study.

The high transmissibility, rapid evolution, and immune escape of SARS-CoV-2 variants can influence the course of infection and, in turn, morbidity and mortality in COVID-19, posing a challenge in controlling transmission rates and contributing to the emergence and spread of new variants. The factors that shape viral genetic variation are consequently essential for understanding the evolution and transmission of SARS-CoV-2, especially in vaccinated individuals where immune response plays a role in the progression and spread of this disease. This study assessed. In this context, we evaluated the impact of immunity induced by the CoronaVac vaccine (Butantan/Sinovac) on intra-host genetic diversity, analyzing 118 whole-genome sequences of SARS-CoV-2 from unvaccinated and vaccinated patients infected with the Gamma variant. Vaccination with CoronaVac favors negative selection at the intra-host level in different genomic regions and prevent greater genetic diversity of SARS-CoV-2, which may help reduce the emergence of new mutations, reinforcing the importance of vaccination in reducing virus transmission.

We introduced a novel biotin-binding peptide for sensing biotin, biotinylated proteins, and nu-cleotides. From a 15-mer library displayed on the RNA coliphage Qβ, a 15-amino acid long peptide (HGHGWQIPVWPWGQG) hereby referred to as nanotag was identified to selectively bind biotin. The targets selection was achieved through panning with elution by infection. The selected peptide was tested as a transducer for an immunogenic epitope of the foot-and-mouth disease virus (FMDV) on Qβ phage platform separated by a linker. The biotin-tag showed no significant in-fluence on the affinity of the epitope to its cognate antibody (SD6). The nanotag bound biotin selectively when fused either to the C- or N-terminus of the epitope. The epitope would not bind or recognize SD6 while positioned at the N-terminus of the nanotag. Additionally, the biotin com-peted linearly with the SD6 antibody in a competitive ELISA. Competition assays using the se-lected recombinant phage itself as a probe, or transducer, enable the operationalization of this technology as a biosensor toolkit to sense and quantify SD6 analyte. Herein, the published Strep II nanotag (DVEWLDERVPLVET) was used as a control and has similar functionalities to our pro-posed novel biotin-tag thereby providing a new platform for developing devices for diagnostic purposes.

Study of RNA-protein interactions and identification of RNA targets are among the key aspects of understanding the RNA biology. Currently, various methods are available to investigate these interactions, in particular, RNA pulldown assay. In the present paper, a method based on the HaloTag technology is presented that is called Halo-RPD (HaloTag RNA PullDown). The proposed protocol uses plants with stable fusion protein expression and the MagneBeads magnetic beads to capture RNA-protein complexes directly from the cytoplasmic lysate of transgenic A. thaliana plants. The key stages described in the paper are as follows: 1) preparation of the magnetic beads 2) tissue homogenization and collection of control samples 3) precipitation and wash of RNA-protein complexes; 4) evaluation of protein binding efficacy; 5) RNA isolation; 6) analysis of the obtained RNA. Recommendations for better NGS assay designs are provided.

Our recent work has focused on the application of infinite group theory and related algebraic geometric tools in the context of transcription factors and microRNAs. We were able to differentiate between “healthy" nucleotide sequences and disrupted sequences that may be associated with various diseases. In this paper, we extend our efforts to the study of messenger RNA metabolism, showcasing the power of our approach. We investigate (i) mRNA translation in prokaryotes and eukaryotes, (ii) polyadenylation in eukaryotes, which is crucial for nuclear export, translation, stability, and splicing of mRNA, (iii) miRNAs involved in RNA silencing and post-transcriptional regulation of gene expression, and (iv) the identification of disrupted sequences that could lead to potential illnesses. To achieve this, we employ (a) infinite (finitely generated) groups fp, with generators representing the r+1 distinct nucleotides and a relation between them [e.g., the consensus sequence in the mRNA translation (i), the poly(A) tail in item (ii), and the miRNA seed in item (iii)], (b) aperiodicity theory, which connects “healthy groups" fp to free groups Fr of rank r and their profinite completion F^r, and (c) the representation theory of groups fp over the space-time-spin group SL2(C), highlighting the role of surfaces with isolated singularities in the character variety. Our approach could potentially contribute to the understanding of the molecular mechanisms underlying various diseases and help develop new diagnostic or therapeutic strategies.

Background: This study aimed to identify the association between occupational stress and depression-well-being by proposing a comprehensive and flexible job burden-capital model with its corresponding hypotheses. Methods: For this research, 1618 valid samples were gathered from the electronic manufacturing service industry in Hunan Province, China; self-rated questionnaires were administered to participants for data collection after obtaining their written consent. The proposed model was fitted and tested through structural equation model analysis. Results: Single-factor correlation analysis results indicated that coefficients between all items and dimensions had statistical significance. The final model demonstrated satisfactory global goodness of fit (CMIN/DF=5.37, AGFI=0.915, NNFI=0.945, IFI=0.952, RMSEA=0.052). Both the measurement and structural models showed acceptable path loadings. Job burden and capital were directly associated with depression and well-being or indirectly related to them through personality. Multi-group structural equation model analyses indicated general applicability of the proposed model to basic features of such a population. Gender, marriage and education led to differences in the relation between occupational stress and health outcomes. Conclusions: The job burden-capital model of occupational stress-depression and well-being was found to be more systematic and comprehensive than previous models.

Nuclear export of viral mRNAs, is an essential step in the HIV replication cycle. This role is played by a small regulatory protein of HIV-1 called Rev.The N-terminal region of Rev contains an arginine-rich sequence. The arginine-rich motif (ARM) is located between amino acids 38-50 and forms an alpha-helical secondary structure. Expression of the structural proteins of human immunodeficiency virus type 1 requires the direct interaction of multiple copies of the viral Rev protein with its highly structured RNA target sequence, the Rev Response element (RRE). The major viral proteins are not produced if this transport of RNA is stopped. Therefore, knowledge of Rev structure is essential for understanding of its cooperative binding to the RRE, for understanding the mechanism of HIV infection and for the development of antiviral drugs that interfere with Rev’s essential functions and for acknowledgment of good candidate drugs for treatment of AIDS. To understand how REV interact with RRE element of HIV-RNA and its formation of oligomeric complex it is better to characterize the domain wise structure of REV with regard in function of each domain. Due to lack of structural data on Rev no single compound is reported as inhibitor of REV expect antiviral drugs. Identification of a high-affinity RNA-binding site for the human immunodeficiency virus type 1 Rev Protein is much more important. The ARM is a highly specific sequence which allows for the multimerization of Rev and also binding of REV with RNA. Here we are first time exploring the structural characteristics of REV protein both in free form and in complex with RNA at domain function level especially explore the role of ARM motif in REV HIV-1 protein as RNA binding sites by molecular dynamics (MD) simulation and homology modeling studies. Results indicate that the arginine-rich motif (ARM) is crucial in stability of this complex. The residues ARG38, 39, 41, 43, 44, 48, 50, and ASN40 are most interacting with nucleobases of RRE in Crystal structure of Rev and Rev-response-element RNA complex. Our study plays a major role in elaboration of binding of RNA with REV and pave the way for further investigation for therapeutically agent for HIV.

Mosquito-borne diseases (MBDs) are a group of illnesses transmitted by mosquitoes and can be caused by bacteria, viruses, or parasites. These diseases represent a significant global burden of infectious diseases, including morbidity and mortality. This systematic review delves into the multifaceted factors contributing to the spread of mosquito-borne diseases (MBDs) in the Middle East and North Africa (MENA) region. Following PRISMA guidelines, a thorough analysis of peer-reviewed articles from May 1990 to Jan 2023 was conducted, highlighting the interplay of population, environmental, disease, and mosquito factors in disease transmission and prevalence. The review incorporated 31 studies that revealed a complex relationship between various risk factors and the presence of MBDs. Significant associations were observed with age, certain occupations, environmental conditions such as rainfall and temperature, sanitation practices, specific pathogen variants, clinical symptoms, and Aedes aegypti mosquitoes. Conversely, gender, socioeconomic status, educational status, and certain sanitation-related factors showed inconsistent association with the spread of MBDs. The review underscores the need for targeted interventions, including vector control, improved sanitation, and educational campaigns to mitigate the spread of MBDs in the MENA region. This review could guide research studies to address data gaps and assist in developing effective surveillance programs in the MENA region. This work emphasizes the need for region-specific public health strategies and further research to understand and curb the burden of these diseases effectively.

Tumor necrosis factor (TNF) inhibitors (anti-TNFs) represent a cornerstone of the treatment of various immune-mediated inflammatory diseases and are among the most commercially successful therapeutic agents. Knowledge of TNF binding partners is critical for identification of the factors able to affect clinical efficacy of the anti-TNFs. Here we report that among eighteen representatives of the multifunctional S100 protein family only S100A11, S100A12 and S100A13 interact with the soluble form of TNF (sTNF) in vitro. The lowest equilibrium dissociation constants (Kd) for the complexes with monomeric sTNF determined using surface plasmon resonance spectroscopy range from 2 nM to 28 nM. The apparent Kd values for the complexes of multimeric sTNF with S100A11/A12 estimated from fluorimetric titrations are 0.1-0.3 µM. S100A12/A13 suppress the cytotoxic activity of sTNF against Huh-7 cells, as evidenced by the MTT assay. Structural modeling indicates that the sTNF-S100 interactions may interfere with the sTNF recognition by the therapeutic anti-TNFs. Bioinformatic analysis reveals dysregulation of TNF and S100A11/A12/A13 in numerous disorders. Overall, we have shown a novel potential regulatory role of the extracellular forms of specific S100 proteins that may affect efficacy of anti-TNF treatment in various diseases.

Streptococcus pneumoniae is an pathogenic and opportunistic Gram-positive bacteria that is the leading cause of community acquired respiratory diseases, varying from mild- to deathly- infections. Appearance of antibiotic resistant isolates has prompted the search for novel targets. One of the most promising approaches is the structure-based knowledge of possible targets in conjunction to rational design and docking of inhibitors of the chosen targets. A useful technique to help solving protein structures is to label them with a heavy atom, like selenium, that facilitates tracing of the some of the amino acid residues. We have chosen two pneumococcal DNA-binding proteins, namely the relaxase domain of MobM protein from plasmid pMV158, and the RelB-RelE antitoxin-toxin protein complex. Through the update of a previous protocol [1] that uses seleno-L-methionine, we could achieve 100% labelling of the proteins. Furthermore, the labelled proteins retained full activity as judged from relaxation of supercoiled plasmid DNA and from gel-retardation assays.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p &lt; 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

In the matrix of bacteria/mitochondria/chloroplasts, Lon acts as the degradation machine for soluble proteins. In stress periods, however, proteostasis and survival depend on the strongly conserved Clp/Hsp100 family. Currently, the targets of ATP-powered unfoldases/disaggregases ClpB and ClpX, and of peptidase ClpP heptameric rings, are still unclear. Trapping experiments and proteome profiling in multiple organisms triggered confusion, so we analyzed the consistency of ClpP-trap targets in bacteria. We also provide meta-analyses of protein interactions in humans, to elucidate where Clp family members are enriched. Furthermore, meta-analyses of mouse complexomics are provided. Genotype-phenotype correlations confirmed our concept. Trapping, proteome, and complexome data retrieved consistent coaccumulation of ClpXP with GFM1 and TUFM orthologs. ClpX shows broad interaction selectivity encompassing mitochondrial translation elongation, RNA granule, and nucleoid; ClpB preferentially attaches to mitochondrial RNA granule and translation initiation components; ClpP is enriched with them all, and associates with release/recycling factors. Mutations in ClpP cause Perrault syndrome, with phenotypes similar to defects in mtDNA/mtRNA. Thus, we propose that ClpB and ClpXP are crucial to counteract misfolded insoluble protein assemblies that contain nucleotide-phosphates. This insight is relevant to improve ClpP-modulating drugs that block bacterial growth, and for the treatment of human infertility, deafness and neurodegeneration.

Vaccine uptake is one of the indicators that has been used to guide immunization programs. This study aimed to evaluate whether the measles vaccine uptake is predicted by measles vaccine hesitancy. A community-based cross-sectional study was conducted in urban districts in Khartoum state in February 2019. Measles vaccine uptake among children was measured as either fully vaccinated or partially/not vaccinated. The Parents Attitude about Childhood Vaccination (PACV) scale was used to measure measles vaccine hesitancy. Multivariate logistic regression was run to identify the predictors of measles vaccination uptake controlling for sociodemographic variables and the adjusted odds ratios (aORs) with 95% CI were calculated. The receiver operator characteristic (ROC) curve was performed, besides area under the curve (AUC) for the PACV was computed. Data was collected from 495 participants. We found that measles vaccine hesitancy (PACV scores) predicted the uptake of measles vaccine after controlling other potential social confounders such as mother’s age and the number of children (aOR 1.055, 95% CI 1.028-1.028). Additionally, the ROC for the PACV yielded area under the curve (AUC 0.686 (95% CI 0.620-0.751, P <0.001). Our findings show that measles vaccine hesitancy in Sudan directly influences the uptake of the measles vaccine. Addressing the determinants of vaccine hesitancy through communication strategies will improve vaccine uptake.

Although significant efforts have been made to combat the spread of vector-borne diseases (VBDs), they still account for more than 17% of all infectious diseases. According to the World Health Organization (WHO), there were 216 million estimated cases in 2016, which is a 9.3% decrease from the estimated cases reported one decade earlier. It is known that the built environment, through features such as openings, can propagate the spread of malaria. There have been some significant efforts directed at addressing this risk. This notwithstanding, there are some knowledge gaps that have resulted in a missed opportunity for synergistically tackling the problem of vectors through leveraging design decisions made by built environment professionals. This work assesses the extent to which design decisions in the built environment can have a positive impact on the efforts directed at mitigating the risk of malaria based on selected cases from East Africa. Secondary data derived from relevant urban health journals as well as repositories curated by leading health agencies such as WHO were synthesized and analyzed using a web of causation approach. The outcome of the analysis is a schema of primary and secondary source (risk) factors. The use of the web of causation approach revealed the existing factor-to-factor interactions that could have a reinforcing effect. This information was used to identify the critical linkages and interdependencies across different factors. The outcome of the analysis was mapped against risk factors that can be linked to decisions made during the six primary phases of the construction life cycle: preliminary phase, conceptual design, detailed design, construction, facilities management, and end of life/disuse. The findings of the research have established that 1) there is, in fact, a built environment–related opportunity that can be leveraged to advance the impact of malaria mitigation effort; 2) cross-disciplinary synergies are critical to managing the interdependencies and complexity of malaria risk factors that have a reinforcing effect; and 3) a knowledge-management framework that serves as a decision support tool would be valuable for sharing data under a push-and-pull mechanism, in which data shared in real time can address the timeliness of mitigating the spread of malaria at the earliest stages for the greatest impact. Based on the findings, a conceptual architecture for a decision support framework has been proposed. This will be developed into a knowledge-management platform in subsequent efforts.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent world-wide. It progresses from simple steatosis to non-alcoholic steatohepatitis (NASH). Fibrosis is often present during NAFLD progression; however, factors determining which subjects develop NASH or fibrosis are unclear. Insulin-like growth factor binding proteins (IGFBP) is a family of secreted proteins involved in senescence and scarring mainly synthetized in the liver. Here we aimed to study the association of IGFBP and its induced senescence with the progression of NAFLD and liver fibrosis. Materials and Methods: 16 weeks old male C57BL/6 mice weighing 23 ± 3 g were fed either Methionine-Choline Deficient or control diet for 2, 8 or 12 weeks. Blood and liver samples were collected; histological assessment of NAFLD and fibrosis was performed. Fat contents were measured. Cellular senescence was evaluated in the liver. IGFBP levels were assessed in liver and serum. Data was expressed as Mean ± SD and analyzed by one-way ANOVA followed Tukey’s test. Lineal regression models were applied for NAFLD and fibrosis progression. p

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. This article tries to compel and discuss the most recent information as a way to rename this protein family. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins).

The advancement of precision medicine critically depends on the robustness and specificity of the carriers used for the targeted delivery of effector molecules in the human body. Numerous nanocarriers have been explored in vivo, to ensure the precise delivery of molecular cargos via tissue-specific targeting, including the endocrine part of the pancreas, thyroid, and adrenal glands. However, even after reaching the target organ, the cargo-carrying vehicle needs to enter the cell and then escape from lysosomal destruction. Most of artificial nanocarriers suffer from intrinsic limitations that either prevent them from completing the specific delivery of the cargo. In this respect, extracellular vesicles (EVs) seem to be the natural tool for payload delivery due to their versatility and low toxicity. However, EV-mediated delivery is not selective and usually short-ranged. By inserting the viral membrane fusion proteins into exosomes, it is possible to increase the efficiency of membrane recognition and also ease the process of membrane fusion. This review describes the molecular details of the viral-assisted interaction between the target cell and extracellular vesicles. We also discuss the question of the usability of viral fusion proteins in developing extracellular vesicle-based nanocarriers with higher efficacy of payload delivery. Finally, this review specifically highlights the role of Gag and RNA binding proteins in RNA sorting into extracellular vesicles.

Understanding the binding behavior and conformational dynamics of intrinsically disordered proteins (IDPs) is crucial for unraveling their regulatory roles in biological processes. However, their lack of stable 3D structures poses challenges for analysis. To address this, we propose an algorithm that explores IDP binding behavior with protein complexes by extracting topological and geometric features from the protein surface model. Our algorithm identifies a geometrically favorable binding pose for the IDP and plans a feasible trajectory to evaluate its transition to the docking position. We focus on IDPs from Homo sapiens and Mus-musculus, investigating their interaction with the Plasmodium Falciparum (PF) pathogen associated with malaria-related deaths. We compare our algorithm with HawkDock and HDOCK docking tools for quantitative (computation time) and qualitative (binding affinity) measures. Our results indicate that our method outperforms the compared methods in computation performance and binding affinity of experimental conformations.

Background: Obesity remains a widely debated issue, often criticized for the limitations in its identification and classification. This study aims to compare two distinct systems for classifying obesity: Body Mass Index (BMI) and body fat percentage (BFP) as assessed by bioelectrical impedance analysis (BIA). By examining these measures, the study seeks to clarify how different metrics of body composition influence the identification of obesity-related risk factors. Methods: The study enrolled 1255 adults, comprising 471 males and 784 females, with a mean age of 36 ± 11.90 years. Participants exhibited varying degrees of weight status, including optimal weight, overweight, and obesity. Body composition analysis was conducted using the TANITA Body Composition Analyzer BC-418 MA III device (T5896, Tokyo, Japan), evaluating the following parameters: current weight, basal metabolic rate (BMR), adipose tissue (%), muscle mass (%), and hydration status (%). Results: Age and psychological factors like cravings, fatigue, stress, and compulsive eating were significant predictors of obesity in the BMI model but not in the BFP model. Additionally, having a family history of diabetes was protective in the BMI model (OR: 0.33) but increased risk in the BFP model (OR: 1.66). The BMI model demonstrates exceptional predictive ability (AUC=0.998). In contrast, the BFP model, while still performing well, exhibits a lower AUC (0.975), indicating slightly reduced discriminative power compared to the BMI model. Conclusions:BMI classification demonstrates superior predictive accuracy, specificity, and sensitivity. This suggests that BMI remains a more reliable measure for identifying obesity-related risk factors compared to the BFP model.

A U.S. government health agency conducted epidemiological studies to evaluate whether exposures to drinking water contaminated with volatile organic compounds at U.S. Marine Corps Base Camp Lejeune, North Carolina, were associated with increased health risks to children and adults. These health studies required knowledge of contaminant concentrations in drinking water—at monthly intervals—delivered to family housing, barracks, and other facilities within the study area. Because concentration data were limited or unavailable during much of the period of contamination (1950s–1985), the historical reconstruction process was used to quantify estimates of monthly mean contaminant-specific concentrations. This paper integrates many efforts, reports, and papers into a synthesis of the overall approach to, and results from, a drinking-water historical reconstruction study. Results show that at the Tarawa Terrace water treatment plant (WTP) reconstructed (simulated) tetrachloroethylene (PCE) concentrations reached a maximum monthly average value of 183 micrograms per liter (ug/L) compared to a one-time maximum measured value of 215 ug/L and exceeded the U.S. Environmental Protection Agency’s current maximum contaminant level (MCL) of 5 ug/L during the period November 1957–February 1987. At the Hadnot Point WTP, reconstructed trichloroethylene (TCE) concentrations reached a maximum monthly average value of 783 ug/L compared to a one-time maximum measured value of 1,400 ug/L during the period August 1953–December 1984. The Hadnot Point WTP also provided contaminated drinking water to the Holcomb Boulevard housing area continuously prior to June 1972, when the Holcomb Boulevard WTP came on line (maximum reconstructed TCE concentration of 32 ug/L) and intermittently during the period June 1972–February 1985 (maximum reconstructed TCE concentration of 66 ug/L). Applying the historical reconstruction process to quantify contaminant-specific monthly drinking-water concentrations is advantageous for epidemiological studies when compared to using the classical exposed versus unexposed approach.

Exogenous RNA comprises the genetic material associated with several diseases which require immediate treatment, and thus mechanisms to hinder intracellular translation and reproduction of RNA viral agents are of great importance. Applying recent developments from this lab in methods relating to the interaction of DNA with steroid hormones, cyclic compounds are presented for intermolecular binding to nucleic acids. The requirements to achieve binding with RNA nucleotide pairs are described, which involve at a minimum functional elements positioned to interact with the lateral phosphate groups for each of the RNA strands through coupling with a positively charged ion, such as Mg2+, Ca2+, or Zn2+ ions; and an intermolecular hydrogen bond with the oxygen element of uracil at the carbon two location. Additional features of the binding molecules are examined for enhancements and differentiation in binding capability and include aromatic groups that have both a structural role of steric hindrance and a functional role to stabilize the binding mechanisms. Several categories of cyclic compounds are associated to have specific binding capabilities, and the interaction of these structures with potential receptor molecules are evaluated for assessment in delivery and binding of the compound to nucleic acids.

Two X chromosomes of female mammals randomly inactivate one of paternal or maternal X chromosome in early embryonic development and all the daughter cells produced from these cells retain the same feature of X chromosome inactivation, which is called X chromosome inactivation (XCI). Studying the mechanisms of XCI is important for understanding epigenetic that plays an important role in age-associated diseases. The previous studies have demonstrated that binding of RNAs and DNAs may play a role in activating gene expression. In this paper, our study aims to explore whether the mechanisms of XCI involve the RNA binding strength to X chromosome DNAs. The bioinformatics analyses based on big data were used to analyze the simulated binding strength of RNAs (RNA binding strength) to 23 chromosomes (including X chromosome and 22 human autosomes) and the characteristics of repetitive sequences in the X-inactivation centre. The results revealed that RNA binding strength of the long arm of the X chromosome that is almost entirely inactivated in XCI was significantly lower than that of all autosomes and the short arm of X chromosome, meanwhile the RNA binding strengths of inactivation regions in X chromosome were significantly lower than that of regions escaping from XCI. Different repetitive sequence clusters within the center of XCI presented a cross distribution characteristic. To further prove whether the repetitive sequences in human X chromosome involve in XCI, we cloned long interspersed element (LINE-1, L1) and short interspersed element (Alu) from human Xq13, the center of XCI, and constructed expression vectors carrying sense-antisense combination repetitive sequences (L1s or Alus). Effects of combined L1 or combined Alu sequences on expression of EGFP reporter gene were examined in stably transfected HeLa cells, which simulates the effects of repetitive sequences located on chromosomes. The results of experiments revealed transcribed L1 repetitive sequences activated EGFP reporter gene expression, so did the Alus. The experiment results suggested repetitive sequences activated genes by interaction of transcribed RNAs and DNAs. Since the binding of RNAs and DNAs can activate gene, so the low RNA binding strength of human X chromosome may be one of reasons of XCI. The cross distribution characteristics of different repetitive sequence clusters leading to a cascade of gene activation or gene inactivation may be the reason of transcriptional silencing one of the X chromosomes in female mammals.

Amidst increasing awareness of diet-health relationships, plant-derived bioactive peptides are recognized for their dual nutritional and health benefits. This study investigates bioactive peptides released after Alcalase hydrolysis of protein from chachafruto (Erythrina edulis), a nutrient-rich South American leguminous plant, focusing on their behavior during simulated gastrointestinal digestion. Evaluating their ability to scavenge radicals, mitigate oxidative stress, and influence immune response biomarkers, the study underscores the importance of understanding peptide interactions in digestion. Methods included previous enzymatic hydrolysis with Alcalase to obtain peptides, and results show significant radical scavenging and oxidative stress protection by chachafruto peptides. These findings highlight the potential of chachafruto bioactive peptides in functional foods and nutraceuticals, supporting human health through dietary interventions.

Mammarenavirus Wenzhouense (WENV) is broadly distributed in Asia, while the he dynamics process of WENV infection remains unclear. A field derived strain of WENV was used to inoculate Sprague-Dawley (SD) rats by intramuscular injection, the process of virus infection was de-tected by controlling time for 28 days. Viral RNA became detectable in the blood at 3 d pi, and remained detectable for about 12 d. In most organ tissues, viral RNA peaked at 7 d pi, then began to decline by 14 d, however remained detectable in intestine and brain tissues at 21 and 28 d pi. Virus shedding had been detected from fecal samples for 5 days from 6 to 11 d pi using qRT-PCR, and was recovered from feces collected at 8 d pi. Horizontal contact infection occurred among cage-mates at 14 and 21 d pi. Antibodies against the nucleocapsid were detected at 5 dpi, next increased and persisted until the end of experiment. The results enabled to discriminate the kinetic of viremic response, virus shedding in feces and horizontal transmission, as well as the potential sites for WENV replication or maintenance of the virus in nature.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

One mechanism by which fructose could exert deleterious effect in metabolism and inflammation is via its potency vis-à-vis de Maillard reaction. We employed simulated stomach and duodenum digestion of ovalbumin to test the hypothesis that indeed AGEs are formed by fructose during simulated digestion of an ubiquitous food protein with intrinsic allergenic potential and under model physiological conditions. Methods: OVA was subjected to simulated gastric and intestinal digestion using standard models, in presence of fructose or glucose (0-100 mM). Peptide fractions were analyzed by fluorescence spectroscopy and intensity at Excitation: λ370 nm, Emission: λ 440nm. Results: AGE adducts form between fructose and OVA which can be found in peptide fractions (< 5 kDa) at times (30 min) and concentration ranges (10 mM) plausibly found in the intestines, whereas no reaction occurs with glucose. The reaction is inhibited by chlorogenic acid at concentrations compatible with those found in the gut. The reaction is inhibited by AG, a specific antiglycation agent. Conclusion: Our proof of principle study shows that fructose-AGE formation on an ubiquitous allergenic protein indeed occurs in one hour and thereby may pave the way for the study of yet another mechanism by which the excess fructose in our Western diets is contributing to disease: intestinal AGE formation, absorption and RAGE engagement.

Helicases are proteins that use the energy of ATP to unwind nucleic acids and to remodel protein-nucleic acid complexes. They are involved in almost every aspect of the DNA and RNA metabolisms and participate in numerous repair mechanisms that maintain cellular integrity. Helicases are classified into 6 superfamilies (SF1-6). The archaeal Lhr-type proteins are SF2 helicases that are mostly uncharacterized. They have been proposed to be a DNA helicase that acts in DNA recombination and repair processes in Sulfolobales and Methanothermobacter. In parallel, a protein annotated as an Lhr2 protein was also found in the network of proteins involved in RNA metabolism in Thermococcales. To this respect, we performed in-depth phylogenomic analyses to report the classification and taxonomic distribution of Lhr-type proteins in Archaea, and to better understand their relationship with bacterial Lhr. Furthermore, with the goal of envisioning the role(s) of aLhr2 in archaeal cells, we deciphered the enzymatic activities of aLhr2 from Thermococcus barophilus (Tbar). We showed that Tbar-aLhr2 is a DNA/RNA helicase acting on DNA:RNA and RNA:RNA duplexes and proposed that aLhr2 helicases are involved in processes dependent of DNA and RNA transactions.

The detection, characterization, and monitoring of SARS-CoV-2 recombinant variants is a challenge to public health authorities worldwide. Recombinant variants, composed of two or more SARS-CoV-2 lineages, often have unknown impacts on transmission, immune escape, and virulence in the early stages of emergence. We examined 4,213 SARS-CoV-2 recombinant SARS-CoV-2 genomes collected between 2020 and 2022 from California to describe regional and statewide trends in prevalence. Many of these recombinant genomes, such as those belonging to the XZ lineage, or novel recombinant lineages, likely originated within the state of California. We discuss the challenges and limitations surrounding Pango lineage assignments, the use of publicly available sequence data, and adequate sample sizes for epidemiologic analyses. Although these challenges will continue as SARS-CoV-2 sequencing volumes decrease globally, this study enhances our understanding of SARS-CoV-2 recombinant genomes to date while providing a foundation for future insights into emerging recombinant lineages.

Sodium hypochlorite (NaOCl) is widely used in public healthcare facilities; this exposure can result in the development of bacterial tolerance to disinfectant, which has known links to antibiotic cross-resistance. However, the mechanism through which cross-resistance to antibiotics and disinfectants develops remains ambiguous. Therefore, this study aimed to examine the phenotypic, and transcriptomic changes caused by disinfectant exposure in gram-negative bacteria and determine the cause of cross-resistance to antibiotics. The results demonstrated that the misuse of disinfectants plays an important role in the emergence of disinfectant resistance and in the increase in antibiotic resistance. Antibiotic resistance may occur from exposure of gram-negative bacteria to subminimal inhibitory concentrations (MICs) of NaOCl. Ten passages of gram-negative bacteria in increasingly higher subMICs of NaOCl disinfectant was sufficient to increase the MIC to &gt;2,500 µg/ml NaOCl, particularly in K. pneumoniae and P. aeruginosa. To determine the development of cross-resistance to antibiotics due to NaOCl exposure, the MICs for each antibiotic before and after exposure of each strain to sublethal concentrations of NaOCl were compared. After overnight incubation with a sublethal concentration of NaOCl, a statistically significant increase in MIC was only observed for imipenem (P&lt;0.01). Investigation of the mechanism of cross-resistance by means of transcriptome analysis revealed that 1,250 µg/ml NaOCl-adapted K. pneumoniae and P. aeruginosa strains increased resistance to imipenem due to increased expression of the resistance-nodulation-cell division (RND) efflux pumps, such as AcrAB-TolC and MexAB/XY-OprM. Therefore, we suggest that exposure to NaOCl can influence the expression of RND efflux pump genes, contributing to imipenem cross-resistance.

Following the detection of highly pathogenic avian influenza (HPAI) virus in countries bordering Kenya to the west, we conducted surveillance among domestic and wild birds along the shores of Lake Victoria. In addition, between 2018 and 2020, we conducted surveillance among poultry and poultry workers in live bird markets and among wild migratory birds in various lakes that are resting sites during migration to assess introduction and circulation of avian influenza viruses in these populations. We tested 7,464 specimens (oropharyngeal and cloacal swabs) from poultry and 6,531 fresh fecal specimens from wild birds for influenza A viruses by real-time RT-PCR. Influenza was detected in 3.9% (n=292) of specimens collected from poultry and 0.2% (n=10) of fecal specimens from wild birds. On hemagglutinin subtyping, most of the influenza A positives from poultry (274/292, 93.8%) were H9. Of 34 H9 specimens randomly selected for further subtyping, all were H9N2. On phylogenetic analysis, these viruses were genetically similar to other H9 viruses detected in East Africa. Only two of the ten influenza A positive specimens from the wild bird fecal specimens were successfully subtyped; sequencing analysis of one specimen collected in 2018 was identified as low pathogenicity avian influenza H5N2 virus of the Eurasian lineage and the second specimen, collected in 2020, was subtyped as H11. A total of 18 OP/NS swabs from poultry workers with ARI (12%) were collected; none were positive for influenza A virus. We observed significant circulation of H9N2 influenza viruses in poultry in live bird markets in Kenya. During the same period, low pathogenic H5N2 virus was detected in a fecal specimen collected in a site hosting a variety of migratory and resident birds. Although HPAI H5N8 was not detected in this survey, these results highlight the potential for introduction and establishment of highly pathogenic avian influenza viruses in poultry populations and the associated risk of spillover to human populations.

Head and neck squamous cell carcinoma (HNSCC) arise from the mucosal epithelium in the oral cavity, pharynx, sino-nasal region, and larynx. Laryngeal squamous cell carcinoma (LSCC) represents one-third of all head and neck cancers. Dysregulated RNA-related pathways define an important molecular signature in this aggressive carcinoma. The Survival Motor Neuron (SMN) protein regulates fundamental aspects of the RNA metabolism but, curiously, its role in cancer is virtually unknown. For the first time, here we focus on SMN in cancer context. We conducted a pilot study in a total of 20 patients with LSCC where SMN was found overexpressed at both the protein and transcript levels. By a cellular model of human laryngeal carcinoma, we demonstrated that SMN impacts cancer-relevant behaviors and perturbs key players of cell migration, invasion, and adhesion. Furthermore, in LSCC we showed a physical interaction between SMN and the epidermal growth factor receptor (EGFR), whose overexpression is an important feature in these tumours. This study candidates SMN as novel therapeutic target in LSSC, and likely in the whole spectrum of HNSCC. Overall, we provide the first analysis of SMN in human cancer.

The proper regulation of RNA processing is critical for muscle development and the fine-tuning of contractile ability between muscle fiber-types. RNA binding proteins (RBPs) regulate the diverse steps in RNA processing including alternative splicing, which generates fiber-type specific isoforms of structural proteins that confer contractile sarcomeres with distinct biomechanical properties. Alternative splicing is disrupted in muscle diseases such as myotonic dystrophy and dilated cardiomyopathy, and is altered after intense exercise as well as with aging. It is therefore important to understand splicing and RBP function, but currently only a small fraction of the hundreds of annotated RBPs expressed in muscle have been characterized. Here we demonstrate the utility of Drosophila as a genetic model system to investigate basic developmental mechanisms of RBP function in myogenesis. We find that RBPs exhibit dynamic temporal and fiber-type specific expression patterns in mRNA-Seq data and display muscle-specific phenotypes. We performed knockdown with 105 RNAi hairpins targeting 35 RBPs and report associated lethality, flight, myofiber and sarcomere defects, including flight muscle phenotypes for Doa, Rm62, mub, mbl, sbr, and clu. Interestingly, knockdown phenotypes of spliceosome components, as highlighted by phenotypes for A-complex components SF1 and Hrb87F (hnRNPA1), revealed level- and temporal-dependent myofibril defects. We further show that splicing mediated by SF1 and Hrb87F is necessary for Z-disc stability and proper myofibril development, and strong knockdown of either gene results in impaired localization of Kettin to the Z-disc. Our results expand the number of RBPs with a described phenotype in muscle and underscore the diversity in myofibril and transcriptomic phenotypes associated with splicing defects. Drosophila is thus a useful model to gain disease-relevant insight into cellular and molecular phenotypes observed when expression levels of splicing factors, spliceosome components and splicing dynamics are altered.

We developed a honey bee RNA-virus vector based on the genome of a picorna-like Deformed wing virus (DWV), the main viral pathogen of the honey bee (Apis mellifera). To test the potential of DWV to be utilized as a vector, the 717 nt sequence coding for the enhanced green fluorescent protein (eGFP), flanked by the peptides targeted by viral protease, was inserted into an infectious cDNA clone of DWV in-frame between the leader protein and the virus structural protein VP2 genes. The in vitro RNA transcripts from egfp-tagged DWV cDNA clones were infectious when injected into honey bee pupae. Stable DWV particles containing genomic RNA of the recovered DWV with egfp inserts were produced, as evidenced by cesium chloride density gradient centrifugation. These particles were infectious to honey bee pupae when injected intra-abdominally. Fluorescent microscopy showed GFP expression in the infected cells and Western blot analysis demonstrated accumulation of free eGFP rather than its fusions with DWV LP and/or VP2 proteins. Analysis of the progeny egfp-tagged DWV showed gradual accumulation of genome deletions for egfp, providing estimates for the rate of loss of a non-essential gene an insect RNA virus genome during natural infection.

With a mild Mediterranean-type climate, Corsica is endemic for canine vector-borne diseases (CVBDs) such as dirofilariosis (a mosquitoes borne-diseases: MBDs), leishmaniosis and ehrlichiosis. The aim of this present study was to evaluate a monthly multi-modal prophylactic strategy (MMP) against CVBDs occurring in Corsica. The study was conducted as a comparative field trial in which eighty dogs allocated into two groups were included: (i) Group 1 consisted of 25 dogs under the MMP [per-os administration of 1.5 tablet of milbemycine oxime-praziquantel and a topical line-on application of a 3.6 mL solution of dinotefuran-permethrin-pyriproxyfen] and (ii) Group 2 under various real-life prophylactic treatment (RLP) based on the use of ectoparasiticide products [different formulations: deltamethrin, fluralaner, fipronil] and/or macrocyclic lactones based-products [milbemycin oxime/praziquantel, milbemycin oxime, moxidectin] during the period ranging from June to October 2017. All animals were followed for one year and had blood drawn at day 0, followed by follow-up at 6 and 12 months. Samples were screened for filariosis using molecular tools as well as for leishmaniosis and ehrlichiosis using indirect immunofluorescence assay (IFA). At the end of the study, no new cases of CVBDs were recorded within Group 1. In Group 2, the cumulative incidence of CVBDs was 20.0% (n= 11; p= 0.015) including dirofilarioses due to Dirofilaria immitis and/or D. repens, with 16.4% (n= 9; p=0.027). Ehrlichiosis was 5.5% (n= 3; p=0.241). No new cases of leishmaniosis were detected in Group 2. The data illustrated that, unlike the RLP treatment which failed to protect at least 20% of dogs, the MMP based on the concurrent administration of milbemycine oxime-praziquantel and dinotefuran-permethrin-pyriproxyfen is efficient to protect dogs against CVBDs in a high-risk area.

The appearance of the novel betacoronavirus 2019-nCoV represents a major threat to human health, and its diffusion around the world is predicted to have dramatic economic consequences. The knowledge of the 3D structures of 2019-nCoV proteins can facilitate the development of diagnostic and therapeutic molecules. Herein, we apply our energy-based method for the prediction of potential epitopes on viral proteins to design peptide-based molecules that can subsequently be used in diagnostic and therapeutic applications. We discuss these aspects in the paper.The designs have not been tested. Our aim is to share information that can be useful in the development of novel biomolecules with potential interesting activities against 2019-nCoV.

Preventing the occurrence of secondary caries serves as one of the significant issues in dental clinic, thus make it indispensable to improving the properties of conventional composite resin (CR) by developing a novel CR. In present study, two groups of experimental CRs loaded with different contents of fluoride-doped nano-zirconia fillers (25 wt% and 50 wt%) were fabricated. The surface topography, mechanical performance, fluoride release, antibacterial effect, aging property and cytotoxicity of the experimental CRs were evaluated subsequently. A uniform distribution of the F-zirconia fillers over the whole surface of resin matrix could be observed. The experimental CRs showed continuous fluoride release within 28 days, which was positively correlated with the content of F-zirconia fillers. Moreover, the amount of fluoride release increased in the acidic buffer. Addition of F-zirconia fillers could improve the color stability, wear resistance and microhardness of the experimental CRs, without reducing the flexure strength. Furtherly, the fluoride ions released continuously from the experimental CRs resulted in effective contact and antibacterial properties, while they showed no cytotoxicity. As a consequence, considerations can be made to employ this new kind of composite resin loaded with fluoride-doped nano-zirconia fillers to meet clinical requirements when the antimicrobial benefits are desired.

The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a major outbreak of coronavirus disease 2019 (COVID-19) and instigated a widespread fear and has threatened global health security. Although phenomenal efforts are in progress to effectively combat this COVID-19 outbreak. Still, no licensed antiviral drugs or vaccines are available, and treatment is limited to supportive care and few repurposed drugs. In this urgency situation, computational drug discovery methods provide both an alternative and a supplement to tiresome high-throughput screening, particularly in the hit-to-lead-optimization stage. Identification of small molecules that specifically target viral replication apparatus has shown the most successful strategy in antiviral drug discovery. The present study deals with the identification of potential compounds that specifically interact with SARS-CoV-2 vital proteins, including main protease (Mpro), Nsp12 RNA-dependent-RNA-polymerase (RdRp) and Nsp13 helicase. A constructive and integrated virtual screening efforts together with molecular dynamics simulations identified potential binding modes and favourable molecular interaction profile of corresponding compounds. Moreover, structurally important binding site residues in conserved motifs located inside the active site are elucidated, which displayed relative importance in ligand binding based on residual energy decomposition analysis. Although the current study lacks experimental validation, the structural information obtained from this computational study paved the way to identify and design specific targeted inhibitors to combat COVID-19 outbreak.

Cytosine (C) to uracil (U) RNA editing is one of the most important post-transcriptional processes, however exploring C-to-U editing events efficiently within the crop mitochondrial genome remains a challenge. An improving predictive RNA editor for crop mitochondrial genomes, iPReditor-CMG, was proposed, which was based on SVM, three common crop mitochondrial genomes and self-sequenced tobacco mitochondrial ATPase. After multi-combination feature extracting, high-dimension feature screening and multi-test independent predicting, the results showed that the average accuracy of intraspecific prediction was 0.85, and the highest value even up to 0.91, which outperformed the previous reference models. While the prediction accuracies were 0.78 between dicotyledons and no more than 0.56 between dicotyledons and monocotyledons, implying a possible similarity in C-to-U editing mechanisms among close relatives. The best model was finally identified with an independent test accuracy of 0.91 and an area under the curve of 0.88, and further suggested that five unreported feature sequences TGACA, ACAAC, GTAGA, CCGTT and TAACA were closely associated with the editing phenomenon. Multiple evaluation findings supported that the iPReditor-CMG could be effectively applied to predict crop mitochondrial editing sites, which may contribute to insight into their recognition mechanisms and even other post-transcriptional events in crop mitochondria.

Rubella infection is typically mild or asymptomatic except when infection occurs during pregnancy. Infection in early pregnancy can cause miscarriage, stillbirth, or congenital rubella syndrome. Only individuals that are still susceptible to rubella infection during child-bearing age are vulnerable to this burden. Rubella containing vaccine (RCV) is safe and effective, providing life-long immunity. However, average age-at-infection increases with increasing vaccination coverage, which could potentially lead to increased disease burden as well, if the absolute risk of infection during child-bearing age increases. Dynamics of rubella transmission were explored using EMOD, a software tool for building stochastic, agent-based infection models. Simulations of pre-vaccine, endemic transmission of rubella virus introduced RCV at varying levels of coverage to determine the expected future trajectories of disease burden. Introducing RCV reduces both rubella virus transmission and disease burden for a period of around 15 years. Increased disease burden is only possible more than a decade post-introduction, and only for contexts with low current burden and high transmission intensity. Low or declining rubella virus transmission intensity is concurrently associated with both greater disease burden and greater vaccine effectiveness. The risk of increasing burden through vaccination only exists for locations with persistently high infectivity, high connectivity, and high fertility. A trade-off between the risk of a small, future burden increase and a large, immediate burden decrease strongly favors RCV introduction.

Synaptic transmission is essential for nervous system function and the loss of synapses is a known major contributor to dementia. Alzheimer’s disease dementia (ADD) is characterized by synaptic loss in the mesial temporal lobe and cerebral neocortex, brain areas associated with memory and cognition. The association of synaptic loss and ADD was established in the late 1980s and it has been estimated that 30-50% of neocortical synaptic protein is lost in ADD, but there has not yet been a quantitative profiling of different synaptic proteins in different brain regions in ADD from the same individuals. Very recently, PET imaging of synapses is being developed, accelerating the focus on the role of synaptic loss in ADD and other conditions. In this study, we quantified densities of two synaptic proteins, the presynaptic protein SNAP25 and the postsynaptic protein PSD95 in human brain using enzyme-linked immunosorbent assays (ELISA). Protein was extracted from the cingulate, hippocampus, frontal, visual, and entorhinal cortex from cognitively unimpaired controls, subjects with mild cognitive impairment (MCI) and demented subjects with different levels of Alzheimer’s pathology. SNAP25 is significantly reduced in ADD when compared to controls in frontal cortex, visual cortex and cingulate; while hippocampus showed a smaller, non-significant reduction and entorhinal cortex concentrations were not different. In contrast, all brain areas showed lower PSD95 concentrations in ADD when compared to non-demented controls, although in hippocampus this failed to reach significance. Interestingly, cognitively unimpaired cases with high levels of AD pathology had higher levels of both synaptic proteins in all brain regions. SNAP25 and PSD95 concentrations significantly correlated with densities of neurofibrillary tangles, amyloid plaques and Mini Mental State Examination scores. Our results suggest that synaptic transmission is affected by ADD in multiple brain regions. Differences were less marked in entorhinal cortex and hippocampus, most likely due to a ceiling effect imposed by the very early development of neurofibrillary tangles in older people in these brain regions.

Disease classification based on biological data is an important area in bioinformatics and biomedical research. It helps the doctors and medical practitioners for the early detection of disease and support them as a computer-aided diagnostic tool for accurate diagnosis, prognosis, and treatment of disease. Earlier Microarray gene expression data have wide application for the classification of disease, but now Next-generation sequencing (NGS) has replaced the Microarray technology. From the last few years, RNA sequence (RNA-Seq) data are widely used for the transcriptomic analysis. Hence, RNA-Seq based classification of disease is in its infancy. In this article, we present a general framework for the classification of disease constructed on RNA-Seq data. This framework will guide the researchers to process RNA-Seq, extract relevant features and apply the appropriate classifier to classify any kind of disease.

The ongoing growth of international occurrence of depression and its ability to co-occur with other serious medical disorders such as heart disease, cancer, diabetes, and Parkinson’s disease is a current public health problem. Inhibitor of DNA-Binding/Differentiation (ID) proteins are part of a group of transcriptional factors that have been seen to be involved in neurocognitive disorders and therefore, may have influence on depressive disorders. Previously, it has been established that environmental estrogenic endocrine disruptors (EEDs) such as polychlorinated biphenyls (PCBs) & bisphenol A (BPA) have played an important role in the impact of depressive disorders. Hence, based on many studies, we consider the impact of these environmental pollutants on the group of ID proteins. Improved understanding of how the interaction of ID proteins by EED exposure can influence depressive disorders will contribute essential evidence that can further benefit our public health community with innovative knowledge to prevent these types of mental illnesses.

Saliva, as a diagnostic medium, offers a promising alternative to blood by virtue of its non-invasive collection, which enhances patient compliance, especially in paediatric and geriatric populations. In this study, we assessed the utility of saliva as a non-invasive medium for measuring V. cholerae-specific serum antibodies in naturally infected individuals. We tested paired serum and saliva samples obtained from a total of 63 cholera patients enrolled in a cohort study. Vibriocidal antibodies assay (IgM/IgG) as markers for accurate determination was used to determine cholera specific antibody levels. Using receiver operating characteristics (ROC) curve, we found that the best cut-off that maximizes (sensitivity + specificity) is 10 titers. At this saliva titer, the sensitivity is 76.9% (95%CI: 60.9%, 87.7%) and specificity is 80.0% (95%CI: 56.6%, 92.5%). Using Spearman’s correlation coefficient, we also found evidence of a positive correlation between Vibrio Cholerae saliva and serum antibodies (rho=0.66, p&lt;0.001). In conclusion, saliva-based diagnostic cholera tests has high diagnostic accuracy, and would be advantageous, cheaper, and quicker for early diagnosis of severe cholera outcomes.

Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus, is significantly underreported in Mongolia due to geographical remoteness, lack of early diagnostics, and poor clinical management. This study aimed to provide a more accurate estimate of CE in Mongolia by comparing data of surgical (reported) and diagnosed (unreported) cases, and assessing the challenges faced by rural doctors in disease management and surveillance. We collected data on surgical cases hospitalized between 2006-2016 and newly diagnosed CE cases in 2016 from eight provinces. Using a quasi-Poisson regression model of the collected data, we used extrapolation to estimate the number of diagnosed cases for the entire country. Additionally, fourty health professionals from all 21 provinces rated local clinical management for CE through a questionnaire. Results reveal that surgical cases (2.2 per year) represent only one-eighth of diagnosed cases (15.9 per year). The laboratory facilities, disease reporting, and cyst classification usage scored below 2. These results highlight the significant underreporting of CE in Mongolia and urges human and animal health experts, along with policymakers, to invest into combating CE, particularly in remote provincial areas. It also emphasizes the need for standard clinical management involving cyst classification according to WHO-IWGE, seamless integration of CE reporting and monitoring mechanisms, which can significantly contribute to the national and global burden estimation of CE.

The detection of coronavirus (COVID-19) is now a critical task for the medical practitioner. The coronavirus spread so quickly between people and approaches 100,000 people worldwide. In this consequence, it is very much essential to identify the infected people so that prevention of spread can be taken. In this paper, the deep feature plus support vector machine (SVM) based methodology is suggested for detection of coronavirus infected patient using X-ray images. For classification, SVM is used instead of deep learning based classifier, as the later one need a large dataset for training and validation. The deep features from the fully connected layer of CNN model are extracted and fed to SVM for classification purpose. The SVM classifies the corona affected X-ray images from others. The methodology consists of three categories of Xray images, i.e., COVID-19, pneumonia and normal. The method is beneficial for the medical practitioner to classify among the COVID-19 patient, pneumonia patient and healthy people. SVM is evaluated for detection of COVID-19 using the deep features of different 13 number of CNN models. The SVM produced the best results using the deep feature of ResNet50. The classification model, i.e. ResNet50 plus SVM achieved accuracy, sensitivity, FPR and F1 score of 95.33%,95.33%,2.33% and 95.34% respectively for detection of COVID-19 (ignoring SARS, MERS and ARDS). Again, the highest accuracy achieved by ResNet50 plus SVM is 98.66%. The result is based on the Xray images available in the repository of GitHub and Kaggle. As the data set is in hundreds, the classification based on SVM is more robust compared to the transfer learning approach. Also, a comparison analysis of other traditional classification method is carried out. The traditional methods are local binary patterns (LBP) plus SVM, histogram of oriented gradients (HOG) plus SVM and Gray Level Co-occurrence Matrix (GLCM) plus SVM. In traditional image classification method, LBP plus SVM achieved 93.4% of accuracy.

Recently, cases of antifreeze poisoning in companion animals, particularly cats, have surged in the Republic of Korea. Ethylene glycol (EG), the toxic primary component of antifreeze, is metabolized into glycolic acid (GA), leading to severe conditions such as metabolic acidosis and acute renal failure. Traditional detection methods, although effective, are often time-consuming owing to complex sample preparation. This study involved a novel analytical method utilizing GC-MS for EG and LC-MS/MS for GA detection, which streamlined the detection process by eliminating the need for derivatization. The method was validated for accuracy and reliability, enabling the rapid and precise identification of EG and GA in biological samples. The study also included the successful application of this method in a case where initial exposure to antifreeze was not apparent, which highlighted the effectiveness of this method in diagnosing poisoning even in cases where clinical history is unclear. The development of this rapid diagnostic approach addresses the urgent need for the efficient detection of antifreeze poisoning, improving animal welfare and supporting forensic investigations.

The emergence of drug-resistant mycobacteria has rendered many clinical drugs and regimens ineffective, imposing significant economic and healthcare burden on individuals and society. Repurposing drugs intended for treating other diseases is a time-saving, cost-effective, and efficient approach for identifying excellent anti-mycobacterial candidates or lead compounds. This study is the first to demonstrate that rupatadine (RTD), a drug used to treat allergic rhinitis, possesses excellent activity against mycobacteria without detectable resistance, particularly Mycobacterium tuberculosis and Mycobacterium marinum, with a minimal inhibitory concentration as low as 3.13 µg/mL. Furthermore, RTD exhibited moderate activity against nonreplicating M. tuberculosis with the minimal inhibitory concentrations lower than drugs targeting the cell wall, suggesting that RTD has the great potential to be modified and used for the treatment of nonreplicating M. tuberculosis. Additionally, RTD exhibits partial synergistic effects when combined with clofazimine, pretomanid, and TB47 against M. tuberculosis, providing the theoretical foundation for the development of treatment regimens. Transcriptomic profiling leads us to speculate that eight essential genes may be the targets of RTD or may be closely associated with the mycobacterial resistance to RTD. In summary, RTD may be a promising hit for further anti-mycobacterial drug or regimen optimization, especially in case of nonreplicating mycobacteria.

The presence of anti SARS-CoV2-RBD antibody (Anti-RBD) prevents severe COVID-19. We aimed to determine the accuracy of a point-of-care Anti-RBD test implemented in person living with HIV (PLWH), systemic lupus erythematosus (SLE), and chronic kidney disease (CKD). We enrolled 182 non-comorbid subjects and 335 persons with comorbid (PLWH, SLE, CKD) to test anti-RBD assay compared to surrogate viral neutralization (SVNT) as the reference test. We performed linear correlation analysis between anti-RBD vs SVNT and a ROC analyses to ascertain anti-RBD cut-off at 30%, 60%, and 90% inhibition of SVNT to calculate accuracy. Correlations of anti-RBD to SVNT among all groups were excellent with R= 0.7903, R=0.7843, R=0.8153 among non-comorbid, SLE and CKD groups, respectively, with significantly higher correlation among the PLWH group (R=0.8877; p-value=0.0072) compared to non-comorbid group. The accuracy of the anti-RBD test among PLWH and CKD group was similar with the non-comorbid but showed lower sensitivity in the SLE group (p=0.000014). The specificity of the test remained high in all groups. In conclusion, the Anti-RBD test had excellent correlation to SVNT. The persistently high specificity in all groups suggests that this test can be reliably utilized to detect presence of low neutralization capacity, prompting additional vaccination.

A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

Chronic kidney disease patients treated by hemodialysis present a high cardio-vascular morbidity and mortality. There is an imperative need for novel biomarkers in identifying and to offer possible therapeutically intervention in these patients. We performed a prospective observational cohort study on 77 patients in the period October 2021 – October 2023. We measured serum plasma levels of Interleukin 1-Beta, Galectin 3, human suppression of tumorigenicity factor 2, bone morphogenetic protein 2 and fibroblastic growth factor 23 at the inclusion. We evaluated the correlations of these biomarkers with cardiac function and structure evaluated by echocardiography. Mean age was 61.02 (±11.81) years, 45 (56.2%) males and with a dialysis vintage of 4.95 (2.4-7.8) years. Median ejection fraction was 51 (43-54 %) and more than two thirds of the patients presented valvular calcifications. Overall mortality was 22%. Interleukin 1-Beta correlated positively with ejection fraction and global longitudinal strain and negatively with left atrium diameter and left ventricle tele systolic diameter. Galectin 3 values negatively correlated with aortic valve fibrosis and mitral valve calcifications and human suppression tumorigenity factor 2 negatively correlated with mitral valve calcifications. Some of these novel biomarkers could be used to better asses the cardio-vascular disease in patients on maintenance hemodialysis.

This paper presents an interpretable support vector machine (SVM) and its application to rehabilitation assessment. We introduce the concept of nearest boundary point to standardize the one-class SVM decision function and determine the shortest path for data from abnormal cases to become those from normal cases. This analytical approach is computationally simple and provides a unique solution. The nearest boundary point of abnormal data can also be used to analyze the cause of abnormal classification and indicate countermeasures for normalization. These properties render the proposed interpretable SVM valuable for medical assessment applications and other problems that require careful consideration of classification results for treatment. Simulation and application results demonstrate the feasibility and effectiveness of the proposed method.

Diversity-generating retroelements (DGRs) are prokaryotic systems providing rapid modification and adaptation of target proteins. In phages, the main targets of DGRs are receptor-binding proteins that are usually parts of tail structures and the variability of such host-recognizing structures enables phage adaptation to changes on the bacterial host surface. Sometimes, more than one target gene containing a hypermutated variable repeat (VR) can be found in phage DGRs. The role of mutagenesis of two functionally different genes is unclear. In this study, several phage genomes that contain DGRs with two target genes were found in the gut virome of healthy volunteer. Bioinformatics analysis of these genes indicated that they encode proteins with different topology; however, both proteins contain the C-type lectin (C-lec) domain with a hypermutated beta-hairpin on its surface. One of the target proteins belongs to a new family of proteins with a specific topology: N-terminal C-lec domain followed by one or more immunoglobulin domains. Proteins from the new family were named tentaclins after TENTACLe+proteIN. The genes encoding such proteins were found in the genomes of prophages and phages from the gut metagenomes. We hypothesized that tentaclins are involved in binding either to bacterial receptors or intestinal/immune cells.

Background. Wnt-pathway proteins play a vital role in kidney development and defects in the Wnt-pathway are associated with kidney disorders. However, the knowledge on the role of Wnt/β-catenin pathway proteins in end-stage renal disease (ESRD) is limited.Aim of the study. To delineate the association of ESRD and Wnt-proteins including the agonistR-spondin 1, the transducer β-catenin and the antagonists Dickkopf-related protein 1 (DKK1) and sclerostin.Methods. Serum Wnt-pathway proteins levels were measured by ELISA, while other biochemicals were measured spectrophotometrically in 60 ESRD patients and 30 normal controls.Results. DKK1 and sclerostin were significantly higher in ESRD than in controls, and β-catenin and the catenin + R-Sponin-1 / DKK1 + sclerostin ratio, reflecting the ratio of agonist and transducer on antagonists (AT/ANTA), were significantly lower in ESRD. Logistic regression analysis showed that ESRD was significantly predicted by increased levels of DDK1 and sclerostin and lowered β-catenin (p<0.001). eGFR was significantly associated with DKK1 and sclerostin (inversely), β-catenin (positively) and the AT/ANTA ratio (r=0.468, p<0.001). DKK1 levels were significantly and positively correlated with urea, creatinine, and copper. DKK1 and sclerostin were inversely associated with hemoglobin and packet cell volume. Catenin was significantly negatively associated with copper, urea and creatinine.Conclusion. Wnt/β-catenin pathway proteins show significant alterations in ESRD, indicating significantly increased levels of antagonists and, therefore, attenuated Wnt/β-catenin pathway activity. The latter is associated with lowered eGFR and increased serum copper levels. Wnt/β-catenin pathway proteins are possible drug targets to treat ESRD or its consequences.

The Aβ cascade and alternations of biomarkers in neuro-inflammation, synaptic dysfunction and neuronal injury followed by Aβ have progressed. But the question is how to use the biomarkers. Here, we examine the evidence and pathogenic implications of protein interactions and the time order of alternation. After the deposition of Aβ, the change of tau, NfL and NG is the main alternation and connection to others. The neuro-inflammation, synaptic dysfunction and neuronal injury function is exhibited prior the structural and metabolic changes in the brain following Aβ deposition. The time order of such biomarkers compared to the tau protein is not clear. Despite the close relationship between biomarkers and plaque Aβ deposition, several factors favor one or the other. There is an interaction between the proteins that CSF SNAP-25, VILIP-1 and YKL-40 can predict the brain amyloid burden. The Aβ cascade hypothesis could be the pathway, but not all subjects are converted to AD, even with very high elevated Aβ. The interaction of biomarkers and the time order of change require further research to identify the right subjects and right molecular target for precision medicine therapies.

Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, some are conjugated to CRM197, a modified diphtheria toxin, and all contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. All of these proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. CRM197 is also present in Hib and meningitis vaccines. Equivalent similarities were found at lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable.

Adhesive-invasive E. coli have been suggested to be associated with the development of Crohn's disease (CD). It is assumed that they can provoke the onset of the inflammatory process as a result of the invasion of intestinal epithelial cells, and then, due to survival inside macrophages, stimulate chronic inflammation and the development of granuloma. In previous reports, we have shown that passage of the СD isolate ZvL2 on minimal medium M9 supplemented with sodium propionate (PA) as a carbon source stimulates, and with glucose - inhibits the adherent-invasive properties and the ability to survive in macrophages. This effect was reversible and not observed for the laboratory strain K12 MG1655. We were able to compare the isogenic strain AIEС in two phenotypes - virulent (ZvL2-PA) and non-virulent (ZvL2-GLU). We showed that, unlike ZvL2-GLU, the ZvL2-PA activates the production of ROS and cytokines when interacting with neutrophils. The laboratory strain does not cause a similar effect. Differences in neutrophil NADH-oxidase activation and ζ potential for ZvL2-GLU and ZvL2-PA are associated with changes in the abundance of membrane proteins. Using differential 2D electrophoresis and LC-MS, we identified membrane proteins that may be associated with the activation of the virulence properties of the СD isolate ZvL2.

Sepsis is a life-threatening complication of an infectious process that results from excessive and uncontrolled activation of the host's pro-inflammatory immune response to a pathogen. Lipopolysaccharide (LPS), also known as endotoxin, which is a major component of the Gram-negative bacteria outer membrane, plays a key role in the development of Gram-negative sepsis and septic shock in humans. To date, no specific and effective drug against sepsis has been developed. This review summarizes data on LPS-binding proteins from marine invertebrates (ILBPs), that inhibit LPS toxic effects, and are of interest as potential drugs for the sepsis treatment. The structure, physicochemical properties, antimicrobial and LPS-binding/neutralizing activity of these proteins and their synthetic analogues are considered in details. Problems that arise during clinical trials of potential anti-endotoxic drugs are discussed.

Mitochondria are semiautonomous organelles, which are pivotal for the energy metabolism of eukaryotic cells. These organelles contain their own genetic system (mtDNA, mitogenome) that encodes to some structural RNAs and organellar proteins. The biogenesis and function of mitochondria is tightly regulated by nuclear-encoded protein cofactors. The mtDNAs of land plants are characteristically large, with a complex mode of gene organization and expression, in particularly at the post-transcriptional level. To become functional, the primary organellar transcripts undergo extensive maturation steps, which include endo- and exo-nucleolytic cleavage, RNA-base editing, and both ‘cis’- and ‘trans’-splicing events. These essential processing steps rely on the activities of a large set of nuclear-encoded factors. Among these, the RNA helicases serve as key players in organellar (mt-)RNA metabolism. This review summarizes the important roles played by these factors in regulating the highly dynamic processes of transcription, RNA processing, and translation within the mitochondria of land plants. We further discuss recent advancements in understanding how dysregulation of mitochondrial RNA helicases affects the organellar gene expression, respiratory functions, and hence the growth, development and physiology of land plants.

Human osteosarcoma (OS) is a rare tumor predominantly affecting long bones and characterized by a poor prognosis. Currently, the first line of intervention consists of surgical resection of primary tumors combined with radiotherapy and chemotherapy, with a profound impact on patient’s life. Since surgical removal of OS frequently results in large resection of bones the use of biomaterials to sustain the stability of remaining tissue and to stimulate bone regeneration is challenging. Moreover, residual neoplastic cells might be responsible for tumor recurrence. Here we explored the potential of doped-bioactive glass as novel therapeutic intervention to both eradicate residual malignant cells and promote bone regeneration. Bioactive glass (BAG) has been extensively studied and employed in the field of regenerative medicine, due to its osseointegration properties and ability to improve bone tissue regeneration. We found that the incorporation of tellurium in BAG selectively kills OS cells through ferroptosis while preserving the viability of hBMSCs, and stimulating their osteodifferentiation. Although the mechanism of Te toxicity is still unclear: i) Te-BAG generates lipid-ROS through LOXs activity but not iron overload; ii) Te-dependent ferroptosis is mediated by GPX4 down-regulation, and iv) abrogates the anti-ferroptotic activity of FSP1, which expression confers resistance of OS to canonical induction of ferroptosis.

We have introduced a sign operator of energy, analogous to the operator helicity, but in the direction of what we call energy vector. However, this energy vector needs a time vector. To give physical senses to the components of such a time vector, we try to explain the time dilation in special relativity and try to relate the components of the time vector to the tunneling times when an electron crosses a potential barrier.

The risk of a fatal outcome was 41% in unvaccinated patients (p = 0.713), which increased by 2.66% with co-infection with two pathogens (p = 0.342) and by 26% with three pathogens (p = 0.005). Additionally, 50% of ICU patients had a triple infection, compared with only 1.3% in the inpatient unit (p = 0.0029). The risk of death and/or ICU admission was 12 times higher (p = 0.042) with an additional pathogen and increased by 95% (p = 0.003) with a third concomitant pathogen. Regular multiplex testing is important for prompt treatment and targeted antibiotic use.

Alzheimer’s disease (AD) poses a significant public health challenge due to its irreversible and progressive nature while lack of a cure. As a potential strategy to combat AD, its prevention becomes increasingly attractive. Mild Cognitive Impairment due to AD (MCI-AD) represents a critical transitional stage between normal age-related cognitive decline and more severe AD conditions, occurring just before dementia onset. Unfortunately, there is currently no established animal model that accurately recapitulates MCI-AD characteristics. While many laboratories have traditionally used normally aged wild-type animals as experimental models, this approach falls short in representing the inherently worse state of MCI-AD compared to normal aging. To address this gap, we introduce an animal model—a transgenic mouse line with genetic inactivation of G protein-coupled receptor kinase-5 (GRK5), commonly known as the GRK5 knockout (GRK5KO) mouse. These GRK5KO mice exhibit amnesia, cognitive deficits, increased β-amyloid levels, neurofibrillary tangle (NFT) immunopositive axonopathy, and hippocampal neurodegenerative changes. Importantly, these pathological alterations predominantly impact the entorhinal, transentorhinal, and hippocampal cortices, aligning with human MCI-AD criteria and Braak stage II of human AD progression. Notably, female GRK5KO mice show approximately 2.5 times more NFT-positive axonopathy than males, mirroring the higher prevalence of AD cases in women. Collectively, existing data strongly supports the GRK5KO mouse as a qualified animal model for studying MCI-AD.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a standardized therapy is still lacking. In this narrative review we focused the antibiotic treatment of CRAB infections in view of newly β-lactam agents (NBLs) like sulbactam/durlobactam and cefiderocol, discussing the main hot points such as the superiority of combination treatment over monotherapy and the best antibiotic partner to use in combination. Sulbactam/durlobactam seems to be the best candi-date to replace current back-bone agents. Cefiderocol, could play a crucial role in combina-tion-regimen. Due to toxicity and the PK/PD limitations, colistin (or polymyxin B) should be used as an alternative agent (when no other options are available). Tigecycline (or minocycline) and fosfomycin could represent suitable partners for both NBLs. Randomized clinical trials (RCTs) are needed to better evaluate the role of NBLs in CRAB infection treatment and to compare the ef-ficacy of tigecycline and fosfomycin as partner antibiotics. Synergism should be tested between NBLs and “old” drugs (rifampicin and trimethoprim/sulfamethoxazole). Huge efforts should be made to accelerate pre-clinical and clinical studies on safer polymyxin candidates with lung im-proved activity, as well as on the i.v. rifabutin formulation.

Alzheimer’s disease (AD), the most common cause of dementia, is characterized by disruptions in memory, cognition, and personality, significantly impacting morbidity and mortality rates among older adults. However, the exact pathophysiological mechanism of AD remains unknown, and effective treatment options for AD are still lacking. Human induced pluripotent stem cells (iPSC) are emerging as promising platforms for disease research, offering the ability to model genetic mutations associated with various conditions. Patient-derived iPSCs are useful for modeling neurodegenerative and neurodevelopmental disorders. In this study, we generated AD iPSCs from peripheral blood mononuclear cells obtained from a 65-year-old patient with AD carrying the E682K mutation in the amyloid precursor protein (APP) gene. Cerebral organoids derived from AD iPSCs recapitulated the AD phenotype, exhibiting significantly increased levels of tau protein. Our analysis revealed that an iPSC disease model of AD is a valuable assessment tool for pathophysiological research and drug screening.

Bartonella species, intracellular parasitic zoonotic pathogens, has drawn increasing attention for their diverse host range and associated human diseases. This study investigates Bartonella infection in small mammals in Yunnan Province, China, focusing on tissue tropism. 333 small mammals were sampled from 13 species, 3 orders, 4 families, and 4 genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified 30, 10, and 5 strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in the Episoriculus leucops (GS136). Tissue distribution analysis revealed varied copy numbers across different tissues, with the highest load in spleen. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting its broad tissue tropism in small mammals.

The combination of encryption and digital watermarking technologies is a trend to achieve full lifecycle data protection. Recently, reversible data hiding in encrypted domain (RDHED) has greatly aroused the interests of many scholars. But the fixed order of first encryption and then watermarking makes this kind of algorithms unsuitable to many applications. Commutative encryption and watermarking (CEW) technology realizes the flexible combination of encryption and watermarking, and suits more applications. However, most existing CEW schemes for vector maps are not reversible and unsuitable to high precision maps. To solve this problem, here we propose a commutative encryption and reversible watermarking (CERW) algorithm for vector maps based on virtual coordinates which are uniformly distributed on the number axis. The CERW algorithm consists of virtual interval step based encryption scheme and coordinate difference based reversible watermarking scheme. In the encryption scheme, the map coordinates are moved randomly by multiples of virtual interval step defined as distance between two adjacent virtual coordinates. In the reversible watermarking scheme, difference expansion (DE) technique is used to embed the watermark bit into the coordinate difference computed based on the relative position of a map coordinate in a virtual interval. Since the relative position of a map coordinate in a virtual interval keeps unchanged during the coordinate scrambling encryption process, the watermarking operation and the encryption operation don’t interfere with each other and the commutativity between encryption and watermarking achieves. Results show that: proposed method has high security, high capacity and good invisibility. In addition, the algorithm is not only applicable to polyline and polygon vector data, but also can be applied to sparsely distributed point data which the traditional DE watermarking algorithm often fails to watermark.

Theoretical studies on the generation of nondiffracting and nondispersive light pulses and their experimental implementation are one of the renowned problems within electromagnetics. Current technologies enable creation of short-duration pulses of a few cycles with high power and fluency. An application of these techniques to the field of nondiffracting and nondispersive pulses requires a proper mathematical description of highly focused vector pulses. In this work, we study vector optical bullets in a dielectric medium with different polarization structures: linear, azimuthal, and radial. We report the differences caused by the vector model compared to the scalar model. We analyze effects caused by superluminal, subluminal, or even negative group velocity on properties of vector optical bullets inside a dielectric material.

Onchocerciasis, or river blindness, has historically been one of the most important causes of blindness worldwide, and a major cause of socio-economic disruption, particularly in sub-Saharan Africa. Its importance as a cause of morbidity and an impediment to economic development in some of the poorest countries in the world motivated the international community to implement several programs to control or eliminate this scourge. Initially, these involved reducing transmission of the causative agent Onchocerca volvulus through controlling the vector population. When ivermectin was found to be a very effective drug for treating onchocerciasis, the strategy shifted to mass drug administration (MDA) of endemic communities. In some countries, both vector control and ivermectin MDA have been used together. However, traditional vector control methods involve treating rivers in which the black fly vectors breed with insecticides, a process which is expensive, requires trained personnel to administer, and is ecologically harmful. In this review, we discuss recent research into alternatives to riverine insecticide treatment, which are inexpensive, ecologically less harmful and which can be implemented by the affected communities themselves. These can dramatically reduce vector densities and, when combined with ivermectin MDA, can accelerate the time to elimination when compared to MDA alone.

This paper describes new horizons in the diversity and taxonomy of negev-like viruses encoding the membrane-embedded SP24 protein. First, our data extend the known host range of SP24-encoding negev-like viruses to include brown algae, fungi, green plants, the phylum Entoprocta, the phylum Mollusca, and vertebrates. Second, our phylogenetic analysis suggests that the evolution of the SP24 gene family may have involved frequent events of inter-order virus genome shuffling. Third, the identification of 2-3 copies of SP24 protein genes in some virus RNAs shows that virus genomes may have acquired additional SP24 genes during the evolutionary process due to duplications or new acquisition steps. Forth, the broad host specificity of some SP24-encoded viruses may be related to an important adaptive role of SP24. Fifth, insect and nematode genomes may acquire viral SP24 genes by putative horizontal transfer from negev-like viruses known to infect species of both taxa.