Viral co-infections, where a host is infected by multiple viruses simultaneously, are common in the human population. Human viral co-infections can lead to complex interactions between viruses and the host immune system, affecting the clinical outcome and posing challenges for treatment. Understanding the types, mechanisms, impacts, and identification methods of human viral co-infections is crucial for the prevention and control of viral diseases. In this review, we first introduce the significance of studying human viral co-infections and summarize the current research progress and gaps in this field. We then classify human viral co-infections into four types based on the pathogenic properties and species of the viruses involved. Next, we discuss the molecular mechanisms of viral co-infections, focusing on virus-virus interactions, host immune responses, and clinical manifestations. We also summarize the experimental and computational methods for identifying viral co-infections, emphasizing the latest advances in high-throughput sequencing and bioinformatics approaches. Finally, we highlight the challenges and future directions in human viral co-infection research, aiming to provide new insights and strategies for the prevention, control, diagnosis, and treatment of viral diseases. This review provides a comprehensive overview of the current knowledge and future perspectives on human viral co-infections, and underscores the need for interdisciplinary collaborations to address this complex and important topic.

In recent years, thanks to continuous technological development, temperature data loggers have been used to collect data from the breeding progress of birds, which can be used, e.g. to obtain information on the length of incubation breaks, to detect the start of incubation or to record unsuccessful breeding. Temperature data loggers have been used in various types of bird nests, but not in a „closed“ nests such as a burrow or cavity. The study presents the results of using a temperature data loggers in natural nest holes of the common kingfisher (Alcedo atthis). Their nests, which lack substantial insulating structures, are primarily influenced by the relatively stable soil temperature. The temperature of the space inside a nest chamber was measured on a continuous basis with an interval of 1 minute between measurements. The measurement was carried out from egg laying/incubation to a successful leave of the nest chamber/death of chicks (5 nests on 3 different streams in 3 breeding seasons). The temperature curves showed the laying of the eggs, the start of incubation, the successful flight out of the nest chamber or the death of the chicks in the nest chamber. It was not always possible to determine exactly when the chicks hatched from the temperature data.

Air pollution, climate change and global warming show direct linkage. Introduction - Background: Research in the field has proposed and demonstrated their link to increased allergenicity in plants, leading to increased allergic diseases. Allergen patterns are changing in response to climate change. Across Europe, up to 12% of the population suffers from allergic diseases (bronchial asthma and allergic rhinitis) caused by the pollen grains. The medical costs of these types of allergies are enormous and are increasing with the spread of common ragweed - Ambrosia artemisiifolia* in Europe. In practice, more and more patients are turning to allergists. Methods: Based on these data, the research aims to identify safety measures and specific legislation to control and eradicate common ragweed in the countries most affected by the spread of this plant in Europe, increase in population exposure in countries affected by the presence of common ragweed and the socio-economic impact of allergic rhinitis and bronchial asthma at European level.[1][2] Our database search did not reveal any other research that has addressed this topic to date. Results: This research identifies specific legislation to the countries most affected by the spread of this plant pollen grains at European level, changes in allergen patterns and monitoring/safety eradication measures decided by local authorities, and data on the spread of common ragweed over the last two decades, costs per treatment, increased allergic rhinitis and bronchial asthma morbidity in the most affected areas. Conclusions: At European level, there are no universally valid models for eradicating this weed. Various methods can be used to limit the spread of common ragweed and its pollen production (e.g. mowing once or twice a year of overgrown land, ploughing, chemical control, public information, etc.). Local and regional cooperation should be considered essential to promote phytosanitary & safety measures and exchange of information on methods to identify and manage the spread of common ragweed. Unified legislation at European level would help all affected countries; reduce morbidity from respiratory allergic diseases and the costs of treating these diseases.

The protein C is a small viral protein encoded in an overlapping frame of the P gene in the sub-family Orthoparamyxovirinae. This protein, expressed by alternative translation initiation, is a virulence factor that regulates viral transcription, replication and production of defective interfering RNA, interferes with the host-cell innate immunity systems and supports assembly of viral particles and budding. We expressed and purified full-length and an N-terminally truncated C protein from Tupaia paramyxovirus (TupV) C protein (genus Narmovirus). We solved the crystal structure of the C-terminal part of TupV C protein at a resolution of 2.4 Å and found that it is structurally similar to Sendai virus C protein, suggesting that despite undetectable sequence conservation, these proteins are homologous. We characterized both truncated and full-length proteins by SEC-MALLS and SEC-SAXS and described their solution structures by ensemble models. We established a minireplicon assay for the related Nipah virus (NiV) and showed that TupV C inhibited the expression of NiV minigenome in a concentration-dependent manner as efficiently as NiV C protein. A previous study found that the Orthoparamyxovirinae C proteins former two clusters without detectable sequence similarity, raising the question of whether they were homologous or instead had originated independently. Since TupV C and SeV C are representative of these two clusters, our discovery that they have a similar structure indi-cates that all Orthoparamyxovirine C proteins are homologous. Our results also imply that, strik-ingly, a STAT1-binding site is encoded by exactly the same RNA region of the P/C gene across Paramyxovirinae, but in different reading frames (P or C) depending on which cluster they belong to.

Migraine and neuropathic pain (NP) are evocative of painful, disabling, chronic conditions which exhibit resembling symptoms and thus considered to share a common etiology. Calcitonin gene-related peptide (CGRP) has gained credit as a target for migraine management; nevertheless, the efficacy and the applicability of CGRP modifiers warrant search for more effective therapeutic targets for pain management. This scoping review overviews human studies of common pathogenic factors in migraine and NP to explore potential novel therapeutic targets. CGRP causes inflammation in the meninges; monoclonal antibodies and inhibitors target CGRP. Gluta-mate-induced hyperexcitability and subsequent sensitization are closely linked to an alteration of the tryptophan (Trp)-kynurenine (KYN) metabolic system; the Trp-KYN system may serve as a potential target. Microglial overaction is observed in migraine and NP; modifying the microglial activity may be a possible approach. Cytokine-induced inflammation is a leading hypothesis of the pathogenesis of the conditions; alleviating neuroinflammation may complement a pain-relieving armamentarium. Transient receptor potential (TRP) ion channels evoke the release of several substances; TRP ion channels may potentially emerge as new targets. The endocannabinoid system plays a major role in the pain trafficking pathway; modification of the system may open a new path toward discovery of new analgesics. Here we highlight the mechanism of those common pathogenic factors to explore therapeutic targets for innovative pain management in migraine and NP.

Powdery mildew is a severe disease causing substantial yield losses in wheat production worldwide. The Chinese wheat landrace Changanhongmai (CAHM) exhibits high resistance to the physiological race E09 of powdery mildew. This study aims to characterize the powdery mildew resistance gene in CAHM, and develop molecular markers for marker-assisted selection of wheat. To investigate the genetic characteristics of this resistant gene, we developed F1 plants, F2 generation population, and F2:3 families from a cross between CAHM and SY225. Genetic analysis demonstrated that all F1 plants were resistant to the disease, while the ratio of resistant to susceptible plants was 3: 1 in both the F2 population and F2:3 families, indicating that CAHM is inherited in a manner of single dominant powdery mildew resistance gene, which was tentatively designated as PmCAHM. By using bulk segregation analysis, we constructed a genetic map encompassing Xgwm273, Xwmc626, Xgwm11, Xgwm18, Xgdm28, Xgpw7812, Xgpw5195, Xwmc694 and PmCAHM. Among these markers, Xgpw7812 and Xgpw5195 were flanking markers tightly linked to PmCAHM at a genetic distance of 2.5 cM and 8.4 cM, respectively. Furthermore, nullisomic-tetrasomic analysis revealed that PmCAHM is located on chromosome 1B. These results indicate that PmCAHM differs from the internationally recognized powdery mildew resistance genes in both location and source. In addition, a new germplasm/line NW1748 with large seeds and powdery mildew resistance was developed from the cross and back cross populations of Fengyou 1718 (FY1718)/CAHM//FY 1718. Therefore, PmCAHM can serve as a novel powdery mildew resistance source for breeding of wheat by using NW1748 as the donor in the future.

Nearly half a century has passed since the discovery of cytoplasmic inheritance of human chloramphenicol resistance. The inheritance was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, a number of mutations in mtDNA were identified as a cause of severe inheritable metabolic diseases with neurological manifestation, and the impairment of mitochondrial functions has been probed in the pathogenesis of a wide range of illnesses including neurodegenerative diseases. Recently growing number of preclinical studies has revealed that animal behaviors are influenced by the impairment of mitochondrial functions and possibly by the loss of mitochondrial stress resilience. Indeed, as high as 54% of patients with one of the most common primary mitochondrial diseases, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, present psychiatric symptoms including cognitive impairment, mood disorder, anxiety, and psychosis. Mitochondria are multifunctional organelles which produce cellular energy and play a major role in other cellular functions including homeostasis, cellular signaling, and gene expression, among other. Mitochondrial functions are observed to be compromised and to become less resilient under continuous stress. Meanwhile, stress and inflammation have been linked to the activation of the tryptophan (Trp)-kynurenine (KYN) metabolic system, which observably contributes to development of pathological conditions including neurological and psychiatric disorders. This narrative review discusses the functions of mitochondria and the Trp-KYN system, the interaction of the Trp-KYN system with mitochondria, and the current understanding of the involvement of mitochondria and the Trp-KYN system in preclinical and clinical studies of major neurological and psychiatric diseases.

This paper discusses some of the most common misconceptions about large language models (LLMs), including the belief that they are sentient or conscious, that they are always accurate, and that they can replace human creativity. The paper also proposes a strategy for overcoming these misbeliefs, which involves educating the public about the capabilities and limitations of LLMs, developing guidelines for the responsible use of LLMs, and conducting more research to understand the potential impact of LLMs on society.

This review is focused on synephrine, the principal phytochemical found in bitter orange and other medicinal plants, and widely used as a dietary supplement for weight loss/body fat reduction. We examine different aspects of synephrine biology, delving into its established and potential molecular targets, as well as its mechanisms of action. We present an overview of the origin, chemical composition, receptors, and pharmacological properties of synephrine, including its anti-inflammatory and anti-cancer activity in various in vitro and animal models. Additionally, we conduct a comparative analysis of the molecular targets and effects of synephrine with those of its metabolite, selective glucocorticoid receptor agonist (SEGRA) Compound A (CpdA), which shares a similar chemical structure with synephrine. SEGRA, including CpdA, have been extensively studied as glucocorticoid receptor activators that have a better benefit/risk profile than glucocorticoids due to the reduced adverse effects. We discuss the potential of synephrine usage as a template for the synthesis of new generation of non-steroidal SEGRA. The review also provides insights into the safe pharmacological profile of synephrine.

This paper explores the application of fisheries management theories to broader environmental issues, including climate change and biodiversity conservation. It underscores the inherent trade-off in fisheries between yield and resource conservation, identifying harvesting as a significant environmental burden. Early recognition of the sustainability concept aimed to address challenges like economic discounts and the tragedy of the commons, contributing to the issue of overfishing. These insights extend beyond fisries to other environmental concerns, particularly climate change. The development of adaptive management, initially tailored to address uncertainties and non-stationarity in fisheries, has found application in diverse environmental issues. Recognizing humans as integral parts of ecosystems highlights the impossibility of achieving zero environmental impact when utilizing natural resources. The paper advocates for passive restoration to prevent overfishing, leveraging nature's resilience. While goals like complete biodiversity restoration are inherent in fisheries, their relevance may not be immediately apparent to other environmentalists. Despite ongoing discussions on the sustainability of ecosystem services, legislation often tends to favor the long-term maximization of fisheries yield. The paper calls for mutual understanding of theories and experiences across various environmental fields, including fisheries, to enhance collaborative efforts in each field.

The existence of a common ancestor to all living organisms in Earth is a necessary corollary of Darwin idea of common ancestry. The Last Universal Common Ancestor (LUCA) has been normally considered as the ancestor of cellular organisms that originated the three domains of life: Bacteria, Archaea and Eukarya. Recent studies about the nature of LUCA indicate that this first organism should present hundreds of genes and a complex metabolism. Trying to bring another of Darwin ideas into the origins of life discussion, we went back into the prebiotic chemistry trying to understand how LUCA could be originated under gradualist assumptions. Along this line of reasoning, it became clear to us that the definition of another ancestral should be of particular relevance to the understanding about the emergence of biological systems. Together with the view of biology as a language for chemical translation, on which proteins are encoded into nucleic acids polymers, we glimpse a point in the deep past on which this Translation mechanism could have taken place. Thus, we propose the emergence of this process shared by all biological systems as a point of interest and propose the existence of this pre-cellular entity named FUCA, as the First Universal Common Ancestor. FUCA was born in the very instant on which RNA-world replicators started to be capable to catalyze the bonding of amino acids into oligopeptides. FUCA has been considered mature when the translation system apparatus has been assembled together with the establishment of a primeval, possibly error-prone genetic code. This is FUCA, the earliest ancestor of LUCA’s lineage.

The main function of dUTPases is to regulate the cellular levels of dUTP and dTTP, thereby playing a crucial role in the DNA repair mechanisms. Despite the fact that mutant organisms with the obliterated dUTPase enzymatic activity remain viable, it is not possible to knockout the dut gene completely due to the lethal consequences of such mutation for the organism. As a result, it is considered that this class of enzymes perform an additional function that is essential for the organism's survival. In this study, we provide the evidence that the dUTPase of bacteriophage T5 possesses supplemental function in addition to its canonical role. We determined the crystal structure of bacteriophage T5 dUTPase with a resolution of 2.0 Å, and discovered a distinct short loop, consisting of 6 amino acid residues which represents unique structural feature specific to the T5-like phages dUTPases. The removal of this element did not affect the overall structure of the homotrimer, but had significant effects on the development of the phage. Furthermore, it has been shown that the enzymatic function and the novel function of bacteriophage T5 dUTPase are unrelated and independent from each other.

Abstract: Background: COVID-19 is a respiratory disease that eventually became pandemic with 300 million people infected around the world. Alongside the improvement in COVID-19 management and vaccine development, identifying biomarkers for COVID-19 has recently reported to help in early prediction and managing severe cases which might improve outcome. The Aim of our study was to find out if there is any correlation between clinical severity and elevated hematological and biochemical markers in Covid-19 patients and its effect on the outcome Methods: We have collected data retrospectively of socio-demographic, medical history, biomarkers, and diseases outcome from five hospitals and health institutions in the Kingdom of Saudi Arabia. Results: Pneumonia was the most common presentation of COVID 19 in our cohort. All biomarkers (D-Dimer, CRP, troponin, LDH and ferritin) except for the mean lowest white blood cells were found to have significant correlation (p<0.05) with worse COVID-19 disease outcomes. There was a sig-nificant association between the inflammatory biomarkers and the disease severity of COVID 19 patients (p<0.001). Patients with evidence of severe respiratory disease particularly who required mechanical ventilation (MV) had higher biomarkers, when compared to those with stable respiratory condition (p<0.001). Conclusion: Identifying biomarkers predicts outcome for COVID-19 patients and may significantly help in the management.

Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder characterized by unexplained left ventricular hypertrophy, with or without left ventricular outflow tract (LVOT) obstruction. Single nuclei RNA-sequencing (snRNA-seq) of both obstructive and nonobstructive HCM patient samples have revealed alterations in communication between various cell types but a direct and integrated comparison between the two HCM phenotypes has not been reported. We performed a bioinformatic analysis of HCM snRNA-seq datasets from obstructive and nonobstructive patient samples to identify differentially expressed genes and distinctive patterns of intercellular communication. Differential gene expression analysis revealed 37 differentially expressed genes, predominantly in cardiomyocytes but also in other cell types, relevant to aging, muscle contraction, cell motility and the extracellular matrix. Intercellular communication was generally reduced in HCM, affecting the extracellular matrix, growth factor binding, integrin binding, PDGF binding and SMAD binding, but with increases in adenylate cyclase binding, calcium channel inhibitor activity, and serine-threonine kinase activity in nonobstructive HCM. Increases in neuron to leukocyte and dendritic cell communication, in fibroblast to leukocyte and dendritic cell communication and in endothelial cell communication to other cell types, largely through changes in expression of integrin-b1 and its cognate ligands, were also noted. These findings indicate both common and distinct physiological mechanisms affecting the pathogenesis of obstructive and nonobstructive HCM and provide opportunities for personalized management of different HCM phenotypes.

Exosomes, natural nanovesicles that contain a cargo of biologically active molecules such as lipids, proteins, and nucleic acids, are released from cells to the extracellular environment. They then act as autocrine, paracrine, or endocrine mediators of communication between cells by delivering their cargo into recipient cells and causing downstream effects. Exosomes are greatly enriched in miRNAs, which are small non-coding RNAs that act as cytoplasmic posttranscriptional repression agents, modulating the translation of mRNAs into proteins, as well as nuclear transcriptional gene activators. Neuronal exosomal miRNAs have important physiologic functions in the Central Nervous System (CNS), including cell-to-cell communication, synaptic plasticity, and neurogenesis, as well as modulating stress and inflammatory responses. Stress-induced changes of exosomal functions include effects on neurogenesis and neuroinflammation, which can lead to the appearance of various neuropsychiatric disorders, such as schizophrenia, major depression, bipolar disorder, and Alzheimer's and Huntington’s's diseases. The current knowledge regarding the roles of exosomes in the pathophysiology of common mental disorders is discussed in this review.

Steroid and hopanoid biomarkers can be found in ancient rocks and may give a glimpse of what life was present at that time. Sterols and hopanoids are produced by two related enzymes, though the evolutionary history of this protein family is complicated by losses and horizontal gene transfers, and appears to be widely misinterpreted. Here, I have added sequences from additional species, and re-analysis of the phylogeny of SHC and OSC indicates a single origin of both enzymes among eukaryotes. This pattern is best explained by endosymbiotic acquisition of both enzymes from a bacterial ancestor, followed by widespread loss of SHC, and two subsequent HGT events to ferns and ascomycetes. Thus, the last common ancestor of eukaryotes would have been bifunctional for both sterol and hopanoid production. Later enzymatic innovations allowed diversification of sterols in eukaryotes. Contrary to previous interpretations, the last eukaryotic common ancestor (LECA) potentially would have been able to produce hopanoids as a substitute for sterols in anaerobic conditions. Without invoking any other metabolic demand, the LECA could have been a facultative aerobe, living in unstable conditions with respect to oxygen level.

In this paper, we prove some common fi xed point theorems on complex partial metric space. The presented results gener- alize and expand some of the literature well-known results. We also explore some of the application of our key results.

Type 2 Diabetes Mellitus and Alzheimer's disease are two diseases with a high incidence today that share similar pathophysiological mechanisms suggesting a potential causal relationship between them. In fact, Alzheimer-associated Mellitus Diabetes is also known as Type 3 Diabetes Mellitus and constitutes a diabetes intricately linked to Alzheimer's disease. Central to this association is insulin resistance, a key factor leading to decreased insulin sensitivity, hyperglycemia, and impaired glucose uptake. Because of this, the brain is altered resulting in energy deficits and neuronal damage associated with neurodegenerative disorder characteristic of Alzheimer's disease. Both diseases exhibit common biochemical and physiological characteristics such as inflammation, mitochondrial dysfunction, oxidative stress, and the formation of advanced glycation end products. Understanding the complex pathophysiology of Type 3 Mellitus Diabetes and identifying common features shared with Diabetes and Alzheimer's disease are essential steps towards potential therapeutic interventions targeting the insulin resistance pathway. The authors of this review on the relationships between type 2 diabetes and Alzheimer's disease have developed two works. In the first (Relationships between Type 2 Diabetes Mellitus and Alzheimer's Disease. I. Common pathogenic mechanisms), authors explore the shared (physiological, genetics and molecular) pathological changes occurring in Type 2 Mellitus Diabetes and Alzheimer's disease as well as pathways such as AMPK, PPARγ, cAMP, and PI3K/Akt as potential targets for managing Type 3 Diabetes Mellitus. By exploring these intricate mechanisms, the goal is to uncover their interdependencies and facilitate the discovery of innovative pharmacological and nutritional (epigenetics) strategies. In the second paper (Relationships between Type 2 Diabetes Mellitus and Alzheimer's Disease. II Potential therapies) we describe possible nutritional intervention, particularly dietary patterns and phytochemicals that can enhance the effects of pharmaceutical drugs designed against pathological mechanisms involved in the complex dual disease Type 2 Diabetes Mellitus and Alzheimer's disease (or in Type 3 Diabetes Mellitus as other authors consider).

With the continuous improvement and observable benefits of electric vehicles (EVs), major logistic companies are introducing more EVs into their conventional fleets. This gives rise to a new type of vehicle routing problem with mixed vehicles, where heterogeneous internal combustion vehicles (ICVs) and electric vehicles are considered in route planning. In addition, certain deliveries that are not efficient on any type of vehicles, are outsourced to third-party common carriers. In this paper, we define this problem as a mixed vehicle routing problem with common carriers (MVRPC). The objective of such problems is to minimize the transportation costs by considering routes with ICVs and EVs, the possibility of visiting recharging stations, outsourcing options, and drivers’ layover regulations. This variant of the vehicle routing problems has many practical applications, particularly in the design of long-haul transportation and last-mile delivery services. Effective MVRPC solutions play a key role in promoting the going Green image and optimally allocating resources. The problem has received limited attention in the literature likely because addressing all the needed aspects is especially challenging. To solve the large-scale problem, we develop a branch-and-cut pricing framework that relies on strong cuts and customized labeling algorithms. Numerical experiments highlight the effectiveness of our algorithm. This success can be attributed to tailored critical resources, dynamically bounded bidirectional labeling procedures, strong dominance criteria, and implementation strategies.

Data on helminth parasites and epizoites is presented for the long-beaked and short-beaked common dolphins from the Southeast Pacific. Sampling in 1985-2000 was conducted mainly at six fishing ports in Peru and Ecuador where cetaceans were landed. From a total of 473 common dolphins sampled, we identified helminths including three species of Trematoda: Nasitrema globicephalae, Pholeter gastrophilus and Braunina cordiformis; three species of Nematoda, which includes Anisakis spp., Crassicauda sp. and Halocercus sp.; and two cestodes Tetrabothrius forsteri and Clistobothrium delphini (formerly Phyllobothrium delphini). No acanthocephalans were observed. No statistically significant sexual and ontogenetic variation in helminth prevalence was detected after which samples were pooled. The highest prevalence in the long-beaked common dolphin (n=440) was observed for N. globicephalae (96.3%) in cranial sinuses, Crassicauda sp. (83.3%) in mammary glands, Crassicauda sp. (78.8%) infesting the cranial sinuses, followed by Cl. delphini (28.6%) in the blubber and P. gastrophilus and B. cordiformis (20.4%) in the digestive tract. Although comparative testing was unfeasible due to minimal samples of short-beaked common dolphin (n=33), several of the same helminth species were found, but not N. globicephalae nor B. cordiformis. No cyamids were encountered while pseudo-stalked barnacles Xenobalanus globicipitis were common. No new (global) helminth host records are revealed for common dolphins, but this study presents a first checklist of parasites separately for the Southeast Pacific long-beaked and short-beaked common dolphins. Future work should include exhaustive laboratory-based necropsies, enhanced sampling of the short-beaked form, focus on intermediate hosts and parasitic pathology, including potential human health impact from consumption of small cetaceans.

Despite the popularity of theraphosids, detailed reports on bite symptoms are still limited to few geographic regions and subfamilies. We therefore examined 363 published bite reports and noticed muscles cramps caused by theraphosids from nearly all continents and subfamilies. Symptoms are mostly locally restricted and mild, but 12.7% of victims experience pronounced cramps with highest incidence rates by Poecilotheriinae, Harpactirinae and Stromatopelminae subfamilies. We discuss how variations in venom quantity correlate with muscle cramp prevalence.

Introduction: Cholelithiasis and consumption of alcohol are the most frequent causes of acute pancreatitis (AP), accounting for about 30 to 40% of the cases, respectively. The frequency of acute biliary pancreatitis is high in a certain population in Brazil. Objective: To estimate the global frequencies of acute biliary pancreatitis (ABP), acute alcoholic pancreatitis (AAP) and the cases considered as acute idiopathic pancreatitis (AIP) in studies published from October 2006 to December 31, 2018. Methods: A systematic review of observational studies was performed from October 2006 to December 31, 2018. A meta-analysis by the random effects model was used to calculate the frequencies of global ABP, AIP and AAP and subgroups. Results: Forty-six studies representing 2,341,007 AP cases were included in 36 countries. The overall estimate for acute biliary pancreatitis (ABP) was 41.6% (95% CI 39.2-44.1), followed by acute alcoholic pancreatitis (AAP) with 20.5% (95% CI) 16.6- 24.6) and acute idiopathic pancreatitis (AIP) in 18.3% (95% CI 15.1-27.7). Conclusion: ABP is the most prevalent etiology of AP, being two times more frequent than second-placed pancreatitis. Latin America has a frequency for ABP much higher than the rest of the world. The importance of the etiologic diagnosis is the treatment of the cause for prevention of recurrence.

Autism spectrum disorder (ASD) is a neuropsychiatric condition characterized by impaired social interactions and repetitive stereotyped behaviors. Growing evidence highlights an important role of the gut-brain-microbiome axis in the pathogenesis of ASD. Research indicates an abnormal composition of the gut microbiome and the potential involvement of bacterial molecules in neuroinflammation and brain development disruptions. Concurrently, attention is directed towards the role of short-chain fatty acids (SCFAs) and impaired intestinal tightness. This comprehensive review emphasizes the potential impact of maternal gut microbiota changes on the development of autism in children, especially considering maternal immune activation (MIA). The following paper evaluates the impact of the birth route on the colonization of the child with bacteria in the first weeks of life. Furthermore, it explores the role of pro-inflammatory cytokines, such as IL-6 and IL-17a and mother’s obesity as potentially environmental factors of ASD. The purpose of the present analysis is to advance our understanding of ASD pathogenesis, while also searching for the positive implications of the latest therapies, such as probiotics, prebiotics or fecal microbiota transplantation, targeting the gut microbiota and reducing inflammation. This review aims to provide valuable insights that could instruct future studies and treatments for individuals affected by ASD.

A Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease of unknown aetiology under growing interest now in view of the increasingly recognized post-COVID syndrome as a new entity with similar clinical presentation. We performed the first cross-sectional study of ME/CFS in community population in Russia and then described and compared some clinical and pathophysiological characteristics of ME/CFS and post-COVID syndrome as neuroimmune disorders. Of the cohort of 76 individuals who suggested themselves suffering from ME/CFS 56 subsequently were confirmed as having CFS/ME according to ≥1 of the 4 most commonly used case definition. Of the cohort of 14 individuals with post-COVID-19 syndrome 14 met diagnostic criteria for ME/CFS. The prevalence of clinically expressed and subclinical anxiety and depression in ME / CFS and post-COVID ME/CFS did not differ significantly from that in healthy individuals. Severity of anxiety / depressive symptoms did not correlate with the severity of fatigue neigther in ME / CFS nor in post-COVID ME/CFS, but the positive correlation was found between the severity of fatigue and 20 other symptoms of ME / CFS related to the domains of “post-exertional exhaustion”, “immune dysfunction”, “sleep disturbances”, "dysfunction of the autonomic nervous system", "neurological sensory / motor disorders" and "pain syndromes". Immunological abnormalities were identified in 12/12 patients with ME / CFS according to the results of laboratory testing. The prevalence of postural orthostatic tachycardia assessed by the active standing test was 37.5% in ME / CFS and 75.0% in post-COVID ME/CFS (the latter was higher than in healthy controls, p = 0.02) There was a more pronounced increase in heart rate starting from the 6th minute of the test in post-COVID ME/CFS compared with the control group. Assessment of the functional characteristics of microcirculation by laser doppler flowmetry revealed obvious and very similar changes in ME/CFS and post-COVID ME/CFS compared to the healthy controls. The identified pattern corresponded to the hyperemic form of microcirculation disorders, usually observed in acute inflammatory processes or in deficiency of systemic vasoconstriction influences.

The nutraceutical value of pomegranate in the treatment of many neoplastic, cardiovascular, viral, inflammatory, metabolic, microbial, intestinal, reproductive and skin diseases is well-documented and is linked to its richness in phenolic compounds. This study aims to evaluate nutraceutical and genetic diversity of novel pomegranate genotypes (G1-G5) in comparison to leading commercial pomegranate varieties i.e. ‘Wonderful’, ‘Primosole’, ‘Dente di Cavallo’ and ‘Valenciana’. Morphometric measurements were carried out on fruits, accompanied by chemical characterization and the development of four new polymorphic SSR markers involved in the flavonoid pathway. The cultivars displayed a marked variability in the weight and shape of fruits, as well as in the weight of arils and juice yield. The highest level of total phenolic content and antioxidant activity was found in ‘Wonderful’ and G4, while the lowest was in ‘Dente di Cavallo’. Furthermore, the results showed that the pomegranate juice, is an excellent source of minerals, especially potassium, which plays a key role in organ functioning. The new flavonoid-related markers effectively differentiated the cultivars with the same diversity pattern as morpho-chemical characterization, so the SSRs developed in the present study can be used as a rapid tool for the identification of pomegranate cultivars with relevant nutraceutical traits.

The structures of recently discovered primarolides A and B suggest their non-enzymatic formation from a common 2-formylbenzophenone precursor. This hypothesis is based on the experimentally proven facile conversion of pestalone (also a 2-formyl-benzophenone) either into the isomeric lactone pestalalactone or the structurally related isoindolinone pestalachloride A. In a related fashion, the racemic isoindolinone natural product mariline A is supposed to biosynthetically originate from the corresponding keto-aldehyde and an aniline, as experimentally supported by model studies. Due to the close structural relationship with known systems, it appears highly probable that primarolides A and B were generated under the fermentation conditions from a massarinin-related 2-formylbenzophenone (proprimarolide) by reaction either with aniline or a nucleophilic catalyst, respectively. Suberoylanilide hydroxamic acid (SAHA), used as an additive during the fermentation, is supposed to act both as a source of aniline and as a nucleophilic catalyst.

Usage of antimicrobials in veterinary practices has always been under scrutiny due to the perceived risk of resulting in antimicrobial-resistant pathogens. This creates the necessity for understanding the role of the prescriber group. Hence, we conducted a cross-sectional survey among veterinary practitioners from August to November 2019 in the Chattogram district of Bangladesh, aiming to assess the practitioner’s perceptions regarding antimicrobial prescribing and antimicrobial resistance (AMR) issue. We collected responses from 100 veterinarians engaged in the treatment of the large animal, poultry, and pet animal through a self-administrated questionnaire. Proportions were calculated for categorical variables and the results are presented using visual aids. Our study revealed two key barriers - scarcity of enough information on antimicrobial used, and the lack of training in the proper prescription of antimicrobials. Participants recognized that prescribing too many varieties of antimicrobials and the use of an incomplete course of drugs as two very important causes for the development of antimicrobial resistance. In addition, prescription of inappropriate doses and incentives from pharmaceutical companies were dubbed as important causes. We also found that along with clinical features and types of organisms, the availability of drugs in the local market and the economic conditions of farmers have potential impacts on the antimicrobials prescribing decision of the veterinarians. However, all participants recognized the emerging threats of AMR. Results suggested that capacity building of veterinarians and the maintenance of strong coordination are crucial in ensuring the proper engagement of veterinarians as the front-line fighters for tackling the AMR issue.

(1) Background: There is not much research about obesity in nursing homes although knowledge will help us to develop customized treatment plans and prevention strategies, which may help to decrease the burden for all persons involved. The objective of conducting this study was to describe the prevalence of obesity and the association between obesity and care problems in nursing home patients. (2) Methods: This study is a secondary data analysis of data collected in an annually performed cross-sectional study called “Nursing Quality Measurement 2.0”. A standardized and tested questionnaire was used to collect data. (3) Results: 1236 nursing home patients took part and 16.7% of them were obese. The multivariate logistic regression analysis results show that urinary incontinence is significantly associated with the presence of obesity (OR 2.111). The other care problems of pressure injuries, fecal and double incontinence, physical restraints, falls and pain were not associated with obesity. (4) Conclusion: The results indicate that, in the nursing home setting, health care staff should pay special attention to the patients’ nutritional and continence status and help patients maintain a normal, healthy weight. Conducting more studies with larger sample sizes is recommended, as this will allow differentiation among different obesity classes.

The following system of equations {x_1 \cdot x_1=x_2, x_2 \cdot x_2=x_3, 2^{2^{x_1}}=x_3, x_4 \cdot x_5=x_2, x_6 \cdot x_7=x_2} has exactly one solution in ({\mathbb N}\{0,1})^7, namely (2,4,16,2,2,2,2). Hypothesis 1 states that if a system of equations S \subseteq {x_i \cdot x_j=x_k: i,j,k \in {1,...,7}} \cup {2^{2^{x_j}}=x_k: j,k \in {1,...,7}} has at most five equations and at most finitely many solutions in ({\mathbb N}\{0,1})^7, then each such solution (x_1,...,x_7) satisfies x_1,...,x_7 \leq 16. Hypothesis 1 implies that there are infinitely many composite numbers of the form 2^{2^{n}}+1. Hypotheses 2 and 3 are of similar kind. Hypothesis 2 implies that if the equation x!+1=y^2 has at most finitely many solutions in positive integers x and y, then each such solution (x,y) belongs to the set {(4,5),(5,11),(7,71)}. Hypothesis 3 implies that if the equation x(x+1)=y! has at most finitely many solutions in positive integers x and y, then each such solution (x,y) belongs to the set {(1,2),(2,3)}. We describe semi-algorithms sem_j (j=1,2,3) that never terminate. For every j \in {1,2,3}, if Hypothesis j is true, then sem_j endlessly prints consecutive positive integers starting from 1. For every j \in {1,2,3}, if Hypothesis j is false, then sem_j prints a finite number (including zero) of consecutive positive integers starting from 1.

The goal of this study was to determine the relative susceptibility of four common equine wound pathogens to ten different types of antimicrobial agents based on minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Additionally, to describe the comparison of bactericidal activity of medical grade Manuka honey, local honey, and commercial, food-grade honey to other commonly used wound dressings. The objective is to provide veterinary practitioners with comparative data on the use of a variety of antimicrobial dressings for inhibiting growth of common wound bacteria. MIC and MBC for Manuka, store, and local honeys were comparable to those of sterile gauze, sugar, and hypertonic saline. Across bacterial species, local honey proved to have more bactericidal activity when compared to Manuka and commercial, food-grade honey. The MIC and MBC for PHMB gauze and foam was consistently at a higher dilution compared to the other antimicrobials. The majority of antimicrobials exhibited stronger inhibitory and bactericidal activity against a Streptococcus zooepidemicus isolate obtained from a wound compared to other bacteria that were ATCC lab acclimated. Additional research for in-vivo applications needs to be done to see whether differences exist in effective wound management.

(1) Background: Respiratory infections are a major public health problem worldwide, with potentially serious consequences. Indeed, these infections remain one of the main causes of morbidity and mortality in children under 5 years old in developing countries. Etiological information on respiratory infections is crucial for prevention and case management strategies. This systematic review aims to describe the etiology of respiratory infections reported in studies carried out in sub-Saharan African countries; (2) Methods: Using PubMed, HINARI and Google scholar search engines, a systematic search was carried out to identify published articles on the etiology of viral and/or bacterial respiratory infections in sub-Saharan Africa in patients of all ages. We have only considered data from sub-Saharan Africa. Papers published from 2010 to 2021, in English or French have been included in this review; (3) Results: After reviewing 115 articles reporting studies carried out in the African continent, only 32 articles were selected of which, studies were conducted in 15 sub-Saharan African countries, including 6/32 (18.75%) in Cameroon. Twenty (62.5%) were cross-sectional studies, and twenty-four (75%) were hospital-based investigations. In these studies, RT-PCR and culture methods were respectively used for viruses and bacteria investigations. Respiratory syncytial virus was the most frequently identified, with prevalence ranging from 0.6% to 59%, followed by rhinovirus (9.3% -73%), influenza virus (flu) A/B (0.9%-69.1%), and human adenovirus (0.9% - 30.8%). Streptococcus pneumoniae (14.2% - 96%), followed by Haemophilus influenzae type b (2.5% - 54%), and Klebsiella pneumoniae (1.4% - 49.9%) were the most frequently detected bacteria; (4) Conclusions: This review has reported that many pathogens, mainly viruses, are associated with acute respiratory infections in sub-Saharan Africa in both children and adults. Unfortunately, the limited geographical distribution of data across sub-Saharan Africa does not allow most of countries to develop an effective strategy for the prevention and treatment of respiratory infections.

The giant anteater (Myrmecophaga tridactyla) is a vulnerable specie from Central and South America and is considered extinct in Belize, Guatemala, El Salvador, and Uruguay. Therefore, studies describing the reproductive characteristics of this species are pivotal for its conservation. Thus, this study aimed to provide a morphological description of their female reproductive tissues. We collected tissue samples from six female giant anteaters, and performed gross, morphological, and histochemical analyses. Five adult and one young subjects were enrolled in the study. In the ovary, classifications were made according to the follicle and oocyte sizes: primordial, primary, secondary, early antral, or antral. Typical follicles with a single oocyte surrounded by a simple or stratified layer of cubic epithelium, atretic follicles, corpora lutea, corpora albicans, and ovarian cysts were also observed. No ovarian lesions were observed. By contrast, endometritis, metritis, mucometra, and endometrial cysts were identified in the uterus. Uterine alterations in these subjects were frequent and could affect reproduction.

In the event of an abrupt sunlight reduction scenario there is a time window that occurs between when food stores would likely run out for many countries (~6 months or less) and ~1 year when resilient foods are scaled up. A promising temporary resilient food is leaf protein concentrate (LPC). Although it is possible to extract LPC from tree biomass (e.g. leaves and needles), neither the yields nor the toxicity of the protein concentrates for humans from the most common tree species has been widely investigated. To help fill this knowledge gap, this study uses high-resolution mass spectrometry and an open source toolchain for non-targeted screening of toxins on five common North American coniferous species: Western Cedar, Douglas Fir, Ponderosa Pine, Western Hemlock, and Lodgepole Pine. The yields for LPC extraction from the conifers ranged from 1% to 7.5%. The toxicity screenings confirm that these trees may contain toxins that can be consumed in small amounts and additional studies including measuring the quantity of each toxin are needed. The results indicate that LPC is a promising candidate to be used as resilient food, but future work is needed before LPCs from conifers can be used as a wide-scale human food.

Marnaviridae viruses are abundant algal viruses that regulate the dynamics of algal blooms in aquatic environments. They employ a narrow host range because they merely lyse their own algal host species. This host-specific lysis is thought to correspond to the unique transmission mechanism of the Marnaviridae viruses. Here, we present the atomic structures of the full and empty capsids of Chaetoceros socialis forma radians RNA virus 1 built in 3.0 Å and 3.1 Å cryo-electron microscopy maps. The empty capsid structure and the structural variability provide insights on its assembly and uncoating intermediates. In conjunction with the previously reported atomic model of the Chaetoceros tenuissimus RNA virus type II capsid, we have identified the common and diverse structural features of the VP1 surface between the Marnaviridae viruses. We have also tested the potential usage of AlphaFold2 for structural prediction of the VP1s and a subsequent structural phylogeny for classifying Marnaviridae viruses by their hosts. These findings will be crucial for inferring the host-specific transmission mechanism in Marnaviridae viruses, which is decisive for monitoring and possibly regulating the occurrence and disappearance of algae blooms.

Phosphate (Pi) deficiency reduces nodule formation and development in different legume species including common bean. Despite the significant progress in the understanding of the genetic responses underlying the adaptation of nodules to Pi deficiency, it is still unclear whether this nutritional deficiency interferes with the molecular dialog between legumes and rhizobia, if so, what part of the molecular dialog is impaired? In this study, we provide evidence demonstrating that Pi deficiency negatively affects critical early molecular and physiological responses required for a successful symbiosis between common bean and rhizobia. We demonstrated that the infection thread formation and the expression of PvNSP2, PvNIN, and PvFLOT2, genes controlling the nodulation process, were significantly reduced in Pi-deficient common bean seedlings. Further transcriptional analysis revealed that the expression of hormones-related genes is compromised in Pi-deficient seedlings inoculated with rhizobia. Additionally, we showed that regardless of the presence or absence of rhizobia, the expression of PvRIC1 and PvRIC2, two genes participating in the autoregulation of nodule number, was higher in Pi-deficient seedlings than in control seedlings. The data presented in this study shed light on the understanding of how Pi deficiency impacts the early steps of the symbiosis between common bean and rhizobia.

The negative impact of drought on plant growth may be modified by different availability of mineral nutrients and by their adaptation to different local habitat conditions. In this study, we examine the impact of drought, fertilization with phosphorus and provenance, as well as their interactions, on the growth and allometric growth relationships between belowground and aboveground organs of common beech (Fagus sylvatica) and sessile oak (Quercus petraea). The research was conducted on saplings originating from two mature mixed stands (dry and wet provenances) dominated by these species. In the common garden experiment, saplings were exposed to regular watering and drought in interaction with moderate and high phosphorus concentrations in the growing substrate (achieved by phosphorus fertilization). Obtained results indicate negative impact of drought and phosphorus fertilization on the growth of both species. In common beech, phosphorus fertilization had a negative impact on its adaptive capacity to drought, because of the unfavourable ratios between fine root mass and mass of other organs. The sessile oak provenances under the impact of drought showed a different root collar diameter/stem height increment ratio, which indicates its different phenotypic plasticity as a consequence of adaptation to different frequencies of dry periods in their natural habitats.

This study investigates the metabolic parallels between stimulated pancreatic beta cells and cancer cells, emphasizing glucose and glutamine metabolism. Addressing the significant public health challenges of Type 2 Diabetes Mellitus (T2DM) and cancer, we aim to deepen understanding of the mechanisms driving insulin secretion and cellular proliferation. Our analysis of anaplerotic cycles and NADPH's role in biosynthesis elucidates their vital functions in both processes. Additionally, we find that both cell types share an antioxidative response mediated by the Nrf2 signaling pathway, glutathione synthesis, and UCP2 upregulation. Notably, UCP2 facilitates the transfer of C4 metabolites, enhancing reductive TCA cycle metabolism. We also uncover that hypoxic responses are transient in beta cells post-stimulation but persistent in cancer cells. By synthesizing these insights, our research suggests novel therapeutic targets for T2DM, highlighting the shared metabolic strategies of stimulated beta cells and cancer cells. This comparative analysis not only illuminates the metabolic complexity of these conditions but also emphasizes the crucial role of metabolic pathways in cell function and survival, offering fresh perspectives for tackling T2DM and cancer challenges.

Most fungal species are commensals, not pathogenic for plants, humans, or animals. However, several species from genera Alternaria, Aspergillus, Trichophyton and Microsporum are common causes of disease, even for immunocompetent individuals, contributing to skin barrier impairment. A total of 68 allergic dogs were selected from a veterinary dermatology and allergy outpatient consultation, for conditions related to Malassezia overgrowth or other fungal complications. Allergy diagnosis was made through anamnestic and clinical criteria and allergy-implicated species were identified by intradermal testing (IDT) and serum determination of specific immunoglobulin E (sIgE). Dermatophagoides farinae, Dactylis glomerata and Malassezia pachydermatis showed as the higher sensitization species from each group. Significant correlations at p<0.05 were found between Dactylis glomerata and Phleum pratense grass pollens, Dermatophagoides farinae and Dermatophagoides pteronyssinus, Acarus siro, Tyrophagus putrescentiae and Lepidoglyphus destructor dust/storage mites, and between fungi like Aspergillus mix and Penicillium or Alternaria alternata. A significant correlation was also found between sensitization to Aspergillus mix and D. farinae, D. pteronyssinus or A. siro. Rather severe dermatitis was observed where positive IDT to Malassezia pachydermatis was found, regardless of the presence of circulating sIgE, allowing us to perceive the usefulness of both sIgE and IDT for allergy diagnosis to fungi.

The importance of statistics in biological research is inevitable. The appliance of statistics is the most powerful tool to support the scientific hypothesis and to give credibility to biological research methodology, to interpret convoluted explanations and conclusions based on the research findings. The evidences from literatures point the persistent statistical errors, selection of non-proper statistical test with the consequence of misinterpretation of the scientific results which are published in international journals. One of the most extensively used statistical tests in the field of biology (preclinical and clinical) is analysis of variance (ANOVA). ANOVA test is in place of multiple T-tests to compare the means of more than two groups at a time; and there are some important points which biologists should be aware of them to avoid possible misinterpretation of results with the consequence of wrong conclusion. Accordingly, the aim of the current review is to help biologists to understand the basic concepts of ANOVA test and reach to a more valid interpretation of achieved results.

Common rust (CR), caused by Puccina sorghi, is one of the major foliar diseases in maize, leading to quality deterioration and yield losses. To dissect the genetic architecture of CR resistance in maize, this study utilized the susceptible temperate inbred line Ye107 as the male parent crossed with three resistant tropical maize inbred lines (CML312, D39, and Y32) to generate 627 F7 recombinant inbred lines (RILs), aiming to identify maize disease-resistant loci and candidate genes for common rust. Phenotypic data exhibited good segregation between resistance and susceptibility, with varying degrees of resistance observed across different subpopulations. Significant genotype effects and genotype × environment interactions were noted with heritability ranging from 85.7% to 92.2%. Linkage analysis and genome-wide association analysis across three environments identified 20 QTLs and 62 significant SNPs. Among them, seven major QTLs explained 66% of the phenotypic variance. Comparison with six SNPs repeatedly identified across different environments revealed overlap between qRUST3-3 and Snp-203,116,453, and Snp-204,202,469. Haplotype analysis indicated two significantly different haplotypes for CR resistance for both of these SNPs. Based on LD decay plots, three co-located candidate genes, namely Zm00001d043536, Zm00001d043566, and Zm00001d043569, were identified within 20 kb up-stream and downstream of these two SNPs. Zm00001d043536 regulates hormone regulation, Zm00001d043566 controls stomatal opening and closure, related to trichome, and Zm00001d043569 is associated with plant disease immune responses. Additionally, we performed candidate gene screening for five additional SNPs repeatedly detected across different environments, resulting in the identification of five candidate genes. These findings contribute to the development of genetic resources for common rust resistance in maize breeding programs.

Anthracnose, caused by the fungus Colletotrichum lindemuthianum, poses a significant and widespread threat to the common bean crop. The use of plant genetic resistance has proven to be the most effective strategy for managing anthracnose disease. The Amendoim Cavalo (AC) Andean cultivar has resistance against multiple races of C. lindemuthianum, which is conferred by the Co-AC gene. Fine mapping of this resistance gene to common bean chromosome Pv01 enabled the identification of Phvul.001G244300, Phvul.001G244400, and Phvul.001G244500 candidate genes for further validation. In this study, we assessed the relative expression of Co-AC candidate genes, as well as other putative genes in vicinity of this locus and known resistance genes, in the AC cultivar following inoculation with the race 73 of C. lindemuthianum. Gene expression analysis revealed significantly higher expression levels of Phvul.001G244500. Notably, Phvul.001G244500 encodes a putative Basic Helix-Loop-Helix transcription factor, suggesting its involvement in the regulation of defense responses. Furthermore, we observed a significant modulation of the expression of defense related genes PR1a, PR1b, and PR2, in a time-course experiment. These findings contribute to the development of improved strategies for breeding anthracnose-resistant common bean cultivars, thereby mitigating the impact of this pathogen on crop yields and ensuring sustainable bean production.

Electronic structure calculations have been carried out to examine the effect of protonation and water molecules on the heme group of peroxidases in different redox (ferric, ferrous, compounds I and II) and spin states. Shared geometries, spectroscopic properties at Soret region, and thermodynamics of peroxidases are discussed. B3LYP and M06-2X density functionals with different basis sets were employed on a common molecular model of the active site (Fe-centred porphine and proximal imidazole). Computed Gibbs free energies indicate that the corresponding aquo complexes are not thermodynamically stable, supporting the five-coordinate Fe(III) centre in native ferric peroxidases, with a water molecule located at a non-bonding distance. Protonation of the ferryl oxygen of compound II is discussed in terms of thermodynamics, Fe–O bond distances, and redox properties. It is demonstrated that this protonation is necessary to account for the experimental data and computed Gibbs free energies that reveal pKa values of compound II about 8.5 – 9.0. Computation suggests that the origin of the general oxidative properties of peroxidase species, as well as their reactivity towards water and protons and Soret spectral properties, mostly resides on the iron porphyrin and its proximal ligand histidine.

Pompeii was connected to the great Serino aqueduct under the principate of Augustus. From that moment on, water became not only a precious resource for the inhabitants but also their true social indicator. It is no coincidence, in fact, that the concentration of sumptuous dwellings is in Regio VI, the district closest to the aqueduct reservoir (castellum aquae in Latin) and the one most equipped with piezometric towers, the first of the network, the ones that would never leave the decorative fountains of the peristyles dry. From this observation follows the original possibility of considering the water network a factor that contributed to designating the morphology of urban neighbourhoods and blocks.

Nucleosome positioning plays an important role in crucial biological processes like replication, transcription, and gene regulation. It has been widely used to predict the genome’s function and chromatin organisation. So far, the studies of patterns in nucleosome positioning have been limited to transcription start sites, CTCFs binding sites, and some promoter and loci regions. The genome-wide organisational pattern remains unknown. We have developed a theoretical model to coarse-grain nucleosome positioning data in order to obtain patterns in their distribution. Using hierarchical clustering on the auto-correlation function of this coarse-grained nucleosome positioning data, a genome-wide clustering is obtained for Candida albicans. The clustering shows the existence beyond hetero- and eu-chromatin inside the chromosomes.

Over the course of the pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple new clinical manifestations, as the consequence of the tropism of the virus, have been recognized. That includes now the neurological manifestations and conditions, such as headache, encephalitis, as well as olfactory and taste disorders. We present a series of ten cases of RT-PCR confirmed SARS-CoV-2 infected patients diagnosed with viral-associated olfactory and taste loss from four different countries.

In the international scenario of agriculture, Brazil stands out as the main producer and consumer of common bean (Phaseolus vulgaris L.) The increase in the productive potential of the crop is mainly due to breeding programs. The objective of this study was to estimate genetic parameters, predict genotypic values with REML/BLUP (Restricted Maximum Likelihood/Best Linear Unbiased Prediction) and, based on these values, study the variability in common bean cultivars with carioca and black grain. Twenty three agromorphological descriptors were evaluated, among them grain yield. Deviance analysis detected significant differences between the cultivars in both groups. Selective accuracy (Ac) was considered high for most of the traits. Broad-sense heritability (h_g² ) ranged from 0.05 to 0.72, but it was low for the trait yield (YLD). In the carioca grain group, the h_g² values for the traits related to plant morphology were higher than in the black group. Nevertheless, the h_g² values in the black group were higher in relation to the pod and seed traits. The correlations for YLD were moderate but different in the two commercial groups studied. In the black group, variables related to the seed morphology were correlated with grain yield, and in the carioca group, traits related to seed quantity. Based on the groupings, variability among the cultivars was observed. Three distinct clusters were formed for the carioca group and four for the black group. Based on the predicted genetic values, genetic variability and the most adapted and stable cultivars were detected among the cultivars in the studied environments.

Objectives: Isolated mild neutropenia is a common clinical problem. The current study aims to validate our previous findings regarding the high prevalence of isolated neutropenia in Southern and Southwestern Saudi Arabia and explore the effect of altitude or regional differences. Methods: In this retrospective cross-sectional study, laboratory results of a commercial laboratory were screened over a period of 5 years (2016–2020) in seven different cities in South and southwestern Saudi Arabia. Participants’ laboratory investigations were reviewed and excluded for any ab-normal complete blood count, renal profile, liver profile, lipid profile, thyroid function test, fasting blood glucose, or HbA1c findings. Descriptive analysis and 95th percentile range were calculated using standard statistical methods. Results: A total of 91,880 complete blood count results were included in the final analysis. isolated neutropenia is common laboratory finding, with a prevalence ranging from 11-23%. The 2.5th percentile of the neutrophil count was lower than 1.5×109/L in all seven cities. Conclusions: Mild to moderate neutropenia is common in Southern and Southwestern Saudi Arabia. Benign ethnic neutropenia (BEN) may explain this high prevalence. Since BEN has no clinical significance, the reference range for normal neutrophil counts needs to be adjusted to reflect the effect of BEN.

Current prenatal genetic evaluation showed a significantly increase in non-invasive screening and the reduction of invasive diagnostic procedures. To evaluate the diagnostic efficacy on detecting common aneuploidies, structural chromosomal rearrangements and pathogenic copy number variants (pCNV), we performed a retrospective analysis on a case series initially analyzed by aneuvysion fluorescence in situ hybridization (FISH) and karyotyping then followed by array comparative genomic hybridization (aCGH). Of the 386 cases retrieved from the past decade, common aneuploidies were detected in 137 cases (35.5%), other chromosomal structural rearrangements were detected in four cases (1%), and pCNV were detected in five cases (1.3%). The relative frequencies for common aneuploidies suggested a under detection of sex chromosome aneuploidies. Approximately 9.5% of cases with common aneuploidies showed a mosaic pattern. Inconsistent results between FISH and karyotyping were noted in cases with pseudo-mosaicism introduced by culture artifact or variable cellular proliferation from cells with mosaic karyotypic complements under in vitro cell culture. Based on findings from this case series, cell-based FISH and karyotyping should be performed to detect common aneuploidies, structural chromosomal abnormalities, and mosaic pattern. DNA-based aCGH and reflex FISH should be performed to detect and confirm genomic imbalances and pCNV. Practice points to ensure the diagnostic accuracy and efficacy were summarized.

Isokinetic testing of the knee joint is the “gold standard” in strength assessment in sport especially in soccer, where it is part of pre-season screening to establish norms in case of injuries. There are many devices on the market that make it difficult to use of normative data. Isokinetics literature in females’ soccer players is scarce in comparison to males. Furthermore, evaluation protocols strongly differ from each other, using different ranges of speeds, movement patterns and output data. Thus, it is difficult for the researcher and the clinician to choose a correct protocol for isokinetic evaluation in female soccer players. The indexes of isokinetic performance that are widely accepted are the hamstring/quadriceps (H/Q) ratio and dominant/non-dominant (D/ND) ratio as reference. In this review are highlighted some common features of isokinetic testing in female soccer players of different levels of qualification. From this study, it emerges that, for a reliable test, 3 reps at the speed of 60°/sec in knee flexion/extension is preferable due to the high reliability and that an optimal H/Q ratio in healthy female soccer players of different level of qualification and age is 50%, while the interlimb differences (D/ND) should be below 10%.

BackgroundIndex level disc herniation following lumbar spinal decompression is somewhat overlooked as postoperative complication, resulting in return of symptoms. It is proposed that the combination of local instability and degenerated disc is more likely to result in disc herniation. There is no literature comparing post-decompression disc herniation rates between different techniques. This study compares the postoperative disc herniation rates of the "mini-open" laminectomy versus the tubular system decompression.MethodsIn a retrospective comparative study, 563 patient files who underwent primary lumbar spinal decompression, were reviewed and divided into two groups, distinguished by surgical technique. Demographic, clinical, and postoperative data were collected and compared using independent two-tailed t-test and Fisher's exact test with significance set at p<0.05. Primary outcome: comparison of post-decompression surgery, index level, disc herniation occurrence between two surgical techniques.ResultsPostoperative index level disc herniation was significantly lower in the minimally invasive surgery group with 2 cases (0.8%) versus 19 cases (5.8%) in the "mini-open" group [p=0.002]. Disc herniation following single level and multi-level operations were also significantly lower in the minimally invasive group compared with the "mini-open" group (2 versus 11 and 0 versus 8 respectively; p<0.05).ConclusionPostoperative index level disc herniation following lumbar spinal decompression occurs in 3.7% of surgeries. Minimally invasive surgery is found to result in less herniations then "mini-open".

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Its treatment includes antiarrhythmic drugs (AADs) to modulate the function of cardiac ion channels. However, AADs have been limited by proarrhythmic effects, non-cardiovascular toxicities as well as often modest antiarrhythmic efficacy. Theoretical models showed that combined blockade of Nav1.5 (and its current INa) and Kv1.5 (and its current, IKur) ion channels yield a synergistic anti-arrhythmic effect without effect on ventricles. We focused on Kv1.5 and Nav1.5 to search for structural similarities in their binding site (BS) for flecainide (a common blocker and widely prescribed AAD), as a first step for prospective rational multi-target directed ligand (MTDL) design strategies. We presented a computational workflow for flecainide BS comparison in a flecainide-Kv1.5 docking model and a solved structure of flecainide-Nav1.5 complex. The workflow includes docking, molecular dynamics, BS characterization and pattern matching. We identified a common structural pattern in flecainide BS for these channels. The latter belongs to the inner cavity and consist of a hydrophobic patch and a polar region, involving residues from S6 helix and P-loop. Since the rational MTDL design for AF is still incipient, our findings could advance multi-target atrial-selective strategies for AF treatment.

High molecular weight glutenin subunits (HMW-GS) and Low molecular weight glutenin subunits (LMW-GS) in mature grains play important roles in the formation of glutenin macropolymer and gluten quality. To characterize the expressed glutenin genes of the bread wheat variety Xinmai 26 during seed development, in this study, we measured the dough rheological properties of mature grains through farinograph and gluten testing system, and revealed its strong gluten quality. The compositions of HMW-GS and LMW-GS were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Further, a total of 18 full-length transcripts were obtained by third-generation RNA sequencing, including 5 transcripts of HMW-GS genes and 13 transcripts of LMW-GS genes (8 intact genes and 5 pseudogenes). The deduced protein structures of transcript sequences exhibit the typical HMW-GS and LMW-GS structural characteristics. Moreover, a specific functional marker was developed to make better use of the extra cysteine residue of 1Dx5 subunit. This study provides an efficient method to accurately identify glutenin genes in bread wheat through matching full-length transcripts to their spectrum of glutenin, which will be helpful to understand the contributions of glutenin genes to wheat quality.

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a significant challenge to global wheat production. Common wheat landraces AUS27507 and AUS27894 displayed stripe rust resistance against several commercially prevailing Pst pathotypes. These genotypes were crossed with a stripe rust susceptible landrace AUS27229 to understand inheritance of resistance and to determine genomic location(s) of underlying gene(s). F3 generations of crosses AUS27507/AUS27229 and AUS27894/AUS27229 showed monogenic segregation for stripe rust resistance under greenhouse conditions. The absence of segregation for stripe rust response among the AUS27507/AUS27894-derived F3 population suggested that both genotypes carry the same gene. The stripe rust resistance gene carried by AUS27507 and AUS27894 was tentatively named YrAW4. Bulked segregant analysis placed YrAW4 in the long arm of chromosome 2B. The AUS27507/AUS27229 F3 population was enhanced to develop an F6 recombinant inbred line (RIL) population for detailed mapping of chromosome 2BL. DArT-based SSR, STS and KASP markers were employed to enrich the 2BL map. DArT-based STS markers sun481 and SNP marker IWB12294 flanked YrAW4 proximally (1.8 cM) and distally (1.2 cM), respectively. Deletion mapping placed sun481 in the deletion bin 2BL-5. All stripe rust resistance genes, previously located on chromosome 2BL, neither express infection type like YrAW4, nor are mapped in the deletion bin 2BL-5. Hence YrAW4 represented a new locus and was formally named Yr72. The robustness of IWB12294 marker in marker-assisted selection was demonstrated by amplification of and alternative allele to that linked Yr72 in 21 common wheat background.

Blood-based circulating cell free DNA(cfDNA) detection offers a non-invasive and easily accessible way for early cancer detection. Despite the extensive utility of cfDNA, there are still many challenges to develop the clinical biomarkers. For example, cfDNA with genetic alterations often compose a small portion of the DNA circulating in plasma, which can be confounded by cfDNA contributed by normal cells. Therefore, filtering out the potential false-positive cfDNA mutations from health population will be important for the cancer-based biomarkers. Additionally, many low-frequency genetic alterations are easily overlooked in small amount of cfDNA-based cancer test. We hypothesize that, the combination of diverse types of cancer studies on cfDNA can provide us a new insight to identify low-frequency genetic variant across cancer types for early clinical detection of cancers. By building a standardized computational pipeline for 1358 cfDNA samples across seven cancer types, we prioritize 129 shard genetic variants in the major cancer types. Further functional analysis of the 129 variants found that they are mainly enriched in ribosome pathways such as cotranslational protein targeting to membrane, some of which are tumor suppressor, oncogene and related to cancer initiation. In summary, our integrative analysis revealed the important roles of ribosome proteins as the common biomarkers in early cancer diagnosis.

DBP and DEHP are two of the most common plasticisers used in modern industries, which have aroused a major concern over their ubiquitous occurrence and hazardous environmental effects. This study presents the first data of phthalates’ occurrence and distribution in the Maltese shoreline sand. DBP and DEHP occurrences’ was investigated in three busy and secluded beaches, respectively. Analytical determination involved quantifying DBP and DEHP from 75 samples using UPLC-MS/MS through triple repeatability. The concentrations ranged between 0.0095–0.07034 µg/g and &lt;LOQ–0.0977 µg/g for DBP and DEHP, respectively. Statistical analysis of the comparison of phthalates in different beaches demonstrated that the occurrence of DBP and DEHP in Maltese shoreline sand varies. The differences in the occurrence of phthalates were attributed to the beaches’ topography and anthropogenic pressures. Analysis of the effects of anthropogenic activities on the occurrence of phthalates showed a positive association. Distribution analysis showed that DBP and DEHP exhibit an uneven distribution along the shoreline. Conversely, different distributions were observed at distances away from the sea. The uneven distributions observed were associated with anthropogenic activities, different chemodynamic properties and wave action. Cluster analysis was performed to prove the interactions between the phthalates’ concentrations and the characteristics of the beaches.

Ancient DNA has given a new vision to the recent history of human evolution. However, by always relying on the information provided by whole genome sequencing, some relevant relationships between modern humans and its archaic relatives have been misinterpreted by hybridization and recombination causes. In contrast, the congruent phylogeny, obtained from non-recombinant uniparental markers, indicates that humans and Neanderthals are sister subspecies, and that the most recent common ancestor of modern humans was not of African origin but Eurasian.

In relation to organizational performance measurement, there is a growing concern about the creation of value for people, society and the environment. The traditional corporate reporting does not adequately satisfy the information needs of stakeholders for assessing an organization’s past and future potential performance. Practitioners and scholars have developed new non-financial reporting frameworks from a social and environmental perspective, giving birth to the field of Integrated Reporting (IR). The Economy for the Common Good (ECG) model and its tools to facilitate sustainability management and reporting can provide a framework to do it. The present study is the first one that empirically validates such metrics on a sample of 206 European firms. Consequently, it allows knowledge to advance as it checks their statistical validity and reliability.

Keywords: Academic Trends; Energy Consumption; Higher Education Institutions; Systematic Literature Review; Scholarly output; University buildings

The use of nitrogen fertilizers can be a source of environmental pollution; the use of or-ganomineral fertilizers can become a nutritional source for crops, ensuring sustainability in the production system. Another alternative approach is through the inoculation and co-inoculation of microorganisms. The objective was to evaluate the development, nutrition, and agronomic yield of common bean through fertilization with organomineral formula "FMO" derived from sewage sludge biosolids, combined with Rhizobium tropici inoculation and co-inoculation with Azospirillum brasilense techniques. Three bean cultivars from different commercial groups, Pérola, BRS Esteio, and BRS Pitanga, were tested. They were subjected to organomineral fertilizer application, orga-nomineral fertilizer application combined with seed inoculation with R. tropici and re-inoculation; seed co-inoculation with R. tropici + A. brasilense prior to sowing, and foliar re-inoculation with R. tropici + A. brasilense. Seed inoculation, combined with foliar re-inoculation at the V4 stage, resulted in higher productivity of common bean. The combination of R. tropici with co-inoculation with A. brasilense generally led to increased productivity compared to mineral nitrogen fertilization. The use of organomineral fertilizer alone enabled gains in development, as well as productivity. The Pérola bean cultivar showed better adaptation to the applied treatments.

Contemporary literature dealing with the governance and exploitation of common-pool natural resources was initiated by Elinor Ostrom in 1990, and has been growing fast ever since. On the contrary, within the same research stream, the study of the presence and economic role of common resources in entrepreneurial organizations is, to date, under-researched. This work endeavors to fill some gaps in this research perspective by: (i) spelling out a new-institutionalist framework for the analysis of the accumulation and governance of common capital resources within organizational boundaries; (ii) considering co-operative enterprises as the organizational form that, on the basis of historical record, and of behavioral and institutional characteristics, demonstrated to be most compatible with a substantial role for common and non-divided asset-ownership and with its governance thereof; (iii) evidencing and explaining the strong connection between cooperative longevity and the presence of non-divided asset ownership. The economic forces influencing the optimal level of self-financed common capital resources in co-operatives are enquired. Conclusions to the paper evidence the main reasons why the new approach can better explain than preceding ones the economic sustainability and longevity of cooperative enterprises.

Uterine pathologies pose a challenge to women’s health on a global scale. Despite extensive research, the causes and origin of some of these common disorders are not well defined yet. This study presents a comprehensive analysis of transcriptome data from diverse datasets encompassing relevant uterine pathologies such as endometriosis, endometrial cancer and uterine leiomyomas. Leveraging the Comparative Analysis of Shapley values (CASh) technique, we demonstrate its efficacy in improving the outcomes of classical differential expression analysis on transcriptomic data derived from microarray experiments. CASh integrates the Microarray game algorithm with Bootstrap resampling, offering a robust statistical framework to mitigate the impact of potential outliers in the expression data. Our findings unveil novel insights into the molecular signatures underlying these gynecological disorders, highlighting CASh as a valuable tool for enhancing the precision of transcriptomics analyses in complex biological contexts. This research contributes to a deeper understanding of gene expression patterns and potential biomarkers associated with these pathologies, offering implications for future diagnostic and therapeutic strategies.

Treatment wetlands (TWs) are Nature-Based Solutions increasingly used worldwide for wastewater (WW) treatment able to remove mineral and organic pollutants through both physical and biochemical process. Besides the reusable effluent, the TWs produce as main output plant biomass that need to be harvested and disposed at least once a year with significant management costs and TW temporary out of service. This study aims (i) to evaluate the potential of TWs biomass for local energy production and (ii) to understand TW hydraulic conductivity (Ks) effects on the biomass biomethane yield. Specifically, it was addressed by determining the Biochemical Methane Potential of common reed (CR) (Phragmites australis) samples collected at three harvest times from the 10-years-old horizontal subsurface treatment wetland (HSTW) used as a secondary WW treatment system for the IKEA® store located in Catania (Eastern Sicily, Italy). Furthermore, the falling head test was conducted to assess the hydraulic conductivity (Ks) variation in the HSTW, in order to understand the influence on the CR biomethane production. Average methane content values were 130.57 Nm3CH4/tVS (±24.29), 212.70 Nm3CH4/tVS (±50.62) and 72.83 Nm3CH4/tVS (±23.19) in August, September, October 2022, respectively. Ks was correlated with both dry matter (R2 = 0.58) and fiber content (R2 = 0.74) and, consequently, affected the biomethane yield that increased at the Ks increases (R2 = 0.30 in August, R2 = 0.57 in September). In the framework of a circular economy, results showed the successfully possibility of integrating the bioenergy production into TWs. The research could contribute (i) to encourage plant operators to reuse biomass from TWs for local energy production and (ii) to help plant operators to understand Ks effects on the biomass biomethane yield, in order to increase the sustainability of the system and to reduce the maintenance costs.

One of the major obstacles confronting the formulation of a mechanistic understanding for Alzheimer’s disease (AD) is its immense complexity – a complexity that traverses the full structural and phenomenological spectrum, including molecular, macromolecular, cellular, neurological and behavioural processes. This complexity is reflected by the equally complex diversity of risk factors associated with AD. However, more than merely mirroring disease complexity, risk factors also provide fundamental insights into the aetiology and pathogenesis of AD as a neurodegenerative disorder since they are central to disease initiation and subsequent propagation. Based on a systematic literature assessment, this review has identified 30 risk factors for AD and then extended the analysis to further identify neuroinflammation as a unifying mechanism present in all 30 risk factors. Although other mechanisms (e.g. vasculopathy) were present in multiple risk factors, dysfunction of the neuroimmune-neuroinflammation axis was uniquely central to all 30 identified risk factors. Though the nature of the neuroinflammatory involvement varied, activation of microglia and the release of pro-inflammatory cytokines was a common pathway shared by all risk factors. This observation provides further evidence for the importance of immunopathic mechanisms in the aetiopathogenesis of AD.

Human Ribonuclease (RNase) 6 is a monocyte and macrophage-derived protein with potent an-timicrobial activity toward uropathogenic bacteria. The RNASE6 gene is heterogeneous in hu-mans due to the presence of single nucleotide polymorphisms (SNPs). RNASE6 rs1045922 is the most common non-synonymous SNP, resulting in a G to A substitution that determines an ar-ginine (R) to glutamine (Q) transversion at position 66 in the protein sequence. By structural analysis we observed that R66Q substitution significantly reduces the positive electrostatic charge at the protein surface. Here, we generated both recombinant RNase 6 -R66 and -Q66 protein variants and determined their antimicrobial activity toward uropathogenic Escherichia coli (UPEC), the most common cause of UTI. We found that the R66 variant, encoded by the major SNP rs1045922 allele, exhibited superior bactericidal activity in comparison to the Q66 variant. The higher bactericidal activity of R66 variant correlated with an increase in the protein lipopolysac-charide binding and bacterial agglutination abilities, while retaining the same enzymatic effi-ciency. These findings encourage further work to evaluate RNASE6 SNP distribution and its impact in UTI susceptibility.

The security of several fully homomorphic encryption (FHE) schemes depends on the intractability assumption of the approximate common divisor (ACD) problem over integers. Subsequent efforts on solving the ACD problem as well as its variants were also developed during the past decade. In this paper, an improved orthogonal lattice (OL) based algorithm, AIOL, is proposed to solve the general approximate common divisor (GACD) problem. The conditions for ensuring the feasibility of AIOL are also presented. Compared to the Ding-Tao’s OL algorithm, the well-know LLL reduction is used only once in AIOL, and when the error vector r is recovered in AIOL, the possible difference between the restored and the true value of p is given. The experimental comparisons towards the Ding-Tao’s algorithm and ours are also provided for validating our improvements.

Bean common mosaic virus from the genus Potyvirus has a wide range of hosts and a very negative impact on cultivated crops from the genus Phaseolus. The risk of viral infection of economically important crops increases even if the carriers of the virus are related plant species growing on agroecological interfaces. Such plant species have emerged as new hosts for BCMV, usually harboring novel genetic variants of the virus. A novel genetic variant of BCMV was isolated from a symptomatic crownvetch plant, where the presence of this virus was confirmed by Western-blotting analysis and by amino acid identities in peptide fragments of CI, HC-pro, and CP proteins using the nanoLC-ESI-Q-TOF. The novel BCMV SVK isolate differed from the most genetically similar one in 0.91% of nucleotides and 1.55% of amino acids. The highest number of amino acid substitutions (8.8% of amino acids) was in the P1 protein, followed by CP (2.44% of amino acids). Minor substitutions were in Hc-pro, CI, and Nib proteins. The symptomatic crownvetch plant was confirmed as a new host and carrier of the novel BCMV isolate.

Alzheimer’s disease (AD) and vascular dementia (VaD) together contribute to almost 90% of all dementia cases leading to major health challenges of our time with a substantial global socioeconomic burden. While in Alzheimer’s disease, the improved understanding of Amyloid beta (Aß) mismetabolism and tau hyperphosphorylation as pathophysiological hallmarks has led to significant clinical breakthroughs, similar advances in VaD are lacking. We thus highlight here the importance of shared pathomechanisms found in AD and VaD: Endothelial damage, blood brain barrier (BBB) breakdown and hypoperfusion inducing oxidative stress, inflammation and demyelination and thus trophic uncoupling in the neurovascular unit. A dysfunctional endothelium and BBB lead to the accumulation of neurotoxic molecules and Aß through impaired clearance, which in turn leads to neurodegeneration. In this context we discuss possible neuropathological parameters, which might serve as biomarkers and thus improve diagnostic accuracy or reveal targets for novel therapeutic strategies for both forms of dementia.

The host glycosylation mechanism synthesizes the carbohydrates of glycoproteins of viral envelopes. Due to the loss of the Cytidine Monophospho-N-Acetylneuraminic Acid Hydroxylase gene by some mammalian species, including humans (negative-CMAH), Neu5Gc is no longer synthesized. Uptake of Neu5Gc by negative-CMAH species, through the intake of food products derived from positive-CMAH mammals, leads to incorporating Neu5Gc-glycans in the glycocalyx (xenosialylation). Neu5Gc, being a Mammalian-associated Carbohydrate Antigen (MCA), acts as a non-self-antigen, inducing an inflammatory reaction (Xenosialitis), and triggering the production of circulating antiNeu5Gc antibodies to attack/remove all incorporated Neu5Gc. In the state of Xenosialitis, the virus-neutralizing antibodies produced by a heavily xenosialylated patient following exposure to viral infection (including SarsCoV2) or anti SarsCoV2 vaccination cross-react against all incorporated non-self Neu5Gc-MCA glycans due to their resemblance with viral envelope antigens synthesized by the host glycosylation mechanism. In addition, the circulating anti-XeSias antibodies determine the massive removal of the circulating neutralizing FC-xeno-contaminated antibodies by the serum, living only the hyper-inflammatory agalattosylated antiviral IgG antibodies. Therefore, we hypothesize that the combination of antibody cross-reaction against non-self Neu5Gc-MCA glycans and the massive removal of the xeno-contaminated newly formed neutralizing antibodies in favor of hyper reactive antibodies, could be the cause of the massive inflammatory reaction (cytokine storm, coagulopathies, neuropathies) observed in Covid 19 patients or after anti-SarsCoV2 vaccination. This analysis is an invitation to investigate the post-infectious and/or post-vaccination adverse phenomena in the light of xenosialization as a key to understanding the severe post viral and post vaccine complications, including SARS-CoV2 infection or related vaccination.

Lime application with other complementary sustainable management practices increases crop yield, but liming is modestly applied in Serbia. This study investigated the influence of liming (1000 kg/ha) combined with the common application of mineral fertilizers on maize yield and the chemical properties of Pseudogley soil. The experiment was conducted near Kraljevo, Western Serbia, on maize hybrid ZP 606, sown in a two-year monoculture. The experiment had three treatments: fertilizer, fertilizer+lime, and control treatment. The soil is acid, poor in humus, and contains an increased content of mobile aluminum. There was a significant increase in yield under the fertilizer and lime+fertilizer treatments, compared with the control. The yield of maize in the limed treatment was 4.4–9% higher than in the fertilizer treatment. The positive effects of liming on soil are related to an increase in pH, base saturation, and available phosphorus and a decrease in available aluminum. In the fertilizer treatment, there was a small decrease in pH and base saturation, whereas the amount of aluminum remained high, indicating that further application of fertilizers without lime can increase the aluminum content and foster its toxicity. The long-term sustainability of maize production in Serbia should include liming as a regular management practice on Pseudogley soil, with the utilization of smaller doses of lime because of the potential CO2 effects. To improve soil health, food, and environmental security, and incorporate new crops, developing a framework promoting liming as a sustainable management practice is of high importance.

In order to investigate the relationship between government policy, the service and design of rural crowdsourcing spaces, the self-efficacy of returning youth, and the innovation performance of businesses, this study focuses on gathering data by distributing questionnaires to returning youth in rural crowdsourcing spaces and developing a structural model. The results demonstrate how important government policies are in encouraging youth entrepreneurship in their local communities. It has the potential to enhance both the development of rural crowdsourcing spaces and the self-efficacy of young entrepreneurs, thereby enhancing the innovative capabilities of local entrepreneurial businesses. Therefore, in order to encourage economic development in rural areas, the government should improve pertinent support measures.

More than 179,000 individuals have fallen ill of the Coronavirus disease (COVID-19) caused by the SARS-CoV-2 virus, which first emerged in China less than four months ago in December 2019. As of today, there exist no approved treatments against COVID-19. Vaccines are being developed, but they will take time, at least one year, to reach the population. Drug repositioning represents a fast track because already approved medicines have been broadly tested through multiple trials. We developed a repositioning strategy that mostly leads to candidates that are commonly used. The advantages are that they will facilitate proof of concept in humans through a “real-world evidence” approach and should be rapidly available to the population. We focus on the established research results that the unfolded protein response (UPR) and autophagy pathways of the host cells are essential to the life cycle of previously known coronaviruses. We performed the relevant bioinformatics analysis to understand and confirm if SARS-CoV-2 may interact with these druggable pathways. Based on these considerations, we prioritized two additional druggable pathways, which are important to the viral life cycle and tightly connected to UPR/autophagy signaling: the mitochondrial permeability transition pores (MPTP) and NLRP-3 inflammasome pathways. These four important pathways are perturbed in most major common diseases and have therefore been targeted by numerous broadly prescribed drugs. We have identified 97 approved drugs that are known to modulate these four identified pathways, and which represent, therefore, interesting repositioning candidates. Although it is indisputable that these drugs should never be used for immediate self-medication against COVID-19, we notice that some of them could also be prescribed to individuals who have COVID-19 comorbidities (e.g., hypertension). It is debated if these comorbidities are linked to the pathology itself (e.g., hypertension) or the drugs used to treat the pathology (e.g., sartans). Therefore, relevant preclinical tests and massive electronic health records (i.e., real-world evidence) must be used to pre-screen them and check the COVID-19 prognosis of individuals taking these drugs.

Postharvest 1-MCP treatment can inhibit lignification of fruit and vegetables. It has been suggested that the mode of action of 1-MCP is through inhibiting ethylene production, but the effect of 1-MCP and ethylene on lignification of common bean remain unknown. This work compared the effect of 0.5 μL L-1 1-MCP and 100 μL L-1 ethylene on lignification of common bean during storage. Postharvest 1-MCP significantly inhibited the increase of lignified cell group, sclerenchyma became thicker, vascular bundles thickened and lignified cells grew during storage, while ethylene is the opposite. 1-MCP inhibited the increase in respiration rate, sucrose phosphate synthase (SPS), sucrose synthase (SuSy), phenylalanine ammonialyase (PAL), cinnamyl-alcohol dehydrogenase (CAD), and peroxidase (POD) activities, whereas ethylene hastened all. Ethylene treatment can be stimulated and 1-MCP inhibited the decline of reducing sugar and cellulose content. Expression of genes, including PvACO1, PvAOG1, PvSuSy, PvPAL3, and Pv4CL1, PvCOMT1 together with lignin content were significantly increased in common bean during storage. 1-MCP treatment markedly inhibited expression of PvACO1, PvSuSy2, PvPAL3, Pv4CL1 and PvCOMT1 genes, while strengthened expression of PvETR1 and PvAOG1, while ethylene was opposite. This work provides evidence that ethylene plays a key role in regulating the lignin biosynthesis of common bean, and also provides strategies for the maintenance of fruit quality during storage.

Given the many approaches to and definitions of gender responsive monitoring and evaluation (M&E) for health programs and interventions there is a lack of clarity on how to operationalize it including what to measure and how to measure it. We conducted a scoping review to understand what makes M&E gender responsive. We included 31 studies and conducted two rounds of extraction to delineate ways in which gender was integrated into M&E. Twelve articles described the use of theory to guide M&E though most were not related to gender. Twelve articles employed a gender score in data collection, most of which measured Likert scale responses related to gender equity. Even though most studies did not use a specific gender framework, most incorporated gender domains in their analysis. Seven studies used participatory methods in the design and implementation of M&E. Most studies conducted M&E on programs or interventions that were designed to be gender intentional and related to gender issues. Gender responsive M&E intentionally integrates gender into the M&E process, regardless of how gender-intentional the program or intervention is. Gender dimensions can be identified through gender theories, models, scores, and frameworks to inform tool development, data collection, analysis, and stakeholder engagement processes.

New information suggests female autistic spectrum disorder (ASD) is much more common than previously thought, with a likely prevalence of 6% and with 80% undiagnosed at the age of 18. ASD then becomes a common comorbidity of female mental illness with nearly one in five women who develop a mental illness being autistic. ASD has heretofore been regarded as a pediatric condition and though now thought to be life long it is still not well recognized by adult health services. Most mental illness first presents in the teens and early twenties. Comorbid ASD is more difficult to diagnose due to diagnostic overshadowing, and ASD comorbidity maks the mental illness more severe and mor difficult to treat. Recognized ASD is readily treatable with an approach sympathetic to neurodiversity. Improving the pathway from adolescence to adulthood by increasing knowledge of autism in adult health services would dramatically improve female mental health at surprisingly little extra cost. It is low hanging fruit in a very fraught area of healthcare. This paper will examine the extent of the problem. It will explore solutions and quantify the gains of appropriate therapy.

In Uganda, the common bean (Phaseolus vulgaris) is often infested by a complex of insect pests, but the bean stem maggots, aphids, bean leaf beetles, and flower thrips are the most important. Whereas yield losses due to these pests have been established, there is limited information on their population dynamics at different stages of crop growth and their effect on yield and yield components. In order to describe the population dynamics of selected common bean pests at various phases of bean crop growth, and their impact on yield and yield components, a study was carried out in Uganda during 2016 second rains and 2017 first rains in three agro-ecological zones. Bean fly, bean aphids, bean leaf beetles, whitefly, striped bean weevil, leaf hoppers, and caterpillars of Lepidopteran species were the main insects observed. Pesticide spray schedules were imposed to generate different populations of insect pests whose effects on yield and its components were determined. The findings indicate that spray regimes significantly influenced the abundance of bean fly, aphids, whitefly, striped bean weevil, and leaf hoppers but not bean leaf beetles and caterpillars. Additionally, except caterpillars, insect pests were significantly influenced by crop growth stages, but only aphids, whiteflies, bean flies and leaf hoppers exhibited a significant negative relationship with grain yield. Furthermore, yield and yield components varied significantly between spray regimes, agro-ecological zones, and seasons. Our study is important in informing growers on the stage of crop growth at which management tactics such as use of insecticides can be applied for different insect pests.

Soil erosion seriously affects vineyards. In this study, the influence of two plant covers on soil moisture and the effect of different physiographic conditions on runoff and sediment yields were evaluated in a rainfed vineyard formed by four fields (NE Spain) during 15 months. One field had spontaneous vegetation as plant cover and three fields had a cover crop of common sainfoin. The vineyards’ rows were dry and stable, whereas the inter-row areas were wet although very variable, and the corridors were wet and very stable. Soil moisture in the inter-row areas with Common sainfoin was much higher than in the rows (62% - 70%) whereas this difference was lower with spontaneous vegetation (40%). Two runoff and sediment traps (STs) were installed in two ephemeral gullies, and 26 time-integrated surveys (TIS) done. The mean and maximum runoff yields were 9.8 and 30.7 l TIS^–1 in ST2 and 13.5 and 30.2 l TIS^–1 in ST3. The mean turbidity was 333 and 19 g l^–1, and the maximum sediment yields were 41,260 and 2,778 g TIS^–1 in ST2 and ST3. Changes in the canopy covers (grapevines and plant covers) and rainfall parameters explained the runoff and sediment dynamics.

Borreliosis is a widely spreading bacterial infection caused by corkscrew-shaped spirochete Borrelia burgdorferi transmitted via the bite of an infected tick. The disease manifests in three stages: early localized, early disseminated, and late stages. Clinical symptoms range from non-specific erythema migrans, fever, fatigue, etc. to system-specific features like carditis, peripheral nerve palsy, etc. The diagnosis mainly relies on clinical findings and serologic testing is done for disease confirmation. The treatment of Lyme disease is an antibiotic with doxycycline as the primary choice. Prophylactic doxycycline is given under specific criteria. Here, we describe a case of a 64-year-old Indian male diagnosed with Lyme disease.

Amyloids were conventionally referred to as extracellular and intracellular accumulation of Aβ42 peptide which causes the formation of plaques and neurofibrillary tangles inside the brain leading to the pathogenesis in Alzheimer’s disease. Subsequently, amyloid-like deposition was found in the etiology of Prion diseases, Parkinson disease, Type II Diabetes and Cancer which was attributed to the aggregation of Prion protein, α-Synuclein, Islet Amyloid Polypeptide Protein and p53 protein respectively. Hence, traditionally amyloids were considered as aggregates formed by the proteins or peptides exclusively. However, since the last decade it has been discovered that other metabolites like single amino acids, nucleobases, lipids, glucose derivatives etc. have propensity to form amyloid-like toxic assemblies. Several studies suggest direct implications of these metabolite assemblies in the patho-physiology of various Inborn errors of metabolisms like Phenylketonuria, Tyrosinemia, Cystinuria and Gaucher’s disease to name a few. In this review, we present a comprehensive literature overview which suggests amyloid-like structure formation as a common phenomenon for the disease progression and pathogenesis in multiple syndromes. The review on this topic is urgently required to create awareness about the understanding of fundamental molecular mechanism behind the origin of diseases from an amyloid perspective and possibly look for a common therapeutic strategy for the treatment of these maladies by designing generic amyloid inhibitors.

Camouflage is an interesting adaptation (for survivability) by organisms in terms of different aggregation or fusion of colourations. Understanding these camouflage strategies in the presence of arsenic on transparent/semi-transparent species is pretty challenging. Previously, several researchers have demonstrated that colouration or pigmentation strategy in an organism is a strategy to merge with the environment to escape from predatory threats. Our study was done on a semi-transparent freshwater prawn species which exhibits a strategy of pigment droplets on its exoskeleton. Unlike previous studies, our findings robustly indicate the fact that pigment droplets are not the only reason for colouration. The pigment droplets rather regulate the darkness of the exoskeleton. However, the transparency of the abdominal muscles additionally plays a crucial role in creating a background of the pigment droplets. The transparency muscles allow light to pass through the abdomen, thus creating a semi-transparent appearance. The degree of semi-transparency is also regulated by the intensity of light. The abdomen and the pigment droplets on the exoskeleton cumulatively as well as contrastingly maintain the transparency and the colour quotient of the prawns. In our study, we have majorly concentrated on the abdominal region of the prawns as it appears to be the key semi-transparent feature of the organism. This research is directed to an ecotoxicological aspect where we showed that arsenic in chronic non-lethal concentration, can notably alter the colouration pattern in this prawn model within a short period of time. Finally, we have used an image processing algorithm to assess the alteration of colouration in this organism.

Thousands of people worldwide suffer from injuries in the peripheral nerve and deal daily with the resulting physiological and functional deficits. Recent advances in this field are still insufficient to guarantee effective outcomes, and the development of new and effective therapeutic options requires the use of valid preclinical models that effectively replicate the characteristics and challenges associated with these injuries in humans. In this study, we established a sheep model for common peroneal nerve injuries that can be applied in preclinical research with the advantages associated with the use of large animal models. In an integrative way, this article includes a detailed description of the anatomy and functionality of the peripheral nerves of sheep’s hind limb, the surgical protocol for accessing the common peroneal nerve, the induction of different types of nerve damage and the application of possible therapeutic options. A neurological exam protocol directed to the common peroneal nerve was also established, allowing to identify the changes and deficits related with the nerve injury and to evaluate the functional progression over time. Finally, a preliminary stereological study was carried out to establish control values for the healthy peroneal common nerves of this model and to identify preliminary differences between therapeutic methods. The ultimate goal is to demonstrate that sheep is a valid model of peripheral nerve injury to be used in pre-clinical and translational works and to evaluate the efficacy and safety of nerve injury therapeutic options before its clinical application in human and veterinary patients.

Vigorous early-season growth rate allows crops to compete more effectively against weeds and to conserve soil moisture in arid areas. Many crop species, including common bean, show genetic variation in growth rate between varieties. Despite this, the genetic basis of the early-season growth-related traits has not been well resolved in the species, in part due to historic phenotyping challenges. Using a range of UAV- and ground-based methods, we evaluated early-season growth vigor of two populations. These growth data were then used to find QTLs associated with several growth parameters. Our results suggest that early-season growth rate is the result of complex interactions between several genetic and environmental factors and highlight the need for the high-precision phenotyping provided by UAVs. The QTLs identified in this study are the first in common bean to be identified remotely using UAV technology and will be useful for developing crop varieties that compete with weeds more effectively. Ultimately, this will reduce crop losses and mitigate the need for herbicides and manual labor for weed control.

Simple patterns often arise from complex systems. For example, human perception of similarity decays exponentially with perceptual distance. The ranking of word usage versus the frequency at which the words are used has a log-log slope of minus one. Recent advances in big data provide an opportunity to characterize the commonly observed patterns of nature. Those observed regularities set the challenge of understanding the mechanistic processes that generate common patterns. This article illustrates the problem with the recent big data analysis of collective memory. Collective memory follows a simple biexponential pattern of decay over time. An initial rapid decay is followed by a slower, longer lasting decay. Candia et al. successfully fit a two stage model of mechanistic process to that pattern. Although that fit is useful, this article emphasizes the need, in big data analyses, to consider a broad set of alternative causal explanations. In this case, the method of signal frequency analysis yields several simple alternative models that generate exactly the same observed pattern of collective memory decay. This article concludes that the full potential of big data will require better methods for developing alternative, empirically testable causal models.

Cry toxins produced by the bacterium Bacillus thuringiensis are of significant agronomic value worldwide due to their potent and highly specific activity against various insect orders. However, some of these pore-forming toxins display specific activity against a range of human cancer cells whilst possessing no known insecticidal activity, Cry41Aa is one such toxin. Cry41Aa has similarities to its insecticidal counterparts in both its 3-domain toxic core structure and pore-forming abilities, but how it has evolved to target human cells is a mystery. This work shows that some insecticidal Cry toxins can enhance the toxicity of Cry41Aa against hepatocellular carcinoma cells, despite possessing no intrinsic toxicity themselves. This interesting crossover is not limited to human cancer cells, as Cry41Aa was found to inhibit some Aedes-active Cry toxins in mosquito larval assays. Here, we present findings that suggest that Cry41Aa shares a receptor with several insecticidal toxins indicating a stronger evolutionary relationship than their divergent activities might suggest.

Broflanilide is a novel active ingredient from a unique insecticide class (IRAC Group 30) and was investigated as a control option against modern insecticide resistant strains of the common bed bug, Cimex lectularius. The susceptibility of technical grade broflanilide and efficacy of a broflanilide-based aerosol formulation (Earth Corp., Japan) were evaluated against five C. lectularius strains (MONH, SYD, DARL, PARRA, RIPPO). Results demonstrated that bed bugs had high susceptibility to broflanilide (RR50: SYD=1.22-fold, DARL=1.03-fold, PARRA=3.65-fold, RIPPO=2.77-fold), compared to the susceptible MONH strain. The aerosol showed high efficacy to adult bed bugs (97.5–100 % mortality to five strains after 24 hrs post-spray) and produced a notable decrease in egg hatch rates (MONH=9.7–23.4 %, PARRA=14.9–22.6 %). The aerosol also demonstrated high residual activity with 97.5–100% mortality in all five bed bug strains within 7 days exposure. The impact of different surface types upon aerosol residual efficacy was limited, although residues on a non-porous surface (tile) killed bed bugs slightly quicker than that on a porous surface (filter paper). The aerosol provided long residual activity to bed bugs, as 6-month-old residues were as equally efficacious to that of fresh residues. Bed bugs did not avoid surfaces treated with the aerosol. The high efficacy (including ovicidal efficacy), long residual activity, and non-avoidance of bed bugs on treated surfaces, demonstrated that broflanilide is highly suitable for modern bed bug management.

Background: Chronic Myeloid Leukemia (CML) is initiated in bone marrow due to chromosomal translocation t(22;9) leading to fusion oncogene BCR-ABL. Targeting BCR-ABL by tyrosine kinase inhibitors (TKI) have changed fatal CML into an almost curable disease. Despite that, TKIs lose their effectiveness due to disease progression. Unfortunately, mechanism of CML progression is poorly understood and common biomarkers for CML progression are unavailable. This study was conducted to find out novel biomarkers of CML progression by employing whole exome sequencing (WES).Materials and Methods: WES of accelerated phase (AP-) and blast crisis (BC-) CML patients was carried out, with chronic phase CML (CP-CML) patients as control. After DNA library preparation and exome enrichment, clustering and sequencing was carried out using Illumina platforms. Statistical analysis was carried out using [SAS/STAT] software version 9.4 and R package employed to find mutations shared exclusively by all AP-/BC-CML. Confirmation of mutations was carried out using Sanger sequencing and protein structure modelling using I-Tasser followed by mutant generation and visualization using PyMOL. Results: Three novel genes (ANKRD36, ANKRD36B and PRSS3) were mutated exclusively in all AP-/BC-CML patients. Only ANKRD36 gene mutations (c.1183_1184 delGC and c.1187_1185 dupTT) were confirmed by Sanger sequencing. Protein modelling studies showed that mutations induce structural changes in ANKRD36 protein. Conclusions: Our studies show that ANKRD36 is a potential common biomarker and drug target of early CML progression. ANKRD36 is yet uncharacterized in human. It has the highest expression in bone marrow, specifically myeloid cells. We recommend carrying out further studies to explore the role of ANKRD36 in biology and progression of CML.

The development of biofortified and stress tolerant common bean lines contribute to counteract micronutrient malnutrition in the current condition of climate variability. Our objective was to evaluate the adaptive responses of biofortified common bean (Phaseolus vulgaris L.) lines under acidic soils and high temperature stress conditions in the Amazon region of Colombia. Adaptive responses were evaluated based on phenological, physiological and agronomic differences under combined stress conditions. A total of 247 common bean lines from the Mesoamerican gene pool were evaluated under field conditions at Florencia, Caquetá, Colombia. The common bean lines evaluated included 146 from F4 families with high iron (Fe) content and 99 common bean lines from F5 families that were obtained from simple crosses, double crosses and backcrosses among different bean lines. Lines with tolerance to combined stress conditions of acidic soil and high temperature were found with grain yields greater than 1,400 kg ha-1 from the F5 (lines: 859, 805, 865, 657) and F4 (lines: 2853, 2796) families. This improved agronomic response is likely due to the greater partitioning of photosynthates from canopy biomass (CB) toward pod formation (pod partitioning index, PPI) and grain filling (pod harvest index, PHI; harvest index, HI), which translated into higher grain yields (GY). GY was correlated with CB (r = 0.36), PPI (r = 0.6), PHI (r = 0.68), and HI (r = 0.8, P&lt;0.001). The physiological responses that contributed toward superior agronomic performance of biofortified common bean lines include greater allocation of energy to the photosynthetic machinery (ΦII) and its dissipation in the form of heat (ΦNPQ) as the leaf temperature differential (LTD) increased under combined stress conditions. Six biofortified common bean lines (F5 lines: 859, 805, 865, 657; F4 lines: 2853, 2796) were identified with multiple stress resistance traits and these lines can serve as parents for further genetic improvement of common bean for multiple stress tolerance in the Amazon region of Colombia.

Anthracnose (ANT) and angular leaf spot (ALS) are significant diseases in common bean, leading to considerable yield losses under specific environmental conditions. The California Dark Red Kidney (CDRK) bean cultivar is known for its resistance to multiple races of both pathogens. Previous studies have identified the CoPv01CDRK/PhgPv01CDRK resistance loci on chromosome Pv01. Here, we evaluated the expression levels of ten candidate genes near the CoPv01CDRK/PhgPv01CDRK loci and plant defense genes using quantitative real-time PCR in CDRK cultivar inoculated with races 73 of Colletotrichum lindemuthianum and 63-39 of Pseudocercospora griseola. Gene expression analysis revealed that the Phvul.001G246300 gene exhibited the most elevated levels, showing remarkable 7.8-fold and 8.5-fold increases for ANT and ALS, respectively. The Phvul.001G246300 gene encodes an abscisic acid (ABA) receptor pyrabactin resistance - PYR1-like (PYL) protein, which plays a central role in crosstalk between ABA and jasmonic acid responses. Interestingly, our results also showed that the other defense genes were initially activated. These findings provide critical insights into the molecular mechanisms underlying plant defense against these diseases and could contribute to the development of more effective disease management strategies in the future.

Rapid eye movement sleep behavior disorder (RBD) is often prodromal to Parkinson’s disease (PD). Thus there should be detectable in vivo functional signatures shared between RBD and PD that aid in disease classification. To assess common in-vivo phenotypes, resting state data was collected on a 3T clinical MRI platform and a novel functional connectivity magnetic resonance imaging (fcMRI) approach, which combined independent component analysis (ICA) and graph theory, was used to evaluate deficits in interconnectivity among 15 PD, 14 RBD and 13 control participants. Whole brain and network-level analyses revealed the largest deficits in network connectivity in PD compared with controls, with less severe differences between RBD and controls. Importantly, the network-level analysis demonstrated decreased network interconnectivity, with the greatest aberrant networks in PD, and a subset in RBD. Additionally, a disease classification algorithm predicted PD cases by being trained on RBD cases with 0.87 sensitivity and 0.68 specificity. The functional alterations in cortical networks in RBD extended beyond the brainstem. These findings demonstrate progressive reductions in connectivity between brain networks, with less severe deficits in RBD than PD. Moreover, RBD phenotypes can be used to predict PD status in a cross-sectional sample, which suggests RBD is an intermediate phenotype.

Middle-aged adults can start to be affected by some arterial diseases, such as abdominal aortic or popliteal artery aneurysms, lower extremity arterial disease, internal carotid or renal artery or subclavian artery stenosis. These vasculopathies are often paucisymptomatic before manifesting themselves with dramatic complications. Therefore, early detection of peripheral artery disease (PAD) and aneurysmal disease is fundamental to reduce the risk of major adverse cardiovascular and limb events. Furthermore, PAD carries a high correlation with silent coronary artery disease (CAD). This study focuses on the most common PADs and aneurysmal diseases, in the attempt to summarize some key points which should selectively drive screen. Since it is evident how we are not in the human and economic possibilities to instrumentally screening wide populations, deep knowledge of semeiotics and careful anamnesis must play a central role in our daily activity as physician. The presence of some risk factors for atherosclerosis, or an already known history of CAD, can raise the clinical suspecion of PAD or aneurysmal disease after a careful clinical history and a deep physical examination. The clinical suspicion must then be confirmed by a first-level ultrasound investigation and, if so, adequate treatments can be adopted to prevent dreadful complications.

Herbivores have evolved several strategies to cope with plant defences. Some herbivores are able to resist toxic compounds, while others can manipulate host immunity. Previously it was found that spider mites collected from non-solanaceous wild host plants consist mostly of individuals that induce tomato defences, but also at low frequencies of individuals that can suppress these defences. Also, it has been shown that mites collected from non-solanaceous plants can adapt to tomato by evolving traits that allow them to suppress defences. Hence, we wanted to know if this trait is also common among mites naturally occurring on tomatoes. Here, we compared three T. urticae populations sampled from tomato at three field sites, and also an outbred population created from them through controlled crosses. We then assessed their fecundity on wild-type (WT) tomato plants and def-1 mutants impaired in inducible JA-defences. We also assessed the magnitude of JA defences they induce in WT plants to discriminate between resistant types (high induction and high performance) and those that can suppress defences (low induction, high performance). We then aligned these data with data on variation in mitochondrial DNA cytochrome oxidase I (COI) and effector 84 (a suppressor of JA-defences in planta), in order to compare genetic diversity patterns among mite lines that induce or suppress defences. We found that suppression is the dominant phenotype in mite strains collected from field-grown tomatoes and that inducers and suppressors predominantly cluster in distinct effector 84 clades. We speculate that effector allelic diversity may be subject to natural selection when these mites colonize a novel host plant, promoting traits to cope with plant resistance, such as defence suppression, which facilitates adaptation.

Abstract: Vulvovaginal candidiasis (VVC) is a mucous membrane infection, with an increased rate of antifungal resistance of Candida species. The in vitro efficacy of farnesol alone or in combination with traditional antifungals, against resistant Candida strains recovered from women with VVC was assessed. In this study, 80 Candida isolats were identified by multi-plex PCR. Antifungal sus-ceptibility of amphotericin B (AMB), fluconazole (FLU), itraconazole (ITZ), voriconazole (VOR), clotrimazole (CTZ) and farnesol was tested by M27-A3/S4 broth micro dilution method. The combinations of farnesol with each antifungal were calculated based on the fractional inhibitor concentration index (FICI). C. glabrata was the predominant species (48.75%) isolated from vaginal discharges, followed by C. albicans (43.75%), C. parapsilosis (3.75%), mixed infection of C. albicans and C. glabrata (2.5%), C. albicans and C. parapsilosis (1%). C. albicans and C. glabrata isolates had lower susceptibility to FLU (31.4% and 23.0%, respectively) and CTZ (37.1% and 33.3%, respectively). Importantly, there was ‟synergismˮ between farnesol-FLU and farnesol-ITZ against C. albicans and C. parapsilosis (FICI= 0.5 and 0.35, respectively), reverting the original azole resistant profile. These findings indicate that farnesol is able to revert to the resistance profile of azole by enhancing the activity of FLU and ITZ in resistant isolates, which is a promising result.

Rett syndrome (RTT) is a rare disease and one of the most abundant causes for intellectual disa-bilities in females. Single mutations in the gene coding for methyl-CpG-binding protein 2 (MECP2), are responsible for the disease. MeCP2 regulates gene expression as a transcriptional regulator as well as through epigenetic imprinting and chromatin condensation. Consequently, numerous biological pathways on multiple levels are influenced however, the exact molecular pathways from genotype to phenotype are currently not fully elucidated. Treatment of RTT is purely symptomatic where no curative options for RTT have yet to reach the clinic. The paucity of this is mainly due to an incomplete understanding of the underlying pathophysiology of the dis-order with no clinically useful common disease drivers, biomarkers or therapeutic targets being identified. With the premise of identifying universal and robust disease drivers and therapeutic targets, here we interrogated a range of RTT transcriptomic studies spanning different species, models and MECP2 mutations. A meta-analysis using RNA sequencing data from brains of RTT mouse models human post-mortem brain tissue and patient-derived induced pluripotent stem cells (iPSC) neurons was performed using Weighted Gene Correlation Network Analysis (WGC-NA). This study identified a module of genes common to all datasets with the following ten hub genes driving the expression ATRX, ADCY7, ADCY9, SOD1, CACNA1A, PLCG1, CCT5, RPS9, BDNF and MECP2. Here we discuss the potential benefits of these genes as therapeutic targets.

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis are heterogeneous, progressive diseases with frequently overlapping symptoms characterized by a loss of neurons. Studies suggested relations between neurodegenerative diseases for many years, e.g., regarding the aggregation of toxic proteins or triggering endogenous cell death pathways. Within this study, publicly available genomic, transcriptomic and proteomic data were gathered from 188 studies and more than one million patients to detect shared genetic patterns between the neurodegenerative diseases and the analyzed omics-layers within conditions. The results show a remarkably high number of shared genes between the transcriptomic and proteomic levels for all diseases while showing a significant relation between genomic and proteomic data only in some cases. A set of 139 genes was found to be differentially expressed in several transcriptomic experiments of all four diseases. These 139 genes showed overrepresented GO-Terms and pathways mainly involved in stress response, cell development, cell adhesion, and the cytoskeleton. Furthermore, the overlap of two and three omics-layers per disease were used to search for overrepresented pathways and GO-Terms. Taken together, we could confirm the existence of many relations between Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis on the transcriptomic and proteomic level by analyzing the pathways and GO-Terms arising in these intersections. The significance of the connection between the transcriptomic and proteomic data for all four analyzed neurodegenerative diseases showed that exploring these omics-layers simultaneously holds new insights that do not emerge from analyzing these omics-layers separately. Our data therefore suggests addressing human patients with neurodegenerative diseases as complex biological systems by integrating multiple underlying data sources.

The main scope of the presented paper is an assessment of the potential repellent effect of selected essential oils (EOs) against Alphitobius diaperinus, which can cause economic losses in storages and poultry industry. Due to development of pesticide resistance in A. diaperinus populations, as well as an attempt to limit extensive usage of potentially harmful pesticides in food-related industries, there is a strong need for development of alternative methods of management of A. diaperinus infestations. Because of cost-effectiveness, availability and low vertebrate toxicity EOs are promising agents in pest management. In presented paper four of-the-shelf EOs: mint, vanilla, lemon and citronella (and their mixtures) were tested as a potential repellents. Moreover, novel preference assay providing an extended analysis of preference and the locomotor response was used. The most effective EOs were, respectively: citronella and lemon. EOs mixtures were generally more repellent than single EOs, with lemon and vanilla 1:1 mixture acting as the strongest repellent. Few of tested EOs caused significant alterations in locomotor activity, although direct relation wasn’t observed. In conclusion, EOs can be potentially used as a repellent agents in A. diaperinus management. Additionally, data on locomotor activity may lead to better design of pull-push strategies in pest management.

In this paper, we introduced many new notions and new contraction named as S-weakly contraction after that we obtained the p-common best proximity point theorems for different types of contractions in the setting of complete metric spaces by using weak P_p-property and proved the uniqueness of these points. Also we presented some examples to prove the validity of our results.

Osteopontin (OPN)-CD44 signaling plays an important role in promoting tumor progression and metastasis. In cancer, OPN and CD44 overexpression is a marker of aggressive disease and poor prognosis, and correlates with therapy resistance. In this study, we aimed to evaluate the association of single nucleotide polymorphisms (SNPs) in the OPN and CD44 genes with clinical outcomes in 307 non-small cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. The potential impact of the variants on plasma OPN levels was also inves-tigated. Multivariate analysis showed that OPN rs11730582 CC carriers had a significantly in-creased risk of death (p = 0.029), while the CD44 rs187116 A allele correlated with reduced risk of locoregional recurrence (p = 0.016) in the curative treatment subset. The rs11730582/rs187116 combination was associated with an elevated risk of metastasis in these patients (p = 0.016). Fur-thermore, the OPN rs1126772 G variant alone (p = 0.018) and in combination with rs11730582 CC (p = 7x10-5) was associated with poor OS in the squamous cell carcinoma subgroup. The rs11730582 CC, rs187116 GG and rs1126772 G, as well as their respective combinations, were in-dependent risk factors for unfavorable treatment outcomes. The impact of rs11730582-rs1126772 haplotypes on OS was also observed. These data suggest that OPN and CD44 germline variants may predict treatment effects in NSCLC.

Background: Distal sensory polyneuropathy (DSP) and distal neuropathic pain (DNP) remain significant challenges for older people with HIV (PWH), necessitating enhanced clinical attention. HIV and certain antiretroviral therapies (ART) can compromise mitochondrial function and impact mitochondrial DNA (mtDNA) replication, which is linked to DSP in ART-treated PWH. Methods: This study investigated mtDNA, mt fission and fusion protein, and mt electron transport chain protein changes in the dorsal root ganglion (DRG) and sural nerve (SuN) from 11 autopsied PWH. In antemortem standardized assessments, six had no or one sign of DSP, while five exhibited two or more DSP signs. Digital droplet polymerase chain reaction (ddPCR) measured mtDNA quantity and the common deletion (CD) in isolated DNA. Results: We found lower mtDNA copy numbers in DSP+ donors. SuN exhibited a higher proportion of mtDNA CD than DRGs in both groups. Mitochondrial electron transport chain (ETC) proteins were altered in DRG of DSP+ compared to DSP- donors, particularly complex I. Conclusion: These findings suggest reduced mtDNA quantity and increased CD abundance may contribute to DSP in PWH, indicating diminished mitochondrial activity in sensory neurons. Accumulated ETC proteins in the DRG imply impaired mitochondrial transport to the sensory neuron's distal portion. Identifying molecules to safeguard mitochondrial integrity could aid in treating or preventing HIV-associated peripheral neuropathy.

Although lymphoma is the most frequent malignancy in common variable immunodeficiency (CVID), solid tumors, especially under influence of oncogenic viruses, are not considered. Furthermore, in vitro genetic studies and cell cultures are not adequate for immune system and HBV interaction. We adopted previously introduced clinical model of host-virus interaction (i.e. infectious process in immunodeficiency) for analysis of B cells and specific IgG role (observational study of a CVID patient who received intravenous immunoglobulin (IVIG)) Suddenly, the patient deteriorated with positive result of HBs, HBV-DNA (369x106copies). In spite of lamivudine therapy and IVIG escalation (from 0.3 to 0.4g/kg), CT showed 11cm intrahepatic tumor (hepatocellular carcinoma). Anti-HBs had been positive in time-lapse analysis (range 111-220 IU/ml). Replacement therapy intensification was complicated by immune complex disease with renal failure. The fulminant HCC in CVID and the development of the tumor as the first sign is interesting. Unfortunately, treatment with hepatitis B immune globulins (HBIG) plays a major role in posttransplant maintenance therapy. Anti-HBs substitution has not been proven to be effective, oncoprotective nor safe. Therefore, immunosuppression in HBV-infected recipients should be carefully minimized, patient selection more precise with the exclusion of HBV-positive donors. Our clinical model show HCC pathway with important humoral host factors, contrary to epidemiological/cohort studies highlighting risk factors only (e.g. chronic hepatitis). Lack of cell cooperation, B cell deficiency observed in CVID plays a crucial role in high HBV replication, especially in carcinogenesis.

Genes and gene trees have been extensively used to study the evolutionary relationships among populations, species, families and higher systematic clades of organisms. This brought modern Biology into a sophisticated level of understanding about the evolutionary relationships and diversification patterns that happened along the entire history of organismal evolution in Earth. Genes however have not been placed in the center of questions when one aims to unravel the evolutionary history of genes themselves. Thus, we still ignore whether Insulin share a more recent common ancestor to Hexokinase or DNA polymerase. This brought modern Genetics into a very poor level of understanding about sister group relationships that happened along the entire evolutionary history of genes. Many conceptual challenges must be overcome to allow this broader comprehension about gene evolution. Here we aim to clear the intellectual path in order to provide a fertile research program that will help geneticists to understand the deep ancestry and sister group relationships among different gene families (or orthologs). We aim to propose methods to study gene formation starting from the establishment of the genetic code in pre-cellular organisms like the FUCA (First Universal Common Ancestor) until the formation of the highly complex genome of LUCA (Last UCA), that harbors hundreds of genes families working coordinated into a cellular organism. The deep understanding of ancestral relationships among orthologs will certainly inspire biotechnological and biomedical approaches and allow a deep understanding about how Darwinian molecular evolution operates inside cells and before the appearance of cellular organisms.

The hybrid zone between chromosome races of the common shrew (Sorex araneus) provides an exceptional model to study the potential role of chromosome rearrangements in the initial steps of speciation. The Novosibirsk and Tomsk races differ by a series of Robertsonian fusions with monobrachial homology. They form a narrow hybrid zone and generate hybrids with both simple (chain of three chromosomes) and complex (chain of eight or nine) synaptic configurations. Using immunolocalisation of the meiotic proteins, we examined chromosome pairing and recombination in males from the hybrid zone. Homozygotes and simple heterozygotes for Robertsonian fusions showed a low frequency of synaptic aberrations (< 10%). The carriers of complex synaptic configurations showed multiple pairing abnormalities, which might lead to reduced fertility. Recombination frequency in the proximal regions of most chromosomes of all karyotypes was much lower than in the other regions. The strong suppression of recombination in the pericentromeric regions and co-segregation of race specific chromosomes involved in the long chains would be expected to lead to linkage disequilibrium between genes located there. Genic differentiation, together with the high frequency of pairing aberrations in male carriers of the long chains, might contribute to maintenance of the narrow hybrid zone.