The global usage of veterinary antibiotics is significant. These antibiotics can be released into the aquatic environment and exert toxic effects on non-target organisms. To explore the physiological effects of tetracycline antibiotics on aquatic life, the growth characteristics of and toxin release from the cyanobacterium Microcystis aeruginosa (M. aeruginosa) were studied. Results showed that the toxicity order of the three target antibiotics was TC (tetracycline) > CTC (chlortetracycline hydrochloride) > OTC (oxytetracycline) in terms of inhibition occurrence time and the EC₁₀ and EC₂₅ values. Further, the target antibiotics regulated the production of MC-LR (microcystin-LR) to different degrees. CTC destroyed the M. aeruginosa cells and resulted in a decreased MC-LR release but stimulated the ability to synthesise MC-LR. OTC had a relatively weaker toxicity compared with CTC, while TC was the most toxic among the three antibiotics. Therefore, TC is friendly to the aquatic environment because it simultaneously reduced the intracellular and extracellular MC-LR content. These results aid our understanding of the effects of tetracycline antibiotics on Microcystis aeruginosa, which is important for environmental evaluation and protection. These results are also helpful for guiding the application of veterinary antibiotics in agricultural settings.

Toxin/antitoxin (TA) systems are used primarily to inhibit phage, reduce metabolic activity during stress, and maintain genetic elements. Given the extreme toxicity of some of the toxins of these TA systems, we were curious how the cell silences toxins, if the antitoxin is inactivated or when toxins are obtained without antitoxins via horizontal gene transfer. Here we find that the RalR (type I), MqsR (type II), GhoT (type V), and Hha (type VII) toxins are inactivated primarily by a mutation that inactivates the toxin promoter or via the chromosomal mutations iraM and mhpR.

Background: Chronic lateral epicondylitis challenges the therapeutical approach; underlying mechanisms are incompletely understood; neuropathic pain and central and peripheral sensitization may explain the fact that botulinum toxin was found to play a role in pain and function management. Methods: We searched the literature for MeSH terms: lateral epicondylitis or synonyms and botulinum toxin. Results: We found 14 papers containing trials on botulinum toxin injection into the tendon or into the extensor muscles (particularly extensor carpi radialis brevis and extensor communis digitorum). We followed the administration pathways, doses, timing and side effects. Conclusion: With chronic course, the focus of the therapy shifts from the afflicted tendon to the inserting muscles, as muscle contracture may create a vicious loop to perpetuate and aggravate the disease. Doses, timing and side effects are discussed.

Intracellular aggregates of the alpha-synuclein protein result in cell loss and dysfunction in Parkinson’s disease and atypical parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as alpha-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby alpha-synuclein aggregates in turn mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of alpha-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of alpha-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunnelling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which alpha-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease.

Mathematical literacy is a very hot issue in the development of mathematics learning, apart from mathematical literacy, another interesting thing is the entrepreneurial spirit that must be given from an early age, especially for vocational students. This research was conducted at SMK Rosma Karawang in the Department of Computer and Network Engineering, West Java Province with the XI grade students. The teaching materials developed by applying the principles of the development model developed with the ADDIE model consist of analysis, design, development, implementation and evaluation. This research and development model is considered suitable for developing teaching tools and materials which is used for the purposes of the learning process. Based on the results of data analysis and processing that have been carried out in this study, the development of teaching materials using the ADDIE model has met the appropriate and valid criteria by media, language and media expert valuators. Another result of developing this teaching material besides meeting the eligibility criteria is that the teaching materials developed are able to increase mathematical literacy and instill entrepreneurial spirit for students.

AB toxins have historically been associated with significant morbidity, mortality through infections such as botulinum, anthrax, cholera, and diphtheria. These AB toxin-mediated diseases remain prevalent in low and middle income countries, with intermittent outbreaks of Shiga toxin-producing Escherichia coli (STEC) or whooping cough by Bordetella pertussis in high-income countries. These reports warrant an investigation to better understand the distinct characteristics of AB toxins derived from different pathogens. As toxigenic pathogens broaden their scope and diversity, it amplifies the complexity of the problems posed by their AB toxins. Here, we discuss the history, structure and characteristics of key AB toxins, and report on historical and ongoing research on these toxins. We also explore research avenues that hold great promise in potentially improving clinical management of toxin-mediated diseases in the future.

The inhibition of alpha-glucosidase and alpha-amylase is one of clinic strategies for remedy the type II diabetes. Herbal medicines are reported to alleviate hyperglycemia. However, the constituents from those sources whether are targeted to the alpha-glucosidase and alpha-amylase still unexplored. This study attempted to select the compounds for efficacy of hypoglycemia via cellular and mouse levels. The results illustrated that the cytotoxicity in all tested compounds at various concentrations except the concentration of 16-hydroxy-cleroda-3,13-dine-16,15-olide (HCD) at 30 µM were not significant difference (p > 0.05) when compared with the untreated control. Acarbose (reference drug), Antroquinonol, Catechin, Quercetin, Actinodaphnine, Curcumin, HCD, Docosanol, Tetracosanol, Berberine, and Rutin could effectively inhibit the alpha-glucosidase activity of Caco-2 cells when compared with the control (maltose). The compounds (Curcumin, HCD, Tetracosanol, Antroquinonol, Berberine, Catechin, Actinodaphnine, and Rutin) could reduce blood sugar level at 30 min in tested mice. The effects of tested compounds on area under curve (AUC) were significant (p < 0.05) among Acarbose, Tetracosanol, Antroquinonol, Catechin, Actinodaphnine, and Rutin along with Berberine and Quercetin. In in vitro (alpha-glucosidase) with in vivo (alpha-amylase) experiments suggest that bioactive compounds can be a potential inhibitor candidate of alpha-glucosidase and alpha-amylase for the alleviation of type II diabetes.

Several pathotypes of enteric E. coli have been identified. The group represented by Shiga toxin-producing E. coli (STEC) is of particular interest. Raw milk and raw milk products are significant sources of STEC infection in humans; therefore, identifying pathogens at the herd level is crucial for public health. Most national surveillance programs focus solely on raw milk and raw milk cheeses that are ready for retail sale, neglecting the possibility of evaluating the source of contamination directly at the beginning of the dairy chain. In order to assess the viability of new molecular methodologies applied to raw milk filters enabling the identification of the presence of STEC serotypes in milk production and apply the same methods to identify the presence of these pathogens in calf feces we analyzed, through a commercial real-time PCR assay, a total of 290 samples coming from 18 different dairy herds; 88 bulk tank milk (BTM), 104 raw milk filters (RMF) and 98 calves’ feces samples. In total 3.4% of BTM, 41.4% of RMF and 73.4% of calves’ feces tested positive for stx presence, supporting our hypothesis that BTM is not a suitable matrix to assess the STEC presence at herd level, underestimating it. Our conclusion is that the surveillance program needs critical and extensive improvements such as RMF and calves’ feces analysis implementation in order to be more efficient in detecting and preventing STEC infections. The epidemiology of these infections and the characteristics of the pathogen clearly show how a One Health approach will be pivotal to improve our capabilities to control the spread of these infections.

Diabetes mellitus (DM) is one of the most dangerous metabolic diseases with high rate of mortality worldwide. It is well known that insulin resistance and deficiency in insulin production from pancreatic β-cells are the main characteristic of DM. Due to the detrimental side effects of the current treatment, there is a considerable need to develop new effective antidiabetic drugs, especially alpha-glucosidase and alpha-amylase inhibitors with lesser adverse effects. These inhibitors are known to be directly involved in the delay of carbohydrate digestion, resulting in a reduction of glucose absorption rate and consequently reduce the post-prandial raise of plasma glucose, which can reduce the risk of long-term diabetes complications. Hence, natural products are well-known sources for the discovery of new scaffold for drugs discovery, including new antidiabetic drugs. The phytochemical investigation of Salvia aurita collected from Hogobach pass, Eastern Cape, South Africa (SA), yielded four known abietane diterpenes namely carnosol (1), rosmanol (2), 7-methoxyrosmanol (3), 12-methoxycarnosic acid (4) and one flavonoid named 4,7-dimethylapigenin (5). Structural characterization of these isolated compounds was conducted using 1 and 2D NMR, in comparison with reported spectroscopic data. These compounds are reported for the first time from S. aurita. The biological evaluation of the isolated compound against alpha-glucosidase exhibited strong inhibitory activities for 3 and 2 with IC50 values of 4.2 ± 0.7 and 16.4 ± 1.1 µg/mL respectively, while 4 and 1 demonstrated strong alpha-amylase inhibitory activity amongst the isolated compounds with IC50 of 16.2 ± 0.3 and 19.8 ± 1.4 µg/mL. Molecular docking analysis confirms strong inhibitory activity of 3 against alpha-glucosidase. Additionally, excellent antioxidant capacities were displayed by 2, 1 and 3 respectively as ORAC (25789.9 ± 10.5; 23961.8 ± 14.1; 23939.3 ± 2.4) µM TE/g; 1 and 2 as FRAP (3917.8 ± 2.1; 1522.3 ± 0.9) µM AAE/g; 5 and 2 as TEAC (3190.4 ± 2.8; 2055.0 ± 2.6) µM TE/g. The methanolic extract of S. aurita is a rich source of abietane diterpenes with excellent antioxidant and anti-diabetic activities that can be useful to modulate oxidative stress, and might possibly be excellent candidates for the management of diabetes. This is the first scientific report on the phytochemical isolation and biological evaluation of alpha-glucosidase and alpha-amylase inhibitory activities of Salvia aurita.

Leishmanial skin lesions are characterized by inflammatory hypoxia alongside the activation of hypoxia inducible factors, HIF-1a and HIF-2a, and subsequent expression of the HIF-a target VEGF-A during Leishmania major infection. However, the factors responsible for HIF-a activation are not known. We hypothesize hypoxia and pro-inflammatory stimuli contribute to HIF-a activation during infection. RNASeq on leishmanial lesions found transcripts associated with HIF-1a signaling are induced. To determine whether hypoxia contributes to HIF-a activation, we followed the fate of myeloid cells infiltrating from the blood and into hypoxic lesions. Recruited myeloid cells experience hypoxia when they enter inflamed lesions, and the length of time in lesions increases their hypoxic signature. To determine whether pro-inflammatory stimuli in the inflamed tissue can also influence HIF-a activation, we subjected macrophages to various pro-inflammatory stimuli and measured VEGF-A. While parasites alone did not induce VEGF-A, and pro-inflammatory stimuli only modestly induce VEGF-A, HIF- stabilization increases VEGF-A during infection. HIF-a stabilization does not impact parasite entry, growth or killing. Alternatively, the absence of ARNT/HIF- signaling enhances parasite internalization. Altogether, these findings suggest HIF-a is active during infection, and while macrophage HIF-a activation promotes lymphatic remodeling through VEGF-A production, HIF-a activation does not impact parasite internalization or control.

The asymmetric skew divergence smooths one of the distributions by mixing it, to a degree determined by the parameter $\lambda$, with the other distribution. Such divergence is an approximation of the KL divergence that does not require the target distribution to be absolutely continuous with respect to the source distribution. In this paper, an information geometric generalization of the skew divergence called the $\alpha$-geodesical skew divergence is proposed, and its properties are studied.

Parkinson’s disease (PD) is a common multisystem neurodegenerative disorder affecting 1% of the population above 60 years. The main neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of alpha synuclein (Syn)-rich Lewy bodies both manifesting with classical motor signs. Syn has emerged as a key protein in PD pathology as it can spread through synaptic networks to reach several anatomical regions of the body contributing to the appearance of non-motor symptoms (NMS) considerate prevalent among individuals before PD diagnosis and persisting throughout the patient’s life. NMS mainly include loss of taste and smell, constipation, psychiatric disorders, dementia, rapid eye movement (REM) sleep behavior impairment, urogenital dysfunction, and cardiovascular impairment. This review summarizes the more recent findings showing the impact of Syn deposits on several prodromal NMS and emphasizes the importance of early detection of Syn toxic species in biofluids and peripheral biopsies as prospective biomarkers in PD.

The ongoing global pandemic caused by coronavirus disease 2019 (COVID-19) has once again demonstrated the significance of the Coronaviridae family in causing human disease outbreaks. As SARS-CoV-2 was first detected in December 2019, information on its tropism, host range, and clinical presentation in animals is limited. Given the limited information, data from other coronaviruses may be useful to inform scientific inquiry, risk assessment and decision-making. We review the endemic and emerging alpha- and betacoronavirus infections of wildlife, livestock, and companion animals, and provide information on the receptor usage, known hosts, and clinical signs associated with each host for 15 coronaviruses discovered in people and animals. This information can be used to guide implementation of a One Health approach that involves human health, animal health, environmental, and other relevant partners in developing strategies for preparedness, response, and control to current and future coronavirus disease threats.

Pore Forming Toxins (PFTs), formed mainly by virulence factors of bacteria, belongs to Pore Forming Protein (PFP) family. Secreted as soluble monomers, they bind specific targets in membranes where their oligomerization and insertion place. Lysenin, a member of the PFTs, forms and oligomer after sphingomyelin binding, the so-called prepore, which become inserted forming a pore after a conformational change triggered by a pH decrease. In crowded conditions, oligomers tends to stay in prepore form because the prepore-to-pore transition is sterically blocked. In this study, we investigate the effect of calcium ions in those crowded conditions, finding that calcium act as a trigger for lysenin insertion. We localize the residues responsible for calcium sensitivity in a small α-helix. Our results are not only one of the few complete structural descriptions of prepore-to-pore transitions but the very first that involves a calcium triggering mechanism. The presence of glutamic or aspartic acids in the insertion domains could be an indication that calcium may be a general trigger for PFTs and more generally PFP.

The toxin-antitoxin (TA) systems have been attracting attention due to their role in regulating prokaryotic cell responses to stress and their biotechnological potential. Much recognition has been given to type II TA system of mesophiles, but so far, limited attention has been given to thermophiles. Here, we are presenting the putative type II TA families encoded on the genomes of four Geobacillus strains. We employed the TA finder tool to mine for TA-coding genes and manually curated the results using various tools. We identified 28 putative TA pairs, distributed over 8 TA families. Among the identified TAs, 15 represent putative novel toxins and antitoxins that have been overlooked or annotated as hypothetical proteins in their genome records. We also identified a potentially new TA composite, AbrB-ParE. Furthermore, we are suggesting the Geobacillus acetyltransferase toxin-antitoxin (GacTA) family which potentially represents one of the unique TA families that has a reverse gene order. Moreover, we are proposing a hypothesis on the regulation of the xre-cog2856 gene expression, which seems to involve c-di-AMP. This study aims for highlighting the significance of studying TAs in Geobacillus, since they have special features. It also aims for facilitating future experimental research.

Ataxin-2 (human gene symbol ATXN2, protein ATXN2) is the disease protein of Spinocerebellar Ataxia type 2 (SCA2). The large expansions of a polyglutamine (polyQ) stretch above a threshold of ~33 glutamines cause the multi-system nervous atrophy SCA2, while intermediate expansions of 29-32 glutamines contribute to the risk of the motor neuron diseases Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Lobar Dementia (FTLD). To elucidate the cellular function of ATXN2, we further characterized its direct interaction with alpha-Actinin-1 (symbol ACTN1), which had been observed in high-throughput yeast-two-hybrid surveys. An endogenous complex of ATXN2 and ACTN1 proteins was detected by co-immunoprecipitation. In vitro GST-tag pull-down experiments showed that the Calponin-Homology-domain at the N-terminus of ACTN1 binds to the N-terminus of ATXN2. Although an impact of the polyQ expansion on the interaction was not evident in pull-down experiments, a recent characterization of aged Atxn2-CAG100-KnockIn mice provides evidence. Both proteins associated in the cytosol and at the plasma membrane, as determined by sedimentation experiments in mouse brain, and by immunofluorescence microscopy of a transfected monkey cell line and of rat primary hippocampal neurons. In view of the roles of ACTN1 for spine plasticity and postsynaptic receptor control via reassembly of cortical actin, our data help to explain the impaired dendrite maintenance in SCA2.

Cardiovascular diseases (CVDs) represent the leading cause of global mortality with 1,7 million deaths a year. One of the alternative systems to drug therapy to minimize the risk of CVDs is represented by alpha-linolenic acid (ALA), an essential fatty acid of the Omega-3 series, known for its cholesterol-lowering effect. The main purpose of this review is to analyze the effects of ALA and investigate the relevant n-6/n-3 ratio in order to maintain functionally beneficial effects. Concerning the lipid-lowering preventive effects, ALA may favorably affect the values of LDL-C and triglycerides in either adult and pediatric populations and it has a positive and protective effect against hypertension, suggesting that ALA is an useful diet-related antihypertensive compound. According to the 2009 EFSA statement, dietary ALA may contribute to reducing the risk of CVDs, thanks to anti-hypertensive, anti-atherosclerotic and cardio-protective effects.

Training researchers and stakeholders is crucial to mitigate the risks associated with toxins and venom. By sharing knowledge on the responsible use of toxins, venoms, chemicals, and data from biosecurity and cyberbiosecurity perspectives, we empower laboratorians to make informed choices. We need to remember that cultivating a culture of sustainable biosafety and biosecurity is vital for one health. This technical note highlights the essence of safeguarding biosecurity and cyberbiosecurity in toxin and venom research laboratories workshop designed and implemented to boost biosecurity.

We previously showed that feeding mice a diet containing 1% mantle tissue decreased food consumption, leading to death. We also isolated and identified toxic substances in the mantle tissue. In the present study, we investigated the characteristics and stability of mantle tissue toxicity. Treatment of mantle tissue with 1 mM HCl, 1 mM NaOH, 1 mM dithiothreitol, and 1 mM H2O2 and heating did not reduce the toxicity of mantle tissue in mice. These results suggest that mantle toxins are stable in tissues, particularly when exposed to acidic and digestive enzymes. We examined whether mantle tissue exhibited acute toxicity. Diets containing 1% and 20% mantle extract showed similar levels of toxicity, demonstrating that feeding of mantle tissue does not lead to acute toxicity. Finally, we examined the toxicity of the mantle tissue against small intestinal tissue. Chronic feeding of mantle tissue to mice changed the color of the small intestine. Real-time PCR analysis showed that mantle tissue feeding caused changes of inflammation and endoplasmic reticulum stress markers in the small intestine. These results suggest that feeding of mantle tissue causes toxicity after causing initial damage to the small intestinal tissue.

Bacillus anthracis, the causative agent of anthrax, has two virulence plasmids: pXO1 and pXO2. Plasmid pXO2 carries the genes of an antiphagocytic capsule synthesis. Plasmid pXO1 carries the genes pagA, lef, and cya encoding anthrax toxins, as well as atxA, which encodes the main regulator of pathogenicity factor expression. In the present paper, we evaluated the polymorphism of the pagA, lef, cya, and atxA genes for 85 B. anthracis strains belonging to different evolutionary lineages and canSNP groups and three B. cereus strains possessing pXO1-like plasmids. We found 19 genotypes (GT) strongly correlated with the main evolutionary lineages; they were mainly correlated with the canSNP group within these lines. In some cases, one GT combined the strains of several canSNP groups, and some canSNP groups were divided into several GTs. The most interesting of such cases were 1) the formation of a separate GT by strains of the A.Br.008/009 group isolated in the former USSR; 2) the presence of a unique GT in some American strains of the A.Br.Aust94 group; 3) the division of the A.Br.001/002 group into two subgroups, one of which may be a transitional link to the group A.Br.Ames; 4) the fact that European isolates of the B.Br.CNEVA group and Arctic strains of the B.Br.001/002 group have a common GT.

By combining general relativity and CPT symmetry, the theory of CPT gravity predicts gravitational repulsion between matter and CPT-transformed matter, i.e. antimatter inhabiting an inverted space-time. Such repulsive gravity turned out to be an excellent candidate for explaining the accelerated expansion of the Universe, without the need for dark energy. The recent results of the ALPHA-g experiment, which show gravitational attraction between antihydrogen atoms and the Earth, seem to undermine this success in the cosmological field. Analyzing the above theory, we find two solutions that can be consistent with the experimental results, while preserving the large-scale gravitational repulsion. The first highlights how repulsive gravity can be the result of the interaction with an inverted space-time, but occupied by matter and not antimatter, and therefore the antimatter present in our space-time has no reason to exhibit gravitational repulsion. The second retains the original CPT transformation, resulting in repulsive gravity between matter and antimatter, but with the caveat that antimatter immersed in our space-time cannot exhibit the PT transformation which is the cause of the repulsion. Finally, it is shown that, in a Newtonian approximation of the geodesic equation, time reversal is not a necessary operation for repulsive gravity, therefore opening the possibility of an expanding cosmos with a single time direction.

Microcystis aeruginosa is a common cyanobacteria found in water blooms and often causes ecological harm. Antibiotics are also increasingly used for the prevention and treatment of bacterial infections in aquaculture. However, since most antibiotics cannot be fully metabolized, they enter the water environment and cause ecological impacts. In this paper, the effects of the two quinolone antibiotics (enrofloxacin and ciprofloxacin) on the population density and microcystins (MCs) production of Microcystis aeruginosa were studied. It is of great significance for the ecological risk assessment of antibiotics to the water environment. The results showed that the 96h EC50 values of enrofloxacin and ciprofloxacin to Microcystis aeruginosa were 56.10mg/L and 49.80mg/L respectively, and the toxicity of ciprofloxacin to Microcystis aeruginosa was slightly stronger than that of enrofloxacin. With the increase of the two quinolone antibiotic concentration, the growth inhibition rate (IR) increased, but when the concentration reached a certain height, the IR would reach its threshold. Long-term exposure to low concentrations of these two quinolone antibiotics is not only more likely to lead to the outbreak of Microcystis aeruginosa, but also increase its toxin production capacity. The highest contents of MCs in enrofloxacin and ciprofloxacin groups were 95.539 μg/g and 93.720 μg/g, respectively. The MCs value of these three enrofloxacin treatment groups was more than above 51.8 times that of control group (CK) on the 4th day; from 8th day to 14th day, the MCs value of these three enrofloxacin treatment groups was more than above 3.2 times that of CK group. For another ciprofloxacin, the MCs value of the treatment group was more than 64.98 times that of the CK group on the 4th day, and from 8th day to 14th day, the MCs value of the treatment group was more than 2.7 times that of the CK group. These findings provide crucial management rationale.

Environmental genetics-related modern methods are shown as important indicators of various cyanotoxins syntheses, and their knowledge and use are critically analyzed. Microcystins and other cyanotoxins loads and syntheses are related to different drivers, like various chemical elements and compounds (especially nutrients, such as nitrogen and phosphorus, and their ratio), then to the light, conductivity, temperature, and other climatical and hydrological factors, to which spatial and geographical features (such as the surface of the water bodies) have to be added. The biotic relationships include different specific and supraspecific, uni- and bilateral links between the cyanobacteria, and subsequently their synthesized toxins, and protozoans (or protoctists), chromists, macrophytes, different systematical and ecological groups of zooplankton, and others. The importance of, but also the gaps in, the knowledge and the scarcity of studies involving ectocrines mediated interactions between different groups of algae and plants are highlighted. The paper ends with an interesting classification of lakes' trophicity, illustrated with conceptual diagrams, based on possible scenarios of cyanobacteria behavior.

The castor plant (Ricinus communis L.) has been known since time immemorial in traditional medicine in the pharmacopeia of Mediterranean and eastern ancient cultures. Moreover, it is still used in folk medicine worldwide. Castor bean has been mainly recommended as anti-inflammatory, anthelmintic, anti-bacterial, laxative, abortifacient, for wounds, ulcers, and many other indications. Many cases of human intoxication occurred accidentally or voluntarily with the ingestion of castor seeds or derivatives. Ricinus toxicity depends on several molecules, among them the most important is ricin, a protein belonging to the family of ribosome-inactivating proteins. Ricin is the most studied of this category of proteins and it is also known to the general public, having been used for biocrimes in several cases. Here, the main steps of ricin research are reported with particular regards to its enzymatic activity, structure and cytotoxicity. Moreover, we discuss ricin toxicity for animals and humans, as well as the relation amongst bioterrorism and ricin and its impact on environmental toxicity. Ricin has also been of great utility to develop a number of immunotoxins specific for the elimination of unwanted cells, mainly cancer cells; some of these immunotoxins gave promising results also in clinical trials.

Rapid assessment of maize yields in smallholder farming system is important to understand its spatial and temporal variability and for timely agronomic decision-support. Imageries acquired with unmanned air vehicles (UAV) offer opportunity to assess agronomic variables at field scale, however, it is not clear if this can be translated into reliable yield assessment on smallholder farms where field conditions, maize genotypes, and management practices vary within short distances. In this study, we assessed the predictability of maize grain yield using UAV-derived vegetation indices (VI), with(out) biophysical variables, in smallholder farms. High-resolution images were acquired with UAV-borne multispectral sensor at 4 and 8 weeks after sowing (WAS) on 31 farmers’ managed fields (FMFs) and 12 nearby Nutrient Omission Trials (NOT), all distributed across 5 locations within the core maize region of Nigeria. The NOTs included non-fertilized and fertilized plots (with and without micronutrients), sown with open-pollinated or hybrid maize genotypes. Acquired multispectral images were post-processed into several three (s) vegetation indices (VIs), normalized difference vegetation index (NDVI), normalized difference red-edge (NDRE), green-normalized difference vegetation index (GNDVI). Biophysical variables, plant height (Ht) and percent canopy cover (CC), were measured with the georeferenced plot locations recorded. In the NOTs, the nutrient status, not genotype, influenced the grain yield variability and outcome. The maximum grain yield observed in NOTs was 9.3 tha^-1, compared to 5.4 tha^-1 in FMF. Without accounting for between- and within-field variations, there was no relationship between UAV-derived VIs and grain yield at 4WAS (r<0.02, P>0.1), but significant correlations were observed at 8WAS (r≤0.3; p<0.001). Ht was positively correlated with grain yield at 4WAS (r=0.5, R²=0.25, p<0.001), and more strongly at 8WAS (r=0.7, R²=0.55, p<0.001), while relationship between CC and yield was only significant at 8WAS. By accounting for within- and between-field variations in NOTs and FMF (separately) through linear mixed-effects modeling, predictability of grain yield from UAV-derived VIs was generally (R²≤0.24), however, the inclusion of ground-measured biophysical variable (mainly Ht) improved the explained yield variability (R² ≥0.62, RMSEP≤0.35) in NOTs but not in FMF. We conclude that yield prediction with UAV-acquired imageries (before harvest) is more reliable under controlled experimental conditions (NOTs), than in actual farmer-managed fields where various confounding agronomic factors can amplify noise-signal within the vegetation canopy.

Three-dimensional (3D) bioprinting promises to be essential in tissue engineering for solving the rising demand for organs and tissues. Some bioprinters are commercially available, but their impact on the field of TE is still limited due to their cost or difficulty to tune. Herein, we present a low-cost easy-to-build printhead for microextrusion-based bioprinting (MEBB) that can be installed in many desktop 3D printers to transform them into 3D bioprinters. We can extrude bioinks with precise control of print temperature between 2 - 60 ºC. We validated the versatility of the printhead, by assembling it in three low-cost open-source desktop 3D printers. Multiple units of the printhead can also be easily put together in a single printer carriage for building a multi-material 3D bioprinter. Print resolution was evaluated by creating representative calibration models at different temperatures using natural hydrogels such as gelatin and alginate, and synthetic ones like poloxamer. Using one of the three modified low-cost 3D printers, we successfully printed cell-laden lattice constructs with cell viabilities higher than 90% after 24h post printing. Controlling temperature and pressure according to the rheological properties of the bioinks was essential in achieving optimal printability and great cell viability. The cost per unit of our device, which can be used with syringes of different volume, is less expensive than any other commercially available product. These data demonstrate an affordable open-source printhead with the potential to become a reliable alternative to commercial bioprinters for any laboratory.

Most of α-thalassemia cases are caused by deletions of the structural α-globin genes. The degree of microcytosis and hypochromia has been correlated with the number of affected α-globin genes, suggesting a promising role of hematologic parameters as predictive diagnostic tools. However, specific cut-off points for these parameters to discriminate between the different subtypes of α-thalassemia remain to be clearly defined. Six hematologic parameters (total number of erythrocytes, hemoglobin concentration, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration and red cell distribution width) were evaluated in 174 cases of deletional α-thalassemia (92 heterozygous α+ thalassemia, 39 homozygous α+ thalassemia, 34 heterozygous α0 thalassemia and 9 cases of Hb H disease). A good correlation between the number of deleted alpha genes and MCV (r = -0.672, p<0.001), MCH (r = -0.788, p<0.001) and RDW (r = 0.633, p<0.001) was observed. The deletion of at least two alpha genes in adult individuals with microcytosis without iron deficiency and normal values of Hb A2 and Hb F should be discarded when MCH levels are lower than 23.15 pg. Furthermore, MCH <21.90 pg and/or MCV <70.80 fL are strongly suggestive of the presence of one α0 allele. Finally, an accurate presumptive diagnosis of Hb H disease can be made if both RDW ≥20% and MCH <18.45 pg are seen.

To close the nutrient-related yield gaps in maize, balanced nutrition using primary and secondary macronutrients as well as micronutrients is recommended. Multi-nutrient diagnostic field trials were conducted in Guinea Savanna of Nigeria to assess the interactive effects of macronutrients and micronutrients on maize grain yields, nutrient uptake as well as N, P and K use efficiencies. The treatments consisted of a control (zero fertilizer applied), an NPK treatment and 10 other treatments in which macronutrient (Mg, S) and/or micronutrients (B, and Zn) were added to the NPK. The experiment was laid out in Randomized Complete Block Design with 3 replications. Data collected were subjected to mixed model with nutrient management strategy as fixed effects while replication nested in location and interaction between location and nutrient management strategy as random effects. The results revealed significant effects (P < 0.05) of nutrient management strategy on maize yield, nutrient uptake and nutrient use efficiencies of N, P and K. The study revealed that yield advantage over the recommended NPK fertilizer as a result of application macronutrients and micronutrients were highest with Mg in Lere (2.4 t ha⁻¹), S + B + Zn in Faskari (2.8 t ha⁻¹), S + B in Doguwa (1.5 t ha⁻¹) and S + Zn in Toro (2.4 t ha⁻¹). Addition of Mg, S and B significantly increases macronutrient uptakes over the recommended NPK only. Agronomic use efficiency, internal utilization efficiency, apparent recovery efficiency and partial factor productivity were significantly increased with the addition of S, Mg, and B but were not improved with Zn application. It was concluded that nutrient limitations to maize in the Guinea Savanna go beyond N, P and K. This study recommends that S, Mg, and B are needed to improve maize productivity and engender improve the use efficiency of NPK fertilizers.

Tumor necrosis factor-α (TNFα), one of the major pro-inflammatory cytokines, plays a key role in an effective immune response. However, the chronic presence of TNFα can lead to several inflammatory disorders like rheumatoid arthritis, psoriasis, Crohn’s disease etc. Inhibition of TNFα by pharmacological inhibitors or antibodies has proven to be effective in palliative treatment to some extent. The aim of this study was to develop an anti-TNFα antibody which may be used as a therapeutic option to inhibit TNFα-mediated cytotoxicity. We characterized several hybridoma clones secreting monoclonal antibodies (mAbs) to human-TNFα. Four mAbs rescued L929 fibroblast cells from TNFα-triggered cell death and one of these, namely C8 was found to have the highest affinity. To gain insights into the mechanism by which mAb C8 inhibits human TNFα-mediated toxicity, the epitope corresponding to the mAb was delineated. The antigenic determinant was found to comprise of the stretch of amino acids 99-120, of which, 102-104 (QRE) form the core epitope. The observation was supported by bioinformatics analyses of an antigen-antibody complex model. In addition, the binding affinity of mAb C8 to TNFα was found to be comparable with that of Infliximab which is a commercially available anti TNFα mAb.

In this study, the fuzzy c- means classifier has been studied with nine other similarity and dissimilarity measures: Manhattan distance, chessboard distance, Bray-Curtis distance, Canberra, Cosine distance, correlation distance, mean absolute difference, median absolute difference and normalised squared Euclidean distance. Both single and composite modes were used with a varying weight constant (m) and also at different α-cuts. The two best single norms obtained were combined to study the effect of composite norms on the datasets used. An image to image accuracy check was conducted to assess the accuracy of the classified images. Fuzzy Error Matrix (FERM) was applied to measure the accuracy assessment outcomes for a Landsat-8 dataset with respect to the Formosat-2 dataset. To conclude FCM classifier with Cosine norm performed better than the conventional Euclidean norm. But, due to the incapability of the FCM classifier to handle noise properly, the classification accuracy was around 75%.

This study is the first report of the successful cultivation of Dinophysis norvegica isolated from Japanese coastal waters (7 of 48 isolated cells were established as the clonal cultures, 14.5%) and their toxin content and production. The strains were maintained at relatively high abundance (>2,000 cells mL-1) for more than one year when fed on Mesodinium rubrum with the addition of Teleaulax amphioxeia. At the end of the one-month incubation, the total amounts of pectenotoxin-2 (PTX2), dinophysistoxin-1 (DTX1) and okadaic acid (OA) were 132.0-375.0 ng mL-1 (n = 7), 0.7-3.6 ng mL-1 (n = 3) and trace level OA (n = 1), respectively. Similarly, the cell quota of PTX2 and DTX1 were 60.6-152.4 pg cell-1 (n = 7) and 0.5-1.2 pg cell-1 (n = 3), respectively. These data indicated that toxin production varies depending on the strains in this species. In the growth experiment, D. norvegica grew, but it was very slow first 12 days. However, after that they grew exponentially with the maximum growth rate of 0.56 divisions day-1 (during Day 24-27), reaching a maximum concentration of 3,000 cells mL-1 at the end of incubation (Day 36), suggesting that they have a long lag phase. In the toxin production, OA was not at a detectable level (≤ 0.010 ng mL-1) during the 36 days of incubation except for Day 6. The concentration of DTX1 and PTX2 showed similar patterns as described for vegetative growth, but the toxin production still increased on Day 36 (1.3 ng mL-1 and 154.7 ng mL-1 in DTX1 and PTX2, respectively). The findings of this study provide novel information on the toxin content and production in D. norvegica as well as details on the culturing and maintenance of the species.

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.

(1) Background: The diphtheria toxoid antigen is a major component in pediatric and booster combination vaccines and is known to raise a protective humoral immune response upon vaccination. Although antibodies are considered critical for diphtheria protection, little is known about the antigenic determinants that maintain humoral immunity. (2) Methods: One hundred twelve 15-mer peptides covering the entire sequence of DTx protein were prepared by Spot-synthesis. Membrane-bound peptides immunoreactivity with sera from mice immunized with triple DTP vaccine allowed mapping of continuous B-cell epitopes, topological studies, MAPs synthesis, and ELISA development. (3) Results: Twenty epitopes were identified, being 2 in the signal peptide, 5 in the CD, 7 in the HBFT domain, and 5 in the RBD. Two 17-mer (CB/Tx-2/12 and CB/DTx-4-13) derived bi-epitope peptides linked by a Gly-Gly spacer were chemically synthesized. The peptides were used as antigens to coat ELISA plates and assayed with human (huVS) and mice vaccined sera (miVS) for in vitro diagnosis of diphtheria. The assay proved to be highly sensitive (99.96%) and specific (100%) either for huVS and miVS and when compared with a commercial ELISA test, demonstrate high performance. (4) Conclusions: Our work displayed the complete picture of the linear B cell IgG response epitope of the DTx responsible for the protective effect and demonstrated the specificity and eligibility to enter phase IIB studies of some epitopes to develop new and fast diagnostic assays.

T-2 toxin produced by fungi of Fusarium genus is highly toxic to human and animals and has been shown to induce apoptosis in various organs/tissues. Apoptosis and autophagy are interconnected processes and these interactions are important for cellular homeostasis as well as pathogenesis. In this study, we report for the first time that T-2 toxin induced autophagy in human liver cells (L02). We showed that T-2 toxin induced the formation of acidic vesicular organelles, concordant with the time and dose-dependent alterations in LC3-phosphatidylethanolamine conjugate (LC3-II) LC3-I/II and p62/SQSTM1 suggesting an enhanced autophagic flux. The T-2 toxin-induced formation of autophagosome and lysosomal fusion was observed by expressing mRFP-GFP-LC3 in L02 cells by lentiviral transduction, and autophagosome was observed by transmission electron microcopy. We found that while T-2 toxin activated both apoptosis and autophagy, activation of autophagy appears to be a leading event reflecting the protective mechanism of cells against the insults by T-2 toxin. Activating autophagy by rapamycin (RAPA) inhibited the apoptosis while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis suggesting the crosstalk of autophagy and apoptosis. In summary, our study showed that activation of autophagy protects liver cells from T-2 toxin-induced apoptosis suggesting autophagy may be targeted for prevention of the T-2 toxin-induced toxicity in human and animals.

I wish to suggest a physiological function for alpha-synuclein (a-syn) that has the potential to explain its role in pathology. Intraneuronal proteinaceous Lewy Bodies (LBs), the pathological hallmark of Parkinson’s disease and other synucleinopathies, consist majorly of a-syn. Ample evidence suggests that LBs are not the result of simple amyloidosis of cytosolic a-syn. Benign soluble unstructured a-syn gets converted into toxic species which preferentially accumulates in LBs. But how these aberrant a-syn molecules are produced in the cytosol, is still not clear. The present hypothesis is an effort to relate a metabolic reaction specific to neuronal function, that is, phase transition, with the pathobiology of a-syn. During high frequency stimulation, which entails rapid phase transition reactions at the presynaptic compartment, aberrant interaction of a-syn with the membrane occasionally generates toxic a-syn molecules. My conjecture is that the physiological function of a-syn is to modulate membrane fluidity by a process wherein it goes through a conformation cycle driven by a flux of energy from mitochondria. It is the range of toxic a-syn produced during aberrant phase transition reaction that is responsible for pathology, not the normal a-syn that reenters the conformation cycle, thereby, resolving the paradox of the Janus-face of a-syn.

Trichothecene mycotoxin T-2 toxin is an important environmental pollutant and poses a global threat to human and animal health. T-2 toxin could induce nephrotoxicity, however, the precise molecular mechanism remains unclear. In this study, the mice were intraperitoneally administrated with a single dose of 2 mg/kg T-2 toxin. The kidney function and ultrastructural observation were also assessed and found T-2 toxin exposure could cause kidney damage. Transmission electron microscopy showed a significant swelling and vacuolization of the mitochondria of renal cell. A total of 1122, 58, and 391 differential expression genes (DEGs) that were predominantly expressed in kidney tissues at 1 d, 3 d, and 7 d after T-2 toxin exposure, respectively. Early transcriptomic changes at 1 d after exposure were down-regulation of DEGs involved in the cell cycle, p53 signaling pathway, and cellular senescence, while up-regulation of DEGs referred to the ribosome pathway. The temporal variations in gene expression pattern in T-2 toxin exposure in mice kidney were presented and cellular metabolism was disturbed at the exposure recovery period with 7 d. In conclusion, this study, for the first time, provided a comprehensive comparative transcriptomic analysis of gene regulation in T-2 toxin exposure-induced nephrotoxicity at different temporal periods and explored the nephrotoxicity mechanism of T-2 toxin at the mRNA level.

Extracellular vesicles (EVs), produced during viral infections, are of emerging interest in understanding infectious processes and host-pathogen interactions. EVs and exosomes in particular have the natural ability to transport nucleic acids, proteins, and other components of cellular or viral origin. Thus, they participate in intercellular communication, immune responses, infectious and pathophysiological processes. Some viruses are known to hijack the cell production and content of EVs for their benefit. Here, we investigated whether two pathogenic flaviviruses i.e. Zika Virus (ZIKV) and Dengue virus (DENV2) could have an impact on the features of EVs. Analysis of EVs produced by infected cells allowed us to identify that the non-structural protein 1 (NS1), described as a viral toxin, was associated with exosomes. This observation could be confirmed under conditions of overexpression of recombinant NS1 from each flavivirus. Using different isolation methods (i.e. exosome isolation kit, size exclusion chromatography, Polyethylene Glycol enrichment, and ELISA capture), we showed that NS1 was present as a dimer at the surface of excreted exosomes and that this association could occur in the extracellular compartment. This finding could be of major importance in a physiological context. Indeed, this capacity of NS1 to address EVs and its implication in the pathophysiology during Dengue or Zika diseases should be explored. Furthermore, exosomes that have demonstrated a natural capacity to vectorize NS1 could serve as useful tools for vaccine development.

In this work, we introduce a new concepts for $\alpha$-type $F$-Suzuki contraction and $\alpha$-type $F$-weak-Suzuki contraction in the context of $b$-metric spaces. Compared to the $\alpha$-type $F$-contraction and $F$-Suzuki contraction mappings, these contractions are essentially weaker. For these type of contraction mappings, sufficient conditions are established for the fixed point's existence and uniqueness in $b$-metric spaces. As a result, the findings encompass several generalizations. To show the usability of our obtained results, we provide a supportive example and an application to a non-linear differential equation with fractional order.

Low soil nitrogen status of savanna soils in Nigeria contributes to the persistent Striga hermonthica (Del.) Benth. infestation that limits maize production. The application of nitrogen fertilizer to Striga-resistant hybrids may reduce Striga infection and increase grain yields. This study assessed the performance of maize hybrids at low (30 kg ha-1) and high (120 kg ha-1) nitrogen application under natural infestation with Striga at Kafin Madaki and Tudun Wada in 2014 and 2015. Results showed that the application of nitrogen at 120 kg ha-1 reduced number of Striga plants by 59% compared to application at 30 kg N ha-1 in Kafin Madaki and by 21% in Tudun Wada. Compared to 30 kg N ha-1, the 120 kg N ha-1 rate also reduced Striga damage rating by 22% in Kafin Madaki and by 33% in Tudun Wada across the hybrids. Hybrids 8338-1 (5.3) and OBASUPER 1 (4.3) were the only entries with Striga damage rating greater than 4.5 (SDR > 4.5) when averaged across the nitrogen levels at both locations. Grain yield was 86 and 98% higher in Kafin Madaki and Tudun Wada, respectively when N was applied at 120 kg N ha-1 than at 30 kg N ha-1. The hybrids M1124-3 and M1227-14 produced grain yields that were significantly higher than those of the other hybrids in all locations. The hybrid 8338-1 produced the lowest grain yield across locations. Our results showed that, the application of 120 kg N ha-1 to Striga resistant maize hybrids will reduce Striga infection and increase grain yield.

Neurodegenerative diseases, including Alzheimer's, Huntington's, Parkinson’s, and Amyotrophic Lateral Sclerosis, involve neuron degeneration linked to the misfolding of amyloidogenic proteins, resulting in β-sheet-enriched aggregates. This phenomenon disrupts the normal folding of proteins critical for cellular function. Genetic mutations, proteolytic cleavage, oxidative stress, and aging contribute to misfolding. Parkinson's disease (PD) is closely tied to alpha-synuclein (αS) misfolding, with A53T mutation and Lewy bodies (LB) in PD brains pivotal to understanding the disease mechanism. Other synuclein homologues (βS, γS) further contribute to synucleinopathies. Mutants (A30P, A53T, E46K, H50Q, and G51D) underscore αS&#39;s role in PD development. This concise review focuses on molecular and pathological aspects of neurodegenerative diseases, emphasizing αS in PD. The integration of genetic, structural, and mechanistic insights highlights the disorders. complexity, paving the way for future therapeutic strategies targeting protein misfolding and aggregation.

A full potential all-electron density functional method within generalized gradient approximation is used to investigate the electronic, elastic and transport properties of cubic copper sulphide and copper selenide. The electronic structure suggests metallic behavior with a zero energy band gap for both materials. Elastic property calculations suggest a stiff material with the bulk to shear modulus ratio of 0.35 and 0.44 for Cu2S and Cu2Se respectively. The transport properties were estimated using the Boltzmann transport approach. Seebeck coefficient, electrical conductivity, thermal conductivity, and power factor all suggest a potential p-type conductivity for Cu2S and n-type conductivity for Cu2Se.

Neurodevelopmental and late-onset neurodegenerative disorders present as separate entities that are clinically and neuropathologically quite distinct. However, recent evidence has highlighted surprising commonalities and converging features at the clinical, genomic, and molecular level between these two disease spectra. This is particularly striking in the context of autism spectrum disorder (ASD) and Parkinson’s disease (PD). Genetic causes and risk factors play a central role in disease pathophysiology and enable the identification of overlapping mechanisms and pathways. Here, we focus on clinico-genetic studies of causal variants and overlapping clinical and cellular features of ASD and PD. Several genes and genomic regions were selected for our review, including SNCA (alpha-synuclein), PARK2 (parkin RBR E3 ubiquitin protein ligase), chromosome 22q11 deletion/DiGeorge region, and FMR1 (fragile X mental retardation 1) repeat expansion, which influence development of both ASD and PD with converging features related to synaptic function and neurogenesis. Both PD and ASD display alterations and impairments at the synaptic level, representing early and key disease phenotypes which support the hypothesis of converging mechanisms between the two types of diseases. Therefore, understanding the underlying molecular mechanisms might inform on common targets and therapeutic approaches. We propose to re-conceptualize how we understand these disorders and provide a new angle into disease targets and mechanisms linking neurodevelopmental disorders and neurodegeneration.

Inflammation is a vital aspect of the body's immune response, appearing either as an acute reaction that swiftly develops (e.g., after injury or during an infection) or as a chronic condition that persists over a prolonged period, often linked with autoimmune disorders or cancer. This study introduces potential TNF-alpha inhibitors investigated by Molecular Docking investigation. They are Dactolisib with a binding energy of -10.1 kcal/mol, Nilotinib with -9.6 kcal/mol, Eltrombopag with -9.7 kcal/mol, Radotinib with -9.6 kcal/mol, and Nilotinib again with -9.7 kcal/mol. Additionally, Hypericin exhibited a notable binding energy of -9.9 kcal/mol, suggesting its potential as a natural TNF-alpha inhibitor. While these computational results are preliminary, they provide a foundation for further biological studies to confirm their efficacy. The significance of these findings extends to the scientific community, offering potential applications in the field of inflammatory diseases.

The genetic diversity of coronavirus (CoV) is high, and its infection in animals has not yet been fully revealed. By RT-PCR detection of partial RNA dependent RNA polymerase (RdRp) gene of CoV, we screened a total of 502 small mammals belonging to 18 species in 12 genera and 4 orders collected in Dali and Nujiang Prefecture of Western Yunnan Province, China. The prevalence of β-CoV in Chevrieri's field mouse (Apodemus chevrieri) and Lancangjiang field mouse (A. ilex) were 3.54% (4/113) and 6.67% (6/90), respectively; the prevalence of α-CoV in White-footed Indochinese rat (Rattus nitidus) and long-tailed red-toothed shrew (Episoriculus leucops) was 75% (3/4) and 5.88% (1/17), respectively. The co-infection rates of β-CoV and α-CoV in Kachin red-backed vole (Eothenomys cachinus), Norway rat (R. norvegicus) were 2.22% (2/90), 3.85% (1/26) respectively. The identity of the partial RdRp genes obtained of 13 strains of β-CoV was 83.42%-99.23% at nucleotide level, and it is worth noting that the two strains from Kachin red-backed vole showed highly homology to BOV-36/IND/2015 from Indian bovine and DcCoV-HKU23 from one-humped camel (Camelus dromedarius) in Morocco, the nucleotide similarity between 97.86%-98.33%. Similarly, the identity of the 7 strains of α-CoV among the partial RdRp sequences was 94.00%-99.18% at nucleotide levels. The viral load in different tissues was measured by quantitative RT-PCR (qRT-PCR). The average CoV viral load in small mammalian intestinal tissue was 1.25×106copies/g, differently, the mean CoV viral load in liver, heart, lung, spleen and kidney tissue was from 1.29×103 to 4.02×103copies/g, which revealed that CoV has extensive tropism of intestinal tissue in small mammals (P &lt; 0.0001). This result revealed the genetic diversity, epidemiology, and infective tropism of α-CoV and β-CoV in small mammals from Dali and Nujiang, which deepens the comprehending of the retention and infection of coronavirus in natural hosts.

With the long-term and large-scale use, herbicides have been well known to influence tritrophic interactions particularly natural enemies of pests in agro-ecosystems. On the other hand, herbivorous insects, especially the generalist pests, have developed antagonistic interaction to different insecticides, toxic plant secondary metabolites and even heavy metals. However, whether exposure to herbicides would affect resistance of insects against insecticides is largely unknown, especially in agricultural pests. Here, we first reported that pre-exposure to two widely used herbicides butachlor and haloxyfop-methyl for 48 h can prime resistance of a generalist agricultural pest Helicoverpa armigera Hübner against insecticide methomyl and fungal toxin aflatoxin B1. In addition, there were no significant differences between control and herbicides-treated caterpillars on weight gain, pupal weight and pupation rates, suggesting that exposure to herbicides induce resistance of H. armigera accompanied with no fitness cost. Moreover, by determining detoxifying enzyme activities and toxicity bioassay with additional inhibitor of cytochrome P450 piperonyl butoxide (PBO), we showed that exposure to herbicides might prime P450-mediated detoxification of H. armigera against insecticide. Based on these results, we propose that exposure to herbicides primes resistance of H. armigera against insecticide by eliciting a clear elevation of predominantly P450 monooxygenase activities in midgut and fat body.

Alpha-B-Crystallin, a member of the small heat shock family of proteins, has been implicated in a variety of cardiomyopathies and in normal cardiac homeostasis. It is known to function as a molecular chaperone, particularly for desmin, but also interacts with a wide variety of additional proteins. The molecular chaperone function is also enhanced by signal-dependent phosphorylation at specific residues under stress conditions. Naturally occurring mutations in CRYAB, the gene that encodes alpha-B-crystallin, have been suggested to alter ionic intermolecular interactions that affect dimerization and affect chaperone function. These mutations have been associated with myofibrillar myopathy, restrictive cardiomyopathy, and hypertrophic cardiomyopathy, and promote pathological hypertrophy through different mechanisms such as desmin aggregation, increased reductive stress or activation of calcineurin-NFAT signaling. This review will discuss the known mechanisms by which alpha-B-crystallin functions in cardiac homeostasis and the pathogenesis of cardiomyopathies and provide insight into potential future areas of exploration.

Shiga-like toxin producing Escherichia coli (STEC) is a well-known cause of foodborne acute diarrheic diseases especially in children and the elderly. The potentially fatal complications associated with toxin production range from bloody diarrhoea and ischemic colitis to kidney failure, haemolytic-uremic syndrome (HUS) and colon perforation. We describe a case and literature review of STEC – induced colitis, highlighting the clinical features, and the necessary tools for the best diagnosis approach and management. Facing challenging differential diagnosis ranging from ischemic colitis, inflammatory bowel disease, to infectious process due to a pathogenic or opportunistic agent, we practiced a step-by-step exploration. Beginning with bacteriological investigation, imagistic screening, and colonoscopy, we could rule out some of initial suppositions and reach the final diagnosis, also considering the pathological results. Although antibiotics are not indicated in this pathology, our patient did receive antibiotics, given the risk of translocation and colon perforation, without associating any complications, as HUS or peritonitis. Detailed and rigorous investigations along with a multi-speciality team are required for a prompt medical support. Coping the symptoms and refraining from further complications are the mainstem of the treatment.

Mosquito-borne viral disease dengue is a global public health problem causing a wide spectrum of clinical manifestations ranging from mild dengue fever to severe dengue with plasma leakage and bleeding which are often associated to fatality. To date, there are no specific medications to treat dengue and prevent the risk of hemorrhage. Dengue is caused by one of the four related antigenically distinct serotypes, DENV-1 to DENV-4. The growing burden that represents the four DENV serotypes has intensified both basic and applied researches to better understand the dengue physiopathology. It has been proposed a significant role for the secreted soluble DENV nonstructural protein 1 (sNS1) glycoprotein in the pathogenesis of severe dengue. Here, we provided an overview on current knowledge about the role of sNS1 in the immunopathogenesis of dengue disease. The reasons for the consideration of sNS1 in the design of future dengue vaccine candidates will be discussed.

Three finger toxins (3FTX) are a group of peptides that affect multiple receptor types. One group of proteins affected by 3FTX are nicotinic acetylcholine receptors (nAChR). Structural information on how neurotoxins interact with nAChR is limited and are confined to a small group of neurotoxins. Therefore, in silico methods are valuable in understanding the interactions between 3FTX and different nAChR subtypes, but there are no established protocols to model 3FTX – nAChR interactions. We developed a homology modeling and protein docking protocol to address this issue and tested its success on three different systems. First, neurotoxin peptides co-crystallized with acetylcholine binding protein (AChBP) were re-docked to assess whether Rosetta protein – protein docking can reproduce the native poses. Second, experimental data on peptide binding to AChBP was used to test whether the docking protocol can qualitatively distinguish AChBP-binders from non-binders. Finally, we docked eight peptides with known α7 and muscle-type nAChR binding properties to test whether the protocol can explain the differential activities of the peptides at the two receptor subtypes. Overall, our docking protocol succeeded in predicting both qualitative and specific aspects of 3FTX binding to nAChR and shed light on some unknown aspects of 3FTX binding to different receptor subtypes.

The TRPV3 calcium ion channel is vital for maintaining skin health and has been associated with various skin-related disorders. Since TRPV3 is involved in the development of skin inflammation, inhibiting TRPV3 could be a potential treatment strategy. Alpha-mangostin isolated from Garcinia mangostana L. extract exhibits diverse positive effects on skin health; however, the underlying mechanisms remain obscure. This study investigated the TRPV3-inhibitory properties of alpha-mangostin on TRPV3 hyperactive mutants associated with Olmsted syndrome and its impact on TRPV3-induced cytokine secretion and cell death. Our findings demonstrate that alpha-mangostin effectively inhibits TRPV3, with an IC50 of 0.077 ± 0.013 μM, showing inhibitory effects on both wild-type and mutant TRPV3. TRPV3 inhibition with alpha-mangostin decreased calcium influx and cytokine release, protecting cells from TRPV3-induced death. These results indicate that alpha-mangostin reduced inflammation in TRPV3-activated skin keratinocytes, suggesting that alpha-mangostin could be potentially used for improving inflammatory skin conditions such as dermatitis.

In interepidemic periods, a sapronoses typically employs a variety of mechanisms for maintaining viability of its causative agent in terrestrial parasitic systems, associated with different adaptive strategies utilized by its populations to survive. Unlike spore-forming bacteria, causative agents of sapronoses use resistant cell forms, which is a viable but nonculturable (VBNC) state, and persistence. Implementation of these strategies is conditioned by effects of various stress factors of the habitat and is characterized by decreased metabolism, alteration of the morphology and physiology of bacterial cell, and cessation of its replication. It is important that the resistant forms of cells retain virulence and, as favorable conditions come, turn back into the active vegetative form again. The discovery of the genetic modules of bacterial toxin–antitoxin systems in recent years has made it possible to identify a number of complicated regulatory molecular mechanisms responsible for maintaining the pathogenic potential of resistant forms of causative agents of natural-focus sapronoses in interepidemic periods.

Shiga toxin (Stx) produced by Escherichia coli is the main pathogenic factor of diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by obstruction of renal microvasculature by platelet-fibrin thrombi. It is well known that the oxidative imbalance generated by Stx induces platelet activation, contributing to thrombus formation. Moreover, activated platelets release soluble CD40 ligand (sCD40L) which in turn contributes to oxidative imbalance, triggering the release of reactive oxidative species (ROS) on various cellular types. The aim of this work was to determine if the interaction between the oxidative response and platelet-derived sCD40L participates in the pathogenic mechanism during HUS. Activated human glomerular endothelial cells (HGEC) by Stx2 induced platelets to adhere to them. Although platelet adhesion did not contribute to endothelial damage, high levels of sCD40L were released to the medium. The release of sCD40L by activated platelets was inhibited by antioxidant treatment. Furthermore, we found increased levels of sCD40L in plasma from HUS patients, which were also able to trigger the respiratory burst in monocytes, in a sCD40L-dependent manner. Thus, we concluded that platelet-derived sCD40L and the oxidative response are reciprocally stimulated during Stx2-associated HUS. This process may contribute to the evolution of glomerular occlusion and the microangiopathic lesions.

Here we first report, how cholera toxin (CT) A subunit (CTA), the bacterial enzyme moiety responsible of cell signaling alteration, can take over the exosomal pathway, spread extracellularly and be transmitted in a cell population. A first evidence for long-term transmission of CT toxic effect via extracellular vesicles was obtained in CHO cells. To follow CT intracellular route towards exosome secretion we adopted a strategy apt to convert multivesicular body (MVB) derived exosomes in traceable fluorescent vectors. CT treated Me665 cells, a human melanoma cell line highly expressing caveolin-1 (Cav-1) and GM1, were used to purify and characterize fluorescent exosomes. Our results clearly show association of CT with exosomes together with typical exosomal markers and the HSP90 and PDI molecules, the required membrane translocation elements of CTA to the cytoplasm. Confocal microscopy proved direct CT containing fluorescent exo transfer into CHO cells coupled with the morphological cell change characteristic of CT action. Moreover, direct assessment of cAMP levels in Me665 cells treated with CT containing exo showed an efficient induction of cAMP increase comparable with CT alone. From our results, we can infer that CT can exploit exosome-mediated cell communication to target and extend its pathophysiological action throughout cell tissues.

Background: Body dysmorphic disorder (BDD) is a psychiatric disorder characterized by excessive preoccupation with imagined defects in appearance. Optical illusions induce illusory effects that distort the presented stimulus thus leading to ambiguous percepts. Using electroencephalography (EEG), we investigated whether BDD is related to differentiated perception during illusory percepts. Methods: 18 BDD patients and 18 controls were presented with 39 optical illusions together with a statement testing whether or not they perceived the illusion. After a delay period, they were prompted to answer whether the statement is right/wrong and their degree of confidence for their answer. We investigated differences of BDD on task performance and self-reported confidence and analysed the brain oscillations during decision-making using nonparametric cluster statistics. Results: Behaviorally, the BDD group exhibited reduced confidence when responding incorrectly, potentially attributed to higher levels of doubt. Electrophysiologically, the BDD group showed significantly reduced alpha power at mid-central scalp areas, suggesting impaired allocation of attention. Interestingly, the lower the alpha power of the identified cluster, the higher the BDD severity, as assessed by BDD psychometrics. Conclusions: Results evidenced that alpha power during illusory processing might serve as a quantitative EEG biomarker of BDD, potentially associated with reduced inhibition of task-irrelevant areas.

In the present work we study the properties of geodesic sub-$ (\alpha,b,s) $-preinvex functions on Hadamard manifolds and establish some basic properties in both general and differential cases. Further, we study sufficient conditions of optimality and proved some new inequalities under geodesic sub-($ \alpha,b,s $)-preinvexity.

Target pests of genetically engineered crops producing both defensive allelochemicals and Bacillus thuringiensis (Bt) toxins often sequentially or simultaneously uptake allelochemicals, Bt toxins, and/or insecticides. How the three types of toxins interact to kill pests remains underexplored. Here we investigated the interactions of Bt toxin Vip3A, plant allelochemical flavone, and insecticide emamectin benzoate in Spodoptera frugiperda. Simultaneous administration of flavone LC25 + Vip3A LC25, emamectin benzoate LC25 + Vip3A LC25, and flavone LC15 + emamectin benzoate LC15 + Vip3A LC15 but not flavone LC25 + emamectin LC25 yielded a mortality significantly higher than their expected additive mortality (EAM). One-day preexposure to one toxin at LC5 followed by 6-day exposure to the same toxin at LC5 plus another toxin at LC50 showed that the mortality of flavone LC5 + Vip3A LC50, emamectin benzoate LC5 + Vip3A LC50, and Vip3A LC5 + emamectin benzoate LC50, were significantly higher than their EAM, while that of flavone LC5 + emamectin benzoate LC50 was significantly lower than their EAM. No significant difference existed among the mortalities of Vip3A LC5 + flavone LC50, emamectin benzoate LC5 + flavone LC50, and their EAMs. The results suggest that the interactions of the three toxins are largely synergistic (inductive) or additive, depending on their combinations and doses.

Adding zinc (II) and formate anions improves the thermal phase-stability of alpha-FAPbI3 materials and the spin-coated thin films of such doped FAPbI¬3 show an increased emission lifetime of up to 3.7 microsecond on quartz. This work investigates the effects of zinc and formate on the stability and time resolved photoluminescence of FAPbI3 perovskites for solar cell applications. Perovskite samples with varying concentrations of zinc and formate were made by incorporating different amounts of zinc formate and zinc iodide and characterized with XRD. Doping levels of 1.7% Zn(II) and 1.0% formate (relative to Pb) seem optimal. The thermal stability of the perovskite powders and thin films were assessed. XRD was virtually unchanged after 6 months. The time-resolved photo-luminescence spectroscopy of the doped spin-coated perovskite samples is reported. The results show that synergy between an anionic and a cationic dopant can take place, making the perovskite thermally more stable with a longer charge carrier lifetime.

Onion is one of the most economically and nutritionally important vegetable crops in West Africa. However, high-yielding varieties that are accessible to farmers remain scarce. Onion lines from the World Vegetable Center’s Allium program were evaluated during the cool and dry season from September to March for three years to identify adapted onion lines suitable for sustainable intensi-fication of production systems in Northern Ghana and Southern Mali. Trials were implemented in the Upper East and Northern Regions of Ghana and in two districts in the Sudan savanna zones of Mali (Bougouni and Koutiala). Nine onion lines, including a check variety were assessed for yield stability using a randomized complete block design. The trials were carried out in “technology parks” under the joint management of farmers and researchers. Onion bulb weight was recorded for each plot after harvest. Separate analyses of variances were performed for each location and season. Analysis of variance of combined locations, seasons and lines was made to determine the most stable varieties using the line-superiority measure and ecovalence stability coefficients. Results indicated that lines AVON1310 and AVON1325 were most stable for yield performance over lo-cations and seasons. From the genotype main effects and genotype-by-environment interaction (GGE) biplot, the best performing lines were AVON1310 (33.32 t.h-1), AVON1308 (28.81 t.h-1) and AVON1325 (31.68 t.h-1). These lines are potential candidates for sustainable intensification of onion production in Ghana and Mali.

PirAB is a binary protein complex secreted by specific strains of Vibrio parahaemolyticus (Vp) that harbor the pVA1 virulence plasmid and express PirAVp and PirBVp toxins. PirABVp causes acute hepatopancreatic necrosis disease (AHPND), a newly emergent penaeid shrimp disease that can cause 70–100% mortality and has resulted in great economic losses since its appearance. The cy-totoxic effect of PirABVp on the epithelial cell of the shrimp hepatopancreas has been extensively reported. Our studies found that the PirBVp subunit has lectin activity and recognizes mucin-like O-glycosidic structures in the shrimp hepatopancreas. The PirAVp subunit may have a stabiliza-tion function of the binary complex. However, we also found that Vp AHPND changes the water microbiota community structure and causes a significant reduction in several bacteria, especially Neptuniibacter spp. We propose that the PirABvp toxin could exhibit a dual role: damage the shrimp hepatopancreas and kill surrounding bacteria.

Hypertension (HT) is a very common risk factor and a frequent cause of morbidity and mortality worldwide mainly due to much increase in overweight (OW) and obesity that manifests in various forms of cardiovascular disease (CVD). There are a number of factors that may cause overweight hypertension (OHT). However, we planned to conduct the present work to study the HT and OHT men for finding the variation, interrelationship and association of important cytokines mainly serum leptin (Lep) and tumor necrosis factor-alpha (TNF-α), serum testosterone (ST), total cholesterol (TC) and inflammatory status by measuring interleukin-6 (IL-6). Three groups of subjects, the normal controls (NC; n:98; age range: 51-60 years), HT (n: 97; age range: 51-60 years) subjects, and OHT (n: 97; age range: 51-60 years) subjects were studied. Comparisons for Lep, ST, TNF-α, IL-6 and TC levels for the subject groups showed significant variations. The ST indicated significant difference only for NC vs. OHT. The IL-6 gave significant difference for NC vs. OHT and HT vs. OHT. The one-way ANOVA showed significant difference among groups for BMI, TC, IL-6, TNF-α, ST and Lep levels. Significant positive linear correlation for all groups among Lep, TNF-α, IL-6 and TC were found. The ST against TC for HT and OHT groups presented non-significant negative linear correlations. The ST showed significant negative linear correlation with other variables. Conclusively, the present study uncovers the interactive impact of serum leptin, TNF-α, testosterone, total cholesterol and IL-6 in hypertensive and overweight-related hypertensive men.

We construct a novel family of summation-integral type hybrid operators in terms of shape parameter $\alpha\in \lbrack 0,1]$ in this paper. Basic estimates, rate of convergence, and order of approximation are also studied using the Korovkin theorem and the modulus of smoothness. We investigate the local approximation findings for these sequences of positive linear operators utilising Peetre's K-functional, Lipschitz class, and second-order modulus of smoothness.

Twelve overnight fasted, healthy, male volunteers received on separate days a test breakfast consisting of (A) 100 g fresh white bread (providing 50 g starch) and 250 mL drinking water, (B) the same bread with a supplement of 10 g alpha-cyclodextrin dissolved in the drinking water (250 mL), and (C) 250 mL drinking water containing 25 g alpha-cyclodextrin. Capillary and venous blood samples were collected before breakfast and at regular intervals for a period of 3 hours thereafter. Plasma glucose was determined in capillary blood and plasma insulin in venous blood samples. Breakfast (A) let to the expected rise in blood glucose and insulin concentrations. Breakfast (C) did not produce a significant glycemic and insulinemic response, demonstrating that alpha-cyclodextrin is not hydrolyzed to glucose in the human digestive tract. Mild intestinal symptoms after the ingestion of alpha-cyclodextrin were reported by 4 subjects. The postprandial rises of plasma glucose and insulin were significantly smaller after breakfast (B) than (A). Under the conditions of this study, alpha-cyclodextrin reduced the glycemic and insulinemic index of white bread by 57 and 55 %, respectively. The postprandial time profile of plasma glucose and insulin suggests that, in an initial phase, the digestion of starch is inhibited by alpha-cyclodextrin almost completely. Yet, despite the delayed and reduced digestion of starch, the intake of breakfast (B) was not associated with flatulence or any other gastrointestinal symptoms.

Data is present in the data sources like Files and Data bases, Retrieval of information from that data sources is one of the important issue nowadays. So for retrieval information from the data sources clustering is used. In the present market different types of clustering algorithms were available. But opting of the clustering is based on user requirements. This paper focuses on the study of hierarchical clustering approach on different conditions or measures or with customer choices like clustering process number of clusters generated at each level, number of levels, attributes range for performing the clustering on the given data set. In brief overview we discuss the hierarchical approach for clustering algorithm with the user opting choices.

Rotational microwave jet spectroscopy studies of the monoterpenol α-fenchol have so far failed to identify its second expected torsional conformer, despite computational predictions that it is only very slightly higher in energy than the most stable conformer. Vibrational FTIR and Raman jet spectroscopy investigations reveal unusually complex OH and OD stretching spectra compared to other alcohols. Via modelling of the torsional states, observed spectral splittings are explained by delocalization of the hydroxy hydrogen atom through quantum tunneling between the two non-equivalent but accidentally near-degenerate conformers separated by a low and narrow barrier. The energy differences between the torsional states are determined to be only 16(1) and 7(1) cm$^{−1}hc$ for the protiated and deuterated alcohol, respectively, which further shrink to 9(1) and 3(1) cm$^{−1}hc$ upon OH or OD stretch excitation. Comparisons are made with the more strongly asymmetric monoterpenols borneol and isopinocampheol as well as with the symmetric, rapidly tunneling propargyl alcohol. Assigned are also for α-fenchol the third – in contrast localized – torsional conformer and the most stable dimer, as well as for propargyl alcohol the two most stable dimers.

We investigate new graph characteristics namely total (vertex, edge) face irregularity strength of gen- eralized plane grid graphs Gmn under k-labeling Phi of type (Alpha, Beta, Gamma). The minimum integer k for which a vertex-edge labelled graph has distinct face weights is called the total face irregularity strength of the graph and is denoted by tfs(Gmn). In this article, the graphs G = (V;E; F) under consideration are simple, fi nite, undirected and planar. We will estimate the exact tight lower bounds for the total face irregularity strength of some families of generalized plane grid graphs.

In this article, the geometry of pseudoparallel, Ricci-generalized pseudoparallel and 2-Ricci-generalized pseudoparallel invariant submanifolds of an almost $\alpha$-cosymplectic $(\kappa,\mu,\nu)$ space has been searched under the some conditions. We also give some characterizations for such submanifolds. I think that obtained new results contribute to differential geometry.

The emergence of multidrug-resistant pathogens such as Listeria monocytogenes and Shiga toxin-producing Escherichia coli (STEC) poses public health challenges, and this has led to a continuous search for effective novel antimicrobial agents. This study aimed to isolate marine actinomycetes from South Africa, evaluate their in vitro antimicrobial activity against Listeria and STEC, and characterize their mechanisms of action. Marine actinoymcetes were isolated and identified by 16S rRNA sequencing. Gas chromatography-mass spectrometry (GC-MS) was used to identify the chemical constituents of bioactive actinomycetes secondary metabolites. Antibacterial activity of the secondary metabolites was assessed by the broth microdilution method and their mode of actions were predicted using computational docking. While five strains showed antibacterial activity during primary screening, only Nocardiopsis dassonvillei strain SOD(B)ST2SA2 exhibited activity during secondary screening for antibacterial activity. GC-MS identified five major bioactive compounds: 1-octadecene, diethyl phthalate, pentadecanoic acid, 6-octadecenoic acid, and tri-fluoroacetoxy hexadecane. SOD(B)ST2SA2`s extract demonstrated the minimum inhibitory con-centration and minimum bactericidal concentration ranging from 0.78–25 mg/ml and 3.13 to > 25 mg/ml, respectively. Diethyl phthalate displayed the lowest bacterial protein binding energies (kcal/mol): −7.2, dihydrofolate reductase; −6.0, DNA gyrase B, and −5.8, D-alanine:D-alanine lig-ase. Thus, marine N. dassonvillei SOD(B)ST2SA2 is a potentially good source of antibacterial compounds that can be used to control STEC and Listeria monocytogenes.

Fusarium culmorum is a major pathogen of grain crops. Infected plants accumulate deoxynivalenol (DON), 3-acetyl-deoxynivalenol (3-ADON), or nivalenol (NIV), which are mycotoxins of the trichothecene B group. These toxins are also produced by F. graminearum species complex. New trichothecenes structurally similar to trichothecenes B but lacking the carbonyl group on C-8, designated NX toxins, were recently discovered in atypical isolates of F. graminearum from North America. Only these isolates and a few strains of a yet to be characterized Fusarium species from South Africa are known to produce NX-2 and other NX toxins. Here we report that among 20 F. culmorum strains isolated from maize, wheat, and oat in Europe and Asia over a period of 70 years, 18 strains produced NX-2 simultaneously with 3-ADON and DON or NIV. Rice cultures of strains producing 3-ADON accumulated NX-2 in amounts corresponding to 2-8% of 3-ADON (1.2 - 36 mg/kg). A strain producing NIV accumulated NX-2 and NIV at comparable amounts (13.6 and 10.3 mg/kg, respectively). In F. graminearum, producers of NX-2 possess a special variant of cytochrome P450 monooxygenase encoded by TRI1 that is unable to oxidize C-8. In F. culmorum, producers and nonproducers of NX-2 possess identical TRI1; the reason for the production of NX-2 is unknown. Our results indicate that production of NX-2 simultaneously with trichothecenes B is a common feature of F. culmorum.

In this study we introduce the new classes $\mathcal{M}_{\alpha}(\sin)$ and $\mathcal{M}_{\alpha}(\cos)$ of $\alpha$-convex functions associated with sine and cosine functions. Also, we obtain the initial coefficient bounds for the first five coefficients of the functions that belong to these classes. Further, we determine the upper bound of Zalcman functional for the class $\mathcal{M}_{\alpha}(\cos)$ for the case $n=3$, showing that the Zalcman conjecture holds for this value. Moreover, the problem of the Fekete-Szeg\H{o} functional estimate for these classes is studied.

Oral cancer ranks sixth among Taiwan's top 10 cancers, and most patients with poor prognosis acquire metastases. The essential fatty acid alpha-linolenic acid (ALA) has been found to diminish many cancer properties. However, the anti-cancer activity of ALA in oral cancer has yet to be determined. Migration and invasion assays confirmed OSCC cells' EMT capabilities, whereas flow cytometry and Western blotting identified the molecular pathways. ALA dramatically reduced cell growth in a concentration dependent manner, according to the findings. Low concentrations of ALA (100 or 200 μM) inhibit colony formation, expression of Twist and EMT-related proteins, expression of MMP2/-9 proteins and enzyme activity, as well as cell migration and invasion. Treatment with high concentrations of ALA (200 or 400 μM) greatly increases JNK phosphorylation and c-jun nuclear accumulation, then upregulates the FasL/caspase8/caspase3 and Bid/cytochrome c/caspase9/caspase3 pathways, leading to cell death. Low concentrations of ALA inhibit SAS and GNM cell migration and invasion by suppressing Twist and downregulating EMT-related proteins, or by decreasing the protein expression and enzyme activity of MMP-2/-9, whereas high concentrations of ALA promote apoptosis by activating the JNK/FasL/caspase 8/caspase 3-extrinsic pathway and the Bid/cytochrome c/caspase 9 pathway. ALA demonstrates potential as a treatment for OSCC patients.

Although domestic cats are susceptible to infection with SARS-CoV-2, the role of the virus in causing feline disease is less well defined. We conducted a large-scale study to identify SARS-CoV-2 infections in UK pet cats, using active and passive surveillance. Remnant feline respiratory swab samples, submitted for other pathogen testing between May 2021 and February 2023, were screened using RT-qPCR. In addition, we appealed to veterinarians for swab samples from cats suspected of having clinical SARS-CoV-2 infections. Bespoke testing for SARS-CoV-2 neutralising antibodies was also performed, on request, in suspected cases. One RT-qPCR-positive cat was identified from the active surveillance (1/549, 0.18 %), during the Delta wave (1/175, 0.57 %). Passive surveillance detected one cat infected with the Alpha variant, and two of ten cats tested RT-qPCR-positive during the Delta wave. No cats tested RT-qPCR-positive after the emergence of Omicron BA.1 and its descendants although 374 were tested by active and eleven by passive surveillance. We describe four cases of SARS-CoV-2 infection in pet cats, identified by RT-qPCR and/or serology, that presented with a range of clinical signs, as well as their SARS-CoV-2 genome sequences. Our results demonstrate that, although uncommon, clinical infections in cats can and do occur.

Pseudopterosin, produced by the sea whip of the genus Antillogorgia, possesses a variety of promising biological activities including potent anti-inflammatory effects. However, few studies examined pseudopterosin in the treatment of cancer cells and, to our knowledge, the ability to inhibit triple negative breast cancer (TNBC) proliferation or invasion has not been explored. Thus, we evaluated the as yet unknown mechanism of action of pseudopterosin: Pseudopterosin was able to inhibit proliferation of TNBC. Interestingly, analyzing breast cancer cell proliferation after knocking down glucocorticoid receptor α (GRα) revealed that anti-proliferative effects of pseudopterosin were significantly inhibited when GRα expression was reduced. Furthermore, pseudopterosin inhibited invasion of MDA-MB-231 3D tumor spheroids embedded in an extracellular-like matrix. Remarkably, the knockdown of GRα in 3D tumor spheroids revealed increased ability of cells to invade the surrounding matrix. In a co-culture, encompassing peripheral blood mononuclear cells (PBMC) and MDA-MB-231 cells, production of interleukin 6 (IL-6) and interleukin 8 (IL-8) significantly increased compared to monoculture. Notably, pseudopterosin proved to block cytokine elevation, representing key players in tumor progression, in the co-culture. Thus, our results reveal pseudopterosin treatment as a potential novel approach in TNBC therapy.

Central adiposity is one of the significant determinants of obesity-related hypertension risk, which may arise due to the abdominal fat depot's pathogenic inflammatory nature. Pro-inflammatory cytokines and adipokines up-regulation through nuclear factor-kappa B (NF-κB) activation in adipose tissue has been considered an essential function in the pathogenesis of obesity-related hypertension. This study aimed to ascertain the NF-κB inhibitor (SN50) effect on TNF-α and angiotensinogen (AGT) secretion and expression in mediating the anti-inflammatory effect through its impact on NF-κB activity in humans adipose tissue. Primary human adipocytes were isolated from 20 subjects among 10 overweight and 10 obese with and without hypertension and treated with 10ng/ml LPS in the presence and absence of NF-κB inhibitor, SN50 (50μg/ml). TNF-α secretion and NF-κB p65 activity were detected in supernatants extracted from cultured cells treated and untreated with LPS (10ng/ml) and SN50 (50μg/ml) using enzyme-linked immunosorbent assay (ELISA). The western blot technique detected the protein of NF-κB p65 and AGT. Gene expression of TNF-α and AGT was detected in cells and performed using quantitative real-time polymerase chain reaction (RT-PCR). Treatment of AbdSc adipocytes with LPS (10ng/ml) caused a significant increase in NF-κB p65 among overweight and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. In contrast, SN50-NF-κB inhibitor causes a reduction of NF-κB p65 in overweight (P= <0.001) and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. Treatment of AbdSc adipocytes with 10ng/ml LPS caused a significant increase in TNF-α secretion in overweight and obese subjects at all-time points (P= <0.001), whereas SN50 leads to a decrease in TNF-α secretion at 3 and 12 hours incubation. Treatment of AbdSc adipocytes with LPS (10ng/ml) caused increased TNF-α and AGT gene expression twofold compared with untreated cells, whereas, in the presence of SN50, it reduces mRNA AGT levels in both groups. Taken together, these adipokines with NF-κB activation may represent essential biomarkers to evaluate hypertension risk and to provide insight into the pathogenesis of obesity-related hypertension.

Spider toxin SNX-482 is a cysteine-rich peptide that interferes with calcium channel activity by binding to voltage-sensing domains of CaV2.3 subtype. Two general binding mechanisms are present in nature: direct binding from the aqueous phase or through lateral diffusion from the membrane, the so-called reduction in dimensionality mechanism. In this work, via coarse-grained and atomistic molecular dynamics simulations, we have systematically studied the spontaneous partitioning of SNX-482 with membranes of different anionic compositions and explored via diffusional analysis both binding mechanisms. Our simulations revealed a conserved protein patch that inserts within the membrane, a preference for binding towards partially negatively charged membranes, and that electrostatics drives membrane binding. Finally, diffusivity calculations showed that the toxin diffusion along the membrane plane is an order of magnitude slower than the aqueous phase suggesting that the critical factor in determin-ing the SNX-482-CaV2.3 binding mechanism is the affinity between the membrane and SNX-482

The protection of first responders from radioactive contamination of alpha emitters that may result from a radiological accident is of great complexity due to the short range of the alpha particle in air of a few cm. To overcome this issue, for the first time a system for near real-time measuring alpha particles remotely mounted on a UAS has been developed, tested and calibrated. The new system, based on an optical system adapted to be installed on the UAS in order to measure the UV-C fluorescent emitting by the alpha particle in air, has been tested and calibrated carried out by laboratory and in field experiments using UV-C leds and ²⁴¹Am sources. In experimental flights, the probability of detecting a point source was determined to be approximately 60%. In case of a surface extended source, a detection efficiency per unit surface activity of ten counts per second per MBq cm^-2 are calculated. A background count rate of UV-C around 26 ± 28 s^-1 for an integration time of 0.1 s was measured during flights, which leads to a decision threshold surface activity of 5 MBq cm^-2.

In this paper, experiences of the last 20 years with the PERALS-technique are described. PERALS stands for Photo Electron Rejecting Alpha Liquid Scintillation. This LSC-technique was developed by Jack McDowell in the 70ies and is a powerful technique for the analyses of many natural alpha nuclides. The principle is based on a selective extraction of the radionuclide from the water phase by means of a complexing or ion pair reagent. The extractant contains also a suitable cocktail for the scintillation counting. Therefore, the extract can be analysed directly after the extraction step. After removing quenchers, such as oxygen, and the proper setting of a pulse shape discriminator, alpha pulses can be counted with a photomultiplier. The paper describes the development of robust analysis schemes for the determination of traces of polonium, radon, radium, strontium, thorium, uranium and other actinides in water samples (groundwater, rain water, river water, drinking water, mineral water, sea water).

Interferon alpha (IFNα) is a protein drug used to treat viral infections and cancer diseases. Due to its poor stability in the gastrointestinal tract, only parenteral administration ensures bioavailability, which is associated with severe side effects. We hypothesized that the nanoencapsulation of IFNα within nanoparticles of the mucoadhesive polysaccharide chitosan would improve the oral bioavailability of this drug. In this work, we produced IFNα-loaded chitosan nanoparticles by the ionotropic gelation method. Their size, size distribution and concentration were characterized by dynamic light scattering and nanoparticle tracking analysis. After confirming their good cell compatibility in Caco-2 and WISH cells, the permeability of unmodified and PEGylated nanoparticles was measured in monoculture (Caco-2) and co-culture (Caco-2/HT29-MTX) cell monolayers. Results indicated that the nanoparticles cross the intestinal epithelium mainly by the paracellular route. Finally, the oral pharmacokinetics in BalbC mice of nanoencapsulated IFNα revealed that it was absorbed reaching an area-under-the-curve of 56.9 pg.h/mL.

Apoptosis and cell cycle arrest induction are targeted in the strategy of cancer therapy. Furthermore, bacterial toxin such as shiga-like toxin producing Escherichia coli has been suggested to be used as novel therapeutic agent against tumor malignancies either as independent anti-neoplastic agents or in combination treatment with chemo or radiotherapy. The aim of study was to investigate the potency of shiga-like toxin originated from local strains of E. coli O157:H7 as a new cancer therapy. As many as 10 culture cells T47D cell line were subjected by crude extract Shiga like toxin originated from five local isolates of E. coli O157:H7 i.e. KL-48(2), SM-25(1), SM-7(1), DS-21(4), and one isolate ATCC 43894 as a control with IC50 doses, respectively. The treatment was observed for 24 h, with two replications. An FITC-Annexin V and PI assay was used to observe apoptosis and necrosis effect, and simultaneously with cell cycle analysis using propidium iodide (PI) staining. Results of study showed T47D cell treated with Shiga-like toxin from local strain KL-48 (2) show the lowest viable cell, followed by SM 7(1), ATCC 43894, SM-25(1), DS-21(4) and contrary with control with each percentages as 15.20, 16.36, 22.17, 22.64, 33.86, and 94.36%, respectively. The results were also confirmed by the induction of the cell cycle arrest in phase G0-G1 as inactive phase, i.e. 66.41, 63.37, 61.52, 55.36 and 47.28% for T47D cell treated with toxin of KL-48(2), ATCC 43894, SM 25(1), SM 7(1), and DS 21(4), respectively. These results show tendency deleterious effect of Shiga-like toxin from local isolates on T47D cell, so that concluded they have potency as a good anticancer drug in Gb3-expressing breast cancer.

A novel binary toxin-positive non-027, non-078 Clostridium difficile strain designated LC693 whose sequence type was ST201 was isolated from the fecal sample of a patient with severe diarrhea in China. To understand the pathogenesis basis of C. difficile ST201, this recently recovered isolate LC693 was then chosen for whole genome sequencing. The project finally generated an estimated genome size of approximately 4.07 Mbp. The genome sequence was then analyzed together with the other two ST201 strains VL-0104 and VL-0391 and compared to the epidemic 027/ST1 and 078/ST11 strains. Phylogenetic analysis demonstrated that the ST201 strains belonged to clade 3. Genome size of the three ST201 strains ranged from 4.07 Mb~4.16 Mb, with an average GC content between 28.5%~28.9%. The ST201 genomes contained more than 40 antibiotic resistance genes and 15 of them were predicted to be associated with vancomycin-resistance, suggesting that they may have a strong antibiotic resistance. The ST201 strains contained a typical clade 3 specific PaLoc with a Tn6218 element inserted, and those genes harbored on their PaLoc that participated in the toxin expression and regulation were highly homologues to the epidemic 027 and 078 strains, with the exception of tcdC. A truncated TcdC was found in the ST201 strains, which is suggestive to have a contribution to the toxin production of the ST201 strains. In addition, the ST201 strains contained intact binary toxin coding and regulation genes, which is also proposed to contribute to the virulence. Genome comparison of the ST201 strains with the epidemic 027 and 078 strain identified 641 genes specific for the C. difficile ST201, and a number of them were predicted as fitness and virulence associated genes. The identification of those genes also contributes to the pathogenesis of the ST201 strain. To our knowledge, this is the first study that the genome sequence of C. difficile ST201 was discussed in detail, and the present study would have a contribution to understanding the pathogenesis basis of C. difficile ST201.

COVID-19 pandemic outbreak challenged the global public health in last couple of years. Throughout the pandemic period, numbers of mutant strains of SARS- CoV-2 created challenges for the infected patients with diverse pathophysiology and immune response. Variant of Concern (VOC) alpha (B.1.1.7), delta (B.1.617.2) and omicron (B.1.1.529) grew most notable for causing the epidemiological manifestations, which eventually caused elevated infectivity resulting in significant mortality. This review indicates the comparative analysis of the immune-pathophysiological mechanisms in respect to the aforementioned strains of SARS-CoV-2.

Background: Diabetic patients are more likely to experience morbidity and mortality as a result of microvascular complications such as retinopathy, neuropathy, nephropathy, and stroke. There are many synthetic anti-diabetic agents available which are expensive and have undesirable pathological effects. Thus, it is essential to look for cost-effective, natural, and safe antidiabetic agents. The aim of this study was to screen phytoconstituent and evaluate the in-vitro and in-silico α-amylase inhibitory activity of ethanolic extract of Adhatoda vasica leaves. Method: The extraction of Adhatoda vasica leaves was performed with ethanol through Soxhlet extraction process. Different concentrations (0.1 mg/ml to 1 mg/ml) of ethanolic extract, Acarbose, and Sitagliptin, were prepared and all concentrations were evaluated for α-amylase inhibitory activity through the spectrophotometric method. Molecular docking (AutodockVina 1.2.0) and toxicity profiling (SToPToX web server) studies were performed. Results: The plant extract showed highest inhibition of α-amylase (56.763±0.0035) at a concentration of 1 mg/ml. This inhibitory activity was supported by the in-silico study. Vasicoline (C5) and quercetin (C9), active constitute of plant Adhatoda vasica, showed the best binding energy of 8.3 and 8.0 Kcal/mol respectively with α-amylase enzyme (PDBID: 4W93). Toxicity study revealed the safety profile of plant extract. Conclusion: It was concluded that Adhatoda vasica leaves possess some bioactive compounds which are responsible for controlling blood glucose levels and its identification, purification, and isolation may lead to the development of newer therapeutic agent with lesser side effects.

Study of gross alpha (GA) and gross beta (GB) activity in road and surface deposited sediments were performed in various geographical areas in three Russian cities. To perform radiation measurements, new methods were applied which allow dealing with low mass and low volume dust size (2-100μm) samples obtained after the size fractionation procedure. The 2-10 μm fraction size has the highest gross beta activity concentration (GB)– 1.32Bq/g in Nizhny Novgorod (NN) and Rostov-On-Don (RND) while the 50-100 μm fraction size in Ekaterinburg. This is maybe associated with the subsistence of radionuclides that conveyed through natural processes and anthropogenic applications. The highest gross alpha activity concentration (GA) in fraction sizes was found in Rostov-on-Don city within the 50-100 μm– 0.22Bq/g. The fraction size 50-100 μmhas a higher gross alpha activity concentration than 2-10 and 10-50 μmfraction sizes due to natural partitioning of the main minerals constituting the urban surface deposited sediment (USDS). The geochemical processes that occur during the formation and transportation of USDS are reflected in the observed dependencies.Developed experimental methods of radiation measurements allowed to the extent the methodological base of urban geochemical studies.

Alpha-fetoprotein (AFP) is a major embryo- and tumor-associated protein capable of binding and transporting variety of hydrophobic ligands including estrogens. AFP has been shown to inhibit estrogen receptor (ER)-positive tumor growth and this can be attributed to its estrogen-binding ability. Despite AFP has long been investigated, its three-dimensional (3D) structure has not been experimentally resolved and molecular mechanisms underlying AFP-ligand interaction remain obscure. In our study we constructed homology-based 3D model of human AFP (HAFP) with the purpose to perform docking of ERα ligands, three agonists (17β-estradiol, estrone and diethylstilbestrol) and three antagonists (tamoxifen, afimoxifene and endoxifen) into the obtained structure. Based on ligand docked scoring function, we identified three putative estrogen- and antiestrogen-binding sites with different ligand binding affinities. Two high-affinity sites were located in (i) a tunnel formed within HAFP subdomains IB and IIA and (ii) opposite side of the molecule in a groove originating from cavity formed between domains I and III, while (iii) the third low-affinity site was found at the bottom of the cavity. 100 ns MD simulation allowed studying their geometries and showed that HAFP-estrogen interactions occur due to van der Waals forces, while both hydrophobic and electrostatic interactions were almost equally involved in HAFP-antiestrogen binding. MM/GBSA rescoring method estimated binding free energies (ΔG_bind) and showed that antiestrogens have higher affinities to HAFP as compared to estrogens. We performed in silico point substitutions of amino acid residues to confirm their roles in HAFP-ligand interactions and showed that Thr132, Leu138, His170, Phe172, Ser217, Gln221, His266, His316, Lys453, and Asp478 residues along two disulfide bonds, Cys224-Cys270 and Cys269-Cys277 have key roles in both HAFP-estrogen and HAFP-antiestrogen binding. Data obtained in our study contribute to understanding mechanisms underlying protein-ligand interactions and anti-cancer therapy strategies based on ER-binding ligands.

Parkinson’s disease and Alzheimer’s disease are the most commonly diagnosed neurodegenerative disorders. Though these disorders differ in terms of their underlying pathophysiology as well as in their clinical features and course, there is a certain degree of overlap between them. This overlap may be partly related to α-synuclein-mediated neuropathological changes. Recent evidence has found that depression is associated with an increased subsequent risk of both these neurological disorders, and that α-synuclein may also play a pathogenic role in depression. The current study examines epidemiological, population genetic and environmental exposure data in relation to the estimated prevalence of depressive disorders, Parkinson’s disease and Alzheimer’s disease using a cross-sectional, country-level analysis. The results of this study are consistent with a significant relationship between depressive disorders and neurodegenerative disorders, a possible shared genetic vulnerability related to functional polymorphisms of the α-synuclein gene SNCA, and potential gene-environment interactions involving fine particulate matter pollution. The significance of these results is discussed in the light of existing translational, clinical and epidemiological research on the links between these disorders.

Inappropriate antimicrobial treatment can pose a risk for developing resistance against antimi-crobial drugs in bacteria. Close human contact might have a higher chance of being transmitted to humans from sheep if the sheep population is a potential reservoir of zoonotic pathogens such as shiga toxin-producing Escherichia coli (E. coli) (STEC). Therefore, this study aimed to exam-ine the sheep population in rural Bangladesh for antimicrobial resistant STEC. We screened 200 faecal samples collected from sheep in three Upazila from the Chattogram district. Phenotypical-ly positive E. coli isolates were examined for two shiga toxin-producing genes – stx1 and stx2. PCR positive STEC isolates were investigated for the presence of antimicrobial resistance genes- blaTEM, sul1 and sul2. In total, 123 of the 200 tested samples were confirmed positive E. coli by cul-tured based methods. PCR results show 17(13.8%) E. coli isolates harboured ≥ one virulent gene (stx1 or/and stx2) of STEC. Six of the tested STEC isolates exhibited blaTEM gene; eight STEC isolates had sul1 gene, and sul2 gene was detected in ten STEC isolates. To our knowledge, this study is the first to reveal a significant proportion of STEC isolated from sheep in rural Bangla-desh harbouring antimicrobial resistance genes.

Saccharomyces cerevisiae cells are killed by zymocin, a tRNase ribotoxin complex from Kluyveromyces lactis, which cleaves anticodons and inhibits protein synthesis. Zymocin’s action requires specific chemical modification of uridine bases in the anticodon wobble position (U34) by the Elongator complex (Elp1-Elp6). Hence, loss of anticodon modification in mutants lacking Elongator or related KTI (K. lactis Toxin Insensitive) genes protects against tRNA cleavage and confers resistance to the toxin. Here, we show that zymocin can be used as a tool to genetically analyse KTI12, a gene previously shown to code for an Elongator partner protein. From a kti12 mutant pool of zymocin survivors, we identify motifs in Kti12 that are functionally directly coupled to Elongator activity. In addition, shared requirement of U34 modifications for nonsense and missense tRNA suppression (SUP4; SOE1) strongly suggests that Kti12 and Elongator cooperate to assure proper tRNA functioning. We show that the Kti12 motifs are conserved in plant ortholog DRL1/ELO4 from Arabidopsis thaliana and seem to be involved in binding of cofactors (e.g. nucleotides, calmodulin). Elongator interaction defects triggered by mutations in these motifs correlate with phenotypes typical for loss of U34 modification. Thus, tRNA modification by Elongator appears to require physical contact with Kti12, and our preliminary data suggest that metabolic signals may affect proper communication between them.

To demonstrate if botulinum toxin type A (BoNT-A) improves mandibular range of motion and muscle sensibility to palpation in refractory myofascial pain (MFP) patients. METHODS: Eighty consecutive female subjects with refractory MFP, were randomly divided into four equal groups (n=20): BoNT-A low (BoNTA-L/10 U in each temporalis and 30 U in each masseter), BoNT-A medium (BoNTA-M/20 U in each temporalis and 50 U in each masseter), BoNT-A high (BoNTA-H/25 U in each temporalis and 75 U in each masseter) and saline solution 0.9% (SS, placebo control group/0.4 mL in each temporalis and 0.6 mL in each masseter). Clinical measurements of the mandibular movements included: pain-free opening, maximum unassisted and assisted opening, and right and left lateral movements. Palpation tests were performed bilaterally in masseter and temporalis muscle. Results were expressed as median, minimum, maximum, and means ± standard deviation (SD). Chi-Square Test was used to compare differences among groups. A 5% probability level was considered significant in all tests RESULTS: Regardless of dose, all parameters of mandibular range of motion significantly improve after 180 days in BoNT- A groups, when compared to the control group. Pain to palpation on muscles, significantly reduced in all BoNT- A groups regardless of dose, when compared to the control group, after 28 and 180 days of treatment. CONCLUSIONS: Independent of doses, BoNT-A improved mandibular range of motion and muscle sensibility to palpation in refractory MFP patients when compared to SS injections.

The study of ecological connectivity is a global priority due to the important role it plays in the conservation of diversity. However, few studies in this context have focused on marine benthic ecosystems. To address this issue, the present work determines the ecological connectivity between two sub-Antarctic macrobenthic assemblages through assessment of the α-, β-, and functional diversity indices. Samples were collected using a van Veen grab at stations located in Bahia Inútil and Seno Almirantazgo. The ecological analysis was based on a total of 113 invertebrate taxa. The mean abundance values were lower in Bahia Inútil (888.9 ± 26.8 ind m-2) than in Seno Almirantazgo (1358.6 ± 43.4 ind m-2). While the mean α-diversity values showed significant differences between assemblages, β- and functional diversity indices presented no significant differences. These results indicate that, despite the distance (56 km) separating the two basins from each other, there is a high degree of connectivity at the functional level between the assemblages, due to the high number of shared species and their functional traits. The species most responsible for this observation were the polychaetes Capitela capitata and Aricidia (Acmira) finitima, as well as the bivalves Nucula pisum and Yoldiella sp. 1. In terms of functional biodiversity, species characterized as omnivorous and with lecithotrophic larval development were mostly responsible for connectivity between assemblages. These results suggest the importance of including β- and functional diversity indices as criteria in the future planning of marine protected areas for the maintenance of marine ecosystem integrity.

Aggregated alpha-synuclein (-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson’s disease (IPD) and multiple system atrophy (MSA), respectively. Initiating factors that culminate in forming LBs/LNs/GCIs remain elusive. Several species of -synuclein exist, including phosphorylated and nitrated forms. It is unclear which -synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant synuclein PTMs in post-mortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three -synuclein PTMs (pS87, pS129, nY39) simultaneously in pathology-affected regions of 15 PD, 5 MSA, 6 neurologically normal controls. All antibodies recognized LBs, LNs, and GCIs, albeit to a variable extent. pS129 -synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures followed by nY39 -synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 -synuclein in MSA. Quantification of the LB scores revealed that pS129 -synuclein was the dominant and earliest -synuclein PTM followed by nY39 -synuclein, while lower amounts of pSer87 -synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments.

The abnormal assembly of α-synuclein (α-Syn) is an initial step in the formation of Lewy bodies in the brain, which finally causes the neuronal death, being considered as a pathological hallmark in Parkinson’s disease (PD). Certain food bioactives or their metabolites at very low concentrations can trespass the blood brain barrier (BBB) that might, thereafter, act simultaneously. The aim of this work was to evaluate the inhibitory and destabilising capacities on α-Syn kinetics and the neuroprotective effects of three well-known bioactive compounds able to cross the BBB and present in foods; melatonin (MEL), protocatechuic acid (PCA) and hydroxytyrosol (HT), and their combinations. For this purpose, different in vitro techniques (Thioflavin T (ThT), Transmission Electronic Microscopy (TEM), electrophoresis and MTT assay) were used. All tested compounds and their combinations were able to abolish the toxicity induced by α-Syn. In addition, the combination of PCA (100 µM) +HT (100 µM) showed the highest inhibitory effect against α-Syn fibril formation and destabilises α-Syn fibrils (88 and 62%, respectively). This is the first time that MEL, PCA and HT prove a joint effect against α-Syn aggregation and toxicity when they are tested together.

The study compared antibacterial potential of hydrolysates of casein and alpha-lactalbumin from cow and goat milk on diarrhea-causing Escherichia coli and Staphylococcus aureus. Milk samples were aseptically obtained from lactating cows and goats. The samples were skimmed; casein was isolated using acetic acid and alpha-lactalbumin by filtrate thermoprecipitation at 75 °C. 50% of each isolate was reconstituted in a buffer and hydrolyzed with papain at 55 °C for 2 hours. The hydrolysates were heated to 75 °C to inactivate papain, cooled and their antibacterial activity determined by disc diffusion method. Results showed alpha-lactalbumins had higher degrees of hydrolysis and antibacterial activity than caseins; goat alpha-lactalbumin had the highest antibacterial activity with mean inhibition zones of 19.60 mm and 19.50 mm on E. coli and S. aureus. Cow alpha-lactalbumin inhibited E. coli more than S. aureus with inhibition zones of 16.80 mm and 12.50 mm. Cow and goat milk casein hydrolysates inhibited E. coli with mean inhibition zones of 8.00 mm and 10.90 mm and inhibited S. aureus with inhibition zones of 4.13 mm and 1.90 mm respectively. The research showed that the milk hydrolysates can be a source of antibiotics for diarrhea treatment. Research should be done to establish the peptide fractions associated with the observed bioactivity.

Following spinal cord injury (SCI), pathological reflexes develop that result in altered bladder function and sphincter dis-coordination, with accompanying changes in the detrusor. Bladder chemodenervation is known to ablate the pathological reflexes, but the resultant effects on the bladder tissue are poorly defined. In a rodent model of contusion SCI, we examined the effect of early bladder chemodenervation with botulinum toxin A (BoNT-A) on bladder histopathology and collagen deposition. Adult female Long Evans rats were given a severe contusion SCI at spi-nal level T9. The SCI rats immediately underwent open laparotomy and received detrusor injec-tions of either BoNT-A (10 U/animal) or saline. At 8 weeks post injury, the bladders were col-lected, weighed, and examined histologically. BoNT-A injected bladders of SCI rats (SCI-BoNT-A) weighed significantly less than saline injected bladders of SCI rats (SCI-saline) (241 ± 25 mg vs. 183 ± 42 mg; p<0.05). Histological analyses showed that SCI resulted in significantly thicker bladder walls due to detrusor hypertrophy and fibrosis compared to bladders from uninjured animals (339 ± 89.0 m vs. 193 ± 47.9 m; p<0.0001). SCI-BoNT-A animals had significantly thinner bladder walls compared to SCI-saline animals (202 ± 55.4 m vs. 339 ± 89.0 m; p<0.0001). SCI-BoNT-A animals had collagen organization in the bladder walls similar to that of uninjured animals. Detrusor chemodenervation soon after SCI appears to preserve bladder tissue integrity, by reducing the development of detrusor fibrosis and hypertrophy associated with SCI.

Smoking is a risk factor for respiratory infections and there is reasonable concern that it may affect COVID-19 susceptibility and severity. Recent studies have focused on the interaction between smoking (and nicotine) and ACE2 expression, suggesting that ACE2 up-regulation could contribute to enhanced viral cell entry. However, case series have shown that there is an unexpectedly low prevalence of smoking among hospitalized COVID-19 cases. Since early April, we were the first to hypothesize that dysfunction of the nicotinic cholinergic system (NCS) may be implicated in the pathophysiology of severe COVID-19. We recently reported that many of the clinical manifestations of severe COVID-19 could be explained by dysregulation of the NCS. In this study, we present an amino acid sequence in the receptor binding domain of the SARS-CoV-2 Spike glycoprotein which is homologous to a sequence of a snake venom toxin. We present the 3D structural location of this “toxin-like” sequence on the Spike Glycoprotein. These findings suggest that SARS-CoV-2 could potentially interact with acetylcholine receptors causing dysregulation of the NCS and the cholinergic anti-inflammatory pathway.

Emerging evidence demonstrated that using a new manufacturing technology to produce γ-aminobutyric acid (GABA)-fortified oolong (GO) tea could relieve human stress and exert versatile physiological benefits. The purpose of this human research aims to investigate therapeutic effects of daily GO tea consumption on the improvement of blood pressure, relaxation-related brain waves and quality of life (QOL) during a period of 28 consecutive days. Total polyphenols, major catechins and free amino acids were analyzed via HPLC assay. Changes of heart rate, blood pressure, α-brain wave (index of relaxation) and eight-item QOL score were investigated on day 0, 7, 14, 21 and 28, respectively. The chemical analysis results showed that GO tea contained the most abundant amino acids and GABA, contributing to the relaxation activity. Among all study participants, daily drinking GO tea could reduce systolic blood pressure on day 21 and diastolic blood pressure on day 28 (p &lt; 0.05, respectively). For participants with pre-hypertension, GO tea could effectively reduce heart rate, systolic and diastolic blood pressure on day 28 (p &lt; 0.05). At the end of the study, incremental changes in alpha-brain wave and QOL scores were also demonstrated (p &lt; 0.05, respectively). This study recommended that GO tea might potentially serve as a natural source of alternative therapy to benefit blood pressure, stress-relief and QOL.

SARS-CoV-2 is severe acute respiratory syndrome coronavirus 2 which induces severe pneumonia that has considerable death rate. In this article, we summarised the evolution of SARS CoV-2 from alpha to omicron variant. The origin, transmission capability, and innate immunity potential of the Omicron variety remain unknown in the aftermath of its appearance. It's also unclear whether further varieties based on Omicron may emerge in the future. However, there is no question that the Omicron version of SARS-CoV-2 would not be the last. The COVID-19 pandemic has become more difficult to control due to the constant appearance of new SARS-CoV-2 mutations. We have discussed about the epidemiology, treatment plans for SARS CoV-2 and preventive strategies for future pandemic.

The present study explored whether exposure to complex childhood trauma (CCT) is reflected in the resting-state electroencephalography (EEG) temporal alpha power of complex trauma-exposed adolescents, given the association of temporal alpha with fear circuitry (learning and conditioning) in a sample of 25 adolescents and similar controls, ages 12-17 years. Both trauma and psychopathology were screened or assessed, and resting-state EEG was recorded, following a preregistered protocol for data collection. Temporal alpha power, corresponding to T5 and T6 electrode location (10-20 international system), was extracted from resting-state EEG in both eyes-open and eyes-closed conditions. We found that in the eyes-open condition, right, but not left, temporal alpha was significantly higher in adolescents exposed to CCT, relative to healthy controls, suggesting that childhood trauma exposure may have a measurable impact on alpha oscillatory patterns, specifically in the right temporal region. Our study highlights the importance of considering neural markers, such as temporal alpha power, in understanding the long-term consequences of CCT exposure in developmental samples, with possible important clinical implications in guiding neuroregulation interventions.

In this paper, we consider the temporal development of the optical density of the H$_\alpha$ spectral line in a hydrogen laser induced plasma. This is achieved by using the so-called duplication method in which the spectral line is re-imaged onto itself and the ratio of the spectral line with it duplication is taken to its measurement without the duplication. We asses the temporal development of the self-absorption of the H$_\alpha$ line by tracking the decay of duplication ratio from its ideal value of 2. We show that when 20% loss is considered along the duplication optical path length, the ratio is 1.8 and decays to a value of 1.25 indicating an optically thin plasma grows in optical density to an optical depth of 1.16 by 400 ns in the plasma decay for plasma initiation conditions using Nd:YAG laser radiation at 120 mJ per pulse in a 1.11$\times10^{5}$ Pa hydrogen/nitrogen gas mixture environment. We also go on to correct the H$_\alpha$ line profiles for the self-absorption impact using two methods. We show that a method in which the optical depth is directly calculated from the duplication ratio is equivalent to standard methods of self-absorption correction when only relative corrections to spectral emissions are needed.

To assess the genetic diversity of circulating dengue virus 2 in Senegal in 2018 we performed molecular characterization by complete genome sequencing and performing phylogenetic analysis. Sequenced strains belong to Cosmopolitan genotype of DENV-2 we observed intra-genotype variability leading to a divergence in two clades with differential geographic distribution. We report two variants namely; the “Northern variant” harbouring three nonsynonymous mutations (V1183M, R1405K, P2266T) located respectively on NS2A, NS2B and NS4A and the “Western variant” with two nonsynonymous mutations (V1185E, V3214E) located respectively in the NS2A gene and the NS5 gene. Findings calls for in depth in vitro and functional study to elucidate the impact of observed mutations on viral fitness, spread, epidemiology and disease outcome.

Background and Objectives: Botulinum toxin injections are commonly used for the treatment of spasticity. However, injection procedures are associated with pain and procedural anxiety. While pharmacological approaches are commonly used to reduce these, inno-vative technology might be considered as a potential non-pharmacological alternative. Given this context, immersive virtual reality (VR) has shown effectiveness in the man-agement of procedural pain[1]. Our retrospective pilot study aimed to assess the potential added value of virtual reality in the management of pain and anxiety during intra-muscular injections of botulinum toxin. Materials and Methods: Twenty-one adult patients receiving botulinum toxin injections were included. A numerical rating scale was used to assess pain and anxiety during the injection procedure. The patient reported the pain experienced during previous injections without VR before injection and the pain expe-rienced in the current procedure with VR after the end of the procedure. Level of satis-faction of VR experience, if they agreed to reuse VR for the subsequent toxin botulinum injection, and if they would recommend VR to other patients were assessed. Results: The use of virtual reality showed a decrease of 1.8 pain-related points compared to without technology. No significant improvement in the level of anxiety was reported. Patients were very satisfied by their VR experience (7.9 out of 10) and would agree to reuse VR in their next injection procedure (88%) and to recommend the use of VR in other patients (100%). Conclusion: VR was useful for managing procedural pain related to botulinum toxin injection in adults, with a high level of satisfaction reported by the patient. VR should be considered as a valuable alternative to pharmacological approach to manage procedural pain during Botulinum toxin injection in adults.

Aggregation of the protein α-Synuclein (αSyn) is a hallmark of Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple systems atrophy, and alleviating the extent of αSyn pathology is an attractive strategy against neurodegeneration. The engineered binding protein β-wrapin AS69 binds monomeric αSyn. AS69 reduces primary and secondary nucleation as well as fibril elongation in vitro. It also mitigates aSyn pathology in a mouse model based on intrastriatal injection of aSyn pre-formed fibrils (PFF). Since the PFF-based model does not represent all aspects of PD, we tested here whether AS69 can reduce neurodegeneration resulting from αSyn overexpression. Human A53T-αSyn was overexpressed in the mouse Substantia nigra (SN) by using recombinant adeno-associated viral vector (rAAV). AS69 was also expressed by rAAV transduction. Behavioral tests and immunofluorescence stainings were used as outcomes.Transduction with rAAV-αSyn resulted in αSyn pathology as reported by phospho-αSyn staining and caused degeneration of dopaminergic neurons in the SN. The co-expression of rAAV-AS69 did not reduce αSyn pathology or degeneration of dopaminergic neurons. We conclude that αSyn monomer binding by rAAV-AS69 was insufficient to protect from aSyn pathology resulting from αSyn overexpression.