bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phylogeny-aware linear B-cell epitope predictor detects candidate targets for specific immune responses to Monkeypox virus
Authors: Campelo Felipe , Reis-Cunha João , Ashford Jodie , Ekárt Anikó , Lobo Francisco P. 
Published: September 2022

AbstractMonkeypox is a disease caused by the Monkeypox virus (MPXV), a double-stranded DNA virus from genusOrthopoxvirusunder familyPoxviridae, that has recently emerged as a global health threat after decades of local outbreaks in Central and Western Africa. Effective epidemiological control against this disease requires the development of cheaper, faster diagnostic tools to monitor its spread, including antigen and serological testing. There is, however, little available information about MPXV epitopes, particularly those that would be effective in discriminating between MPXV infections and those by other virus from the same family. We used the available data from the Immune Epitope Database (IEDB) to generate and validate a predictive model optimised for detecting linear B-cell epitopes (LBCEs) fromOrthopoxvirus, based on a phylogeny-aware data selection strategy. By coupling this predictive approach with conservation and similarity analyses, we identified nine specific peptides from MPXV that are likely to represent distinctive LBCEs for the diagnostic of Monkeypox infections, including the independent detection of a known epitope experimentally characterised as a potential specific diagnostic target for MPXV. The results obtained indicate ability of the proposed pipeline to uncover promising targets for the development of cheaper, more specific diagnostic tests for this emerging viral disease. A full reproducibility package (including code, data, and outputs) is available athttps://doi.org/10.5281/zenodo.7838331.
Transcriptome-wide characterization of piRNAs during the developmental process of European honey bee larval guts
Authors: Xu Ya-Jing , Long Qi , Fan Xiao-Xue , Ye Ya-Ping , Zhang Kai-Yao , Zhang Jia-Xin , Zhao Hao-Dong , Yao Yu-Tong , Ji Ting , Lin Zhe-Guang , Fu Zhong-Min , Chen Da-Fu , Guo Rui 
Published: September 2022

AbstractpiRNAs play pivotal roles in suppressing transposons, maintaining genome stability, regulating gene expression, and modulating development and immunity. However, there are few piRNA-associated studies on honey bee, and the regulatory role of piRNAs in the development of bee guts is largely unknown. In this current work, the differential expression pattern of piRNAs during the developmental process of the European honey bee (Apis mellifera) was analyzed, and target prediction of differentially expressed piRNAs (DEpiRNAs) was then conducted, followed by investigation of regulatory networks and the potential function of DEpiRNAs in regulating larval gut development. Here, a total of 843 piRNAs were identified in the larval guts ofA. mellifera; among these, 764 piRNAs were shared by 4- (Am4 group), 5- (Am5 group), and 6-day-old (Am6 group) larval guts, while 11, 67, and 1, respectively, were unique. The first base of piRNAs in each group had a cytosine (C) bias. Additionally, 61 up-regulated and 17 down-regulated piR-NAs were identified in the Am4 vs. Am5 comparison group, further targeting 9, 983 genes, which were involved in 50 GO terms and 142 pathways, while two up-regulated and five down-regulated piRNAs were detected in the Am5 vs. Am6 comparison group, further targeting 1, 936 genes, which were engaged in 41 functional terms and 101 pathways. piR-ame-742536 and piR-ame-856650 in the Am4 vs. Am5 comparison group as well as piR-ame-592661 and piR-ame-31653 in the Am5 vs. Am6 comparison group were found to link to the highest number of targets. Further analysis indicated that targets of DEpiRNAs in these two comparison groups were seven development-associated signaling pathways such as Hippo and Notch signaling pathways, seven immune-associated pathways including endocytosis and the Jak/STAT signaling pathway, and three energy metabolism pathways, namely sulfur metabolism, nitrogen metabolism, and oxidative phosphorylation. Moreover, the expression trends of five randomly selected DEpiRNAs were verified based on stem-loop RT-PCR and RT-qPCR. These results were suggestive of the overall alteration of piRNAs during the larval developmental process and demonstrated that DEpiRNAs potentially modulate development-, immune-, and energy metabolism-associated pathways by regulating expression of corresponding genes via target binding, further affecting the development ofA. melliferalarval guts. Our data offer novel insights into the development of bee guts and lay a basis for clarifying the developmental mechanism underlying the larval guts of European honey bee.
The class XIV myosin ofToxoplasma gondii, TgMyoA, is druggable in an animal model of infection
Authors: Kelsen Anne , Kent Robyn S , Snyder Anne K , Wehri Eddie , Bishop Stephen J , Stadler Rachel V , Powell Cameron , di Genova Bruno Martorelli , Rompikuntal Pramod K , Boulanger Martin J , Warshaw David M , Westwood Nicholas J , Schaletzky Julia , Ward Gary E 
Published: September 2022

AbstractToxoplasma gondiiis a widespread apicomplexan parasite that can cause severe disease in its human hosts. The ability ofT. gondiiand other apicomplexan parasites to invade into, egress from, and move between cells of the hosts they infect is critical to parasite virulence and disease progression. An unusual and highly conserved parasite myosin motor (TgMyoA) plays a central role inT. gondiimotility. The goal of this work was to test whether pharmacological inhibition of TgMyoA can alter disease progression in an animal model of infection. To this end, we sought to identify small molecule inhibitors of TgMyoA by screening a collection of 50,000 structurally diverse small molecules for inhibitors of the recombinant motors actin-activated ATPase activity. The top hit to emerge from the screen, KNX-002, inhibited TgMyoA with little to no effect on any of the vertebrate myosins tested. KNX-002 was also active against parasites, inhibiting parasite motility and growth in culture in a dose-dependent manner. We used chemical mutagenesis, selection in KNX-002, and targeted sequencing to identify a mutation in TgMyoA (T130A) that renders the recombinant motor less sensitive to compound. Compared to wild-type parasites, parasites expressing the T130A mutation showed reduced sensitivity to KNX-002 in motility and growth assays, confirming TgMyoA as a biologically relevant target of KNX-002. Finally, KNX-002 was shown to slow disease progression in mice infected with wild-type parasites, but not parasites expressing the resistance-conferring TgMyoA T130A mutation. These data demonstrate the specificity of KNX-002 for TgMyoA, bothin vitroandin vivo, and validate TgMyoA as a druggable target for toxoplasmosis. Since TgMyoA is essential for virulence, conserved in apicomplexan parasites, and distinctly different from the myosins found in humans, pharmacological inhibition of MyoA offers a promising new approach to treating the devastating diseases caused byT. gondiiand other apicomplexan parasites.
Metataxonomic insights in the distribution ofLactobacillaceaein foods and food environments
Authors: Parente Eugenio , Zotta Teresa , Giavalisco Marilisa , Ricciardi Annamaria 
Published: September 2022

AbstractMembers of the familyLactobacillaceae, which now includes species formerly belonging to the generaLactobacillusandPediococcus, but alsoLeuconostocaceae, are of foremost importance in food fermentations and spoilage, but also as components of animal and human microbiota and as potentially pathogenic microorganisms. Knowledge of the ecological distribution of a given species and genus is important, among other things, for the inclusion in lists of microorganisms with a Qualified Presumption of Safety or with beneficial use. The objective of this work is to use the data in FoodMicrobionet database to obtain quantitative insights (in terms of both abundance and prevalence) on the distribution of these bacteria in foods and food environments.We first explored the reliability of taxonomic assignments using the SILVA v138.1 reference database with full length and partial sequences of the 16S rRNA gene for type strain sequences. Full length 16S rRNA gene sequences allow a reasonably good classification at the genus and species level in phylogenetic trees but shorter sequences (V1-V3, V3-V4, V4) perform much worse, with type strains of many species sharing identical V4 and V3-V4 sequences. Taxonomic assignment at the genus level of 16S rRNA genes sequences and the SILVA v138.1 reference database can be done for almost all genera of the familyLactobacillaceaewith a high degree of confidence for full length sequences, and with a satisfactory level of accuracy for the V1-V3 regions. Results for the V3-V4 and V4 region are still acceptable but significantly worse. Taxonomic assignment at the species level for sequences for the V1-V3, V3-V4, V4 regions of the 16S rRNA gene of members of the familyLactobacillaceaeis hardly possible and, even for full length sequences, and only 49.9% of the type strain sequences can be unambiguously assigned to species.We then used the FoodMicrobionet database to evaluate the prevalence and abundance ofLactobacillaceaein food samples and in food related environments. Generalist and specialist genera were clearly evident. The ecological distribution of several genera was confirmed and insights on the distribution and potential origin of rare genera (Dellaglioa, Holzapfelia, Schleiferilactobacillus) were obtained.We also found that combining Amplicon Sequence Variants from different studies is indeed possible, but provides little additional information, even when strict criteria are used for the filtering of sequences.
Quantifying the bioavailable energy in an ancient hydrothermal vent on Mars and a modern Earth-based analogue
Authors: Rucker Holly R. , Ely Tucker D. , LaRowe Douglas E. , Giovannelli Donato , Price Roy E. 
Published: September 2022

AbstractPutative alkaline hydrothermal systems on Noachian Mars were potentially habitable environments for microorganisms. However, the types of reactions that could have fueled microbial life in such systems and the amount of energy available from them have not been quantitatively constrained. In this study, we use thermodynamic modeling to calculate which catabolic reactions could have supported ancient life in a saponite-precipitating hydrothermal vent system in the Eridania basin on Mars. To further evaluate what this could mean for microbial life, we evaluated the energy potential of an analogue site in Iceland, the Strytan Hydrothermal Field (SHF). Results show that out of the 85 relevant redox reactions that were considered, the highest energy-yielding reactions in the Eridania hydrothermal system were dominated by methane formation. By contrast, Gibbs energy calculations carried out for Strytan indicate that the most energetically favorable reactions are CO2 and O2 reduction coupled to H2 oxidation. In particular, our calculations indicate that an ancient hydrothermal system within the Eridania basin could have been a habitable environment for methanogens using NH4+ as an electron acceptor. Differences in Gibbs energies between the two systems were largely determined by oxygen – its presence on Earth and absence on Mars. However, Strytan can serve as a useful analogue for Eridania when studying methane producing reactions that do not involve O2.
The protein phosphatases MoPtc1 and MoPtc2 are induced during pathogen-host interactions and play synergistic roles in regulating MAPK pathways inMagnaporthe oryzae
Authors: Anjago Wilfred M. , Biregeya Jules , Shi Mingyue , Chen Yixiao , Wang Yupeng , Chen Meilian , Aron Osakina , Norvienyeku Justice , Yu Wenyi , Wang Zonghua , Dongmei Zhang 
Published: September 2022

AbstractReversible protein phosphorylation is essential in cellular signal transduction. The rice blast fungusMagnaporthe oryzae, contains six putative type 2c protein phosphatases namely; MoPtc1, MoPtc2, MoPtc5, MoPtc6, MoPtc7 and MoPtc8 respectively. In this study, we carried out transcription expression analysis and found that MoPtc1, MoPtc2 and MoPtc7 are significantly induced during pathogen-host interactions. Subsequent deletions of MoPtc1 or MoPtc2 not only resulted in increased sensitivity to cell wall stress mediated by Congo red but also increased phosphorylation of Mps1-MAPK. By immunoblot analysis, we found that deletion of both MoPtc1 and MoPtc2 resulted in overstimulation of both the HOG1 and Pmk1 pathways inM. oryzae. We also demonstrate that MoPtc1 is recruited directly to Osm1 by the adaptor protein MoNbp2 to inactivate the Osm1 during hypoosmotic stress unlike in budding yeast. Finally, we show that type 2c protein phosphatases are localized in different cellular compartments in the life cycle ofMagnaporthe oryzae. Taken together type 2C protein phosphatases MoPtc1 and MoPtc2 play synergistic roles in regulating MAPK signaling pathways inM. oryzae. This work expands our understanding of the MAPK signaling regulation circuits inM. oryzaeand the essential roles of type 2C phosphatases in fine-tuning phosphorylation levels of MAPK during fungal development.
Optogenetic induction of chronic glucocorticoid exposure in early-life impairs stress-response in larval zebrafish
Authors: Nagpal Jatin , Eachus Helen , Lityagina Olga , Ryu Soojin 
Published: September 2022

AbstractOrganisms respond to stressors through a coordinated set of physiological and behavioural responses. Zebrafish provides an opportunity to study conserved mechanisms underlying the stress-response that is regulated largely by the neuroendocrine Hypothalamus-Pituitary-Adrenal/Interrenal (HPA) axis, with glucocorticoids (GC) as the final effector. In this study, we evaluated the effect of chronically active GC signalling in early life on the baseline and stress evoked GC(cortisol) levels in larval zebrafish. To this end, we employed an optogenetic actuator, Beggiatoa photoactivated adenylyl cyclase, expressed in the interrenal cells of zebrafish and demonstrate that its chronic activation leads to hypercortisolaemia and dampens the acute-stress evoked cortisol levels, across a variety of stressor modalities during early life. This blunting of stress-response, a phenotype reported by many studies to be observed in human subjects exposed to early-life trauma, was conserved in ontogeny at a later developmental stage. Furthermore, we observe a strong reduction of proopiomelanocortin (POMC)-expressing cells in the pituitary as well as global upregulation of FKBP5 gene expression, impinging on the negative feedback regulation elicited by elevated cortisol levels. Going forward, we propose that this model can be leveraged to tease apart the mechanisms underlying developmental programming of HPA axis by early-life stress and its implications for vulnerability and resilience to stress in adulthood.
Clomipramine inhibits dynamin GTPase activity by L-α-phosphatidyl-L-serine stimulation
Authors: Miyoshi Hiroshi , Otomo Masahiro , Takahashi Kiyofumi 
Published: September 2022

AbstractThree dynamin isoforms play critical roles in clathrin-dependent endocytosis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cellsviaclathrin-dependent endocytosis. We previously reported that 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine (clomipramine) inhibits the GTPase activity of dynamin 1, which is in mainly neuron. Therefore, we investigated whether clomipramine inhibits the activity of other dynamin isoforms in this study. We found that, similar to its inhibitory effect on dynamin 1, clomipramine inhibited the L-α-phosphatidyl-L-serine-stimulated GTPase activity of dynamin 2, which is expressed ubiquitously, and dynamin 3, which is expressed in the lung. Inhibition of GTPase activity raises the possibility that clomipramine can suppress SARS-CoV-2 entry into host cells.Graphical Abstract
Involvement of epithelial-mesenchymal transition genes in small cell lung cancer phenotypic plasticity
Authors: Groves Sarah M. , Panchy Nicholas , Tyson Darren R. , Harris Leonard A. , Quaranta Vito , Hong Tian 
Published: September 2022

AbstractSmall cell lung cancer (SCLC) is an aggressive cancer recalcitrant to treatment, arising predominantly from epithelial pulmonary neuroendocrine (NE) cells. Intra-tumor heterogeneity plays critical roles in SCLC disease progression, metastasis and treatment resistance. At least five transcriptional SCLC NE and non-NE cell subtypes were recently defined by gene expression signatures. Transition from NE to non-NE cell states and cooperation between subtypes within a tumor likely contribute to SCLC progression by mechanisms of adaptation to perturbations. Therefore, gene regulatory programs distinguishing SCLC subtypes or promoting transitions are of great interest. Here, we systematically analyze the relationship between SCLC NE/non-NE transition and epithelial to mesenchymal transition (EMT)—a well-studied cellular process contributing to cancer invasiveness and resistance—using multiple transcriptome datasets from SCLC mouse tumor models, human cancer cell lines and tumor samples. The NE SCLC-A2 subtype maps to the epithelial state. In contrast, SCLC-A and SCLC-N (NE) map to a mesenchymal state (M1) that is distinct from the non-NE mesenchymal state (M2). The correspondence between SCLC subtypes and the EMT program paves the way for further work to understand gene regulatory mechanisms of SCLC tumor plasticity with applicability to other cancer types.
Efficacy and safety of acupuncture for postpartum hypogalactia: Protocol for a systematic review and meta-analysis
Authors: Bao Qiong-Nan , Zhou Yuan-Fang , Yin Zi-Han , Qiu-Bi  , Zhao Hong-Bin , Zhang Zhen-Yong , Liang Fan-Rong 
Published: September 2022

ABSTRACTIntroductionBreast milk is recognised as the best natural food for neonates, but many women experience postpartum hypogalactia (PH). Randomised trials have found that acupuncture exert therapeutic effect on women with PH. However, systematic reviews on the efficacy and safety of acupuncture are still lacking; therefore, this systematic review aims to evaluate the efficacy and safety of acupuncture for PH.Methods and analysisEight English databases (PubMed, Cochrane Library, MEDLINE, EMBASE, EBSCO, Scopus, Ovid, Web of Science) and four Chinese databases (China National Knowledge Infrastructure, Wan-Fang, Chinese Biomedical Literature, Chinese Scientific Journal) will be systematically searched from their establishment to 1 September 2022. Randomised controlled trials (RCTs) of the efficacy of acupuncture for PH will be reviewed. The study selection, data extraction, and research quality evaluation will be conducted independently by two reviewers. The primary outcome is the change in serum prolactin level from baseline to the end of treatment. Secondary results include milk secretion volume, total effectiveness rate, degree of mammary fullness, rate of exclusive breastfeeding, infant weight gain, and adverse events. A meta-analysis will be performed using RevMan V.5.4 statistical software. Otherwise, a descriptive analysis will be conducted. The risk of bias will be assessed using the revised Cochrane risk-of-bias tool.Ethics and disseminationThis systematic review protocol does not require ethical approval because it does not include private information/data of the participants. This article will be published in peer-reviewed journals.PROSPERO registration numberCRD42022351849Strengths and limitations of this studyThis study will be the first systematic review to evaluate the efficacy and safety of acupuncture for PH by including available clinical trials that have been published in the past.The quality of the included trials will be assessed using the Revised Cochrane Risk of Bias Tool (RoB2) for Randomised Trials.This study will provide more reliable evidence for clinical management because most RCTs on acupuncture for PH have small sample sizes.This study will include only English and Chinese trials, which may lead to missing studies in other languages.
Effects of social determinants of health on obesity among urban women of reproductive age
Authors: Amugsi Dickson A , Dimbuene Zacharie T. 
Published: September 2022

AbstractBackgroundObesity (body mass index greater than or equal to 30kg/m2) is a major global public health problem. It is spreading very fast in low- and middle-income countries and has reached world record levels in some of them. In Ghana, it has increased by over 65% among urban women in the past three decades. This study investigated the effects of social determinants of health on obesity among women in urban Ghana.MethodsThe study analysed the Ghana demographic and health survey data. These are nationally representative data collective every five years across low- and middle-income countries. A total of 1,204 urban women were included in the analysis. The outcome variable of interest was body mass index. We used logistic regression to model the effects of the various social determinants of health on obesity.ResultsThe results showed that 40% (95% confidence interval (CI)=25.4, 57.0) and 36.7% (95% CI=25.6, 49.3) of women who had higher education and those whose partners had higher education suffered from obesity, respectively. Women living in rich households had a five times higher prevalence of obesity than those in poor households (28.8% vs 5.7%). Further, 33.4% (95% CI=18.5, 19.3) of women who occupied managerial positions were obese. The results from the multivariable logistic regression analysis suggested that compared to women in poor households, those in rich households were 3.4 times (95% CI=1.31, 8.97) more likely to suffer from obesity. Women whose main occupation was agriculture were 81% (aOR=0.19; 95% CI=0.034, 0.99) less likely to suffer from obesity than those with no occupation.ConclusionsThe results suggest that the various SDHs significantly influence women’s obesity. Women and partner education levels, occupying a managerial position, and living in rich households increase the risk of obesity. Interventions to address the rising obesity in urban Ghana should have specific packages targeted at these sub-groups.
High serum uric acid levels are associated with worse cognitive performance: A cross-sectional study
Authors: Khaled Yousef , Abdelhamid Aya A. , Al-Mazroey Hissa , Almannai Abdulrahman K. , Fetais Sara , Al-Srami Aisha S. , Ahmed Shaima , Al-Hajri Noora , Chivese Tawanda , Djouhri Laiche 
Published: September 2022

Abstract(1)BackgroundThe association between raised serum uric acid and cognitive dysfunction remains a debated issue. In the present study, we investigated whether serum uric acid is associated with cognitive performance in a cohort of healthy individuals in Qatar;(2)MethodsWe conducted a cross-sectional study on a cohort of individuals aged 40 to 80 years old, without a diagnosis of dementia, schizophrenia, and stroke, who participated in Qatar Biobank. Cognitive performance was assessed using the CANTAB’s paired episodic memory test and reaction time test. The participants were divided into two groups, one group with a normal serum uric acid level (<350 μmol/l) and the other with high serum uric acid levels (>350 μmol/l). Two multivariable linear regression models were applied to determine the association between serum uric acid and memory test performance score and between serum uric acid and reaction time test performance score;(3)ResultsA total of 996 individuals with median age 48.0 years, IQR: (44.5, 54.0), of which 48.2% were male, were included. After adjusted multivariable linear regression, high serum uric acid levels were strongly associated with poor performance in the paired episodic memory test (beta -6.25, 95%CI - 10.65 to -1.84, p= 0.006). However, after adjusted multivariable linear regression, we found no significant association between high serum uric acid and performance in the reaction time test (beta - 13.24, 95%CI -138.77 to 112.29, p= 0.836,);(4)ConclusionsIn a cohort of healthy individuals in Qatar, high serum uric acid levels are associated with worse performance in visual memory and new learning domains of cognitive function but no significant effect on processing speed function.