bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of orally administered crofelemer on the incidence and severity of neratinib-induced diarrhea in female dogs
Authors: Guy Michael K. , Teixeira Andre , Shirer Allison , Bolognese James , Chaturvedi Pravin 
Published: February 2023

AbstractManagement guidelines for cancer therapy-related diarrhea (CTD) should be revised because newer targeted therapies have increased CTD burden, with high incidence and/or severity of diarrhea for some agents that inhibit epidermal growth factor receptor and receptor tyrosine kinases. Neratinib, a pan-HER tyrosine kinase inhibitor, approved for breast cancer treatment, causes severe diarrhea in >95% of patients. Crofelemer, a novel intestinal chloride ion channel modulator, is an approved antidiarrheal for patients with HIV receiving antiretroviral therapy. The objective of this study was to evaluate the effectiveness of crofelemer prophylaxis in reducing the incidence and severity of neratinib-induced diarrhea without loperamide in dogs. Female dogs received neratinib orally daily concomitantly with either matching placebo tablets (CTR) or crofelemer 125 mg delayed-release tablet two or four times/day (BID or QID) for 28 consecutive days. At the end of treatment, 37.5%, 75%, and 87.5% of the CTR, BID, and QID dogs were ‘responders’ defined as ≤7 loose/watery stools/week for at least 2 of 4 weeks (p<0.05). The average number of watery stools per week was 9, 6, and 6 in the CTR, BID, and QID groups, respectively (p<0.05). The average number of weeks with no loose/watery stools was 1.3, 2.1, and 2.3 for the CTR, BID, and QID groups, respectively (p<0.05). The weekly mean fecal scores and stool consistency were 5.1, 3.9, and 4.1 for the CTR, BID, and QID groups (p<0.05). In this 28-day preclinical study, crofelemer prophylaxis without loperamide reduced the incidence and severity of neratinib-associated diarrhea in female dogs by 30%.Ethical ComplianceAll procedures performed in studies involving canine participants were in accordance with the ethical standards of the institutional and/or national research committee and applicable Institutional Animal Care and Use Committee (IACUC).
Food availability early in life impacts among and within individual variation in behaviour
Authors: Beyts Cammy , Martin Julien G. A. , Colegrave Nick , Walsh Patrick 
Published: February 2023

AbstractThe availability of food during early life has been proposed as a key proximate mechanism for the development of variation in behaviour among and within individuals.Individuals can vary amongst each other in their personality, plasticity and predictability and if an individual’s behaviour is correlated across contexts this can lead to behavioural, plasticity and predictability syndromes.In this study, we used a split brood design to raise African clawed frog tadpoles (Xenopus laevis) on a high or low diet in food availability and measured the distance they swam in a familiar and unfamiliar context eight times during their development.In a familiar context, we found that there was an increase in among individual variance in plasticity and predictability in the high food treatment. This shows that when resources are not restricted, individuals are not constrained in the expression of their behaviour at certain phenotypic levels.In an unfamiliar context, we found a different response, with an increase in individual variance in personality in the low but not the high feed tadpoles. As unfamiliar contexts may be riskier, our results highlight that individuals receiving less food may take greater foraging risks in novel contexts.Across contexts, we found a predictability syndrome in the high but not the low feed tadpoles, highlighting that cross-context behaviours can become decoupled in some developmental conditions but remain intact in others.Together our findings show that early life conditions contribute to among individual variation in behaviour but that these may only impact the phenotype at specific phenotypic levels and are context specific.We emphasise that having a fundamental understanding of how early development may promote or constrain individual variation can provide a greater understanding of how individuals and populations may respond to novel conditions brought about by anthropogenic activity.
Yeast extract improves growth in rainbow trout (Oncorhynchus mykiss) fed a fishmeal-free diet and modulates the hepatic and distal intestine transcriptomic profile
Authors: Frohn Laura , Peixoto Diogo , Guyomar Cervin , Teixeira Carla , Terrier Frédéric , Aguirre Pierre , Maman Haddad Sarah , Bobe Julien , Costas Benjamin , Richard Nadège , Pinel Karine , Skiba-Cassy Sandrine 
Published: February 2023

AbstractReplacing fishmeal with alternative protein sources and improving new ingredients diets with feed additives are major objectives in aquaculture. The aim of this study was to evaluate benefits for rainbow trout (Oncorhynchus mykiss) of supplementing a fishmeal-free diet, composed of processed animal proteins, with yeast extract. Juvenile rainbow trout (initial weight 37 ± 2 g) were fed either with a control diet (19% fishmeal) or with a diet based on terrestrial animal by-products (17%) supplemented or not with 3% of yeast extract. Effects of the diets were evaluated in a 4-week digestibility trial and a 12-week growth experiment. Fish health was investigated by measuring plasma immune markers and performing histological study of the gut. Underlying molecular responses were investigated using unbiased transcriptomic analysis of the liver and distal intestine. Results indicated that supplementing with 3% yeast extract did not influence nutrient digestibility substantially. Nevertheless, fish fed the supplemented fishmeal-free diet grew more than those fed the non-supplemented processed animal protein diet. Plasma and structural parameters indicated no exacerbated immune response or signs of intestinal inflammation in fish fed the fishmeal-free diets. However, plasma total immunoglobulin M levels and intestinal villi were significantly higher in fish fed the diet supplemented with yeast extract. The transcriptomic analysis revealed that the diets influenced immune, inflammatory, pathogen fighting and coagulation gene-related expressions. These results suggest that the dietary inclusion of yeast can enhance a fishmeal-free diet by improving rainbow trout performances and potentially their robustness.
An efficient method for high molecular weight bacterial DNA extraction suitable for shotgun metagenomics from skin swabs
Authors: Serghiou Iliana R. , Baker Dave , Evans Rhiannon , Matthew J. Dalby , Kiu Raymond , Trampari Eleftheria , Phillips Sarah , Watt Rachel , Atkinson Thomas , Murphy Barry , Hall Lindsay J. , Webber Mark A. 
Published: February 2023

AbstractThe human skin microbiome represents a variety of complex microbial ecosystems that play a key role in host health. Molecular methods to study these communities have been developed but have been largely limited to low-throughput quantification and short amplicon sequencing, providing limited functional information about the communities present. Shotgun metagenomic sequencing has emerged as a preferred method for microbiome studies as it provides more comprehensive information about the species/strains present in a niche and the genes they encode. However, the relatively low bacterial biomass of skin, in comparison to other areas such as the gut microbiome, makes obtaining sufficient DNA for shotgun metagenomic sequencing challenging. Here we describe an optimised high-throughput method for extraction of high molecular weight DNA suitable for shotgun metagenomic sequencing. We validated the performance of the extraction method, and analysis pipeline on skin swabs collected from both adults and babies. The pipeline effectively characterised the bacterial skin microbiota with a cost and throughput suitable for larger longitudinal sets of samples. Application of this method will allow greater insights into community compositions and functional capabilities of the skin microbiome.Impact StatementDetermining the functional capabilities of microbial communities within different human microbiomes is important to understand their impacts on health. Extraction of sufficient DNA is challenging, especially from low biomass samples, such as skin swabs suitable for shotgun metagenomics, which is needed for taxonomic resolution and functional information. Here we describe an optimised DNA extraction method that produces enough DNA from skin swabs, suitable for shotgun metagenomics, and demonstrate it can be used to effectively characterise the skin microbiota. This method will allow future studies to identify taxonomic and functional changes in the skin microbiota which is needed to develop interventions to improve and maintain skin health.Data SummaryAll sequence data and codes can be accessed at:NCBI Bio Project ID: PRJNA937622DOI:https://github.com/quadram-institute-bioscience/coronahit_guppyDOI:https://github.com/ilianaserghiou/Serghiou-et-al.-2023-Codes
Dissociable roles of human frontal eye fields and early visual cortex in presaccadic attention – evidence from TMS
Authors: Hanning Nina M. , Fernández Antonio , Carrasco Marisa 
Published: February 2023

AbstractShortly before each saccadic eye movement, presaccadic attention improves visual sensitivity at the saccade target1–5at the expense of lowered sensitivity at non-target locations6–11. Some behavioral and neural correlates of presaccadic attention and covert attention –which likewise enhances sensitivity, but during fixation12–are similar13. This resemblance has led to the debatable13–18notion that presaccadic and covert attention are functionally equivalent and rely on the same neural circuitry19–21. At a broad scale, oculomotor brain structures (e.g., FEF) are also modulated during covert attention22–24– yet by distinct neuronal subpopulations25–28. Perceptual benefits of presaccadic attention rely on feedback from oculomotor structures to visual cortices29,30(Fig. 1a); micro-stimulation of FEF in non-human primates affects activity in visual cortex31–34and enhances visual sensitivity at the movement field of the stimulated neurons35–37. Similar feedback projections seem to exist in humans: FEF+ activation precedes occipital activation during saccade preparation38,39and FEF TMS modulates activity in visual cortex40–42and enhances perceived contrast in the contralateral hemifield40. We investigated presaccadic feedback in humans by applying TMS to frontal or visual areas during saccade preparation. By simultaneously measuring perceptual performance, we show the causal and differential roles of these brain regions in contralateral presaccadic benefits at the saccade target and costs at non-targets: Whereas rFEF+ stimulation reduced presaccadic costs throughout saccade preparation, V1/V2 stimulation reduced benefits only shortly before saccade onset. These effects provide causal evidence that presaccadic attention modulates perception through cortico-cortical feedback and further dissociate presaccadic and covert attention.
Signatures of co-evolution and co-regulation in the CYP3A and CYP4F genes in humans
Authors: Richard-St-Hilaire Alex , Gamache Isabel , Pelletier Justin , Grenier Jean-Christophe , Poujol Raphael , Hussin Julie G 
Published: February 2023

1AbstractCytochromes P450 (CYP450) are hemoproteins generally involved in the detoxification of the body of xenobiotic molecules. They participate in the metabolism of many drugs and genetic polymorphisms in humans have been found to impact drugs responses and metabolic functions. In this study, we investigate the genetic diversity forCYP450genes. We found that two clusters,CYP3AandCYP4F, are notably differentiated across human populations with evidence for selective pressures acting on both clusters: we found signals of recent positive selection inCYP3AandCYP4Fgenes and signals of balancing selection inCYP4Fgenes. Furthermore, unusual linkage disequilibrium pattern is detected in both clusters, suggesting co-evolution of genes within clusters. Several of these selective signals co-localize with expression quantitative trait loci, which suggest co-regulation and epistasis within these highly important gene families. We also found that SNPs under selection in Africans within theCYP3Acluster are associated toCYP3A5expression levels which are causally associated with reticulocytes count, as established by mendelian randomization. Furthermore, as theCYP3AandCYP4Fsubfamilies are involved in the metabolism of nutrients and drugs, our findings linking natural selection and gene expression in these gene clusters are of importance in understanding population differences in human health.
Discovery and characterization of cross-reactive intrahepatic antibodies in severe alcoholic hepatitis
Authors: Ahmadi Ali Reza , Song Guang , Gao Tianshun , Ma Jing , Han Xiaomei , Hu Mingwen , Cameron Andrew M , Wesson Russell , Philosophe Benjamin , Ottmann Shane , King Elizabeth A , Gurakar Ahmet , Qi Le , Peiffer Brandon , Burdick James , Anders Robert A , Zhou Zhanxiang , Feng Dechun , Lu Hongkun , Chen Chien-Sheng , Qian Jiang , Gao Bin , Zhu Heng , Sun Zhaoli 
Published: February 2023

AbstractThe pathogenesis of antibodies in severe alcoholic hepatitis (SAH) remains unknown. We sought to determine if there was antibody deposition in SAH livers and whether antibodies extracted from SAH livers were cross-reactive against both bacterial antigens and human proteins. We analyzed immunoglobulins (Ig) in explanted livers from SAH patients (n=45) undergoing liver transplantation and tissue from corresponding healthy donors (HD, n=10) and found massive deposition of IgG and IgA isotype antibodies associated with complement fragment C3d and C4d staining in ballooned hepatocytes in SAH livers. Ig extracted from SAH livers, but not patient serum exhibited hepatocyte killing efficacy in an antibody-dependent cell-mediated cytotoxicity (ADCC) assay. Employing human proteome arrays, we profiled the antibodies extracted from explanted SAH, alcoholic cirrhosis (AC), nonalcoholic steatohepatitis (NASH), primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), hepatitis B virus (HBV), hepatitis C virus (HCV) and HD livers and found that antibodies of IgG and IgA isotypes were highly accumulated in SAH and recognized a unique set of human proteins as autoantigens. The use of anE. coliK12 proteome array revealed the presence of unique anti-E. coliantibodies in SAH, AC or PBC livers. Further, both Ig andE. colicaptured Ig from SAH livers recognized common autoantigens enriched in several cellular components including cytosol and cytoplasm (IgG and IgA), nucleus, mitochondrion and focal adhesion (IgG). Except IgM from PBC livers, no common autoantigen was recognized by Ig andE. colicaptured Ig from AC, HBV, HCV, NASH or AIH suggesting no cross-reacting anti-E. coliautoantibodies. The presence of cross-reacting anti-bacterial IgG and IgA autoantibodies in the liver may participate in the pathogenesis of SAH.
Genomic differences and species delimitation: a case for two species in the zoonotic cestodeDipylidium caninum
Authors: Jesudoss Chelladurai Jeba R J , Abraham Aloysius , Quintana Theresa , Smith Vicki , Ritchie Deb 
Published: February 2023

AbstractDipylidium caninum(Linnaeus, 1758) is a common zoonotic cestode of dogs and cats worldwide. Previous studies have demonstrated the existence of largely host associated canine and feline genotypes based on infection studies, genetic differences at the nuclear 28S rDNA gene and complete mitochondrial genomes. There have been no comparative studies at a genome-wide scale. Here, we sequenced the genomes of a dog and cat isolate ofDipylidium caninumfrom the United States using the Illumina platform and conducted comparative analyses with the reference draft genome. Complete mitochondrial genomes were used to confirm the genotypes of the isolates.D. caninumcanine and feline genomes generated in this study had mean coverage depths of 45x and 26x and an average identity of 98% and 89% respectively when compared to the reference genome. SNPs were 20 times higher in the feline isolate. Comparison and species delimitation using universally conserved orthologs and protein coding mitochondrial genes revealed that the canine and feline isolates are different species. Data from this study builds a base for future integrative taxonomy. Further genomic studies from geographically diverse populations are necessary to understand implications for taxonomy, epidemiology, veterinary clinical medicine, and anthelmintic resistance.
Pleiotropic contribution ofrbfox1to psychiatric and neurodevelopmental phenotypes in a zebrafish model
Authors: Antón-Galindo Ester , Adel Maja , García-Gonzalez Judit , Leggieri Adele , López-Blanch Laura , Irimia Manuel , Norton William HJ , Brennan Caroline H , Fernàndez-Castillo Noèlia , Cormand Bru 
Published: February 2023

ABSTRACTRBFOX1is a highly pleiotropic gene that contributes to several psychiatric and neurodevelopmental disorders. Both rare and common variants inRBFOX1have been associated with several psychiatric conditions, but the mechanisms underlying the pleiotropic effects ofRBFOX1are not yet understood. Here we found that, in zebrafish,rbfox1is expressed in spinal cord, mid- and hindbrain during developmental stages. In adults, expression is restricted to specific areas of the brain, including telencephalic and diencephalic regions with an important role in receiving and processing sensory information and in directing behaviour. To investigate the effect ofrbfox1deficiency on behaviour, we usedrbfox1sa15940, arbfox1loss-of-function line. We found thatrbfox1sa15940mutants present hyperactivity, thigmotaxis, decreased freezing behaviour and altered social behaviour. We repeated these behavioural tests in a secondrbfox1loss-of-function line with a different genetic background,rbfox1del19, and found thatrbfox1deficiency affects behaviour similarly in this line, although there were some differences.rbfox1del19mutants present similar thigmotaxis, but stronger alterations in social behaviour and lower levels of hyperactivity thanrbfox1sa15940fish. Taken together, these results suggest thatrbfox1deficiency leads to multiple behavioural changes in zebrafish that might be modulated by environmental, epigenetic and genetic background effects, and that resemble phenotypic alterations present inRbfox1-deficient mice and in patients with different psychiatric conditions. Our study thus highlights the evolutionary conservation ofrbfox1function in behaviour and paves the way to further investigate the mechanisms underlyingrbfox1pleiotropy on the onset of neurodevelopmental and psychiatric disorders.
Phosphorylation motif dictates GPCR C-terminal domain conformation and arrestin interaction
Authors: Guillien Myriam , Mouhand Assia , Sagar Amin , Fournet Aurélie , Allemand Frédéric , Pereira Glaécia A. N. , Thureau Aurélien , Bernadó Pau , Banères Jean-Louis , Sibille Nathalie 
Published: February 2023

AbstractArrestin dependent G protein-coupled receptor (GPCR) signaling pathway is regulated by the phosphorylation state of GPCR’s C-terminal domain, but the molecular bases of arrestin:receptor interaction are to be further illuminated. Here we investigated the impact of phosphorylation on the conformational features of the C-terminal region from three Rhodopsin-like GPCRs, the vasopressin V2 Receptor (V2R), the Growth Hormone Secretagogue or ghrelin Receptor type 1a (GHSR) and the β2-Adernergic Receptor (β2AR). Using phosphomimetic variants, we identified pre-formed secondary structure elements, or short linear motif (SLiMs), that undergo specific conformational transitions upon phosphorylation. Of importance, such conformational transition favors arrestin-2 binding. Hence, our results suggest a model in which the cellular signaling specificity of GPCRs is encoded in the phosphorylation-dependent structuration of the C-terminal regions, which will subsequently modulate arrestin conformation and therefore GPCR:arrestin signaling outcomes.
Extensive re-modelling of the cell wall during the development ofStaphylococcus aureusbacteraemia
Authors: Douglas Edward J.A. , Palk Nathanael , Brignoli Tarcisio , Altwiley Dina , Boura Marcia , Laabei Maisem , Recker Mario , Cheung Gordon Y.C. , Liu Ryan , Hsieh Roger C. , Otto Michael , O’Brien Eoin , McLoughlin Rachel M. , Massey Ruth C. 
Published: February 2023

Introductory Paragraph / AbstractThe bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogenStaphylococcus aureusmanages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to survive exposure to serum, the critical first step in the development of bacteraemia. The expression of one of these genes,tcaA,was found to be induced upon exposure to serum, and we show that it is involved in the elaboration of a critical virulence factor, the wall teichoic acids (WTA), within the cell envelope. The activity of the TcaA protein alters the sensitivity of the bacteria to cell wall attacking agents, including antimicrobial peptides, human defence fatty acids, and several antibiotics. This protein also affects the autolytic activity and lysostaphin sensitivity of the bacteria, suggesting that in addition to changing WTA abundance in the cell envelope, it also plays a role in peptidoglycan crosslinking. With TcaA rendering the bacteria more susceptible to serum killing, while simultaneously increasing the abundance of WTA in the cell envelope, it was unclear what effect this protein may have during infection. To explore this, we examined human data and performed murine experimental infections. Collectively, our data suggests that whilst mutations intcaAare selected for during bacteraemia, this protein positively contributes to the virulence ofS. aureusthrough its involvement in altering the cell wall architecture of the bacteria, a process that appears to play a key role in the development of bacteraemia.