bluuebunny/crossref_metadata_2025_split huggingface dataset:
Finding and exploring reproducible cell phenotypes with the Stemformatics data portal
Authors: Choi Jarny , Butcher Suzanne , Angel Paul , Bransfield Jack , Barry Jake , Faux Noel , Shaban Bobbie , Pillai Priyanka , Michalewicz Aleks , Wells Christine 
Published: June 2023

AbstractStemformatics is an established online data portal which hosts hundreds of curated gene expression datasets. It has been serving the stem cell research community for over a decade, by hosting transcriptional profiles of pluripotent and adult stem cells and their progeny from multiple tissues and derivation methods. The portal provides easy-to-use online tools to explore gene expression patterns in published data. In recent years, Stemformatics has shifted its focus from curation to collation and integration of public data with shared phenotypes. It now hosts several integrated expression atlases based on human myeloid cells, which allow for easy cross-dataset comparisons and discovery of emerging cell subsets and activation properties. The inclusion of laboratory-derived cell types enables users to benchmark their own data, to assist with cell-type standardisation or improve cell-derivation methods. The sample annotations have been greatly improved to enable better data integration, and the website has also undergone a major upgrade to modernise its visualisation tools. An application programming interface server also provides the data directly for computational users. Stemformatics is an open-source project and readily available at stemformatics.org.
Bacteriophage diet breadth is impacted by interactions between bacteria
Authors: Bisesi Ave T. , Möbius Wolfram , Nadell Carey , Hansen Eleanore G. , Bowden Steven D. , Harcombe William R. 
Published: June 2023

AbstractPredators play a central role in shaping community structure, function, and stability. The degree to which bacteriophage predators (viruses that infect bacteria) evolve to be specialists with a single bacterial prey species versus generalists able to consume multiple types of prey has implications for their effect on microbial communities. The presence and abundance of multiple bacterial prey types can alter selection for phage generalists, but less is known about how interactions between prey shapes diet breadth in microbial systems. Using a phenomenological mathematical model of phage and bacterial populations, we find that the dominant phage strategy depends on prey ecology. Given a fitness cost for generalism, generalist predators maintain an advantage when prey species compete, while specialists dominate when prey are obligately engaged in cross-feeding interactions. We test these predictions in a synthetic microbial community with interacting strains ofEscherichia coliandSalmonella entericaby competing a generalist T5-like phage able to infect both prey against P22vir, anS. enterica-specific phage. Our experimental data conform to our modeling expectations when prey are competing or obligately mutualistic, although our results suggest that thein vitrocost of generalism is caused by a biological mechanism not represented in our model. Our work demonstrates that interactions between bacteria play a role in shaping ecological selection on diet breadth in bacteriophage and emphasizes the diversity of ways in which fitness trade-offs can manifest.
Imidacloprid disrupts larval molting regulation and nutrient energy metabolism, causing developmental delay in honey beeApis mellifera
Authors: Li Zhi , Wang Yuedi , Qin Qiqian , Chen Lanchun , Dang Xiaoqun , Ma Zhengang , Zhou Zeyang 
Published: June 2023

AbstractImidacloprid is a global health threat that severely poisons the economically and ecologically important honeybee pollinator,Apis mellifera. However, its effects on developing bee larvae remain largely unexplored. Our pilot study showed that imidacloprid causes developmental delay in bee larvae, but the underlying toxicological mechanisms remain incompletely understood. In this study, we exposed bee larvae to imidacloprid at environmentally relevant concentrations of 0.7, 1.2, 3.1, and 377 ppb. There was a marked dose-dependent delay in larval development, characterized by reductions in body mass, width, and growth index. However, imidacloprid did not affect on larval survival and food consumption. The primary toxicological effects induced by elevated concentrations of imidacloprid (377 ppb) included inhibition of neural transmission gene expression, induction of oxidative stress, gut structural damage, and apoptosis, inhibition of developmental regulatory hormones and genes, suppression of gene expression levels involved in proteolysis, amino acid transport, protein synthesis, carbohydrate catabolism, oxidative phosphorylation, and glycolysis energy production. In addition, we found that the larvae may use antioxidant defenses and P450 detoxification mechanisms to mitigate the effects of imidacloprid. Ultimately, this study provides the first evidence that environmentally exposed imidacloprid can affect the growth and development of bee larvae by disrupting molting regulation and limiting the metabolism and utilization of dietary nutrients and energy. These findings have broader implications for studies assessing pesticide hazards in other juvenile animals.
Catalpol inhibits HHcy-induced EndMT in endothelial cells by modulating ROS/NF-κB signaling
Authors: Wu Chengyan , Zhao Rusheng , Li Yuanhao , Li Peixia , Liu Huibing , Wang Libo , Wang Xuehui 
Published: June 2023

AbstractBackgroundHyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis (AS), the molecular mechanisms of its pathogenesis are not fully understood. Endothelial dysfunction is the key initiating link in AS. However, whether endothelial-mesenchymal transition (EndMT) is involved in the regulation of HHcy-induced endothelial dysfunction and the role of catalpol in it remain unexplored.Methods and ResultsIn vitroHHcy-treated primary human umbilical vein endothelial cells (HUVECs) were used to construct a model of endothelial dysfunction, and the antioxidants N-acetylcysteine (NAC) and catalase alcohol were administered. The endothelial dysfunction model was constructed by observing cell morphological changes, measuring intracellular reactive oxygen species (ROS) content, quantifying EndMT marker proteins (VE-cadherin, α-SMA, N-cadherin) and p-p65 and p65 protein expression by western blot, and detecting VE-cadherin and α-SMA fluorescence intensity by immunofluorescence.In vivoC57BL/6N mice were given a diet fed with 4.4% high methionine chow to construct a HHcy mice model and were treated with catalpol. The model was further validated by measuring the concentration of homocysteinemia (Hcy) in mice, HE and Masson staining to observe the pathological changes in the endothelium of aortic roots, immunohistochemistry to detect the expression of EndMT marker protein, immunofluorescence to detect the fluorescence intensity of p-p65, and fluorescent probe method to detect the content of ROS in the endothelium of aorta. The results showed that catalpol significantly inhibited HHcy-induced endothelial cell morphological transformation, reduced HHcy-induced increase in intracellular ROS content and α-SMA, N-cadherin, p-p65 protein expression, increased HHcy-induced decrease in VE-cadherin, CD31 protein expression, and was able to protect against endothelial pathological changes in the aortic root and reduce aortic endothelial ROS content.ConclusionsCatalpol inhibits HHcy-induced EndMT, and the underlying mechanism may be related to the ROS/NF-κB signaling pathway. Catalpol may be a potential drug for the treatment of HHcy-related AS.
Multiple sex chromosomes ofYponomeutaermine moths suggest a role of sexual antagonism in sex chromosome turnover in Lepidoptera
Authors: Irena Provazníková , Martina Dalíková , Anna Voleníková , Peter Roessingh , Ken Sahara , Jan Provazník , František Marec , Petr Nguyen 
Published: June 2023

AbstractSex chromosome-autosome fusions give rise to neo-sex chromosomes, which provide an insight into early evolution of sex chromosomes and drivers of chromosomal fusions. While sex chromosome-autosome fusions are scarce in vertebrates with female heterogamety (♀ZW/♂ZZ), they are common in moths and butterflies (Lepidoptera), the most species rich group with heterogametic females. This contradicts theoretical model that assumes chromosome fusions to be random and predicts them to be rare in taxa with high chromosome number such as Lepidoptera. In the present study we analyzed sex chromosomes in nine ermine moths of the genusYponomeuta(Yponomeutidae) and their two outgroups,Teinoptila gutella(Yponomeutidae) andPlutella xylostella(Plutellidae). We employed genomicin situhybridization to identify sex chromosomes and used a custom designed microarray to identify Z-linked genes. Our results confirmed a multiple sex chromosome system Z1Z2W to be present inT. gutellaand allYponomeutaspp. except forY. tokyonella. The multiple sex chromosome system resulted from a fusion between the W chromosome and autosome homeologous to theBombyx morichromosome 2 (BmChr2). The BmChr2 bears a cluster of genes with ovary-specific expression which suggests that sexually antagonistic selection could have driven fixation of the fusion in a common ancestor ofYponomeutaandTeinoptilagenera. We hypothesize that sex chromosome turnover in Lepidoptera could be driven by sexual antagonism.
TaxaHFE: A machine learning approach to collapse microbiome datasets using taxonomic structure
Authors: Oliver Andrew , Kay Matthew , Lemay Danielle G. 
Published: June 2023

ABSTRACTMotivationBiologists increasingly turn to machine learning models not just to predict, but to explain. Feature reduction is a common approach to improve both performance and interpretability of models. However, some biological data sets, such as microbiome data, are inherently organized in a taxonomy, but these hierarchical relationships are not leveraged during feature reduction. We sought to design a feature engineering algorithm to exploit relationships in hierarchically organized biological data.ResultsWe designed an algorithm, called TaxaHFE, to collapse information-poor features into their higher taxonomic levels. We applied TaxaHFE to six previously published datasets and found, on average, a 90% reduction in the number of features (s.d = 5.1%) compared to using the most complete taxonomy. Using machine learning to compare the most resolved taxonomic level (i.e., species) against TaxaHFE-preprocessed features, models based on TaxaHFE features achieved an average increase of 3.47% in receiver operator curve area under the curve (ROC-AUC). Compared to other hierarchical feature engineering implementations, TaxaHFE introduces the novel ability to consider both categorical and continuous response variables to inform the feature set collapse. Importantly, we find TaxaHFE’s ability to reduce hierarchically organized features to a more information-rich subset increases the interpretability of models.Availability and ImplementationTaxaHFE is available as a Docker image and as R code athttps://github.com/aoliver44/taxaHFE.
Approximate Bayesian computational methods to estimate the strength of divergent selection in population genomics models
Authors: Lukaszewicz Martyna , Salia Ousseini Issaka , Hohenlohe Paul A. , Buzbas Erkan O. 
Published: June 2023

AbstractStatistical estimation of parameters in large models of evolutionary processes using SNP data is often too computationally inefficient to pursue using exact model likelihoods. Approximate Bayesian Computation (ABC) to perform statistical inference about parameters of large models takes the advantage of simulations to bypass direct evaluation of model likelihoods. We use forward-in-time simulations of a mechanistic model of divergent selection with variable migration rates, modes of reproduction (sexual, asexual), length and number of migration-selection cycles, and investigate the computational feasibility of ABC to perform statistical inference and study the quality of estimates on the position of loci under selection and the strength of selection. We evaluate usefulness of summary statistics well-known to capture the strength of selection, and assess their informativeness under divergent selection. We also evaluate the effect of genetic drift with respect to an idealized deterministic model with single-locus selection. We discuss the role of the recombination rate as a confounding factor in estimating the strength of divergent selection, and we answer the question for which part of the parameter space of the model we recover strong signal for estimating the selection and make recommendations which summary statistics perform well in estimating selection.
Cleaving DNA with DNA: cooperative tuning of structure and reactivity driven by copper ions
Authors: Dantu Sarath Chandra , Khalil Mahdi , Bria Marc , Saint-Pierre Christine , Gasparutto Didier , Sicoli Giuseppe 
Published: June 2023

Abstract/SummaryA copper-dependent self-cleaving DNA (DNAzyme or dexoxyribozyme) previously isolated byin vitroselection has been analyzed by a combination of Molecular Dynamics simulations and advanced EPR/ESR spectroscopy, providing insights on the structural and mechanistic features of the cleavage reaction at unprecedented resolution. The minimized 46-nucleotide deoxyribozyme forms duplex and triplex substructures that flank a highly conserved catalytic core. The self-cleaving construct forms a bimolecular complex that has a distinct substrate and enzyme domains. Cleavage of the substrate is directed at one of two adjacent nucleotides and proceedsviaan oxidative cleavage mechanism that is unique to the position cleaved. The use of isotopologues of nucleotides allowed us to provide atomic resolution for the copper-substrate complex. The spectroscopic analysis overcomes the major drawbacks related to the ‘metal-soup’ scenario, also known as ‘super-stoichiometric’ ratios of cofactorsversussubstrate, conventionally required for the cleavage reaction within those nucleic acids-based enzymes. Our results pave the way for analysis on mixtures where metals/lanthanides are used as cofactors, having demonstrated that our approach may reach resolution of single nucleotide and beyond. Furthermore, the insertion of cleavage reaction within more complex architectures is now a realistic option towards the applicability of spectroscopic studies, bothin vitroandin vivomatrices.
Effects of sequence-dependent non-native interactions in equilibrium and kinetic folding properties of knotted proteins
Authors: Especial João N. C. , Faísca Patrícia F. N. 
Published: June 2023

AbstractDetermining the role of non-native interactions in folding dynamics, kinetics and mechanisms is a classical problem in protein folding. More recently, this question has witnessed a renewed interest in light of the hypothesis that knotted proteins require the assistance of non-native interactions to fold efficiently. Here, we conducted extensive equilibrium and kinetic Monte Carlo simulations of a simple off-lattice C-alpha model to explore the role of non-native interactions in the thermodynamics and kinetics of three proteins embedding a trefoil knot in their native structure. We find that equilibrium knotted conformations are stabilized by non-native interactions that are non-local, and proximal to native ones, thus enhancing them. Additionally, non-native interactions increase the knotting frequency at high temperature, and in partially folded conformations below the transition temperature. While non-native interactions clearly enhance the efficiency of the transition from an unfolded conformation to a partially folded knotted one, they are not required to efficiently fold a knotted protein. Indeed, a native centric interaction potential drives the most efficient folding transition, provided that the simulation temperature is well below the transition temperature of the considered model system.
APlasmodium falciparumgenetic cross reveals the contributions ofpfcrtandplasmepsin II/IIIto piperaquine drug resistance
Authors: Kane John , Li Xue , Kumar Sudhir , Button-Simons Katrina A. , Vendrely Brenneman Katelyn M. , Dahlhoff Haley , Sievert Mackenzie A.C. , Checkley Lisa A. , Shoue Douglas A. , Singh Puspendra P. , Abatiyow Biley A. , Haile Meseret T. , Nair Shalini , Reyes Ann , Tripura Rupam , Peto Tom , Lek Dysoley , Kappe Stefan H.I. , Dhorda Mehul , Nkhoma Standwell C , Cheeseman Ian H. , Vaughan Ashley M. , Anderson Timothy J. C. , Ferdig Michael T. 
Published: June 2023

AbstractPiperaquine (PPQ) is widely used in combination with dihydroartemisinin (DHA) as a first-line treatment against malaria parasites. Multiple genetic drivers of PPQ resistance have been reported, including mutations in thePlasmodium falciparum chloroquine resistance transporter(pfcrt) and increased copies ofplasmepsin II/III(pm2/3). We generated a cross between a Cambodia-derived multi-drug resistant KEL1/PLA1 lineage isolate (KH004) and a drug susceptible parasite isolated in Malawi (Mal31). Mal31 harbors a wild-type (3D7-like) pfcrtallele and a single copy ofpm2/3,while KH004 has a chloroquine-resistant (Dd2-like) pfcrtallele with an additional G367C substitution and four copies ofpm2/3. We recovered 104 unique recombinant progeny and examined a targeted set of progeny representing all possible combinations of variants atpfcrt and pm2/3for detailed analysis of competitive fitness and a range of PPQ susceptibility phenotypes, including PPQ survival assay (PSA), area under the dose-response curve (AUC), and a limited point IC50(LP-IC50). We find that inheritance of the KH004pfcrtallele is required for PPQ resistance, whereas copy number variation inpm2/3further enhances resistance but does not confer resistance in the absence of PPQ-R-associated mutations inpfcrt. Deeper investigation of genotype-phenotype relationships demonstrates that progeny clones from experimental crosses can be used to understand the relative contributionsof pfcrt, pm2/3,and parasite genetic background, to a range of PPQ-related traits and confirm the critical role of the PfCRT G367C substitution in PPQ resistance.ImportanceResistance to PPQ used in combination with DHA has emerged in Cambodia and threatens to spread to other malaria-endemic regions. Understanding the causal mutations of drug resistance and their impact on parasite fitness is critical for surveillance and intervention, and can also reveal new avenues to limiting the evolution and spread of drug resistance. An experimental genetic cross is a powerful tool for pinpointing the genetic determinants of key drug resistance and fitness phenotypes and have the distinct advantage of assaying the effects of naturally evolved genetic variation. Our study was significantly strengthened because the full a range of copies of KH004pm2/3was inherited among the progeny clones, allowing us to directly test the roleof pm2/3copy number on resistance-related phenotypes in the context of a uniquepfcrtallele. Our multi-gene model suggests an important role for both loci in the evolution of this ACT resistant parasite lineage.
Does improved (Limu) maize variety adoption improves rural households’ food security: evidence from Dale Wabara district, Ethiopia
Authors: Tesfa Bikila , Eneyew Adugna , Mitiku Fikadu 
Published: June 2023

AbstractAdopting improved agricultural technology is important instruments to ensure household food security. There is, however, limited empirical evidence on impacts of adoption of improved maize varieties grown by smallholder farmers. Consequently, the study examined the impact of Limu maize variety adoption on rural households’ food security in Dale Wabara District, Ethiopia. Quantitative and qualitative data were collected from both primary and secondary sources. Three-stage sampling technique was employed to select 319 households for primary data collection. Binary logit model regression model and propensity score matching model were used to investigate determinants of Limu maize variety adoption and its impact on rural households’ food security, respectively. Furthermore, daily calorie intake per adult equivalent was used to measure food security status of household in study area. According to the results of the binary logit regression model households head education, family size, total land size, frequency of extension visits, livestock ownership and availability of Limu maize seed increases the likelihood of household’s adoption of Limu maize variety. The result of propensity score matching model shows that adoption of improved Limu maize variety significantly improve household food security (daily calorie intake). Empirical evidence shows that adopter households are better-off than non-adopter households in terms of their daily calorie intake. Thus, it can be concluded that Limu maize variety adoptions significantly contribute to the economic and social development of smallholder farmers by increasing food security status in study areas. It is therefore recommended that wider distribution of Limu maize variety has to be prioritized to improve food security in study areas.
An X Chromosome Transcriptome Wide Association Study Implicates ARMCX6 in Alzheimer’s Disease
Authors: Zhang Xueyi , Gomez Lissette , Below Jennifer , Naj Adam , Martin Eden , Kunkle Brian , Bush William S. 
Published: June 2023

AbstractBackgroundThe X chromosome is often omitted in disease association studies despite containing thousands of genes which may provide insight into well-known sex differences in the risk of Alzheimer’s Disease.ObjectiveTo model the expression of X chromosome genes and evaluate their impact on Alzheimer’s Disease risk in a sex-stratified manner.MethodsUsing elastic net, we evaluated multiple modeling strategies in a set of 175 whole blood samples and 126 brain cortex samples, with whole genome sequencing and RNA-seq data. SNPs (MAF>0.05) within thecis-regulatory window were used to train tissue-specific models of each gene. We apply the best models in both tissues to sex-stratified summary statistics from a meta-analysis of Alzheimer’s disease Genetics Consortium (ADGC) studies to identify AD-related genes on the X chromosome.ResultsAcross different model parameters, sample sex, and tissue types, we modeled the expression of 217 genes (95 genes in blood and 135 genes in brain cortex). The average model R2was 0.12 (range from 0.03 to 0.34). We also compared sex-stratified and sex-combined models on the X chromosome. We further investigated genes that escaped X chromosome inactivation (XCI) to determine if their genetic regulation patterns were distinct. We found ten genes associated with AD at p < 0.05, with onlyARMCX6in female brain cortex (p = 0.008) nearing the significance threshold after adjusting for multiple testing (α = 0.002).ConclusionsWe optimized the expression prediction of X chromosome genes, applied these models to sex-stratified AD GWAS summary statistics, and identified one putative AD risk gene,ARMCX6.