bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transfer learning applied in predicting small molecule bioactivity
Authors: Tian Li , Huang Hugh Hongkai , Martin Eric , Wei Judy Ying , Xu Shaoyong , Huang Junzhou 
Published: January 2025

AbstractDespite over a half-century of effort by computational chemists, developing accurate empirical QSAR (Quantitative Structure-Activity Relationships) models for predicting bioactivity directly from chemical structure has remained elusive. The difficulties have been especially pronounced for virtual screening, finding new active compounds substantially different from the known chemical matter used to train the models. Recent breakthroughs have been achieved by employing transfer of learning across huge numbers of bioactivity assays, greatly increasing the amount and diversity of chemical and biological information that informs each model. An early example was Profile-QSAR (pQSAR), a 2-level stacked model, where level-2 PLS (Partial Least Squares) models characterize compounds by their profile of bioactivity predictions from individual level-1 random forest regression QSAR models built on up to 10,000+ other assays. This study introduces metaNN, a meta-learner that trains deep neural networks (DNN) for each individual assay initialised from a well-generalized consensus DNN optimized across all assays. Comparison of the results suggested that while Profile-QSAR and metaNN perform similarly overall, metaNN works slightly better for smaller assays which were well-predicted by the consensus DNN; whereas pQSAR struggled more with smaller assays, due to the large number of level-1 models but was less sensitive to similarity to an overall consensus. An ensemble average of both methods combined the strengths of each, working better than either alone. The similar performance of the 2 largely orthogonal algorithms raises questions about whether we are approaching a limit of prediction accuracy in transfer learning, for this application scenario.
Involvement of PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1 in COPII assembly by interacting with SAR1 GTPase
Authors: Lung (龍惠方) Hui-Fang , Chu Jia-Dong , Liu Tzu-Yin 
Published: January 2025

AbstractThe plant-specific endoplasmic reticulum (ER)-resident PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1 (PHF1) is structurally related to SEC12, which initiates the coat protein complex II (COPII) assembly as a guanine nucleotide exchange factor (GEF) by activating the small GTPase SAR1. In contrast, PHF1 loses the conserved catalytic residues critical for GEF activity and instead specifically assists the ER exit of the plant PHOSPHATE TRANSPORTER1 (PHT1) family. However, the underlying molecular mechanism remains to be elucidated. In this study, we showed that the overexpression ofArabidopsis thalianaPHT1;1 (AtPHT1;1) but not of SUGAR TRANSPORTER 1 (AtSTP1) caused a portion ofAtPHF1 distribution intoAtSAR1b-,AtSAR1c- andAtSEC24a-labeled ER exit sites in the tobacco transient expression system. Based on thein-plantatripartite split-GFP association,AtPHF1 interacted withAtSAR1b andAtSAR1c but not with other COPII-related proteins. By performing the miniTurbo-based proximity labeling in agro-infiltrated tobacco leaves, we verified the interaction ofAtPHF1 andAtSAR1b and demonstrated its physiological relevance by co-immunoprecipitation of the endogenousAtPHF1 andAtPHT1;1/2/3 proteins withAtSAR1c-GFP usingArabidopsistransgenic lines. Furthermore, while both the cytosolic and transmembrane domains ofAtPHF1 contribute to the interaction withAtSAR1b andAtSAR1c,AtPHF1 preferentially interacted with the GDP-locked inactive form ofAtSAR1b. On the basis of these findings, we propose that by interacting with SAR1 GTPase, PHF1 participates in the early step of COPII recruitment for the ER export of PHT1 proteins.
Re-visiting the potential impact of doxycycline post-exposure prophylaxis (doxy-PEP) on the selection of doxycycline resistance inNeisseriacommensals
Authors: Robinson Leah R. , McDevitt Caroline J. , Regan Molly R. , Quail Sophie L. , Swartz Makenna , Wadsworth Crista B. 
Published: January 2025

ABSTRACTDoxycycline post-exposure prophylaxis (doxy-PEP) is a preventative strategy demonstrated to reduce bacterial sexually transmitted infections in high-risk populations. However, the impact of doxy-PEP on antibiotic resistance acquisition in key members of our microbiomes, is as of yet unclear. For example, commensalNeisseriaare known reservoirs of resistance for gonococci through horizontal gene transfer (HGT), and are more likely to experience bystander selection due to doxy-PEP as they are universally carried. Thus, the consequences of doxycycline selection on commensalNeisseriawill be critical to investigate to understand possible resistance mechanisms that may be transferred to an important human pathogen. Here, we usein vitroantibiotic gradients to evolve fourNeisseriacommensals (N. cinerea, N. canis, N. elongata, and N. subflava,n=4 per species) across a 20-day time course; and use whole genome sequencing to nominate derived mutations. After selection, 12 of 16 replicates evolved doxycycline resistance (> 1 μg/mL). Across resistant lineages: An A46T substitution in the repressor of the Mtr efflux pump (MtrR) and a V57M substitution in the 30 ribosomal protein S10 were clearly associated with elevated MICs. Additional mutations in ribosomal components also emerged in strains with high MICs (i.e.,16S rRNA G1057C, RplX A14T). We find the MtrR 46T, RpsJ 57M, and RplX 14T circulating in natural commensal populations. Furthermore,in vitroco-evolution ofN. gonorrhoeaewithNeisseriacommensals demonstrated rapid transfer of the pConj plasmid toN. subflavaandN. cinerea, and pblatoN. cinerea. Finally, collection of novel commensals from human hosts reveals 46% of isolates carrying doxycycline resistance; and doxycycline resistance was significantly greater in participants self-reporting doxycycline use in the past 6 months. High-level doxycycline resistance (> 8 μg/mL) was always associated with carriage of the ribosomal protection protein (tetM)and pConj. Ultimately, characterizing the contemporary prevalence of doxycycline resistance, and underlying resistance mechanisms, in commensal communities may help us to predict the long-term impact of doxy-PEP onNeisseria, and the likelihood of transferring particular genotypes across species’ boundaries.
Source of dietary protein alters the abundance of proteases, intestinal epithelial and immune proteins both directly and via interactions with the gut microbiota
Authors: Awan Ayesha , Bartlett Alexandria , Blakeley-Ruiz J. Alfredo , Richie Tanner , Ziegler Amanda , Kleiner Manuel 
Published: January 2025

AbstractDietary protein has been shown to impact long-term health outcomes differentially depending on its amount and source. It has been suggested that interactions of the gut microbiota with dietary proteins mediate some of the effects of dietary protein on health outcomes. However, it remains unclear what specific host responses drive the health effects of dietary proteins from different plant and animal sources. Additionally, which specific host responses are mediated by interactions of dietary protein source with the gut microbiota and which host responses are caused by dietary proteins directly is not well understood. We used metaproteomics to quantify dietary, host, and microbial proteins in fecal samples of conventional and germ-free mice fed purified dietary protein from six different plant and animal sources, including casein, egg-white, soy, brown rice, pea, and yeast. We characterized differences in the host fecal proteome across the six dietary protein sources as well as between the conventional and germ-free mice for each source to determine how the host responds to the different dietary protein sources and the role of the gut microbiota in mediating these responses. We found that both the source of dietary protein and the presence or absence of the gut microbiota drive the host response to dietary protein source in the fecal host proteome. Host proteins pertaining to immune response, digestion, and barrier function were differentially abundant in different protein sources with and without the gut microbiota. These changes in the host response correlated with changes in microbial composition and differences in protein digestibility. Our results show how dietary protein sources, through their interactions with the gut microbiota, impact several aspects of host physiology.
Canaries differentially modulate solo and overlapping singing during the transition to the breeding season
Authors: Totiger Santhosh , Alcami Pepe 
Published: January 2025

AbstractSongbirds sing different song types depending on the social context. Songs can be categorized into two types based on their timing relative to other birds’ songs: solo and temporally-over-lapping songs. Overlapping songs have been typically characterized in the breeding season, in which they are associated with an aggressive social context. However, whether both song types occur year long, and whether they show differential modulation of their frequency and properties during the transition between the non-breeding and the breeding season has been rarely studied. Here we investigate, in a group of domesticated canaries(Serinus canaria), the variation of singing in both song types at the transition between the nonbreeding and the breeding season. We found that both song types were present outside the breeding season. Whereas for solo songs, duration and its variability, fraction of time singing and number of songs increased as the breeding season approached, overlapping songs showed opposite trends. Furthermore, both song types were distributed more homogeneously as the daylength increased. Overall, the differential changes of both song types at the seasonal time scale suggest differential underlying mechanisms and functions of these two song types found in a social setting.
Structural insights into mechanisms of zinc scavenging by theCandida albicanszincophore Pra1
Authors: Syrjanen Johanna L , Nore Alexandre , Roselletti Elena , Chakraborty Tanmoy , Perera Rajika L , Wilson Duncan 
Published: January 2025

AbstractCandida albicanscauses more than 400,000 life-threatening, and half a billion mucosal infections annually. In response to infection, the host limits availability of essential micronutrients, including zinc, to restrict growth of the invading pathogen. As assimilation of zinc is essential forC. albicanspathogenicity, its limitation induces the secretion of the zincophore protein Pra1 to scavenge zinc from the host. Pra1 also plays a number of important roles in host-pathogen interactions and is conserved in most fungi. However, the structure of fungal zincophores is not known. Here, we present the first cryogenic electron microscopy structures ofC. albicansPra1 in its apo- and zinc- bound states, at 2.8 and 2.5 Å resolution respectively. Our work reveals a hexameric ring-like assembly with multiple zinc binding sites. Through genetic studies, we show that one of these zinc binding sites is essential forC. albicansgrowth under zinc restriction but does not affect the inflammatory properties of Pra1. These data provide a foundation for future work to explore the structural basis of Pra1-mediated host-pathogen interactions,C. albicanszinc uptake, as well therapeutics development.
The complete λ-carrageenan depolymerization cascade from a marine Pseudoalteromonad revealed by structural analysis of the enzymes
Authors: Vickers Chelsea J. , Hettle Andrew G. , Hobbs Joanne K. , Shapiro-Ward Sarah , Pluvinage Benjamin , Medley Brendon J. , McGuire Bailey E. , Mihalynuk Liam , Nitin  , Zandberg Wesley F. , Boraston Alisdair B. 
Published: January 2025

AbstractCarrageenans are a complex group of polysaccharides derived from the cell walls of red macroalgae. They are an abundant, yet recalcitrant nutrient source for most marine heterotrophic bacteria. Some member species of thePseudoalteromonasgenus are effective at metabolizing carrageenan. However, the enzymatic pathway for λ-carrageenan, one of the most sulfated naturally occurring polysaccharides, remains unknown. Using detailed structural analysis by X-ray crystallography we reveal the sophisticated and cyclic enzymatic cascade deployed byPseudoalteromonas distincta(strain U2A) to utilize λ-carrageenan. The cascade incorporates ten glycoside hydrolases and five sulfatases that are specific for λ-carrageenan and cooperate to completely deconstruct this polysaccharide, thus yielding galactose monosaccharides for subsequent energy production. The detailed molecular understanding of λ-carrageenan depolymerisation provided includes structural evidence for a lesser described sulfatase catalytic mechanism and elucidation of a distinct catabolic cascade that is unique from previously described carrageenan metabolic pathways. This insight also holds potential for the application of enzymatic logic in the generation of high value products from abundant natural biopolymers, such as carrageenans.
A neural signature of touch aversion and interpersonal problems in Borderline Personality Disorder
Authors: Voelter Jella , Postin Danilo , Croy Ilona , Hurlemann René , Scheele Dirk 
Published: January 2025

AbstractIntroductionPatients with borderline personality disorder (BPD) suffer from severe social impairments and interpersonal problems. Social touch can provide comfort and facilitate the maintenance of social bonds, and preliminary evidence indicates a negative evaluation of social touch in patients with BPD. However, the neural mechanisms underlying aberrant touch processing in BPD and its role for social impairments are still unclear.MethodsWe recruited 55 BPD patients and 31 healthy controls and used functional magnetic resonance imaging to probe neural responses to slow (i.e. C-tactile (CT)-optimal; affective) and fast (i.e. CT-suboptimal; discriminative) touch before and after four weeks of a residential dialectical behavior therapy (DBT) program. In addition to assessing BPD symptoms and interpersonal problems, we evaluated touch allowance maps and the attitude towards social touch.ResultsBPD patients showed a comprehensive negative bias towards social touch before the DBT, evident in a significantly more negative attitude towards and reduced comfort zones of social touch compared to healthy controls. Moreover, reduced comfort zones of social touch were associated with more interpersonal problems. Activation in the posterior insular cortex in response to CT-optimal touch was significantly reduced and correlated with the severity of interpersonal problems in BPD patients. Despite significant improvements in overall BPD symptom load, dysfunctional social touch processing persisted after four weeks of DBT, indicating trait-like disturbances in BPD.ConclusionsAn impaired insula-mediated integration of affective and sensory components of touch may constitute a clinically relevant biological signature of the complex interpersonal problems in BPD.
Sex Differences in the Comorbidity between Attention Deficit-Hyperactivity Disorder and Posttraumatic Stress Disorder: A Systematic Literature Review and Meta-Analysis
Authors: Wilson Julia , Fida Doruntina , Maurer Rie , Wiley Aleta , Rajasekera Therese , Spagnolo Primavera 
Published: January 2025

AbstractObjectiveAttention Deficit-Hyperactivity Disorder (ADHD) and Posttraumatic Stress Disorder (PTSD) are often comorbid and share a common core of symptoms. However, sex and gender-related factors significantly influence their prevalence, clinical presentation, and diagnosis. Here, we conducted a systematic literature review and meta-analysis to examine sex differences in ADHD/PTSD comorbidity during childhood and adulthood.MethodsA scoping review of PsycINFO and PubMed yielded 13 eligible studies with complete outcome data. We conducted fixed-effects meta-analyses of the sex-stratified prevalence of ADHD/PTSD using pooled odds ratios (OR) with a 95% confidence interval (CI). Fixed-effects subgroup analyses were performed using age as a subgroup. Effect size heterogeneity was assessed using the I2index and Cochran’s Q test.ResultsIn the whole sample (N= 13,585; F= 7005, M= 6580), the diagnosis of ADHD/PTSD was significantly higher in females than in males (OR = 1.32,p= 0.02). Between-study heterogeneity was low-to-moderate and not significant (I2= 41%;p= 0.06), validating the fixed-effects model. Age-stratified subgroup analyses revealed higher ADHD/PTSD odds in females compared to males only in adult populations (OR=1.41;p =0.01). Additionally, females were more likely to be diagnosed with both disorders in studies where ADHD was the primary diagnosis (OR = 1.60;p =0.002), and in studies employing structured clinical interviews as diagnostic tools (OR = 1.46;p =0.009).ConclusionsOur study is the first to show that the association between ADHD and PTSD is stronger in females, suggesting that ADHD may increase risk for PTSD in a sex-specific manner.
Dynamic global acetylation remodeling during the yeast heat shock response
Authors: Hardman-Kavanaugh Rebecca E. , Storey Aaron J. , Stuecker Tara N. , Hood Stephanie E. , Barrett-Wilt Gregory A. , Krishnamurthi Venkata R. , Wang Yong , Byrum Stephanie D. , Mackintosh Samuel G. , Edmondson Rick D. , Wahls Wayne P. , Tackett Alan J. , Lewis Jeffrey A. 
Published: January 2025

AbstractAll organisms experience stress and must rapidly respond to changing conditions. Thus, cells have evolved sophisticated rapid-response mechanisms such as post-translational protein modification to rapidly and reversibly modulate protein activity. One such post-translational modification is reversible lysine acetylation, where proteomic studies have identified thousands of acetylated proteins across diverse organisms. While the sheer size of the ‘acetylome’ is striking, the function of acetylation for the vast majority of proteins remains largely obscure. Here, we show that global acetylation plays a previously unappreciated role in the heat shock response ofSaccharomyces cerevisiae.We find that dysregulated acetylation renders cells heat sensitive, and moreover, that the acetylome is globally remodeled during heat shock over time. Using quantitative acetyl-proteomics, we identified ∼400 high-confidence acetyl marks across ∼200 proteins that significantly change in acetylation when cells are shifted to elevated temperature. Proteins with significant changes in lysine acetylation during heat shock strongly overlap with genes induced or repressed by stress. Thus, we hypothesize that protein acetylation augments the heat shock response by activating induced proteins and inactivating repressed proteins. Intriguingly, we find nearly 40 proteins with at least two acetyl marks that significantly change in the opposite directions. These proteins are strongly enriched for chaperones and ribosomal proteins, suggesting that these two key processes are coordinately regulated by protein acetylation during heat shock. Moreover, we hypothesize that the same type of activating and inactivating marks that exist on histones may be a general feature of proteins regulated by acetylation. Overall, this work has identified a new layer of post-translational regulation that likely augments the classic heat shock response.
Role of the curvaton after the last Planck dataset
Authors: Choi Gongjun , Ke Wenqi , Olive Keith A. 
Published: January 2025

The expected improvements in the precision of inflationary physics observables including the scalar spectral index ns and the tensor-to-scalar ratio r will reveal more than just the viability of a particular model of inflation. In the presence of a curvaton field χ, supposedly dead models of inflation can be resurrected, as these observables are affected by curvaton perturbations. For currently successful models, improved constraints will enable us to constrain the properties of extra decaying scalar degrees of freedom produced during inflation. In this work, we demonstrate these diverse uses of a curvaton field with the most recent constraints on (ns,r) and two exemplary inflation models, a Starobinsky-like model and a model of new inflation. The specific models used as examples can be derived in the context of supergravity. Our analysis invokes three free parameters: the curvaton mass mχ, its decay rate Γχ, and the reheating temperature TRH produced by inflaton decays. We systematically analyze possible postinflationary era scenarios of a curvaton field. By projecting the most recent cosmic microwave background (CMB) data on (ns,r) into this parameter space, we can either set constraints on the curvaton parameters from successful models of inflation (so that the success is not spoiled) or determine the parameters that are able to save a model for which ns is predicted to be below the experimental data. We emphasize that the initial value of ⟨χ2⟩∝H4/mχ2 produced during inflation is determined from a stochastic approach and thus not a free parameter in our analysis. We also investigate the production of local non-Gaussianity fNL(loc) and apply current CMB constraints to the parameter space. Intriguingly, we find that a large value of fNL(loc) of O(1) can be produced for both of the two representative inflation models.

Published by the American Physical Society
2025
Workplace practices and work-life balance in Europe: the role of gender and home and family care
Authors: Ferreira Pedro , Gomes Sofia , Lopes João M. 
Published: January 2025

Purpose
The purpose of this study is to explore the ways in which work practices promote work-life balance when family time is available (as a spillover effect from work to personal life) and how differently they affect men and women.

Design/methodology/approach
A quantitative and longitudinal approach is taken based on data from a large database made up of 71,758 workers from 36 European countries, collected in 2021 by the European Working Conditions Survey. After preliminary analysis (including exploratory and confirmatory factorial analysis), the partial least square method was used to test the hypothesis of the conceptual model.

Findings
The results of this study reveal that some work practices (autonomy and confidence at work) positively affect work-life balance. The time available for family and domestic care positively affects work-life balance, and this effect is more relevant for women than for men.

Practical implications
These results are important for organizations that wish to promote not only family-friendly work practices but also above all gender-friendly work practices.

Originality/value
Based on a large sample of European workers, this study makes an important contribution by filling the gap on the understanding and importance of mechanisms outside the organizational context for promoting work-life balance through work practices, thus extending the notion of spillover effects while considering gender differences.