bluuebunny/crossref_metadata_2025_split huggingface dataset:
Convergence and horizontal gene transfer drive the evolution of anaerobic methanotrophy in archaea
Authors: Woods Philip H. , Speth Daan R. , Laso-Pérez Rafael , Utter Daniel R. , Ruff S. Emil , Orphan Victoria J. 
Published: May 2024

1AbstractDespite their large environmental impact and multiple independent emergences, the processes leading to the evolution of anaerobic methanotrophic archaea (ANME) remain unclear. This work uses comparative metagenomics of a recently evolved but understudied ANME group, ‘CandidatusMethanovorans’ (ANME-3) to identify evolutionary processes and innovations at work in ANME which may be obscured in earlier evolved lineages. Within members ofMethanovorans, we identified convergent evolution in carbon and energy metabolic genes as likely drivers of ANME evolution. We also identified erosion of genes required for methylotrophic methanogenesis along with horizontal acquisition of multi-heme cytochromes and other loci uniquely associated with ANME. The assembly and comparative analysis of multiple Methanovorans genomes offers important functional context for understanding the niche-defining metabolic differences between methane-oxidizing ANME and their methanogen relatives. Furthermore, this work illustrates the multiple evolutionary modes at play in the transition to a novel and globally important metabolic niche.
ATP and glutamate coordinate contractions in the freshwater spongeEphydatia muelleri
Authors: Ho Vanessa R , Goss Greg G , Leys Sally P 
Published: May 2024

AbstractSponges (phylumPorifera) are an early diverging animal lineage that lacks both conventional nervous and muscular systems, and yet they are able to produce coordinated whole-body contractions in response to disturbances. Little is known about the underlying signaling mechanisms in coordinating such responses. Previous studies demonstrated that sponges respond specifically to neuroactive chemicals such as L-glutamate and γ-amino-butyric acid (GABA), which trigger and prevent contractions respectively. Genes for purinergic P2X-like receptors are present in several sponge genomes, leading us to ask whether ATP works with glutamate to coordinate contractions in sponges as it does in other animal nervous systems. Using pharmacological approaches on the freshwater spongeEphydatia muelleri, we show that ATP is involved in coordinating contractions. Bath applications of ATP cause a rapid, sustained expansion of the excurrent canals in a dose-dependent manner. Complete contractions occur when ATP is added in the presence of apyrase, an enzyme that hydrolyzes ATP. Applying ADP, the first metabolic product of ATP hydrolysis, triggers complete contractions, whereas AMP, the subsequent metabolite, does not trigger a response. Blocking ATP from binding and activating P2X receptors with pyridoxalphosphate-6-azophenyl-2’,4’-disulfonic acid (PPADS) prevents both glutamate- and ATP-triggered contractions, suggesting that ATP works downstream of glutamate. Bioinformatic analysis revealed two P2X receptor sequences, one which groups with other vertebrate P2X receptors. Altogether, our results confirm that purinergic signaling by ATP is involved in coordinating contractions in the freshwater sponge suggesting a role of ATP-mediated signaling that predates the evolution of the nervous system and multicellularity in animals.Summary statementNerveless sponges coordinate a sneeze-like reflex using glutamate and ATP signaling to expel water from the body.
Linking regulatory variants to target genes by integrating single-cell multiome methods and genomic distance
Authors: Dorans Elizabeth , Jagadeesh Karthik , Dey Kushal , Price Alkes L. 
Published: May 2024

AbstractMethods that analyze single-cell paired RNA-seq and ATAC-seq multiome data have shown great promise in linking regulatory elements to genes. However, existing methods differ in their modeling assumptions and approaches to account for biological and technical noise—leading to low concordance in their linking scores—and do not capture the effects of genomic distance. We propose pgBoost, an integrative modeling framework that trains a non-linear combination of existing linking strategies (including genomic distance) on fine-mapped eQTL data to assign a probabilistic score to each candidate SNP-gene link. We applied pgBoost to single-cell multiome data from 85k cells representing 6 major immune/blood cell types. pgBoost attained higher enrichment for fine-mapped eSNP-eGene pairs (e.g. 21x at distance >10kb) than existing methods (1.2-10x; p-value for difference = 5e-13 vs. distance-based method and < 4e-35 for each other method), with larger improvements at larger distances (e.g. 35x vs. 0.89-6.6x at distance >100kb; p-value for difference < 0.002 vs. each other method). pgBoost also outperformed existing methods in enrichment for CRISPR-validated links (e.g. 4.8x vs. 1.6-4.1x at distance >10kb; p-value for difference = 0.25 vs. distance-based method and < 2e-5 for each other method), with larger improvements at larger distances (e.g. 15x vs. 1.6-2.5x at distance >100kb; p-value for difference < 0.009 for each other method). Similar improvements in enrichment were observed for links derived from Activity-By-Contact (ABC) scores and GWAS data. We further determined that restricting pgBoost to features from a focal cell type improved the identification of SNP-gene links relevant to that cell type. We highlight several examples where pgBoost linked fine-mapped GWAS variants to experimentally validated or biologically plausible target genes that were not implicated by other methods. In conclusion, a non-linear combination of linking strategies, including genomic distance, improves power to identify target genes underlying GWAS associations.
Investigating psychobiological causes and mechanisms in functional seizures and functional motor symptoms: Study protocol
Authors: Pick Susannah , David Anthony S. , Edwards Mark J. , Goldstein Laura H. , Hodsoll John , Merritt Millman L. S. , Nicholson Timothy R. , Reinders A.A.T.S. , Stanton Biba , Winston Joel S. , Mehta Mitul A. , Chalder Trudie , Hotopf Matthew 
Published: May 2024

AbstractIntroductionAdvances have been made in understanding the aetiology of functional neurological disorder (FND); however, its pathophysiological mechanisms have not been definitively demonstrated. Evidence suggests interacting roles for altered emotional processing and interoception, elevated autonomic arousal, and dissociation, but there is limited evidence demonstrating their causal influence on specific FND symptoms. Our superordinate aim is to elucidate potentially shared and distinct aetiological factors and mechanisms in two common FND subtypes, functional seizures (FS) and functional motor symptoms (FMS).MethodsThis study has a multimodal, mixed between- and within-groups design. The target sample is 50 individuals with FS, 50 with FMS, 50 clinical controls (anxiety/depression), and 50 healthy controls. Potential aetiological factors (e.g., adverse life events, physical/mental health symptoms, dissociative tendencies, interoceptive insight/sensibility) will be assessed with a detailed medical history interview and self-report questionnaires. A laboratory session will include a neurocognitive battery, psychophysiological testing, cardiac interoception and time estimation tasks and an isometric handgrip task. A subsample will undergo magnetic resonance imaging, including structural, resting-state and task-based scans combined with psychophysiological recording. Remote monitoring with ecological momentary assessment and wearables will measure variability in FND symptoms and in patients’ daily lives and their potential predictors/correlates for ≥2 weeks. Longitudinal follow-ups at 3, 6, and 12-months will monitor longer-term outcomes in the clinical groups.DiscussionThis study employs multimodal research methods to rigorously examine several putative mechanisms in FND, at subjective/experiential, behavioural, and physiological levels. The study will test causal hypotheses about the role of altered emotional processing, autonomic arousal, dissociation and interoception in the initiation or exacerbation of FND symptoms, directly comparing these processes in FS and FMS to healthy and clinical controls. This is the first study of its kind, with potential to reveal important targets for prevention and treatment of FND in future.
Early detection of anastomotic leakage in upper gastrointestinal surgery
Authors: Merboth Felix , Sonntag Friederike , Sonntag Katharina , Reißfelder Christoph , Stange Daniel E. , Weitz Jürgen , Bogner Andreas 
Published: May 2024

AbstractBackgroundAlthough surgical methods for upper gastrointestinal tract cancer continue to advance with the aim of reducing the incidence of anastomotic leakage (AL), it remains a prevalent and serious complication. Therefore, early identification of patients at high risk for AL is necessary for timely therapeutic measures.MethodsWe retrospectively identified patients with AL who underwent elective gastric/esophageal resection at our department between 2005 and 2017. Using propensity score matching, a comparison group without AL but with comparable baseline characteristics was developed. Several previously published risk scores (o-POSSUM, E-PASS, Steyerberg, NUn score) were calculated, and their predictive accuracy for presence of AL was compared.ResultsSteyerberg Risk Score, o-POSSUM, and E-PASS were found to be unsuitable for early detection of an anastomotic problem. However, an increased NUn score on the fourth to seventh postoperative day was independently associated with the presence of AL. The test accuracy (0.631-0.714), sensitivity (28.9%-50.5%), and specificity (72.5%-89.5%) were marginally satisfactory. When only C-reactive protein levels were considered, similar test accuracy (0.629-0.717), sensitivity (47.5%-69.9%), and specificity values (51.5%-81.6%) were observed using a cut-off of 150 mg/l.ConclusionsThe NUn score showed no superiority over CRP values in the prediction of AL. Therefore, further diagnostics should be carried out from the fourth postoperative day if the CRP is > 150 mg/l. However, large-scale registry studies and artificial intelligence may aid in more appropriate determination of patient-specific risks in the future.
Body image and appearance distress among military veterans and civilians with an injury-related visible difference: A comparison study
Authors: Keeling Mary , Harcourt Diana , White Paul , Evans Sarah , Williams Victoria S. , Kiff James , Williamson Heidi 
Published: May 2024

AbstractInjuries sustained during military conflict can significantly impact appearance. Yet, little is known about the psychosocial experiences of veterans with conflict-related appearance-altering injuries (AAI) and whether current civilian interventions are appropriate for veterans. To inform the development of acceptable and effective support for veterans with appearance–related psychosocial difficulties, this study aimed to identify factors associated with psychosocial adjustment to an altered appearance among both veterans and civilians with AAI. A cross-sectional online survey study was conducted. N = 121 veterans and N = 197 civilians who had sustained AAI took part. Multivariable regression was used to examine factors related to adjustment in the two groups. Overall, both groups reported similar experiences, with some key exceptions. Veterans reported significantly greater depression and Post Traumatic Stress Disorder, significantly lower Body Image (BI) psychological flexibility, BI life engagement, and higher perceived appearance-related stigma. BI psychological flexibility was identified as a key predictor of appearance-related outcomes in both groups. Self-compassion predicted social anxiety and depression symptoms in both groups, but only appearance outcomes among civilians. Based on these identified associated factors, it is suggested that both groups, but particularly veterans, may benefit from an Acceptance and Commitment Therapy-based intervention, including explicit self-compassion activities, and practical social skills training.
Prevalence and determinants of tobacco use among school-going adolescents in 53 African countries: evidence from Global Youth Tobacco Surveys
Authors: Pokothoane Retselisitsoe , Agerfa Terefe Gelibo , Miderho Christus Cito , Mdege Noreen Dadirai 
Published: May 2024

ABSTRACTIntroductionTobacco use typically begins during adolescence. There is a lack of comprehensive evidence on the use of different tobacco products among adolescents in Africa.Aims and MethodsWe used the most recent Global Youth Tobacco Surveys data from 53 African countries, covering 2003 – 2020, to estimate the overall and gender-specific prevalence of each type of tobacco product by country, Africa region, World Bank income group, and age group. We further used independent logit regression models to assess the determinants of the use of different types of tobacco products. The datasets covered 204,537 primary/secondary school- going adolescents aged 11 - 17 years. Pooled prevalence estimates were computed using the individual-level data.ResultsThe overall prevalence of any tobacco use among African adolescents was 14.3% [95% CI: 13.5, 15.3]. Specifically, the prevalence for cigarette smoking was 6.4% [95% CI: 5.9, 7.0], for other smoked tobacco was 6.7% [95% CI: 6.0, 7.4], for smokeless tobacco use was 6.4% [95% CI: 5.9, 6.9], and for shisha smoking was 5.2% [95% CI: 4.4, 6.1]. The prevalence of dual use of smoked and smokeless tobacco was 3.0% [95% CI: 2.8, 3.2], and that of shisha and cigarettes was 1.5% [95% CI: 1.2, 2.0]. The prevalence of any tobacco use was higher among boys (17.4%) than girls (10.6%). Exposure to anti-tobacco smoking messages, exposure to smoking at home and school, the age restriction to tobacco purchases, and peer pressure were positively associated with the tobacco use, irrespective of product type. Being a female was a protective factor of tobacco use for almost all products. Country-level factors such as predominant religion, African region, and World Bank income group were significant factors only for cigarettes and shisha smoking.ConclusionsThe prevalence of tobacco use among African adolescents aged 11 - 17 years is high, but similar across different tobacco products. Peer pressure and school environment significantly influence adolescents’ decisions to participate in tobacco use. Policymakers could prioritize implementing large pictorial health warnings about tobacco dangers covering the entire packaging of different products.IMPLICATIONSAfrican countries and regions need to strengthen tobacco control policies that are most effective in reducing tobacco consumption among young people, such as increasing tobacco taxes, textual and graphic health warnings and banning tobacco industry influence: advertising and any sponsorships. It is also important to have comprehensive surveillance systems that monitor the use of the whole range of tobacco and nicotine products overtime.
The ARC Toolbox: Artificial Languages with Rhythmicity Control
Authors: Titone Lorenzo , Milosevic Nikola , Meyer Lars 
Published: May 2024

AbstractStatistical learning is the ability to extract and retain statistical regularities from the environment. In language, extracting statistical regularities—so-called transitional probabilities, TPs—is crucial for segmenting speech and learning new words. To investigate whether neural activity synchronizes with these statistical patterns, so-called neural frequency-tagging paradigms have been employed. Here, brain activity is recorded while a stream of syllables is presented at one fixed rate (e.g., 3.3 Hz) and rhythmic patterns of low-TP events are present at a different rate (e.g., 1.1 Hz). Such studies report neural tracking of both syllables and TPs; that is, for both acoustic and abstract events, respectively. However, recent criticism pointed out that the possible confounding of acoustic and abstract rhythms limits the interpretability of this work. Here, we present a new Python toolbox that minimizes this confounding by creatingArtificial languages with Rhythmicity Controls(ARC). ARC features a phonological rhythmicity index (PRI) to quantify the confounding periodicity of phonological features at the TP rate. It implements a pseudo-random-walk approach to ensure unconfounded TP stationarity throughout streams of arbitrary length. We provide a step-by-step guide to generate artificial pseudowords based on a pre-specified syllable inventory and create controlled lexicon streams. Simulation results show that ARC lexicons minimize PRI and TP variance, not only relative to sets of random syllable groups, but also to benchmarking sets of artificial languages used in the prior literature. ARC should be used by future work in order to suppress the confounding of acoustics and TPs in artificial language learning experiments.
EEfinder, a tool for identification of bacterial and viral endogenized elements in eukaryotic genomes
Authors: Dias Yago José Mariz , Dezordi Filipe Zimmer , Wallau Gabriel da Luz 
Published: May 2024

ABSTRACTHorizontal transfer is a phenomenon of genetic material transmission between species with no parental relationship. It has been characterized among several major branches of life, including among prokaryotes, viruses and eukaryotes. Genetic elements derived from horizontal transfer are known as Endogenous Bacterial Elements and Endogenous Viral Elements. Endogenous elements characterization provides a snapshot of past host-pathogen interactions and coevolution as well as a reference sequence information to remove false positive results from viral metagenomic studies. However, there is a current lack of standardized tools for endogenous elements identification, which hinder comparative studies and reproducibility within this field. Here we describe EEfinder, a new tool for identification and classification of endogenous elements derived from horizontal transfer. The tool was developed to include six standard steps performed in this type of analysis: data cleaning, pairwise alignment, filtering candidate elements, taxonomy assignment, merging of truncated elements and flanks extraction. We evaluated the sensitivity of EEfinder to identify endogenous elements through comparative analysis using data from the literature and showed that EEfinder can systematically identify endogenous elements with bacterial/viral origin.
Microbial trait multifunctionality drives soil organic matter formation potential
Authors: Whalen Emily D. , Grandy A. Stuart , Geyer Kevin M. , Morrison Eric W. , Frey Serita D. 
Published: May 2024

AbstractSoil microbes are a major source of organic residues that accumulate as soil organic matter (SOM), the largest terrestrial reservoir of carbon on Earth. As such, there is growing interest in determining the microbial traits that drive SOM formation and stabilization; however, whether certain microbial traits consistently predict SOM accumulation across different functional pools (e.g., total vs. stable SOM) is unresolved. To address these uncertainties, we incubated individual species of fungi in SOM-free model soils, allowing us to directly relate the physiological, morphological, and biochemical traits of fungi to their SOM formation potentials. We find that the formation of different SOM functional pools is associated with distinct fungal traits, and that ‘multifunctional’ species with intermediate investment across this key grouping of traits (namely, carbon use efficiency, growth rate, turnover rate, and biomass protein and phenol contents) promote SOM formation, functional complexity, and stability. Our results highlight the limitations of categorical trait-based frameworks that describe binary (high/low) trade-offs between microbial traits, instead emphasizing the importance of synergies among microbial traits for the formation of functionally complex SOM.
An acidic loop in the FHA domain of the yeast meiosis-specific kinase Mek1 interacts with a specific motif in a subset of Mek1 substrates
Authors: Weng Qixuan , Wan Lihong , Straker Geburah C. , Deegan Tom. D. , Duncker Bernard P. , Neiman Aaron M. , Luk Ed , Hollingsworth Nancy M. 
Published: May 2024

ABSTRACTThe meiosis-specific kinase Mek1 regulates key steps in meiotic recombination in the budding yeast,Saccharomyces cerevisiae.MEK1limits resection at the double strand break (DSB) ends and is required for preferential strand invasion into homologs, a process known as interhomolog bias. After strand invasion,MEK1promotes phosphorylation of the synaptonemal complex protein Zip1 that is necessary for DSB repair mediated by a crossover specific pathway that enables chromosome synapsis. In addition, Mek1 phosphorylation of the meiosis-specific transcription factor, Ndt80, regulates the meiotic recombination checkpoint that prevents exit from pachytene when DSBs are present. Mek1 interacts with Ndt80 through a five amino acid sequence, RPSKR, located between the DNA binding and activation domains of Ndt80. AlphaFold Multimer modeling of a fragment of Ndt80 containing the RPSKR motif and full length Mek1 indicated that RPSKR binds to an acidic loop located in the Mek1 FHA domain, a non-canonical interaction with this motif. A second protein, the 5’-3’ helicase Rrm3, similarly interacts with Mek1 through an RPAKR motif and is an in vitro substrate of Mek1. Genetic analysis using various mutants in theMEK1acidic loop validated the AlphaFold model, in that they specifically disrupt two-hybrid interactions with Ndt80 and Rrm3. Phenotypic analyses further showed that the acidic loop mutants are defective in the meiotic recombination checkpoint, and in certain circumstances exhibit more severe phenotypes compared to theNDT80mutant with the RPSKR sequence deleted, suggesting that additional, as yet unknown, substrates of Mek1 also bind to Mek1 using an RPXKR motif.ARTICLE SUMMARYThe FHA domain is conserved module best known for creating protein complexes by binding to phosphorylated threonines on target proteins. This work identified a non-canonical mechanism by which the FHA domain of the yeast meiosis-specific kinase Mek1 interacts with two of its substrates, Ndt80 and Rrm3. An acidic loop within the FHA domain binds to RPXKR motifs in Ndt80 and Rrm3. Genetic evidence suggests that this FHA domain acidic loop is required binding to additional Mek1 substrates.