bluuebunny/crossref_metadata_2025_split huggingface dataset:
What’s UPDOG? A novel tool for trans-ancestral polygenic score prediction
Authors: Howard David M. , Pain Oliver , Gillett Alexandra C. , Vassos Evangelos , Lewis Cathryn M. 
Published: May 2023

AbstractPolygenic scores provide an indication of an individual’s genetic propensity for a trait within a test population. These scores are calculated using results from genetic analysis conducted in discovery populations. However, when the test and discovery populations have different ancestries, predictions are less accurate. As many genetic analyses are conducted using European populations, this hinders the potential for making predictions in many of the underrepresented populations in research. To address this, UP and Downstream Genetic scoring (UPDOG) was developed to consider the genetic architecture of both the discovery and test cohorts before calculating polygenic scores. UPDOG was tested across four ancestries and six phenotypes and benchmarked against five existing tools for polygenic scoring. In approximately two-thirds of cases UPDOG improved trans-ancestral prediction, although the increases were small. Maximising the efficacy of polygenic scores and extending it to the global population is crucial for delivering personalised medicine and universal healthcare equality.
Molecular logic for cellular specializations that initiate the auditory parallel processing pathways
Authors: Jing Junzhan , Hu Ming , Ngodup Tenzin , Ma Qianqian , Lau Shu-Ning Natalie , Ljungberg Cecilia , McGinley Matthew J. , Trussell Laurence O. , Jiang Xiaolong 
Published: May 2023

AbstractThe cochlear nuclear complex (CN), the starting point for all central auditory processing, comprises a suite of neuronal cell types that are highly specialized for neural coding of acoustic signals, yet molecular logic governing cellular specializations remains unknown. By combining single-nucleus RNA sequencing and Patch-seq analysis, we reveal a set of transcriptionally distinct cell populations encompassing all previously observed types and discover multiple new subtypes with anatomical and physiological identity. The resulting comprehensive cell-type taxonomy reconciles anatomical position, morphological, physiological, and molecular criteria, enabling the determination of the molecular basis of the remarkable cellular phenotypes in the CN. In particular, CN cell-type identity is encoded in a transcriptional architecture that orchestrates functionally congruent expression across a small set of gene families to customize projection patterns, input-output synaptic communication, and biophysical features required for encoding distinct aspects of acoustic signals. This high-resolution account of cellular heterogeneity from the molecular to the circuit level illustrates molecular logic for cellular specializations and enables genetic dissection of auditory processing and hearing disorders with unprecedented specificity.
HIC1 interacts with FOXP3 multi protein complex: a novel mechanism to regulate human regulatory T cell differentiation and function
Authors: Ahmad Andrabi Syed Bilal , Batkulwar Kedar , Bhosale Santosh D. , Moulder Robert , Khan Meraj Hasan , Buchacher Tanja , Khan Mohd Moin , Arnkil Ilona , Rasool Omid , Marson Alexander , Kalim Ubaid Ullah , Lahesmaa Riitta 
Published: May 2023

AbstractTranscriptional repressor, hypermethylated in cancer 1 (HIC1) participates in a range of important biological processes, such as tumor repression, immune suppression, embryonic development and epigenetic gene regulation. Further to these, we previously demonstrated that HIC1 provides a significant contribution to the function and development of regulatory T (Treg) cells. However, the mechanism by which it regulates these processes was not apparent. To address this question, we used affinity-purification mass spectrometry to characterize the HIC1 Interactome in human Treg cells. Altogether 61 high-confidence interactors were identified, including IKZF3, which is a key transcription factor in the development of Treg cells. The biological processes associated with these interacting proteins include protein transport, mRNA processing, non-coding (ncRNA) transcription and RNA metabolism. The results revealed that HIC1 is part of a FOXP3-RUNX1-CBFB protein complex that regulates Treg signature genes thus improving our understanding of HIC1 function during early Treg cell differentiation.HighlightsSystematic characterization of HIC1 interactome in regulatory T cells by Affinity Purification-Mass SpectrometryHIC1 binds to theRUNX1promoter and regulates its expressionHIC1-a part of FOXP3-RUNX1-CBFB transcriptional complexGraphical abstract
Prolonged Cell Cycle Arrest in Response to DNA damage in Yeast Requires the Maintenance of DNA Damage Signaling and the Spindle Assembly Checkpoint
Authors: Zhou Felix Y. , Waterman David P. , Ashton Marissa , Caban-Penix Suhaily , Memisoglu Gonen , Eapen Vinay V. , Haber James E. 
Published: May 2023

AbstractCells evoke the DNA damage checkpoint (DDC) to inhibit mitosis in the presence of DNA double-strand breaks (DSBs) to allow more time for DNA repair. In budding yeast, a single irreparable DSB is sufficient to activate the DDC and induce cell cycle arrest prior to anaphase for about 12 to 15 hours, after which cells “adapt” to the damage by extinguishing the DDC and resuming the cell cycle. While activation of the DNA damage-dependent cell cycle arrest is well-understood, how it is maintained remains unclear. To address this, we conditionally depleted key DDC proteins after the DDC was fully activated and monitored changes in the maintenance of cell cycle arrest. Degradation of Ddc2ATRIP, Rad9, Rad24, or Rad53CHK2results in premature resumption of the cell cycle, indicating that these DDC factors are required both to establish and to maintain the arrest. Dun1 is required for establishment, but not maintenance of arrest, whereas Chk1 is required for prolonged maintenance but not for initial establishment of the mitotic arrest. When the cells are challenged with 2 persistent DSBs, they remain permanently arrested. This permanent arrest is initially dependent on the continuous presence of Ddc2, Rad9, and Rad53; however, after 15 hours these proteins become dispensable. Instead, the continued mitotic arrest is sustained by spindle-assembly checkpoint (SAC) proteins Mad1, Mad2, and Bub2 but not by Bub2’s binding partner Bfa1. These data suggest that prolonged cell cycle arrest in response to 2 DSBs is achieved by a handoff from the DDC to specific components of the SAC. Furthermore, the establishment and maintenance of DNA damage-induced cell cycle arrest requires overlapping but different sets of factors.
Phylogeographical evidence for historical long-distance dispersal in the flightless stick insectRamulus mikado
Authors: Suetsugu Kenji , Nozaki Tomonari , Hirota Shun K , Funaki Shoichi , Ito Katsura , Isagi Yuji , Suyama Yoshihisa , Kaneko Shingo 
Published: May 2023

AbstractExploring how organisms overcome geographical barriers to dispersal is a fundamental question in biology. Passive long-distance dispersal events, although infrequent and unpredictable, have a considerable impact on species range expansions. Despite limited active dispersal capabilities, many stick insect species have vast geographical ranges, indicating that passive long-distance dispersal is vital for their distribution. A potential mode of passive dispersal in stick insects is via the egg stage within avian digestive tracts, as suggested by experimental evidence. However, detecting such events under natural conditions is challenging due to their rarity. To indirectly assess the importance of historical avian-mediated dispersal, we examined the population genetic structure of the flightless stick insectRamulus mikadobased on a multifaceted molecular approach (COI haplotypes, nuclear SSR markers, and genome-wide SNPs). Subsequently, we identified unique phylogeographic patterns, including the discovery of identical COI genotypes spanning considerable distances, which substantiates the notion of passive long-distance genotypic dispersal. Overall, all the molecular data revealed low and mostly non-significant genetic differentiation among populations, with identical or very similar genotypes across distant populations. We propose that long-distance dispersal facilitated by birds is the most plausible explanation for the unique phylogeographic pattern observed in this flightless stick insect.
DNA methylation rates scale with maximum lifespan across mammals
Authors: Crofts Samuel. J. C. , Latorre-Crespo Eric , Chandra Tamir 
Published: May 2023

AbstractDNA methylation rates have previously been found to broadly correlate with maximum lifespan in mammals, yet no precise relationship has been observed. We developed a statistically robust framework to compare methylation rates at conserved age-related sites across mammals. We found that methylation rates negatively scale with maximum lifespan in both blood and skin. The emergence of explicit scaling suggests that methylation rates are - or are linked to - an evolutionary constraint on maximum lifespan acting across diverse mammalian lineages.
The Prolonged Terminal Phase of Human Life Induces Survival Response in the Skin Transcriptome
Authors: Abouhashem Ahmed S , Singh Kanhaiya , Srivastava Rajneesh , Liu Sheng , Mathew-Steiner Shomita S , Gu Xiaoping , Kacar Sedat , Hagar Amit , Sandusky George E. , Roy Sashwati , Wan Jun , Sen Chandan K 
Published: May 2023

AbstractHuman death marks the end of organismal life under conditions such that the components of the human body continue to be alive. Such postmortem cellular survival depends on the nature (Hardy scale of slow-fast death) of human death. Slow and expected death typically results from terminal illnesses and includes a prolonged terminal phase of life. As such organismal death process unfolds, do cells of the human body adapt for postmortem cellular survival? Organs with low energy cost-of-living, such as the skin, are better suited for postmortem cellular survival. In this work, the effect of different durations of terminal phase of human life on postmortem changes in cellular gene expression was investigated using RNA sequencing data of 701 human skin samples from the Genotype-Tissue Expression (GTEx) database. Longer terminal phase (slow-death) was associated with a more robust induction of survival pathways (PI3K-Akt signaling) in postmortem skin. Such cellular survival response was associated with the upregulation of embryonic developmental transcription factors such asFOXO1,FOXO3,ATF4andCEBPD. Upregulation of PI3K-Akt signaling was independent of sex or duration of death-related tissue ischemia. Analysis of single nucleus RNA-seq of post-mortem skin tissue specifically identified the dermal fibroblast compartment to be most resilient as marked by adaptive induction of PI3K-Akt signaling. In addition, slow death also induced angiogenic pathways in the dermal endothelial cell compartment of postmortem human skin. In contrast, specific pathways supporting functional properties of the skin as an organ were downregulated following slow death. Such pathways included melanogenesis and those representing the skin extracellular matrix (collagen expression and metabolism). Efforts to understand the significance of death as a biological variable (DABV) in influencing the transcriptomic composition of surviving component tissues has far-reaching implications including rigorous interpretation of experimental data collected from the dead and mechanisms involved in transplant-tissue obtained from dead donors.
Deciphering molecular heterogeneity and dynamics of human hippocampal neural stem cells at different ages and injury states
Authors: Yao Junjun , Dai Shaoxing , Zhu Ran , Tan Ju , Zhao Qiancheng , Yin Yu , Sun Jiansen , Du Xuewei , Ge Longjiao , Xu Jianhua , Hou Chunli , Li Nan , Li Jun , Ji Weizhi , Zhu Chuhong , Zhang Runrui , Li Tianqing 
Published: May 2023

AbstractWhile accumulated publications support the existence of neurogenesis in the adult human hippocampus, the homeostasis and developmental potentials of neural stem cells (NSCs) under different contexts remain unclear. Based on our generated single-nucleus atlas of the human hippocampus across neonatal, adult, aging and injury, we dissected the molecular heterogeneity and transcriptional dynamics of human hippocampal NSCs under different contexts. We further identified new specific neurogenic lineage markers that overcome the lack of specificity found in some well-known markers. Based on developmental trajectory and molecular signatures, we found that a subset of NSCs exhibit quiescent properties after birth, and most NSCs become deep quiescence during aging. Furthermore, certain deep quiescent NSCs are re-activated following stroke injury. Together, our findings provide valuable insights into the development, aging, and re-activation of the human hippocampal NSCs, and help to explain why adult hippocampal neurogenesis is infrequently observed in humans.
Rad53 regulates the lifetime of Rdh54 at homologous recombination intermediates
Authors: Hu Jingyi , Ferlez Bryan , Dau Jennifer , Crickard J. Brooks 
Published: May 2023

AbstractRdh54 is a conserved DNA translocase that participates in homologous recombination (HR), DNA checkpoint adaptation, and chromosome segregation.Saccharomyces cerevisiaeRdh54 is a known target of the Mec1/Rad53 signaling axis, which globally protects genome integrity during DNA metabolism. While phosphorylation of DNA repair proteins by Mec1/Rad53 is critical for HR progression little is known about how specific post translational modifications alter HR reactions. Phosphorylation of Rdh54 is linked to protection of genomic integrity but the consequences of modification remain poorly understood. Here, we demonstrate that phosphorylation of the Rdh54 C-terminus by the effector kinase Rad53 regulates Rdh54 clustering activity as revealed by single molecule imaging. This stems from phosphorylation dependent and independent interactions between Rdh54 and Rad53. Genetic assays reveal that loss of phosphorylation leads to phenotypic changes resulting in loss-of-heterozygosity (LOH) outcomes. Our data highlight Rad53 as a key regulator of HR intermediates through activation and attenuation of Rdh54 motor function.
A Study of Microbial Diversity in a Biofertilizer Consortium
Authors: Hernández-Álvarez Cristóbal , Peimbert Mariana , Rodríguez-Martin Pedro , Trejo-Aguilar Dora , Alcaraz Luis D. 
Published: May 2023

AbstractBiofertilizers supply living microorganisms to help plants grow and maintain their health. In this study, we examine the microbiome composition of a commercial biofertilizer that has been proven to promote plant growth. Using ITS and 16S rRNA gene sequence analyses, we describe the microbial communities of the biofertilizer, with 182 fungal species and 964 bacterial genera identified. The biofertilizer contains a variety of microorganisms that had been reported to enhance nutrient uptake, phytohormone production, stress tolerance, and pathogen resistance in plants. Plant roots created a microenvironment that boosted bacterial diversity but filtered fungal communities. We propose using plant roots as bioreactors to sustain dynamic environments that promote the proliferation of microorganisms with biofertilizer potential. However, preserving the fungal-inoculated substrate is crucial to maintain fungal diversity in the root fraction. The study suggests that bacteria grow close to plant roots, while root-associated fungi may be a subset of the substrate fungi. These findings indicate that the composition of the biofertilizer may be influenced by the selection of microorganisms associated with plant roots, which could have implications for the effectiveness of the biofertilizer in promoting plant growth.
TreeGOER: a database with globally observed environmental ranges for 48,129 tree species
Authors: Kindt Roeland 
Published: May 2023

AbstractThe BIOCLIM algorithm provides a straightforward method to estimate the effects of climate change on the distribution of species. Estimating the core ranges of species from 5% and 95% quantiles of bioclimatic variables, the algorithm remains widely used even when more sophisticated methods of species distribution modelling have become popular. Where sufficient representative observations are available, I expect that BIOCLIM correctly identifies locations that would not be suitable in a future climate. To accommodate climate change investigations based on BIOCLIM for 48,129 tree species (a substantial subset of known tree species), I developed theTreeGOER(Tree Globally Observed Environmental Ranges) database, providing information on environmental ranges for 38 bioclimatic, 8 soil and 3 topographic variables. The database can be accessed from:https://doi.org/10.5281/zenodo.7922928. Statistics that include 5% and 95% quantiles were estimated for a cleaned and taxonomically standardized occurrence data set with different methods of outlier detection, with estimates for roughly 45% of species being based on 20 or more observation records. Inferred core bioclimatic ranges of species along global temperature and moisture index gradients and across continents follow the known global distribution of tree diversity such as its highest levels in moist tropical forests and the ‘odd man out’ pattern of lower levels in Africa. To demonstrate how global analyses for large numbers of tree species can easily be done inRwithTreeGOER, here I present two case studies. The first case study investigated latitudinal trends of tree vulnerability and compared these with previous results obtained for urban trees. The second case study focused on tropical areas, compared trends in different longitudinal zones and investigated patterns for the moisture index.TreeGOERis expected to benefit researchers conducting biogeographical and climate change research for a wide range of tree species at a variety of spatial and temporal scales.
Differences in 5’untranslated regions highlight the importance of translational regulation of dosage sensitive genes
Authors: Wieder Nechama , D’Souza Elston N. , Martin-Geary Alexandra C. , Lassen Frederik H. , Talbot-Martin Jonathan , Fernandes Maria , Chothani Sonia P. , Rackham Owen J.L. , Schafer Sebastian , Aspden Julie L. , MacArthur Daniel G. , Davies Robert W. , Whiffin Nicola 
Published: May 2023

AbstractBackgroundUntranslated regions (UTRs) are important mediators of post-transcriptional regulation. The length of UTRs and the composition of regulatory elements within them are known to vary substantially across genes, but little is known about the reasons for this variation in humans. Here, we set out to determine whether this variation, specifically in 5’UTRs, correlates with gene dosage sensitivity.ResultsWe investigated 5’UTR length, the number of alternative transcription start sites, the potential for alternative splicing, the number and type of upstream open reading frames (uORFs) and the propensity of 5’UTRs to form secondary structures. We explored how these elements vary by gene tolerance to loss-of-function (LoF; using the LOEUF metric), and in genes where changes in dosage are known to cause disease. We show that LOEUF correlates with 5’UTR length and complexity. Genes that are most intolerant to LoF have longer 5’UTRs (P<1×10−15), greater TSS diversity (P<1× 10−15), and more upstream regulatory elements than their LoF tolerant counterparts. We show that these differences are evident in disease gene-sets, but not in recessive developmental disorder genes where LoF of a single allele is tolerated.ConclusionsOur results confirm the importance of post-transcriptional regulation through 5’UTRs in tight regulation of mRNA and protein levels, particularly for genes where changes in dosage are deleterious and lead to disease. Finally, to support gene-based investigation we release a web-based browser tool, VuTR (https://vutr.rarediseasegenomics.org/), that supports exploration of the composition of individual 5’UTRs and the impact of genetic variation within them.
Lip movements and lexical features improve speech tracking differently for clear and multi-speaker speech
Authors: Haider Chandra Leon , Park Hyojin , Hauswald Anne , Weisz Nathan 
Published: May 2023

AbstractVisual speech plays a powerful role in facilitating auditory speech processing and has been a publicly noticed topic with the wide usage of face masks during the Covid-19 pandemic. In a previous magnetoencephalography (MEG) study we showed that occluding the mouth area significantly impairs neural speech tracking. To rule out the possibility that this deterioration is due to degraded sound quality, in the present follow-up study, we presented participants with audiovisual (AV) and audio-only (A) speech. We further independently manipulated the trials by adding a face mask and a distractor speaker. Our results clearly show that face masks only affect speech tracking in AV conditions, not in A conditions. This shows that face masks indeed primarily impact speech processing by blocking visual speech and not by acoustic degradation. Furthermore, we observe differences in the speech features that are used for visual speech processing. On the one hand, processing in clear speech, but not in noisy speech, is profiting more from lexical unit features (phonemes and word onsets) hinting at improved phoneme discrimination. On the other hand, we observe an improvement in speech tracking driven by the modulations of the lip area in clear speech and conditions with a distractor speaker, which might aid by providing temporal cues for subsequent auditory processing. With this work, we highlight the effects of face masks in AV speech tracking and show two separate ways how visual speech might support successful speech processing.
The role of learned song in the evolution and speciation of Eastern and Spotted towhees
Authors: Du’Mottuchi Ximena León , Creanza Nicole 
Published: May 2023

ABSTRACTOscine songbirds learn vocalizations that function in mate attraction and territory defense. Sexual selection pressures on these learned songs could accelerate speciation. The Eastern and Spotted towhees are sister species that diverged recently (0.28 Ma) but now have partially overlapping ranges with evidence of some hybridization; widespread community-science recordings of these species, including songs within their zone of overlap and from potential hybrids, enable us to investigate whether song differentiation might facilitate their reproductive isolation. Here, we quantify 16 song features to analyze geographic variation in Spotted and Eastern towhee songs and test for species-level differences. We then use random-forest models to measure how accurately their songs can be classified by species, both within and outside the zone of overlap. While no single song feature reliably distinguishes the two species, a random-forest model trained on 16 features accurately classified 89.5% of songs; interestingly, species classification was less accurate in the zone of overlap. Finally, our analysis of the limited publicly available genetic data from each species supports the hypothesis that they are reproductively isolated. Together, our results suggest that, in combination, small variations in song features may contribute to these sister species’ ability to recognize their species-specific songs.