bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral administration of GnRH via a cricket vehicle stimulates spermiation in tiger salamanders (Ambystoma tigrinum)
Authors: Chen Devin M. , Chen Li-Dunn , Kouba Carrie K. , Songsasen Nucharin , Roth Terri L. , Allen Peter J. , Kouba Andrew J. 
Published: August 2023

AbstractMore than 50% of caudates are threatened with extinction and are in need ofex-situbreeding programs to support conservation efforts and species recovery. Unfortunately, many salamander populations under human care can experience reproductive failure, primarily due to missing environmental cues necessary for breeding. Assisted reproductive technologies (ARTs) are a useful suite of techniques for overcoming or bypassing these missing environmental cues to promote breeding. Exogenous hormones are used to stimulate natural breeding behaviors or gamete expression forin-vitrofertilization or biobanking and are typically administered intramuscularly in caudates. While effective, intramuscular injection is risky to perform in smaller-bodied animals, resulting in health and welfare risks. This research investigated the spermiation response to hormone administration through a non-invasive oral route using the tiger salamander (Ambystoma tigrinum) as a model species. Male salamanders were randomly rotated six weeks apart through four treatments (n = 11 males/treatment) in which animals received a resolving dose of gonadotropin-releasing hormone (GnRH) as follows: (1) Prime-Only (0.0 µg/g); (2) Low (0.25 µg/g); (3) Medium (1.0 µg/g); and (4) High (2.0 µg/g). All males were given a GnRH priming dose (0.25 µg/g) 24 hours prior to the resolving dose. Exogenous hormone was delivered inside of a cricket (Gryllodes sigillatus) that was presented as a food item by tweezers. Sperm samples were collected at 1, 3, 6, 9, 12, and 24 hours after the resolving dose and analyzed for quantity and quality. For all treatments, sperm concentration was produced in an episodic pattern over time. The Prime-Only treatment had a lower (p < 0.05) percent of sperm exhibiting normal morphology compared to treatments utilizing a resolving dose of GnRH. Overall, oral administration of GnRH is a feasible route of inducing spermiation in salamanders, yielding sperm of sufficient quantity and quality forin-vitrofertilization and biobanking efforts.
Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice
Authors: Boukas Leandros , Luperchio Teresa Romeo , Razi Afrooz , Hansen Kasper D. , Bjornsson Hans T. 
Published: August 2023

AbstractMany Mendelian developmental disorders caused by coding variants in epigenetic regulators have now been discovered. Epigenetic regulators are broadly expressed, and each of these disorders typically exhibits phenotypic manifestations from many different organ systems. An open question is whether the chromatin disruption – the root of the pathogenesis – is similar in the different disease-relevant cell types. This is possible in principle, since all these cell-types are subject to effects from the same causative gene, that has the same kind of function (e.g. methylates histones) and is disrupted by the same germline variant. We focus on mouse models for Kabuki syndrome types 1 and 2, and find that the chromatin accessibility abnormalities in neurons are mostly distinct from those in B or T cells. This is not because the neuronal abnormalities occur at regulatory elements that are only active in neurons. Neurons, but not B or T cells, show preferential chromatin disruption at CpG islands and at regulatory elements linked to aging. A sensitive analysis reveals that the regions disrupted in B/T cells do exhibit chromatin accessibility changes in neurons, but these are very subtle and of uncertain functional significance. Finally, we are able to identify a small set of regulatory elements disrupted in all three cell types. Our findings reveal the cellular-context-specific effect of variants in epigenetic regulators, and suggest that blood-derived “episignatures” may not be well-suited for understanding the mechanistic basis of neurodevelopment in Mendelian disorders of the epigenetic machinery.
Multivalent GU-rich oligonucleotides sequester TDP-43 in the nucleus by inducing high molecular weight RNP complexes
Authors: Zhang Xi , Das Tanuza , Chao Tiffany F. , Trinh Vickie , Carmen Rogger , Ling Jonathan , Kalab Petr , Hayes Lindsey R. 
Published: August 2023

ABSTRACTTDP-43 nuclear clearance and cytoplasmic aggregation are hallmarks of TDP-43 proteinopathies. We recently demonstrated that binding to endogenous nuclear GU-rich RNAs sequesters TDP-43 in the nucleus by restricting its passive nuclear export. Here, we tested the feasibility of synthetic RNA oligonucleotide-mediated augmentation of TDP-43 nuclear localization. Using biochemical assays, we compared the ability of GU-rich oligonucleotides to engage in multivalent, RRM-dependent binding with TDP-43. When transfected into cells, (GU)16 attenuated TDP-43 mislocalization induced by transcriptional blockade or RanGAP1 ablation. Clip34nt and (GU)16 accelerated TDP-43 nuclear re-import after cytoplasmic mislocalization. RNA pulldowns confirmed that multivalent GU-oligonucleotides induced high molecular weight RNP complexes, incorporating TDP-43 and possibly other GU-binding proteins. Transfected GU-repeat oligos disrupted TDP-43 cryptic exon repression, likely by diverting TDP-43 from endogenous RNAs, except for Clip34nt which contains interspersed A and C. Thus, exogenous multivalent GU-RNAs can promote TDP-43 nuclear localization, though pure GU- repeat motifs impair TDP-43 function.
Anopheles gambiaemosGILT regulates innate immune genes andzpgexpression
Authors: Arora Gunjan , Tang Xiaotian , Cui Yingjun , Yang Jing , Chuang Yu-Min , Joshi Jayadev , Sajid Andaleeb , Dong Yuemei , Cresswell Peter , Dimopoulos George , Fikrig Erol 
Published: August 2023

AbstractGene-edited mosquitoes lacking agamma-interferon-inducible lysosomal thiol reductase-like protein, namely (mosGILTnull) have lowerPlasmodiuminfection, which is linked to impaired ovarian development and immune activation. The transcriptome ofmosGILTnullA. gambiaewas therefore compared to wild type (WT) by RNA-sequencing to delineate mosGILT-dependent pathways. Compared to WT mosquitoes,mosGILTnullA. gambiaedemonstrated altered expression of genes related to oogenesis, 20-hydroxyecdysone synthesis, as well as immune-related genes. Serendipitously, the zero population growth gene,zpg, an essential regulator of germ cell development was found to be one of the most downregulated genes inmosGILTnullmosquitoes. These results provide the crucial missing link between two previous studies on the role ofzpgandmosGILTin ovarian development. This study further demonstrates that mosGILT has the potential to serve as a target for the biological control of mosquito vectors and to influence thePlasmodiumlife cycle within the vector.
Characterization ofN-glycosylation and its Functional Role in SIDT1-Mediated RNA Uptake
Authors: Yang Tingting , Xiao Haonan , Chen Xiulan , Zheng Le , Guo Hangtian , Wang Jiaqi , Jiang Xiaohong , Zhang Chen-Yu , Yang Fuquan , Ji Xiaoyun 
Published: August 2023

AbstractThe mammalian SID-1 transmembrane family members, SIDT1 and SIDT2, are multi-pass transmembrane proteins that mediate the cellular uptake and intracellular trafficking of nucleic acids, playing important roles in the immune response and tumorigenesis. Previous work has suggested that human SIDT1 and SIDT2 areN-glycosylated, but the precise site-specificN-glycosylation information and its functional contribution remain unclear. In this study, we employ high-resolution liquid chromatography tandem mass spectrometry to comprehensively map theN-glycosites and quantify theN-glycosylation profiles of SIDT1 and SIDT2. Further molecular mechanistic probing elucidates the essential role ofN-linked glycans in regulating cell surface expression, RNA binding, protein stability, and RNA uptake of SIDT1. Our results provide crucial information about the potential functional impact ofN-glycosylation in the regulation of SIDT1-mediated RNA uptake and provide insights into the molecular mechanisms of this promising nucleic acid delivery system, with potential implications for therapeutic applications.
A patchwork pathway for catabolism of the sulfosugar sulfofucose
Authors: Li Jinling , Lee Mihwa , Yang Shuxin , Lewis Jessica M. , Herisse Marion , Pidot Sacha J. , Scott Nichollas E. , Williams Spencer J. 
Published: August 2023

AbstractWe report the isolation ofParacoccus onubensisstrain Merri, which can grow on the rare sulfosugar sulfofucose (6-deoxy-6-sulfo-D-galactose) as sole carbon source, leading to its breakdown and release of sulfite. Genome sequencing and comparative proteomics of samples grown on glucose versus sulfofucose identified a genetic locus containing most of the genes for a sulfoglycolytic pathway for breakdown of sulfofucose to the 3-carbon organosulfonate sulfolactaldehyde, and a biomineralization pathway for catabolism of sulfolactaldehyde to pyruvate and sulfite. A candidate sulfotagatose-1-phosphate aldolase was expressed and was active on the epimeric substrate sulfofructose-1-phosphate. Its 3D X-ray structure revealed a close homology to sulfofructose-1-phosphate aldolase from the sulfoglycolytic Embden-Meyerhof-Parnas pathway. A patchwork sulfofucose catabolism pathway is proposed involving a sulfofucolytic Embden-Meyerhof-Parnas and short-chain organosulfonate biomineralization pathway.SignificanceSulfosugars are important compounds in the biogeochemical sulfur cycle and are produced by a wide range of photosynthetic plants, algae and cyanobacteria. While the pathways for the biosynthesis and catabolism of sulfoquinovose are well studied, much less is known about the rarer sulfosugar sulfofucose. We report a bacterium that can use sulfofucose as sole carbon source and achieve its complete breakdown to produce sulfite. We propose that sulfofucose catabolism is achieved using enzymes of the sulfoglycolytic Embden-Meyerhof-Parnas pathway that tolerate a change in stereochemistry at C4 of the sulfosugar. The sulfolactaldehyde output of this pathway is broken down to sulfite through a biomineralization pathway via sulfolactate. Microbial metabolism of this rare sulfosugar can be achieved through repurposing enzymes within known sulfosugar and short-chain organosulfonate catabolism catabolism.
A sum of its parts: A systematic review evaluating biopsychosocial and behavioral determinants of perinatal depression
Authors: Longoria Kayla D. , Nguyen Tien C. , Franco-Rocha Oscar , Garcia Sarina R. , Lewis Kimberly A. , Gandra Sreya , Cates Frances , Wright Michelle L. 
Published: August 2023

AbstractIntroductionDepression is one of the most common yet underdiagnosed perinatal complications and our understanding of the pathophysiology remains limited. Though perinatal depression is considered to have a multifactorial etiology, integrative approaches to investigation are minimal. This review takes an integrative approach to systematically evaluate determinants and potential interactions among determinants of perinatal depression across four domains (i.e., biological, behavioral, environmental, social) and appraise the quality of methods applied.MethodsFour databases (i.e., PubMed, CINAHL, APA PsycInfo, and Web of Science) were systematically searched to identify studies examining determinants of perinatal depression in adult perinatal persons (≥ 18 years). Articles were excluded if the outcomes were not focused on perinatal persons and depression or depression symptoms, the evaluation of depression was specific to a discrete facet of the perinatal period with probable psychological consequences (e.g., abortion, fetal/infant loss, adoption), or was considered grey literature. The Critical Appraisal Skills Programme and AXIS tools were used to guide and standardize quality appraisal assessments and determine the level of risk of bias.ResultsOf the 454 articles identified, 25 articles were included for final review. A total of 14 categories of determinants were investigated: biological (5), behavioral (4), social and environmental (5). Though only 28% of studies simultaneously considered determinants under more than one domain, a pattern of interactions with the tryptophan pathway emerged when determinants across domains were aggregated. Concerns for risk of bias were noted or were unclear for three types of bias: 13 (52%) selection bias, 3 (12%) recall bias, and 24 (96%) measurement bias.ConclusionsFuture research is needed to explore interactions among determinants and the tryptophan pathway; to strengthen the methods applied to this area of inquiry; and to generate evidence for best practices in reporting, selecting, and applying methods for measuring determinants and perinatal depression.
Neo-epitope identification by weakly-supervised peptide-TCR binding prediction
Authors: Gao Yuli , Gao Yicheng , Li Wannian , Wu Siqi , Xing Feiyang , Zhou Chi , Fu Shaliu , Chuai Guohui , Chen Qinchang , Zhang He , Liu Qi 
Published: August 2023

AbstractThe identification of T cell neo-epitopes is fundamental and computational challenging in tumor immunotherapy study. As the binding of pMHC - T cell receptor (TCR) is the essential condition for neo-epitopes to trigger the cytotoxic T cell reactivity, several computational studies have been proposed to predict neo-epitopes from the perspective of pMHC-TCR binding recognition. However, they often failed with the inaccurate binding prediction for a single pMHC -TCR pair due to the highly diverse TCR space. In this study, we proposed a novel weakly-supervised learning framework,i.e.,TCRBagger, to facilitate the personalized neo-epitope identification with weakly-supervised peptide-TCR binding prediction by bagging a sample-specific TCR profile.TCRBaggerintegrates three carefully designed learning strategies,i.e. a self-supervised learning strategy, a denoising learning strategy and a Multi-Instance Learning (MIL) strategy in the modeling of peptide-TCR binding. Our comprehensive tests revealed thatTCRBaggerexhibited great advances over existing tools by modeling interactions between peptide and TCR profiles. We further appliedTCRBaggerin different clinical settings, including (1) facilitating the peptide-TCR binding prediction under MIL using single-cell TCR-seq data. (2) improving the patient-specific neoantigen prioritization compared to the existing neoantigen identification tools. Collectively,TCRBaggerprovides novel perspectives and contributions for identifying neo-epitopes as well as discovering potential pMHC-TCR interactions in personalized tumor immunotherapy.
MethanotrophicMethanoperedensarchaea host diverse and interacting extrachromosomal elements
Authors: Shi Ling-Dong , West-Roberts Jacob , Schoelmerich Marie C. , Penev Petar I. , Chen LinXing , Amano Yuki , Lei Shufei , Sachdeva Rohan , Banfield Jillian F. 
Published: August 2023

AbstractMethane emissions that contribute to climate change can be mitigated by anaerobic methane-oxidizing archaea such asMethanoperedens. SomeMethanoperedenshave huge extrachromosomal genetic elements (ECEs) called Borgs that may modulate their activity, yet the broader diversity ofMethanoperedensECEs is little studied. Here, we report small enigmatic linear ECEs, circular viruses and unclassified ECEs, that we predict replicate withinMethanoperedens. The linear ECEs have features such as inverted terminal repeats, pervasive tandem repeats, and coding patterns that are strongly reminiscent of Borgs, but they are only 52 kb to 145 kb in length. They share proteins with Borgs andMethanoperedens. Thus, we refer to them as mini-Borgs. Mini-Borgs are genetically diverse and we assign them to at least five family-level groups. We also identify eight novel families ofMethanoperedensviruses, some of which encode multiheme cytochromes, and unclassified circular ECEs that encode TnpB genes. A population-heterogeneous CRISPR array is in close proximity to the TnpB and has spacers that target otherMethanoperedensECEs including previously reported plasmids. The diverse groups of ECEs exchange genetic information with each other and withMethanoperedens, likely impacting the activity and evolution of these environmentally important archaea.
The Calcium-sensing receptor is an important regulator of female visceral and perivascular adipocyte function
Authors: Higgins Erin , Galofre Zaniah Gonzalez , McAbney John , Leiper James , Dowsett Laura 
Published: August 2023

AbstractThe Calcium-sensing receptor (CaSR) is a G protein-coupled receptor activated by fluctuations in extracellular calcium concentrations. Its importance in calcium homeostasis has long been established, though its role in other tissues is not well understood. Obesity is a major epidemic with both clinical and social consequences, therefore, understanding the full function and regulation of adipocytes is of critical importance. Adipocyte CaSR has previously been linked to lipolysis and inflammationin vitro. In this study, we set out to further our understanding of adipocyte CaSRin vivovia the generation of an adipocyte specific CaSR knockout mouse (CaSRAd-/-). We found female CaSRAd-/-mice weighed less than wildtype littermates with a significant reduction in visceral adipocyte size potentially due to increased expression of brown fat markers UCP-1 and Cidea. We also established that CaSR is expressed in perivascular adipose tissue (PVAT) and that its deletion protects female mice from PVAT driven hypercontractility. In contrast CaSR deletion had no effect on male body mass, adipocyte size or vascular reactivity. In conclusion, CaSR seems to be of importance in female but not male visceral and perivascular adipose tissue.
Alzheimer’s disease linked Aβ42 exerts product feedback inhibition on γ-secretase impairing downstream cell signaling
Authors: Zoltowska Katarzyna Marta , Das Utpal , Lismont Sam , Enzlein Thomas , Maesako Masato , Houser Mei CQ , Franco María Luisa , Özcan Burcu , Moreira Diana Gomes , Karachentsev Dmitry , Becker Ann , Hopf Carsten , Vilar Marçal , Berezovska Oksana , Mobley William , Chávez-Gutiérrez Lucía 
Published: August 2023

ABSTRACTAmyloid β (Aβ) peptides accumulating in the brain are proposed to trigger Alzheimer’s disease (AD). However, molecular cascades underlying their toxicity are poorly defined.Here, we explored a novel hypothesis for Aβ42 toxicity that arises from its proven affinity for γ-secretases. We hypothesized that the reported increases in Aβ42, particularly in the endolysosomal compartment, promote the establishment of a product feedback inhibitory mechanism on γ-secretases, and thereby impair downstream signaling events.We show that human Aβ42 peptides, but neither murine Aβ42 nor human Aβ17-42 (p3), inhibit γ-secretases and trigger accumulation of unprocessed substrates in neurons, including C-terminal fragments (CTFs) of APP, p75 and pan-cadherin. Moreover, Aβ42 treatment dysregulated cellular homeostasis, as shown by the induction of p75-dependent neuronal death in two distinct cellular systems.Our findings raise the possibility that pathological elevations in Aβ42 contribute to cellular toxicity via the γ-secretase inhibition, and provide a novel conceptual framework to address Aβ toxicity in the context of γ-secretase-dependent homeostatic signaling.
Genome-based metabolic and phylogenomic analysis of the type strains ofTerrisporobactermayombei,Terrisporobacter petroleariusandTerrisporobacter glycolicus
Authors: Böer Tim , Bengelsdorf Frank R. , Bömeke Mechthild , Daniel Rolf , Poehlein Anja 
Published: August 2023

AbstractTo date, three validly published type strains of the genusTerrisporobacterare covered by draft genome sequences, and the genes and pathway responsible for acetogenesis have not been analyzed. Here, we report complete genome sequences of the bacterial type strainsTerrisporobacter petroleariusJCM 19845T,Terrisporobacter mayombeiDSM 6539TandTerrisporobacter glycolicusDSM 1288T. Functional annotation, KEGG pathway module reconstructions and screening for virulence factors were performed. Various species-specific vitamin, cofactor and amino acid auxotrophies were identified and a model for acetogenesis ofTerrisporobacterwas constructed. The complete genomes harbored a gene cluster for the reductive proline-dependent branch of the Stickland reaction located on an approximately 21 kb plasmid, which is exclusively found in theTerrisporobactergenus. Phylogenomic analysis of availableTerrisporobactergenomes suggested a reclassification of most isolates asT. glycolicusintoT. petrolearius.
Influence of Temperate Forest Autumn Leaf Phenology on Segmentation of Tree Species from UAV Imagery Using Deep Learning
Authors: Cloutier Myriam , Germain Mickaël , Laliberté Etienne 
Published: August 2023

AbstractRemote sensing of forests has become increasingly accessible with the use of unoccupied aerial vehicles (UAV), along with deep learning, allowing for repeated high-resolution imagery and the capturing of phenological changes at larger spatial and temporal scales. In temperate forests during autumn, leaf senescence occurs when leaves change colour and drop. However, the influence of leaf senescence in temperate forests on tree species segmentation using a Convolutional Neural Network (CNN) has not yet been evaluated. Here, we acquired high-resolution UAV imagery over a temperate forest in Quebec, Canada on seven occasions between May and October 2021. We segmented and labelled 23,000 tree crowns from 14 different classes to train and validate a CNN for each imagery acquisition. The CNN-based segmentation showed the highest F1-score (0.72) at the start of leaf colouring in early September and the lowest F1-score (0.61) at peak fall colouring in early October. The timing of the events occurring during senescence, such as leaf colouring and leaf fall, varied substantially between and within species and according to environmental conditions, leading to higher variability in the remotely sensed signal. Deciduous and evergreen tree species that presented distinctive and less temporally-variable traits between individuals were better classified. While tree segmentation in a heterogenous forest remains challenging, UAV imagery and deep learning show high potential in mapping tree species. Our results from a temperate forest with strong leaf colour changes during autumn senescence show that the best performance for tree species segmentation occurs at the onset of this colour change.