bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating fine-scale breeding habitat use by amphibians in a continuous wetland using environmental DNA
Authors: Guenat Julie Morgane , Gander Antoine , Fumagalli Luca , Lavanchy Guillaume 
Published: February 2023

ABSTRACTDesigning effective conservation plans to protect species from extinction requires a better understanding of their ecology. Conventional methods used to investigate habitat use are time consuming, and detectability of cryptic species is often insufficient. Environmental DNA (eDNA)-based approaches now provide an alternative for ecosystems monitoring and assessment. Nevertheless, to our knowledge, such methods have never been applied to investigate habitat use at a fine scale in a continuous wetland environment. Here, we used an eDNA metabarcoding approach to characterize the breeding habitat use of local amphibian species in a wet meadow expanse along the southern shore of Lake Neuchâtel, Switzerland. We retrieved DNA from six out of the seven species expected to be present. We tested the influence of six abiotic environmental variables on overall species communities as well as individual species occurrences. We showed that the main factor structuring species communities was water temperature, and that the distribution of three amphibian species was associated with several environmental variables. Our results indicate that the eDNA approach is a promising tool to study species’ ecology at a small scale in continuous wetland habitats.
CD82 expression marks the endothelium to hematopoietic transition at the onset of blood specification in human
Authors: Menegatti Sara , Potts Bethany , Paredes Roberto , Garcia-Alegria Eva , Murtuza Baker Syed , Kouskoff Valerie 
Published: February 2023

SUMMARYDuring embryonic development, all blood progenitors are initially generated from endothelial cells that acquire a hemogenic potential. Blood progenitors emerge through an endothelial-to-hematopoietic transition regulated by the transcription factor RUNX1. To date, we still know very little about the molecular characteristics of hemogenic endothelium and the molecular changes underlying the transition from endothelium to hematopoiesis. Here, we analysed at the single cell level a human embryonic stem cell-derived endothelial population containing hemogenic potential. RUNX1-expressing endothelial cells, which harbour enriched hemogenic potential, show very little molecular differences to their endothelial counterpart suggesting priming toward hemogenic potential rather than commitment. Additionally, we identify CD82 as a marker of the endothelium-to-hematopoietic transition. CD82 expression is rapidly upregulated in newly specified blood progenitors then rapidly downregulated as further differentiation occurs. Together our data suggest that endothelial cells are first primed toward hematopoietic fate, then rapidly undergo the transition from endothelium to blood.
Integrative single-cell transcriptomics clarifies adult neurogenesis and macroglia evolution
Authors: Morizet David , Foucher Isabelle , Alunni Alessandro , Bally-Cuif Laure 
Published: February 2023

AbstractMacroglia fulfill essential functions in the adult vertebrate brain, producing and maintaining neurons and regulating neuronal communication. However, we still know little about their emergence and diversification. We used the zebrafishD. rerioas a distant vertebrate model with moderate glial diversity as anchor to reanalyze datasets covering over 600 million years of evolution. We identify core features of adult neurogenesis and innovations in the mammalian lineage with a potential link to the rarity of radial glia-like cells in adult humans. Our results also suggest that functions associated with astrocytes originated in a multifunctional cell type fulfilling both neural stem cell and astrocytic functions before these diverged. Finally, we identify conserved elements of macroglial cell identity and function and their time of emergence during evolution.One-Sentence SummaryRadial glia of the adult zebrafish forebrain associate transcriptomic features of adult neural stem cells and astrocytes
Singular superlet transform achieves markedly improved time-frequency super-resolution for separating complex neural signals
Authors: Kesgin Kaan , Jörntell Henrik 
Published: February 2023

AbstractTime-frequency decomposition is a well-established method to unmix signals generated by multiple sources with unique characteristics. However, there are cases of high signal complexity where existing time-frequency decomposition tools are insufficient for localizing and representing short-bursting signals. One example is the currently highly popular extracellular low-impedance recordings from multi-electrode arrays in the brainin vivowhere each neuron repeatedly generates a specific signal ‘fingerprint’ (characteristic spike waveform) that can be mixed with the signals of 100s of other sources, including the spikes of nearby neurons. Here we derive the singular superlet transform (SST) method, which enables highly localized representations of fast and short bursts compared to other super-resolution spectral estimators, while also requiring orders of magnitude fewer operations. We demonstrate a substantial edge of SST over current methods in isolating specific neuronal spikes with high-fidelity in challenging, complex recording signals from neocortexin vivo. We also exemplify SST’s generic signal processing capability by achieving outstanding resolution in the decomposition of complex acoustic data.
Continuous, long-term crawling behavior characterized by a robotic transport system
Authors: Yu James , Dancausse Stephanie , Paz Maria , Faderin Tolu , Gaviria Melissa , Shomar Joseph , Zucker Dave , Venkatachalam Vivek , Klein Mason 
Published: February 2023

AbstractDetailed descriptions of behavior provide critical insight into the structure and function of nervous systems. InDrosophilalarvae and many other systems, short behavioral experiments have been successful in characterizing rapid responses to a range of stimuli at the population level. However, the lack of long-term continuous observation makes it difficult to dissect comprehensive behavioral dynamics of individual animals and how behavior (and therefore the nervous system) develops over time. To allow for long-term continuous observations in individual fly larvae, we have engineered a robotic instrument that automatically tracks and transports larvae throughout an arena. The flexibility and reliability of its design enables controlled stimulus delivery and continuous measurement over developmental time scales, yielding an unprecedented level of detailed locomotion data. We utilize the new system’s capabilities to perform continuous observation of exploratory behavior over a duration of six hours with and without a thermal gradient present, and in a single larva for over 30 hours. Long-term free-roaming behavior and analogous short-term experiments show similar dynamics that take place at the beginning of each experiment. Finally, characterization of larval thermotaxis in individuals reveals a bimodal distribution in navigation efficiency, identifying distinct phenotypes that are obfuscated when only analyzing population averages.
From Policy to Practice: Tracking an Open Science Funding Initiative
Authors: Ratan Kristen , McIntosh Souad , Shah Hetal V. , Lewis Matt , Dumanis Sonya B. , Vines Timothy H. , Schekman Randy , Riley Ekemini A 
Published: February 2023

AbstractThis is a critical moment in the open science landscape. Over the past few years there has been growing momentum to improve open research policies and require grantees to share all research outputs, from datasets to code to protocols, inFAIR (findable, accessible, interoperable and reusable [FAIR]) repositorieswith persistent identifiers attached. The Aligning Science Across Parkinson’s (ASAP) initiative has made substantial investments in improving open science compliance monitoring for its grantees, requiring grantees to update their manuscripts if not all research outputs have been linked in the initial manuscript version. Here, we evaluate ASAP’s effectiveness in improving research output sharing for all articles processed through the ASAP compliance workflow between March 1, 2022, and October 1, 2022. Our ultimate goal in sharing our findings is to assist other funders and institutions as they consider open science implementation. By normalizing the open science and compliance process across funding bodies, we hope to simplify and streamline researcher, institutional, and funder workflows, allowing researchers to focus on science by easily leveraging resources and building upon the work of others.
Three rules for epigenetic inheritance of human Polycomb silencing
Authors: Shafiq Tiasha A. , Moazed Danesh 
Published: February 2023

AbstractHeritable expression of developmental genes is mediated by autoregulating transcription factor networks (TFNs) and Polycomb repressive chromatin silencing complexes (PRCs). Whether the mammalian Polycomb pathway mediates DNA sequence-independent epigenetic memory at genes being activated by TFNs remains unknown. Here, we show that, in human cells, newly induced Polycomb silencing at initially active developmental genes can be inherited for many cell divisions. However, when Polycomb silencing is similarly induced near ubiquitously expressed housekeeping genes, it is not heritable. Inheritance requires the recognition of CG-rich DNA by a Polycomb accessory protein, MTF2/PCL2, the histone H3 lysine 27 trimethylation (H3K27me3) and histone H2A lysine 119 mono-ubiquitination (H2AK119ub1) activities of PRC1 and PRC2, and their associated positive feedback (read-write). In the absence of H3K27me3, H2AK119ub1 can mediate inheritance of silencing by a mechanism that requires the recognition of H2AK119ub1 by the variant Polycomb Repressive Complex 1. These findings indicate that inheritance of Polycomb silencing in human cells (1) depends on sequence features of developmental gene loci (2) requires PRC1 and H2AK119ub1, and (3) can be mediated by PRC1-H2AK119ub1 independently of H3K27me3.
SMCHD1 loss triggers DUX4 expression by disrupting splicing in FSHD2
Authors: Engal Eden , Sharma Aveksha , Taqatqa Nadeen , Bentata Mercedes , Jaffe-Herman Shiri , Geminder Ophir , Lewis Reyut , Gotkine Marc , Salton Maayan , Drier Yotam 
Published: February 2023

AbstractStructural Maintenance of Chromosomes Flexible Hinge Domain Containing 1 (SMCHD1) is a non-canonical member of the structural maintenance of chromosomes (SMC) protein family involved in the regulation of chromatin structure, epigenetic regulation, and transcription. Mutations in SMCHD1 cause facioscapulohumeral muscular dystrophy type 2 (FSHD2), a rare genetic disorder characterized by progressive muscle weakness and wasting, believed to be caused by aberrant expression of DUX4 in muscle cells. Here we suggest a new role for SMCHD1 as a regulator of alternative splicing in various cell types. We demonstrate how SMCHD1 mutations cause splicing alterations of DNA Methyltransferase 3 Beta DNMT3B which can lead to hypomethylation, DUX4 expression, and FSHD pathogenesis. Analyzing RNA-seq data from muscle biopsies of FSHD2 patients and Smchd1 knocked out cells, we found that hundreds of genes were mis-spliced upon loss of SMCHD1. At least 20% of mis-spliced genes were associated with abnormalities of the musculature. Moreover, we show that mis-spliced exons tend to be bound by SMCHD1, and these exons demonstrate a slower elongation rate, suggesting SMCHD1 binding promotes exon exclusion by slowing RNA polymerase II (RNAPII). Specifically, we discovered that SMCHD1 mutations promote the splicing of the DNMT3B1 isoform of DNMT3B by perturbing RNAPII elongation rate and recruitment of the splicing factor RBM5. The mis-splicing of DNMT3B leads to hypomethylation of the D4Z4 region and DUX4 overexpression. These results suggest that mis-splicing by SMCHD1 may play a major role in FSHD2 pathogenesis by promoting the mis-splicing of different targets including DNMT3B, and highlight the potential for targeting splicing as a therapeutic strategy for this disorder.Significance statementOur study sheds light on how the loss of SMCHD1 drives the pathogenesis of facioscapulohumeral muscular dystrophy (FSHD), a rare genetic disorder characterized by muscle weakness and wasting. We found that SMCHD1 mutations led to changes in splicing of hundreds of genes, 20% of which were related to muscle abnormalities. We found that SMCHD1 tends to bind mis-spliced exons and that its binding slows down the elongation rate of RNA polymerase II often leading to the exclusion of the exon. One of these targets is DNA Methyltransferase 3 Beta (DNMT3B), and we show that the isoform promoted by SMCHD1 mutations leads to hypomethylation of a repeat region near DUX4 and to DUX4 overexpression, a known cause for FSHD. Our results provide insight into the molecular mechanisms underlying this disorder, and suggest splicing modulation as a therapeutic strategy for FSHD.
Ultrasensitive response explains the benefit of combination chemotherapy despite drug antagonism
Authors: Patterson Sarah C. , Pomeroy Amy E. , Palmer Adam C. 
Published: February 2023

AbstractMost aggressive lymphomas are treated with combination chemotherapy, commonly as multiple cycles of concurrent drug administration. Concurrent administration is in theory optimal when combination therapies have synergistic (more than additive) drug interactions. We investigated pharmacodynamic interactions in the standard 4-drug ‘CHOP’ regimen in Peripheral T-Cell Lymphoma (PTCL) cell lines, and found that CHOP consistently exhibits antagonism and not synergy. We tested whether staggered treatment schedules could improve tumor cell kill by avoiding antagonism, using month-longin vitromodels of concurrent or staggered treatments. Surprisingly, we observed that tumor cell kill is maximized by concurrent drug administration despite antagonistic drug-drug interactions. We propose that an ultrasensitive dose response, as described in radiology by the linear-quadratic (LQ) model, can reconcile these seemingly contradictory experimental observations. The LQ model describes the relationship between cell survival and dose, and in radiology has identified scenarios favoring hypofractionated radiation – the administration of fewer large doses rather than multiple smaller doses. Specifically, hypofractionated treatment can be favored when cells require an accumulation of DNA damage, rather than a ‘single hit’, in order to die. By adapting the LQ model to combination chemotherapy and accounting for tumor heterogeneity, we find that tumor cell kill is maximized by concurrent administration of multiple drugs, even when chemotherapies have antagonistic interactions. Thus, our study identifies a new mechanism by which combination chemotherapy can be clinically beneficial that is not reliant on positive drug-drug interactions.
Improving the annotation of the cattle genome by annotating transcription start sites in a diverse set of tissues and populations using CAGE sequencing
Authors: Salavati M. , Clark R. , Becker D. , Kühn C. , Plastow G. , Dupont S. , Moreira G.C.M. , Charlier C. , Clark E.L. 
Published: February 2023

AbstractUnderstanding the genomic control of tissue-specific gene expression and regulation can help to inform the application of genomic technologies in farm animal breeding programmes. The fine mapping of promoters (transcription start sites [TSS]) and enhancers (divergent amplifying segments of the genome local to TSS) in different populations of cattle across a wide diversity of tissues provides information to locate and understand the genomic drivers of breed- and tissue-specific phenotypes. To this aim we used Cap Analysis Gene Expression (CAGE) sequencing to define TSS and their co-expressed short-range enhancers (<1kb) in the ARS-UCD1.2_Btau5.0.1Y reference genome (1000bulls run9) and analysed tissue- and population specificity of expressed promoters. We identified 51,295 TSS and 2,328 TSS-Enhancer regions shared across the three populations (Holstein, Charolais x Holstein and Kinsella beef composite [KC]). In addition, we performed a comparative analysis of our cattle dataset with available data for seven other species to identify TSS and TSS-Enhancers that are specific to cattle. The CAGE dataset will be combined with other transcriptomic information for the same tissues generated in the BovReg project to create a new high-resolution map of transcript diversity across tissues and populations in cattle. Here we provide the CAGE dataset and annotation tracks for TSS and TSS Enhancers in the cattle genome. This new annotation information will improve our understanding of the drivers of gene expression and regulation in cattle and help to inform the application of genomic technologies in breeding programmes.
SalmonellaTyphimurium effector SseI regulates host peroxisomal dynamics to acquire lysosomal cholesterol for better intracellular growth
Authors: Raj Desh , Nair Abhilash Vijay , Sharma Jyotsna , Prakash Shakti , Kaushik Aman , Basu Swarnali , Sahu Shikha , Singh Shriya , Bhosale Vivek , Chandra Tulika , Ghoshal Uday C , Dasgupta Arunava , Siddiqi Mohammad Imran , Gupta Shashi Kumar , Chakravortty Dipshikha , Ammanathan Veena , Lahiri Amit 
Published: February 2023

AbstractIntracellularSalmonellaresides and multiplies in cholesterol-rich specialized compartment calledSalmonella-containing vacuoles (SCVs) and avoids fusion with acidic lysosomes. Given, lysosomes are primary organelle that redistributes LDL derived cholesterol to other organelles; we questioned how lysosomal cholesterol can be transported to SCV. We demonstrate here that peroxisomes are recruited to SCVs in human primary macrophages, epithelial cells and functions as pro-bacterial organelles. Further, this interaction is assisted by SseI, aSalmonellaeffector protein containing mammalian peroxisome targeting sequence. SseI localizes to peroxisome, interacts and activates a host Ras GTPase, ARF-1 on the peroxisome membrane. Activation of ARF-1 leads to recruitment of phosphatidylinsolitol-5- phosphate-4 kinase to generate phosphatidylinsolitol-4-5-bisphosphate on peroxisomes. Accordingly, theΔsseIstrain showed reduced virulence in cell lines and during mice infection. Taken together, our work identified a fascinating mechanism by which a pathogen targets host organelles via its secretory effectors and exploits host metabolic intermediates for its intracellular proliferation.
Comparative Features of Calretinin, Calbindin and Parvalbumin Expressing Interneurons in Mouse and Monkey Primary Visual and Frontal Cortices
Authors: Medalla Maria , Mo Bingxin , Nasar Rakin , Zhou Yuxin , Park Junwoo , Luebke Jennifer I 
Published: February 2023

ABSTRACTMuch is known about differences in pyramidal cells across cortical areas and species, but studies of interneurons have focused on comparisons within single cortical areas and/or species. Here we quantified the distribution and somato-dendritic morphology of interneurons expressing one or more of the calcium binding proteins (CaBPs) calretinin (CR), calbindin (CB) and/or parvalbumin (PV) in mouse (Mus musculus) versus rhesus monkey (Macaca mulatta) in two functionally and cytoarchitectonically distinct regions- the primary visual and frontal cortical areas. The density, laminar distribution and morphology of interneurons were assessed in serial brain sections using immunofluorescent multi-labeling, stereological counting and 3D reconstructions. There were significantly higher densities of CB+ and PV+ neurons in visual compared to frontal areas in both species. The main species difference was the significantly greater density and proportion of CR+ interneurons and lower extent of CaBP co-expression in monkey compared to mouse cortices. Cluster analyses revealed that the somato-dendritic morphology of layer 2-3 inhibitory interneurons is more dependent on CaBP expression than on species and area. Only modest effects of species were observed for CB+ and PV+ interneuron morphologies, while CR+ neurons showed no difference. By contrast to pyramidal cells which show highly distinctive area- and species-specific features, here we found more subtle differences in the distribution and features of interneurons across areas and species. These data yield insight into how nuanced differences in the population organization and properties of neurons may underlie specializations in cortical regions to confer species and area-specific functional capacities.Key Points:Somato-dendritic morphology of distinct interneurons did not substantially scale and vary across areas and species- differences were mainly dependent on CaBP expression.Cortical diversity in inhibitory function across areas and species is thus likely to be derived from differential laminar distribution and densities of distinct interneuron subclasses.In contrast to pyramidal cells which differ widely in distribution and morphology across areas and species, the features of interneurons appears to be relatively more conserved across areas and species.
Forest cover is more important than habitat integrity or landscape configuration in determining habitat use by mammals in a human-modified landscape in Colombia
Authors: Pardo Lain E. , Gómez-Valencia Bibiana , Deere Nicolas J. , Varón Yenifer Herrera , Soto Carolina , Noguera-Urbano Elkin A. , Sánchez-Clavijo Lina M. , Romero Luis , Díaz-Pulido Angélica , Quintero José Manuel Ochoa 
Published: February 2023

AbstractHuman activities shape the structure of landscapes in different ways and hence modify animal communities depending on the type and intensity of these activities. The Montes de Maria subregion of Colombia has experienced a heavy transformation of most areas despite covering one of the last remnants of dry forest, a critically endangered ecosystem. However, the effects of this transformation have been little explored. Here, we used a multispecies occupancy model (MSOM) to understand the relative influence of three components of land-use change – deforestation (remaining habitat amount), degradation of habitat quality (habitat quality) and fragmentation (landscape configuration) on mammalian habitat use across a mosaic of tropical dry forest in Colombia. Our data suggest that the percentage of forest cover was substantially important for herbivores, and consistently showed a moderate effect on the entire community and some individual species. High variability in species-specific responses to the examined variables hindered broad taxonomic generalizations, nevertheless, we detected a moderate positive effect of forest cover in both diet specialists and generalists species, as well as in species with small home ranges. Although omnivores responses, tended to use less complex landscapes (mosaics of land uses), there was high uncertainty in this response. The lack of substantial effects on most species, and the absence of threatened species across this anthropogenic landscape, suggests that the current community is composed of species tolerant to habitat modifications, but not only diet generalist species. This is most likely the result of a long filtering process caused by land use transformation and hunting which could have caused non-sensitive species to distribute relatively homogenously across this landscape. Our results suggest that conservation strategies in the study area should focus on conserving and expanding as much forest as possible rather than only improving the quality of already existing forest patches.