bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Environmental DNA to Reconstruct Amphibian Communities at Sites Infected withBatrachochytrium salamandrivoransin the Netherlands
Authors: Davison Anna M. , Spitzen–van der Sluijs Annemarieke , O’Donnell Matthew J. , Prasetyo Andhika P. , Broadhurst Holly A. , Sales Naiara G. , Herder Jelger E. , Coscia Ilaria , McDevitt Allan D. 
Published: November 2023

AbstractThe recently discoveredBatrachochytrium salamandrivorans(Bsal) fungus can cause high mortality rates in some European salamanders and newts (urodelans) and has the potential to expand its currently small invasive range in Europe. Therefore, monitoring its distribution and better understanding both the species threatened and the mechanics of infection are essential in mitigating the damageBsalmay cause. Environmental DNA (eDNA) has emerged as a promising non-invasive method for detecting both this fungal pathogen and the amphibian communities in infected areas. We applied these methods in the province Gelderland, the Netherlands where the pathogen has previously been detected and is expanding its range, with the goal of detecting the natural amphibian community present. We sampled 27 water bodies in the region surrounding the known outbreak sites. We used data from aBsal-specific qPCR assay to determine its presence-absence and applied an eDNA metabarcoding approach to characterize the amphibian communities using two different primer sets. The 12S vertebrate primer set outperformed the 16S amphibian primer set and detected all the expected amphibians in the study area:Bufo bufo, Lissotriton vulgaris, Pelobates fuscus, Pelophylax spp.,Rana temporariaandTriturus cristatus.Bsalwas detected at eight of the ponds. A distance-based redundancy analysis found a weak but significant relationship betweenBsalpresence and the composition of amphibian communities using eDNA. This study provides the foundation for future studies onBsaland its relationship with amphibian communities in Europe, highlighting the need for further research into the mechanisms of persistence and transmission between water bodies.
Regulation of adipocyte dedifferentiation at the skin wound edge
Authors: Yao Longbiao , Jeong Sunhye , Kwon Hae Ryong , Olson Lorin E. 
Published: November 2023

ABSTRACTAdipocytes have diverse roles in energy storage and metabolism, inflammation, and tissue repair. Mature adipocytes have been assumed to be terminally differentiated cells. However, recent evidence suggests that adipocytes retain substantial phenotypic plasticity, with potential to dedifferentiate into fibroblast-like cells under physiological and pathological conditions. Here, we develop a two-step lineage tracing approach based on the observation that fibroblasts express platelet-derived growth factor receptor alpha (Pdgfra) while adipocytes express Adiponectin (Adipoq) but notPdgfra. Our approach specifically tracesPdgfra+cells that originate fromAdipoq+adipocytes. We find many traced adipocytes and fibroblast-like cells surrounding skin wounds, but only a few traced cells localize to the wound center. In agreement with adipocyte plasticity, traced adipocytes incorporate EdU, downregulate Plin1 and PPARγ, and upregulate αSMA. We also investigate the role of potential dedifferentiation signals using constitutively active PDGFRα mutation,Pdgfraknockout, orTgfbr2knockout models. We find that PDGF and TGFβ signaling both promote dedifferentiation, and PDGFRα does so independently of TGFβR2. These results demonstrate an intersectional genetic approach to trace the hybrid cell phenotype ofPdgfra+adipocytes, which may be important for wound repair, regeneration and fibrosis.
baRulho: an R package to quantify degradation in animal acoustic signals
Authors: Araya-Salas Marcelo , Grabarczyk Erin E. , Quiroz-Oliva Marcos , García-Rodríguez Adrián , Rico-Guevara Alejandro 
Published: November 2023

AbstractAnimal acoustic signals are shaped by selection to convey information based on their tempo, intensity, and frequency. However, sound degrades as it propagates over space and across physical obstacles (e.g., vegetation or infrastructure), which affects communication potential. Therefore, transmission experiments are designed to quantify change in signal structure in a given habitat by broadcasting and re-recording animal sounds at increasing distances.We introduce ‘baRulho’, an R package designed to simplify the implementation of sound transmission experiments. We highlight the package features with a case study testing the effects of habitat and acoustic structure on signal transmission. Synthesized sounds that varied in frequency, duration, and frequency and amplitude modulation were broadcast and re-recorded at five increasing distances in open and closed understory at the Bosque de Tlalpan, Mexico City. With this data, we showcase baRulho’s functions to prepare master sound files, annotate re-recorded test sounds, as well as to calculate and visualize measures that quantify degradation of acoustic signals in the time and frequency domain.Degradation measures in baRulho adequately quantified acoustic degradation, following predicted patterns of sound transmission in natural environments. Re-recorded signals degraded less in open habitats compared to closed habitats, with higher-frequency sounds exhibiting more degradation. Furthermore, frequency modulated sounds degraded to a greater extent than pure tones. The increased attenuation and reverberation observed in higher frequency sounds and closed habitats suggest that factors such as absorption and scattering by vegetation play significant roles in transmission patterns.The R package ‘baRulho’ provides an open-source, user-friendly suite of tools designed to facilitate analysis of animal sound degradation. Notably, it offers similar results to other sound analysis software but with significantly reduced processing time. Moreover, the package minimizes the potential for user error through automated test file annotation and verification procedures. We hope that baRulho can help enhance accessibility to transmission experiments within the research community, ultimately contributing to a deeper understanding of the ecological drivers of animal communication systems.
A Novel Role for Phospholamban in the Thalamic Reticular Nucleus
Authors: Klocke Benjamin , Britzolaki Aikaterini , Saurine Joseph , Ott Hayden , Krone Kylie , Bahamonde Kiara , Thelen Connor , Tzimas Christos , Sanoudou Despina , Kranias Evangelia G. , Pitychoutis Pothitos M. 
Published: November 2023

ABSTRACTThe thalamic reticular nucleus (TRN) is a critical brain region that greatly influences vital neurobehavioral processes, including executive functioning and the generation of sleep rhythms. Recently, TRN dysfunction was suggested to underlie hyperactivity, attention deficits, and sleep disturbances observed across various devastating neurodevelopmental disorders, including autism, schizophrenia and attention-deficit/hyperactivity disorder (ADHD). Notably, a highly specialized sarco- endoplasmic reticulum calcium (Ca2+) ATPase 2 (SERCA2)-dependent Ca2+signaling network operates in the dendrites of TRN neurons to regulate their high-frequency bursting activity. Phospholamban (PLN) is a prominent regulator of the SERCA2 with an established role in maintaining Ca2+homeostasis in the heart; although the interaction of PLN with SERCA2 has been largely regarded as cardiac-specific, our findings challenge this view and suggest that the role of PLN extends beyond the cardiovascular system to impact brain function. Specifically, we found PLN to be expressed in the TRN neurons of the adult mouse brain and utilized global constitutive and innovative conditional genetic mouse models, in combination with 5-choice serial reaction time task (5-CSRTT) and electroencephalography (EEG)-based somnography to assess the role of PLN in regulating executive functioning and sleep, two complex behaviors that map onto thalamic reticular circuits. Overall, the results of the present study show that perturbed PLN function in the TRN results in aberrant thalamic reticular behavioral phenotypes in mice (i.e., hyperactivity, impulsivity and sleep deficits) and support a novel role for PLN as a critical regulator of the SERCA2 in the thalamic reticular neurocircuitry.
Reconstitution of a Biofilm Adhesin System from a Sulfate-Reducing Bacterium inPseudomonas fluorescens
Authors: Karbelkar Amruta A. , Font Maria E. , Smith T. Jarrod , Sondermann Holger , O’Toole George A. 
Published: November 2023

AbstractBiofilms of the sulfate reducing bacterium (SRB)Desulfovibrio vulgarisHildenborough (DvH) can facilitate metal corrosion in various industrial and environmental settings leading to substantial economic losses; however, the mechanisms of biofilm formation by DvH are not yet well-understood. Evidence suggests that a large adhesin, DvhA, may be contributing to biofilm formation in DvH. ThedvhAgene and its neighbors encode proteins that resemble the Lap system, which regulates biofilm formation byPseudomonas fluorescens, including a LapG-like protease DvhG and effector protein DvhD, which has key differences from the previously described LapD. By expressing the Lap-like adhesion components of DvH inP. fluorescens, our data support the model that the N-terminal fragment of the large adhesin DvhA serves as an adhesin “retention module” and is the target of the DvhG/DvhD regulatory module, thereby controlling cell-surface location of the adhesin. By heterologously expressing the DvhG/DvhD-like proteins in aP. fluorescensbackground lacking native regulation (ΔlapGΔlapD) we also show that cell surface regulation of the adhesin is dependent upon the intracellular levels of c-di-GMP. This study provides insight into the key players responsible for biofilm formation by DvH, thereby expanding our understanding of Lap-like systems.SignificanceCorrosion leads to ∼2.5 trillion US dollars in economic losses, 20% of which are estimated to be microbially induced. Biofilms of sulfate reducing bacteria (SRB), especially the genusDesulfovibrio, are important members of the corrosion consortium and accelerate deterioration of metals. Understanding how biofilms are formed by SRB can provide important clues to mitigate this challenge. In this study, we used genetic and biochemical tools to investigate the mechanism of biofilm formation byDesulfovibrio vulgarisHildenborough. Our study reveals critical genes responsible for regulating the secretion of a large adhesin known to be required for biofilm formation.
Inhibition of FAM19A5 restores synaptic loss and improves cognitive function in mouse models of Alzheimer’s disease
Authors: Kim Han-Byul , Yoo Sangjin , Kwak Hoyun , Ma Shi-Xun , Kim Ryunhee , Lee Minhyeok , Ha Nui , Pyo Soonil , Kwon Soon-Gu , Cho Eun-Ho , Lee Sang-Myeong , Jang Juwon , Kim Wonkyum , Park Hae-Chul , Baek Minkyung , Park Yosub , Park Ji-Young , Park Jin-Woo , Hwang Sun Wook , Hwang Jong-Ik , Seong Jae Young 
Published: November 2023

AbstractIntroductionAlzheimer’s disease (AD) is characterized by the dysregulation of synaptic balance, with progressive loss of synapses outpacing formation, ultimately leading to cognitive decline. However, the lack of effective strategies for restoring lost synapses poses a major barrier to improving clinical outcomes.MethodsWe developed NS101, a monoclonal antibody targeting FAM19A5, a brain-secreted protein. Its preclinical efficacy in restoring synapses and cognition was evaluated using APP/PS1 and P301S mice. The clinical safety and target engagement of NS101 were examined in human participants.ResultsFAM19A5 binds to LRRC4B, a postsynaptic adhesion molecule, leading to synapse reduction. Blocking this interaction with NS101 normalized the rate of synapse elimination in AD mice. This synaptic rebalancing restored the number and function of synapses, resulting in improved cognition. Systemically administered NS101 facilitated the transport of brain FAM19A5 into the bloodstream.DiscussionTargeting FAM19A5 may hold clinical promise for treating AD by restoring synaptic balance.
Genome-wide detection of somatic mosaicism at short tandem repeats
Authors: Sehgal Aarushi , Ziaei-Jam Helyaneh , Shen Andrew , Gymrek Melissa 
Published: November 2023

AbstractMotivationSomatic mosaicism, in which a mutation occurs post-zygotically, has been implicated in several developmental disorders, cancers, and other diseases. Short tandem repeats (STRs) consist of repeated sequences of 1-6bp and comprise more than 1 million loci in the human genome. Somatic mosaicism at STRs is known to play a key role in the pathogenicity of loci implicated in repeat expansion disorders and is highly prevalent in cancers exhibiting microsatellite instability. While a variety of tools have been developed to genotype germline variation at STRs, a method for systematically identifying mosaic STRs (mSTRs) is lacking.ResultsWe introduce prancSTR, a novel method for detecting mSTRs from individual high-throughput sequencing datasets. Unlike many existing mosaicism detection methods for other variant types, prancSTR does not require a matched control sample as input. We show that prancSTR accurately identifies mSTRs in simulated data and demonstrate its feasibility by identifying candidate mSTRs in whole genome sequencing (WGS) data derived from lymphoblastoid cell lines for individuals sequenced by the 1000 Genomes Project. Our analysis identified an average of 76 and 577 non-homopolymer and homopolymer mSTRs respectively per cell line as well as multiple cell lines with outlier mSTR counts more than 6 times the population average, suggesting a subset of cell lines have particularly high STR instability rates.AvailabilityprancSTR is freely available athttps://github.com/gymrek-lab/trtools.DocumentationDetailed documentation is available athttps://trtools.readthedocs.io/Contactmgymrek@ucsd.edu
Rapid and prolonged response of oligodendrocyte lineage cells in standard acute cuprizone demyelination model revealed byin situhybridization
Authors: He Yuehua , Xie Hua , Zhang Liuning , Feng Yuanyu , Long Yu , Xu ZhengTao , Zou Yanping , Zheng Wei , Wang Shuming , He Yongxiang , Li Jiong , Xiao Lin 
Published: November 2023

AbstractDietary administration of a copper chelator, cuprizone (CPZ), has long been reported to induce intense and reproducible demyelination of several brain structures such as the corpus callosum (CC) in mice, followed by spontaneous remyelination after drug withdrawal. Despite the widespread use of CPZ as an animal model for demyelinating diseases such as multiple sclerosis (MS), the mechanism by which it induces demyelination and then allows robust remyelination is still unclear. An intensive mapping of the oligodendrocyte (OL) lineage cell dynamics during the de-and remyelination course would be of particular importance for a deeper understanding of this model. Here, using a panel of OL lineage cell markers asin situhybridization (ISH) probes, includingPdgfra, Plp, Mbp, Mog, Enpp6, combined with immunofluorescence staining of CC1, SOX10, we provide a detailed dynamic profile of OL lineage cells during the entire course of the model from 3.5 days, 1, 2, 3, 4,5 weeks of CPZ treatment, i.e. the demyelination period, as well as after 1, 2, 3, 4 weeks of recovery (drug withdrawal) from 5 weeks of CPZ treatment, i.e. the remyelination period. The result showed an unexpected early death of mature OLs and response of OL progenitor cells (OPCs) in vivo upon CPZ challenge, and a prolonged upregulation of myelin-forming OLs compared to the intact control even 4 weeks after CPZ withdrawal. These data may point to the need to optimize the timing windows for the introduction of pro-remyelination therapies in demyelinating diseases such as MS, and may serve as a basic reference system for future studies of the effects of any intervention on demyelination and remyelination using the CPZ model.
Enhanced surface accessibility of SARS-CoV-2 Omicron spike protein due to an altered glycosylation profile
Authors: Wang Dongxia , Zhang Zijian , Baudys Jakub , Haynes Christopher , Osman Sarah H. , Zhou Bin , Barr John R. , Gumbart James C. 
Published: November 2023

AbstractSARS-CoV-2 spike (S) proteins undergo extensive glycosylation, aiding proper folding, enhancing stability, and evading host immune surveillance. In this study, we used mass spectrometric analysis to elucidate the N-glycosylation characteristics and disulfide bonding of recombinant spike proteins derived from the SARS-CoV-2 Omicron variant (B.1.1.529) in comparison with the D614G spike variant. Furthermore, we conducted microsecond-long molecular dynamics simulations on spike proteins to resolve how the different N-glycans impact spike conformational sampling in the two variants. Our findings reveal that the Omicron spike protein maintains an overall resemblance to the D614G spike variant in terms of site-specific glycan processing and disulfide bond formation. Nonetheless, alterations in glycans were observed at certain N-glycosylation sites. These changes, in synergy with mutations within the Omicron spike protein, result in increased surface accessibility of the macromolecule, including ectodomain, receptor-binding domain, and N-terminal domain. These insights contribute to our understanding of the interplay between structure and function, thereby advancing effective vaccination and therapeutic strategies.TeaserThrough mass spectrometry and molecular dynamics simulations, SARS-CoV-2 Omicron spike is found to be less covered by glycans when compared to the D614G spike variant.
A communication hub for phosphoregulation of kinetochore-microtubule attachment
Authors: Zahm Jacob A. , Harrison Stephen C. 
Published: November 2023

AbstractThe Mps1 and Aurora B kinases regulate and monitor kinetochore attachment to spindle microtubules during cell division, ultimately ensuring accurate chromosome segregation. In yeast, the critical attachment components are the Ndc80 and Dam1 complexes (Ndc80c and DASH/Dam1c, respectively). Ndc80c is an 600-Å long heterotetramer that binds microtubules through a globular “head” at one end and centromere-proximal kinetochore components through a globular knob at the other end. Dam1c is a heterodecamer that forms a ring of 16-17 protomers around the shaft of the single kinetochore microtubule in point-centromere yeast. The ring coordinates the approximately eight Ndc80c rods per kinetochore. In published work, we showed that a site on the globular “head” of Ndc80c, including residues from both Ndc80 and Nuf2, binds a bipartite segment in the long, C-terminal extension of Dam1. Results reported here show, both by in vitro binding experiments and by crystal structure determination, that the same site binds a conserved segment in the long N-terminal extension of Mps1 and a similarly conserved segment in the N-terminal extension of Ipl1 (yeast Aurora B). Together with results from experiments in yeast cells and from biochemical assays reported in two accompanying papers, the structures and graded affinities identify a communication hub for ensuring uniform bipolar attachment and for signaling anaphase onset.
Phylogeny Inference Under Time-Decaying Migration and Varying Information Content
Authors: Shaik Zaynab , Bergh Nicola G. , Verboom G. Anthony , Oxelman Bengt 
Published: November 2023

AbstractPostspeciation gene flow is widespread across the Tree of Life but is ignored as a cause of gene tree discordance under the standard multispecies coalescent. Where interspecific migration has occurred but is not modelled explicitly, effective population sizes, divergence times and topology can be seriously misestimated. Isolation-with-migration and multispecies coalescent-with-introgression models explicitly model migration but include additional parameters that limit their computational viability with even moderately sized molecular data sets. Here we simulate the evolution of sequences which vary in molecular information content under the coalescent while allowing continuous, tree-wide gene flow/migration between contemporaneous branches, the rate of which decreases with time since divergence. Using simulated sequences, we evaluate the performance of DENIM under rapidly to gradually time-decaying migration and benchmark its performance against the standard MSC method StarBeast3. DENIM consistently outperforms StarBeast3, both in phylogenetic accuracy and computational performance per core. Rapidly decaying migration is associated with improved topology and divergence time estimates under both DENIM and StarBeast3. While species tree estimation accuracy is not improved by increasing the number of loci from 30 to 60 under either method, model convergence is slowed considerably. By contrast, increasing sequence length to 10,000 bp has no clear effect on convergence rates, but shows a tendency towards increased accuracy in DENIM. We apply DENIM and StarBeast3 with a 36-locus empirical bat data set and recover species trees identical in topology to those obtained with 12,931 loci. Our work demonstrates that DENIM can deliver accurate phylogenetic estimates in the presence of both deep coalescence and empirically realistic migration patterns using as few as 30 loci with single-core runtimes of 2-3 days.
Cancer-associated fibroblasts serve as decoys to suppress NK cell anti-cancer cytotoxicity
Authors: Ben-Shmuel Aviad , Gruper Yael , Levi-Galibov Oshrat , Rosenberg-Fogler Hallel , Carradori Giulia , Stein Yaniv , Dadiani Maya , Naumova Mariia , Nevo Reinat , Morzaev-Sulzbach Dana , Yagel Gal , Mayer Shimrit , Gal-Yam Einav Nili , Scherz-Shouval Ruth 
Published: November 2023

AbstractCancer associated fibroblasts (CAFs) are among the most abundant components of the breast tumor microenvironment (TME) and major contributors to immune modulation. CAFs are well-known to regulate the activity of diverse types of immune cells including T cells, macrophages and dendritic cells, however little is known about their interaction with Natural killer (NK) cells, which constitute an important arm of anti-tumor immunity. Here we find, using mouse models of cancer and ex-vivo co-cultures, that CAFs inhibit NK cell cytotoxicity towards cancer cells. We unravel the mechanism by which this suppression occurs, through ligand-receptor engagement between NK cells and CAFs leading to CAF cytolysis, which in turn diminishes the expression of activating receptors on NK cells, promoting cancer escape from NK cell surveillance. Analysis of breast cancer patient samples reveals enrichment of NK cells in CAF-rich regions, and upregulation of NK binding ligands on CAFs which is correlated with poor disease outcome. These results reveal a CAF-mediated immunosuppressive decoy mechanism with implications for treatment of solid tumors.