bluuebunny/crossref_metadata_2025_split huggingface dataset:
Partitioning variability in animal behavioral videos using semi-supervised variational autoencoders
Authors: Whiteway Matthew R , Biderman Dan , Friedman Yoni , Dipoppa Mario , Buchanan E Kelly , Wu Anqi , Zhou John , Bonacchi Niccolò , Miska Nathaniel J , Noel Jean-Paul , Rodriguez Erica , Schartner Michael , Socha Karolina , Urai Anne E , Salzman C Daniel ,   The International Brain Laboratory, Cunningham John P , Paninski Liam 
Published: February 2021

AbstractRecent neuroscience studies demonstrate that a deeper understanding of brain function requires a deeper understanding of behavior. Detailed behavioral measurements are now often collected using video cameras, resulting in an increased need for computer vision algorithms that extract useful information from video data. Here we introduce a new video analysis tool that combines the output of supervised pose estimation algorithms (e.g. DeepLabCut) with unsupervised dimensionality reduction methods to produce interpretable, low-dimensional representations of behavioral videos that extract more information than pose estimates alone. We demonstrate this tool by extracting interpretable behavioral features from videos of three different head-fixed mouse preparations, as well as a freely moving mouse in an open field arena, and show how these interpretable features can facilitate downstream behavioral and neural analyses. We also show how the behavioral features produced by our model improve the precision and interpretation of these downstream analyses compared to using the outputs of either fully supervised or fully unsupervised methods alone.
Tetrameric UvrD helicase is located at theE. colireplisome due to frequent replication blocks
Authors: Wollman Adam J. M , Syeda Aisha H. , Howard Jamieson A. L. , Payne-Dwyer Alex , Leech Andrew , Warecka Dominika , Guy Colin , McGlynn Peter , Hawkins Michelle , Leake Mark C. 
Published: February 2021

SUMMARYDNA replication in all organisms must overcome nucleoprotein blocks to complete genome duplication. Accessory replicative helicases inEscherichia coli, Rep and UvrD, help remove these blocks and aid the re-initiation of replication. Mechanistic details of Rep function have emerged from recent live cell studies; however, the division of UvrD functions between its activities in DNA repair and role as an accessory helicase remain unclear in live cells. By integrating super-resolved single-molecule fluorescence microscopy with biochemical analysis, we find that UvrD self-associates into tetrameric assemblies and, unlike Rep, is not recruited to a specific replisome protein despite being found at approximately 80% of replication forks. Instead, its colocation with forks is likely due to the very high frequency of replication blocks composed of DNA-bound proteins, including RNA polymerase and factors involved in repairing DNA damage. Deletingrepand DNA repair factor genesmutSanduvrA, and inhibiting transcription through RNA polymerase mutation and antibiotic inhibition, indicates that the level of UvrD at the fork is dependent on UvrD’s function. Our findings show that UvrD is recruited to sites of nucleoprotein blocks via different mechanisms to Rep and plays a multi-faceted role in ensuring successful DNA replication.
Characterizing gene expression responses to biomechanical strain in anin vitromodel of osteoarthritis
Authors: Hung Anthony , Housman Genevieve , Briscoe Emilie A. , Cuevas Claudia , Gilad Yoav 
Published: February 2021

AbstractOsteoarthritis (OA) is a common chronic degenerative joint disease affecting articular cartilage and underlying bone. Both genetic and environmental factors appear to contribute to the development of this disease. Specifically, pathological levels of biomechanical stress on joints play a notable role in disease initiation and progression. Population-level gene expression studies of cartilage cells experiencing biomechanical stress may uncover gene-by-environment interactions relevant to OA and human joint health. To build a foundation for such studies, we applied differentiation protocols to develop anin vitrosystem of chondrogenic cell lines (iPSC-chondrocytes). We characterized gene regulatory responses of three human iPSC-chondrocyte lines to cyclic tensile strain treatment. We measured the contribution of biological and technical factors to gene expression variation in this system and, even in this small sample, found several genes that exhibit inter-individual expression differences in response to mechanical strain, including genes previously implicated in OA. Expanding this system to include iPSC-chondrocytes from a larger number of individuals will allow us to characterize and better understand gene-by-environment interactions related to OA and joint health.
Outbreeding depression as a selective force on mixed mating in the mangrove rivulus fish,Kryptolebias marmoratus
Authors: Gresham Jennifer D. , Lewis Kever A. , Summers Stephanie P. , Gresham Percy E. , Earley Ryan L. 
Published: February 2021

AbstractMixed mating, a reproduction strategy utilized by many plants and invertebrates, optimizes the cost to benefit ratio of a labile mating system. One type of mixed mating includes outcrossing with conspecifics and self-fertilizing one’s own eggs. The mangrove rivulus fish (Kryptolebias marmoratus)is one of two vertebrates known to employ both self-fertilization (selfing) and outcrossing. Variation in rates of outcrossing and selfing within and among populations produces individuals with diverse levels of heterozygosity. I designed an experiment to explore the consequences of variable heterozygosity across four ecologically relevant conditions of salinity and water availability (10‰, 25‰, and 40‰ salinity, and twice daily tide changes). I report a significant increase in mortality in the high salinity (40‰) treatment. I also report significant effects on fecundity measures with increasing heterozygosity. The odds of laying eggs decreased with increasing heterozygosity across all treatments, and the number of eggs laid decreased with increasing heterozygosity in the 10‰ and 25‰ treatments. Increasing heterozygosity also was associated with a reduction liver mass and body condition in all treatments. My results highlight the fitness challenges that accompany living in mangrove forests ecosystem and provide the first evidence for outbreeding depression on reproductive and condition-related traits.
DNA reconciles morphology and colouration in the drunk blenny genusScartichthys(Teleostei: Blenniidae) and provides insights into their evolutionary history
Authors: Delrieu–Trottin E. , Salvo H. Hartmann , Agudelo P. Saenz , Landaeta M. F. , Matus A. Perez 
Published: February 2021

AbstractThe blenniids of the genusScartichthysare one of the most common fishes of Central and South American Pacific coastal reefs. This being said, Scartichthys spp. remain difficult to identify in the field, and identification is particularly challenging across the ca. 6000 km where three of the four currently accepted species are known to occur in sympatry. A reason for this is that the main taxonomic characters from traditional taxonomy are indeed elusive. Additionally, At the same time, species can display multiple colour patterns in the field, depending on their ontogenetic stage, habitat association, and reproductive behaviour. Overall, molecular characterization is warranted to help address these issues. Here, we have used a novel approach to revise the genus by combining colouration, morphological, and molecular data of representative specimens of the four currently valid species and seven described colour patterns. From this, we show that only three of the four species should be considered as valid;Scartichthys gigas(Steindachner, 1876),S. variolatus(Valenciennes, 1836), andS. viridis(Valenciennes, 1836); while S. crapulatus Williams 1990 should be synonymized withS. viridis. In the same way, our analyses show that one of the colour patterns attributed so far only toS. gigasis characteristic of the juvenile stages ofS. viridis. Our time-calibrated phylogeny shows that this genus is relatively young and that the estimated time of divergence betweenScartichthys gigasandS. viridisis around 1.71 Ma. In comparison, the Desventuradas and Juan Fernandez Islands endemicS. variolatusdiverged about 1.95 Ma. Our results help to clarify the taxonomy of Scartichthys.SIGNIFICANCE STATEMENTThe blenniids of the genus Scartichthys are one of the most common fishes of Central and South American Pacific coastal reefs. Here we provide an updated phylogeny of this genus, comparing for the first time morphological, coloration, and molecular data in combination to resolve a 30-year-old discord among ecologists and taxonomists and discuss the potential underlying evolutionary processes that led to their presentday distribution.
High-order interactions maintain or enhance structural robustness of a coffee agroecosystem network
Authors: González González Cecilia , Van Cauwelaert Emilio Mora , Boyer Denis , Perfecto Ivette , Vandermeer John , Benítez Mariana 
Published: February 2021

AbstractThe capacity of highly diverse systems to prevail has proven difficult to explain. In addition to methodological issues, the inherent complexity of ecosystems and issues like multicausality, non-linearity and context-specificity make it hard to establish general and unidirectional explanations. Nevertheless, in recent years, high order interactions have been increasingly discussed as a mechanism that benefits the functioning of highly diverse ecosystems and may add to the mechanisms that explain their persistence. Until now, this idea has been explored by means of hypothetical simulated networks. Here, we test this idea using an updated and empirically documented network for a coffee agroecosystem. We identify potentially key nodes and measure network robustness in the face of node removal with and without incorporation of high order interactions. We find that the system’s robustness is either increased or unaffected by the addition of high order interactions, in contrast with randomized counterparts with similar structural characteristics. We also propose a method for representing networks with high order interactions as ordinary graphs and a method for measuring their robustness.HighlightsThe robustness of a coffee-associated ecological network is either increased or unaffected by the incorporation of high order interactions.A method is proposed for representing high order interactions in ordinary networks.A method is proposed to measure the robustness of networks with high order interactions.High order interactions may promote the persistence of diverse ecosystems.
Loss of FAS1 function reveals rescue of an aberrant intra-S-phase checkpoint by the G2/M checkpoint regulator SOG11[OPEN]
Authors: Eekhout Thomas , Dvorackova Martina , Garcia José Antonio Pedroza , Dadejova Martina Nespor , Kalhorzadeh Pooneh , Van den Daele Hilde , Vercauteren Ilse , Fajkus Jiri , De Veylder Lieven 
Published: February 2021

ABSTRACTThe WEE1 and ATR kinases represent important regulators of the plant intra-S-phase checkpoint, as evidenced by the hypersensitivity ofWEE1KOandATRKOroots to replication inhibitory drugs. Here, we report on the identification of a defective allele of theFASCIATA1(FAS1) subunit of the chromatin assembly factor 1 (CAF-1) complex as a suppressor ofWEE1- or ATR-deficient plants. We demonstrate that lack ofFAS1activity results in the activation of an ATM- and SOG1-mediated G2/M-arrest that makes the ATR and WEE1 checkpoint regulators redundant. This ATM activation accounts for telomere erosion and loss of ribosomal DNA described for thefas1plants. Knocking outSOG1in thefas1 wee1background restores replication stress sensitivity, demonstrating that SOG1 plays a prominent role as secondary checkpoint regulator in plants that fail to activate the intra-S-phase checkpoint.One-Sentence SummaryLack of the chromatin assembly factor-1 subunit FAS1 results in a DNA damage response that overrules the need for replication checkpoint activators.
Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome
Authors: Chandra Sunandini , Mannino Philip J. , Thaller David J. , Ader Nicholas R. , King Megan C. , Melia Thomas J. , Lusk C. Patrick 
Published: February 2021

AbstractMechanisms that turnover components of the nucleus and inner nuclear membrane (INM) remain to be fully defined. We explore how components of the INM are selected by a cytosolic autophagy apparatus through a transmembrane nuclear envelope-localized cargo adaptor, Atg39. A split-GFP reporter shows that Atg39 localizes to the outer nuclear membrane (ONM) and thus targets the INM across the nuclear envelope lumen. Consistent with this, sequence elements that confer both nuclear envelope localization and a membrane remodeling activity are mapped to the Atg39 lumenal domain; these lumenal motifs are required for the autophagy-mediated degradation of an integral INM protein. Interestingly, correlative light and electron tomography shows that the overexpression of Atg39 leads to the expansion of the ONM and the enclosure of a network of INM-derived vesicles in the nuclear envelope lumen. Thus, we propose an outside-in model of nucleophagy where INM is delivered into vesicles in the nuclear envelope lumen, which can be targeted by the autophagosome.
Sialic acid ligands of CD28 block co-stimulation of T cells
Authors: Edgar Landon J. , Thompson Andrew J. , Vartabedian Vincent F. , Kikuchi Chika , Woehl Jordan L. , Teijaro John R. , Paulson James C. 
Published: February 2021

AbstractEffector T cells comprise the cellular arm of the adaptive immune system and are essential for mounting immune responses against pathogens and cancer. To reach effector status, co-stimulation through CD28 is required. Here, we report that sialic acid-containing glycans on the surface of both T cells and APCs are alternative ligands of CD28 that compete with binding to its well-documented activatory ligand CD80 on the APC, resulting in attenuated co-stimulation. Removal of sialic acids enhances T cell activation and enhances the activity of effector T cells made hypofunctional via chronic viral infection through a mechanism that is synergistic with antibody blockade of the inhibitory PD-1 axis. These results reveal a previously unrecognized role for sialic acids in attenuation of CD28 mediated co-stimulation of T cells.One Sentence SummarySialic acids attenuate the second signal required for T cell activation.
Sequences in the Human papillomavirus Type 18 (HPV18) Upstream Regulatory Region regulate Viral Genome Replication, Establishment and Persistence
Authors: Coursey Tami L. , Van Doorslaer Koenraad , McBride Alison A. 
Published: February 2021

AbstractDuring persistent human papillomavirus infection, the viral genome replicates as an extrachromosomal plasmid that is efficiently partitioned to daughter cells during cell division. We have previously shown that an element which overlaps the HPV18 transcriptional enhancer promotes stable DNA replication of replicons containing the viral replication origin. Here we perform comprehensive analyses to elucidate the function of this maintenance element. We conclude that no unique element or binding site in this region is absolutely required for persistent replication and partitioning, and instead propose that the overall chromatin architecture of this region is important to promote efficient use of the replication origin. These results have important implications on the genome partitioning mechanism of papillomaviruses.
Regulation of large-conductance Ca2+- and voltage-gated K+channels by electrostatic interactions with auxiliary β subunits
Authors: Tian Yutao , Heinemann Stefan H. , Hoshi Toshinori 
Published: February 2021

AbstractLarge-conductance Ca2+- and voltage-gated K+(BK KCa1.1) channel complexes include pore-forming Slo1 α subunits and often auxiliary β subunits, latter of which noticeably modify the channel’s pharmacological and gating characteristics. In the absence of intracellular Ca2+, β1 and β4 modestly shift the overall voltage dependence of the channel to the positive direction by decreasing the probability that the ion conduction gate is open without any allosteric influence from the channel’s voltage or Ca2+sensors. This intrinsic open probability is also critically regulated by the intracellular-facing329RKK331segment of human Slo1 (hSlo1) downstream of the transmembrane segment S6 in association with two negatively charged residues in S6 (E321 and E324) (Tian et al., Proc Natl Acad Sci USA, 116, 8591-8596, 2019). This study examined how β1/β4 and the RKK segment function together to control the channel gate. With select mutations in the RKK segment, inclusions of β1 or β4 can dramatically increase the intrinsic gate opening probability and shift the overall voltage dependence of the channel to the negative direction by up to 200 mV without Ca2+. This remarkable shift is mediated at least in part by electrostatic interactions between the Slo1 RKK and β N-terminal segments as suggested by the results of double-mutant cycle analysis, ionic strength experiments, and molecular modelling. With or without auxiliary β subunits, the Slo1 RKK and E321/E324 segments are thus critical determinants of the intrinsic open probability of the ion conduction gate and changes in the electrostatic environment near the RKK-EE segments are a potential mechanism of pharmacological gating modifiers.
A massive 7T fMRI dataset to bridge cognitive and computational neuroscience
Authors: Allen Emily J. , St-Yves Ghislain , Wu Yihan , Breedlove Jesse L. , Dowdle Logan T. , Caron Brad , Pestilli Franco , Charest Ian , Hutchinson J. Benjamin , Naselaris Thomas , Kay Kendrick 
Published: February 2021

AbstractExtensive sampling of neural activity during rich cognitive phenomena is critical for robust understanding of brain function. We present the Natural Scenes Dataset (NSD), in which high-resolution fMRI responses to tens of thousands of richly annotated natural scenes are measured while participants perform a continuous recognition task. To optimize data quality, we develop and apply novel estimation and denoising techniques. Simple visual inspections of the NSD data reveal clear representational transformations along the ventral visual pathway. Further exemplifying the inferential power of the dataset, we use NSD to build and train deep neural network models that predict brain activity more accurately than state-of-the-art models from computer vision. NSD also includes substantial resting-state and diffusion data, enabling network neuroscience perspectives to constrain and enhance models of perception and memory. Given its unprecedented scale, quality, and breadth, NSD opens new avenues of inquiry in cognitive and computational neuroscience.
A novel two-generation approach for understanding the population dynamics of gregarious parasitoids
Authors: Samková Alena , Raška Jan , Hadrava Jiří , Skuhrovec Jiří 
Published: February 2021

AbstractParasitoids, as important natural enemies, help maintain balance in natural ecosystems. Their population dynamics is generally predicted from the number of individuals. Here, using gregarious parasitoids as models, we show that this traditional approach omits one important parameter: the mother’s manipulation of offspring fertility due to the clutch size–body size– fertility correlation. As a result of this correlation, when females deliberately adjust the number of offspring laid in a host, they determine not only the number but also the body sizes and reproductive potentials of those offspring. For the first time in the model speciesAnaphes flavipes, we determined the parasitoid’s offspring fertility from clutch size. Using this, we experimentally clarified the advantage of specific clutch size combinations and we show that identical fertility in the F1 generation can lead to distinctly different fertility values in the F2 generation. Even with the same number of hosts, lower fertility in the F1 generation can cause higher fertility in the F2 generation. Based on these results, we propose a novel two-generation approach which includes the clutch size–body size–fertility correlation. Our novel approach provides a new perspective for determining the individual fitness levels of gregarious parasitoids with new options for the modelling of parasitoid population dynamics.
Germline activity of the heat shock factor HSF-1 programs the insulin-receptordaf-2inC. elegans
Authors: Das Srijit , Min Sehee , Prahlad Veena 
Published: February 2021

AbstractThe mechanisms by which maternal stress alters offspring phenotypes remain poorly understood. Here we report that the heat shock transcription factor HSF-1, activated in theC. elegansmaternal germline upon stress, epigenetically programs the insulin-like receptordaf-2by increasing repressive H3K9me2 levels throughout thedaf-2gene. This increase occurs by the recruitment of theC. elegansSETDB1 homolog MET-2 by HSF-1. Increased H3K9me2 levels atdaf-2persist in offspring to downregulatedaf-2,activate theC. elegansFOXO ortholog DAF-16 and enhance offspring stress resilience. Thus, HSF-1 activity in the mother promotes the early life programming of the insulin/IGF-1 signaling (IIS) pathway and determines the strategy of stress resilience in progeny.One Sentence SummaryHSF-1 recruits MET-2 to silencedaf-2and mediate early life programming ofC. elegansupon stress
Ribosomes in RNA granules are stalled on mRNA sequences that are consensus sites for FMRP association
Authors: Anadolu Mina N. , Sun Jingyu , Kailasam Senthilkumar , Simbriger Konstanze , Markova Teodora , Jafarnejad Seyed Mehdi , Lefebvre Francois , Ortega Joaquin , Gkogkas Christos G. , Sossin Wayne S. 
Published: February 2021

AbstractLocal translation in neurons is mediated in part by the reactivation of stalled polysomes. Stalled polysomes may be enriched within the pellet of sucrose gradients used to separate polysomes from monosomes. We find that this fraction, isolated from P5 rat brains of both sexes, is enriched in proteins implicated in stalled polysome function, such as the fragile X mental retardation protein (FMRP) and Up-frameshift mutation 1 homolog (UPF1). Cryo-EM analysis of ribosomes in this fraction indicates they are stalled, mainly in the hybrid state. Ribosome profiling of this fraction showed an abundance of footprint reads derived from mRNAs of cytoskeletal proteins implicated in neuronal development and an enrichment of footprint reads on RNA binding proteins. Compared to those usually found in ribosome profiling studies, the footprint reads were more extended on their 3’end and were found in reproducible peaks in the mRNAs. These peaks were enriched in motifs previously associated with mRNAs cross-linked to FMRP in vivo, independently linking the ribosomes in the sedimented pellet to the ribosomes associated with FMRP in the cell. The data supports a model in which specific sequences in mRNAs act to stall translation elongation in neurons.