bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromatin accessibility and microRNA expression in nephron progenitor cells during kidney development
Authors: Clugston Andrew , Bodnar Andrew , Cerqueira Débora Malta , Phua Yu Leng , Lawler Alyssa , Boggs Kristy , Pfenning Andreas , Ho Jacqueline , Kostka Dennis 
Published: March 2021

AbstractMammalian nephrons originate from a population of nephron progenitor cells (NPCs), and it is known that NPCs’ transcriptomes change throughout nephrogenesis during healthy kidney development. To characterize chromatin accessibility and microRNA (miRNA) expression throughout this process, we collected NPCs from mouse kidneys at embryonic day 14.5 (E14.5) and postnatal day zero (P0) and assayed cells for transposase-accessible chromatin and small RNA expression. We observe 46,374 genomic regions of accessible chromatin, with 2,103 showing significant changes in accessibility between E14.5 and P0. In addition, we detect 1,104 known microRNAs, with 114 showing significant changes in expression. Genome-wide, changes in DNA accessibility and microRNA expression highlight biological processes like cellular differentiation, cell migration, extracellular matrix interactions, and developmental signaling pathways such as Notch. Furthermore, our data identify novel candidate cis-regulatory elements forEya1andPax8, both genes with a role in NPC differentiation; we also associate expression-changing microRNAs, includinglet-7-5p,miR-125b-5p,miR-181a-2-3p, andmiR-9-3p,with candidate cis-regulatory elements. Overall, our data characterize NPCs during kidney development and point out new candidate regulatory elements for genes and microRNA with key roles in nephrogenesis.
Implicit and explicit learning of Bayesian priors differently impacts bias during perceptual decision-making
Authors: Thakur V. N. , Basso M. A. , Ditterich J. , Knowlton B. J. 
Published: March 2021

ABSTRACTKnowledge without awareness, or implicit knowledge, influences a variety of behaviors. It is unknown however, whether implicit knowledge of statistical structure informs visual perceptual decisions or whether explicit knowledge of statistical probabilities is required. Here, we measured visual decision-making performance using a novel task in which humans reported the orientation of two differently colored translational Glass patterns; each color associated with different orientation probabilities. The task design allowed us to assess participants’ ability to learn and use a general orientation prior as well as a color specific feature prior. Classifying decision-makers based on a questionnaire revealed that both implicit and explicit learners implemented a general orientation bias by adjusting the starting point of evidence accumulation in the drift diffusion model framework. Explicit learners additionally adjusted the drift rate offset. When subjects implemented a stimulus specific bias, they did so by adjusting primarily the drift rate offset. We conclude that humans can learn priors implicitly for perceptual decision-making and depending on awareness implement the priors using different mechanisms.
Differential impact of transdiagnostic, dimensional psychopathology on multiple scales of functional connectivity
Authors: Seok Darsol , Beer Joanne , Jaskir Marc , Smyk Nathan , Jaganjac Adna , Makhoul Walid , Cook Philip , Elliott Mark , Shinohara Russell , Sheline Yvette I. 
Published: March 2021

AbstractIntroductionDimensional psychopathology strives to associate different domains of cognitive dysfunction with brain circuitry. Connectivity patterns as measured by functional magnetic resonance imaging (fMRI) exist at multiple scales, with global networks of connectivity composed of microscale interactions between individual nodes. It remains unclear how separate dimensions of psychopathology might differentially impact these different scales of organization.MethodsPatients experiencing anxious misery symptomology (depression, anxiety and trauma; n = 192) were assessed for symptomology and received resting-state fMRI scans. Three modeling approaches (seed-based correlation analysis [SCA], support vector regression [SVR] and Brain Basis Set Modeling [BSS]), each relying on increasingly dense representations of functional connectivity patterns, were used to associate connectivity patterns with six different dimensions of psychopathology: anxiety sensitivity, anxious arousal, rumination, anhedonia, insomnia and negative affect. Importantly, a full 50 patients were held-out in a testing dataset, leaving 142 patients as training data.ResultsDifferent symptom dimensions were best modeled by different scales of brain connectivity: anhedonia and anxiety sensitivity were best modeled with single connections (SCA), insomnia and anxious arousal by mesoscale patterns (SVR) and negative affect and ruminative thought by broad, cortex-spanning patterns (BBS). Dysfunction within the default mode network was implicated in all symptom dimensions that were best modeled by multivariate models.ConclusionThese results suggest that symptom dimensions differ in the degree to which they impact different scales of brain organization. In addition to advancing our basic understanding of transdiagnostic psychopathology, this has implications for the translation of basic research paradigms to human disorders.
Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates
Authors: Poulen Gaëtan , Aloy Emilie , Bringuier Claire M. , Mestre-Francés Nadine , Artus Emaëlle V.F. , Cardoso Maïda , Perez Jean-Christophe , Goze-Bac Christophe , Boukhaddaoui Hassan , Lonjon Nicolas , Gerber Yannick N. , Perrin Florence E. 
Published: March 2021

AbstractNo curative treatment is available for any deficits induced by spinal cord injury (SCI). Following injury, microglia undergo highly diverse activation processes, including proliferation, and play a critical role on functional recovery.In a translational objective, we investigated whether a transient pharmacological reduction of microglia proliferation after injury is beneficial for functional recovery after SCI in mice and nonhuman primates. The colony stimulating factor-1 receptor (CSF1R) regulates proliferation, differentiation, and survival of microglia, we thus used an oral administration of GW2580, a CSF1R inhibitor.First, transient post-injury GW2580 administration in mice improves motor function recovery, promotes tissues preservation and/or reorganization (identified by coherent anti-stokes Raman scattering microscopy), and modulates glial reactivity.Second, post-injury GW2580-treatment in nonhuman primates reduces microglia proliferation, improves functional motor function recovery, and promotes tissue protection. Notably, three months after lesion microglia reactivity returned to baseline value.Finally, to initiate the investigation on molecular mechanisms induced by a transient post-SCI GW2580-treatment, we used microglia-specific transcriptomic analysis in mice. Notably, we detected a downregulation in the expression of inflammatory-associated genes and we identified genes that were up-regulated by SCI and further downregulated by the treatment.Thus, a transient oral GW2580 treatment post-injury may provide a promising therapeutic strategy for SCI patients and may also be extended to other central nervous system disorders displaying microglia activation.
The dynamics of cell-free DNA from urine and blood after a full marathon
Authors: Shishikura Yasuhiro , Tokinoya Katsuyuki , Aita Yuichi , Sekine Nanami , Sugasawa Takehito , Yoshida Yasuko , Kosaki Keisei , Kumamoto Shota , Ishikura Keisuke , Kuji Tomoaki , Kawakami Yasushi , Nabekura Yoshiharu , Maeda Seiji , Takekoshi Kazuhiro 
Published: March 2021

AbstractPurposeCell-free DNA (cfDNA) has been investigated as a minimally invasive biomarker for many diseases, particularly cancer. An increase in cfDNA has been observed during exercise. Neutrophil extracellular traps (NETs) may be the origin of cfDNA in response to acute exercise, but the mechanisms of generation of cfDNA during exercise remain unclear. In this study we investigated the dynamics of serum and urinary cfDNA levels and determined the relevance of other biomarkers to serum and urinary cfDNA levels and fragment size after a full marathon.MethodsSamples were collected from 23 healthy male subjects. Blood and urine samples were collected before and immediately, two hours, and one day after the full marathon. The measurements included serum and urinary cfDNA, creatine kinase, myoglobin, creatinine, white blood cells, platelets, and lactoferrin from blood, and amylase, albumin, and creatinine from urine.ResultsSerum and urinary cfDNA levels increased after a full marathon. Creatine kinase, myoglobin, and creatinine in blood, and albumin and creatinine in urine also increased significantly after a full marathon. Serum cfDNA showed peak values about 180 bp after the full marathon. Values over 1000 bp were present at two hours post-marathon. Urinary cfDNA showed peak values from 35 bp to 50 bp after the full marathon. Values over 1000 bp appeared at Immediately and two hours post marathon.ConclusionThis study revealed that both serum and urinary cfDNA levels transiently increased after a full marathon. In addition, these cfDNA fragment varied in size.
Cross-modal perceptual enhancement of unisensory targets is uni-directional and does not affect temporal expectations
Authors: Ball Felix , Nentwich Annika , Noesselt Toemme 
Published: March 2021

AbstractPrevious studies demonstrated that redundant target stimuli can enhance performance due to multisensory interplay and interactively facilitate performance enhancements due to temporal expectations (TE; faster and accurate reactions to temporally expected targets). Here we tested whether other types of multisensory interactions – i.e. interactions evoked by temporally flanking irrelevant stimuli – can result in similar performance patterns and boost not only unisensory target perception (multi-vs. unisensory sequences) but also unisensory temporal expectations (expected vs. unexpected). To test our hypothesis, we presented sequences of 12 stimuli (10 Hz) which either consisted of auditory (A), visual (V) or alternating auditory-visual stimuli (e.g. A-V-A-V-…) with either auditory (AV(A)) or visual (AV(V)) targets. Participants had to discriminate target frequency which was unpredictable by temporal regularities (expected vs. unexpected target positions) and by stimulation sequence (A, V, AV(A), AV(V)). Moreover, we ran two experiments in which we presented redundant multisensory targets and manipulated the speed of the stimulation sequence (10 vs. 15 Hz stimulus trains) to control whether the results of Experiment 1 depended on sequence speed. Performance for unisensory targets was affected by temporally flanking distractors, with multisensory interactions selectively improving unisensory visual target perception. Yet, only redundant multisensory targets reliably affected TEs. Together, these results indicate that cross-modal facilitation of unisensory target perception in fast stimulus streams is uni-directional, but also differs from multisensory interactions evoked by redundant targets; more specifically, it appears to be context-dependent (task, design etc.) whether unisensory stimulation (unlike redundant target stimulation) allows for the generation of temporal expectations.
Daily torpor reduces the energetic consequences of habitat selection for a widespread bat
Authors: Alston Jesse M. , Dillon Michael E. , Keinath Douglas A. , Abernethy Ian M. , Goheen Jacob R. 
Published: March 2021

AbstractHomeothermy requires increased metabolic rates as temperatures decline below the thermoneutral zone, so homeotherms typically select microhabitats within or near their thermoneutral zones during periods of inactivity. However, many mammals and birds are heterotherms that relax internal controls on body temperature when maintaining a high, stable body temperature is energetically costly. Such heterotherms should be less tied to microhabitats near their thermoneutral zones, and because heterotherms spend more time in torpor and expend less energy at colder temperatures, heterotherms may even select microhabitats in which temperatures are well below their thermoneutral zones. We studied how temperature and daily torpor influence selection of diurnal roosts by a heterothermic bat (Myotis thysanodes). We (1) quantified the relationship between ambient temperature and daily duration of torpor, (2) simulated daily energy expenditure over a range of microhabitat (roost) temperatures, and (3) quantified the influence of roost temperature on roost selection. While warm roosts substantially reduced energy expenditure of simulated homeothermic bats, heterothermic bats modulated their use of torpor to maintain a constant level of energy expenditure over the course of a day. Daily torpor expanded the range of energetically economical microhabitats, such that roost selection was independent of roost temperature. Our work adds to a growing literature documenting functions of torpor beyond its historical conceptualization as a last-resort measure to save energy during extended or acute energetic stress.
Mechanism of REST/NRSF Regulation of Clustered Protocadherin α Genes
Authors: Tang Yuanxiao , Jia Zhilian , Xu Honglin , Da Lin-Tai , Wu Qiang 
Published: March 2021

ABSTRACTRepressor element-1 silencing transcription factor (REST) or neuron-restrictive silencer factor (NRSF) is a zinc-finger (ZF) containing transcriptional repressor that recognizes thousands of neuron-restrictive silencer elements (NRSEs) in mammalian genomes. How REST/NRSF regulates gene expression remains incompletely understood. Here, we investigate the binding pattern and regulation mechanism of REST/NRSF in the clustered protocadherin (PCDH) genes. We find that REST/NRSF directionally forms base-specific interactions with NRSEs via tandem ZFs in an anti-parallel manner but with striking conformational changes. In addition, REST/NRSF recruitment to theHS5-1enhancer leads to the decrease of long-range enhancer-promoter interactions and downregulation of the clusteredPCDHαgenes. Thus, REST/NRSF repressesPCDHαgene expression through directional binding to a repertoire of NRSEs within the distal enhancer and variable target genes.
Smartphone-assisted real-time estimation of chlorophyll and carotenoid contents in spinach following the inversion of red and green color features
Authors: Agarwal Avinash , Dongre Piyush Kumar , Gupta Snehasish Dutta 
Published: March 2021

AbstractPurposeChlorophyll (Chl) content is a reliable indicator of leaf nitrogen content and plant health status. Currently available methods for image-based Chl estimation require complex mathematical derivations and high-throughput imaging set-up along with multiplex image-preprocessing steps. Further, the influence of carotenoid (CAR) content has been largely ignored in the process. The present study describes a smartphone-based leaf image analysis method for real-time estimation of Chl content and Chl/CAR ratio.MethodsColor features were obtained from RGB (red, green, blue) images of spinach leaves using a smartphone, and inverse R and G values were calculated. Correlation analysis of color indices and photosynthetic pigment (PP) contents was performed, followed by principal component analysis (PCA). Linear mathematical modeling was performed for describing regression equations for predicting PP contents.Results1/R and 1/G showed strong positive linear correlation (0.93 <r2< 0.96) with Chl and CAR contents, respectively. Furthermore, 1/R+1/G and [1/R]/[1/G] presented strong positive linear correlation with Chl + CAR (r2= 0.95) and Chl/CAR (r2= 0.88), respectively. PCA confirmed the association of color indices with the respective PP features, which were subsequently estimated using the correlation models. A smartphone-based companion application was developed using the linear models for non-invasive, real-time estimation of Chl content and Chl/CAR ratio.ConclusionThe ratios 1/R and 1/G indicate the contents of Chl and CAR via linear models. The smartphone application developed using the linear models enables real-time estimation of Chl content and Chl/CAR ratio without complicated image preprocessing steps or mathematical derivations.
αB-crystallin affects the morphology of Aβ(1-40) aggregates
Authors: Müller Henrik , Dias David M. , van der Zalm Anna , Baldwin Andrew J. 
Published: March 2021

SummaryαB-crystallin (ABC) is a human small heat shock protein that is strongly linked to Alzheimer’s disease (AD).In vitro, it can inhibit the aggregation and amyloid formation of a range of proteins including Aβ(1-40), a primary component of AD amyloid plaques. Despite the strong links, the mechanism by which ABC inhibits amyloid formation has remained elusive, in part due to the notorious irreproducibility of aggregation assays involving preparations of Aβ-peptides of native sequence. Here, we present a recombinant expression protocol to produce native Aβ(1-40), devoid of any modifications or exogenous residues, with yields up to 4 mg/LE. coli. This material provides highly reproducible aggregation kinetics and, by varying the solution conditions, we obtain either highly ordered amyloid fibrils or more disordered aggregates. Addition of ABC slows the aggregation of Aβ(1-40), and interferes specifically with the formation of ordered amyloid fibrils, favouring instead the more disordered aggregates. Solution-state NMR spectroscopy reveals that the interaction of ABC with Aβ(1-40) depends on the specific aggregate morphology. These results provide mechanistic insight into how ABC inhibits the formation of amyloid fibrils.HighlightsProtocol for production of native recombinant Aβ(1-40)Amyloid formation under physiological conditions is highly reproducibleBoth ordered fibrils and disordered aggregates can be reliably formedαB-crystallin specifically inhibits amyloid fibril assembling, favouring disordered aggregateseTOC blurbMülleret al.introduce a protocol for the highly reproducible production of amyloid from native Aβ(1-40) and determine that the human chaperone ABC specifically destabilises them in favour of disordered aggregates. NMR shows that ABC can distinguish between aggregate morphologies.Graphical Abstract
A chloride efflux transporter OsBIRG1 regulates grain size and salt tolerance in rice
Authors: Ren Zhijie , Bai Fenglin , Xu Jingwen , Wang Li , Wang Xiaohan , Zhang Qian , Feng Changxin , Niu Qi , Zhang Liying , Li Mengou , Song Jiali , Bao Fang , Liu Liangyu , He Yikun , Ma Ligeng , Qiu Jinlong , Tian Wang , Hou Congcong , Li Legong 
Published: March 2021

SummaryGrain size is determined by the number of cells and cell size of the grain. Regulation of grain size is crucial for improving crop yield. However, the genes and underlying molecular mechanisms controlling grain size remain elusive. Here we report a member of Detoxification efflux carrier (DTX)/Multidrug and Toxic Compound Extrusion (MATE) family transporter,BIGRICEGRAIN 1 (BIRG1), negatively regulates the grain size in rice.BIRG1is highly expressed in reproductive organs and roots. Inbirg1grain, the size of the outer parenchyma layer cells of spikelet hulls is noticeably larger but the cell number is not altered compared with that in the wild-type (WT) grain. When expressed inXenopusoocytes, BIRG1 exhibits chloride efflux activity. In line with the role of BIRG1 in mediating chloride efflux, thebirg1mutant shows reduced tolerance to salt stress under which the chloride level is toxic. Moreover, thebirg1grains contain higher level of chloride compared to WT grains when grown under normal paddy field. Thebirg1roots accumulate more chloride than those of WT under saline condition. Collectively, our findings suggest that BIRG1 functions as a chloride efflux transporter regulating grain size and salt tolerance via controlling chloride homeostasis in rice.
Hibernation slows epigenetic aging in yellow-bellied marmots
Authors: Pinho Gabriela M. , Martin Julien G. A. , Farrell Colin , Haghani Amin , Zoller Joseph A. , Zhang Joshua , Snir Sagi , Pellegrini Matteo , Wayne Robert K. , Blumstein Daniel T. , Horvath Steve 
Published: March 2021

AbstractSpecies that hibernate live longer than would be expected based solely on their body size. Hibernation is characterized by long periods of metabolic suppression (torpor) interspersed by short periods of increased metabolism (arousal). The torpor-arousal cycles occur multiple times during hibernation, and it has been suggested that processes controlling the transition between torpor and arousal states cause aging suppression. Metabolic rate is also a known correlate of longevity, we thus proposed the ‘hibernation-aging hypothesis’ whereby aging is suspended during hibernation. We tested this hypothesis in a well-studied population of yellow-bellied marmots (Marmota flaviventer), which spend 7-8 months per year hibernating. We used two approaches to estimate epigenetic age: the epigenetic clock and the epigenetic pacemaker. Variation in epigenetic age of 149 samples collected throughout the life of 73 females were modeled using generalized additive mixed models (GAMM), where season (cyclic cubic spline) and chronological age (cubic spline) were fixed effects. As expected, the GAMM using epigenetic ages calculated from the epigenetic pacemaker was better able to detect nonlinear patterns in epigenetic age change over time. We observed a logarithmic curve of epigenetic age with time, where the epigenetic age increased at a higher rate until females reached sexual maturity (2-years old). With respect to circannual patterns, the epigenetic age increased during the summer and essentially stalled during the winter. Our enrichment analysis of age-related CpG sites revealed pathways related to development and cell differentiation, while the season-related CpGs enriched pathways related to central carbon metabolism, immune system, and circadian clock. Taken together, our results are consistent with the hibernation-aging hypothesis and may explain the enhanced longevity in hibernators.