bluuebunny/crossref_metadata_2025_split huggingface dataset:
New fossils ofAustralopithecus sedibareveal a nearly complete lower back
Authors: Williams Scott A. , Prang Thomas C. , Meyer Marc R. , Nalley Thierra K. , Van Der Merwe Renier , Yelverton Christopher , García-Martínez Daniel , Russo Gabrielle A. , Ostrofsky Kelly R. , Eyre Jennifer , Grabowski Mark , Nalla Shahed , Bastir Markus , Schmid Peter , Churchill Steven E. , Berger Lee R. 
Published: May 2021

AbstractAdaptations of the lower back to bipedalism are frequently discussed but infrequently demonstrated in early fossil hominins. Newly discovered lumbar vertebrae contribute to a near-complete lower back of Malapa Hominin 2 (MH2), offering additional insights into posture and locomotion inAustralopithecus sediba. We show that MH2 demonstrates a lower back consistent with human-like lumbar lordosis and other adaptations to bipedalism, including an increase in the width of intervertebral articular facets from the upper to lower lumbar column (“pyramidal configuration”). This contrasts with recent work on lordosis in fossil hominins, where MH2 was argued to demonstrate no appreciable lordosis (“hypolordosis”) similar to Neandertals. Our three-dimensional geometric morphometric (3D GM) analyses show that MH2’s nearly complete middle lumbar vertebra is human-like in shape but bears large, cranially-directed transverse processes, implying powerful trunk musculature. We interpret this combination of features to indicate thatA. sedibaused its lower back in both human-like bipedalism and ape-like arboreal positional behaviors, as previously suggested based on multiple lines of evidence from other parts of the skeleton and reconstructed paleobiology ofA. sediba.
Physically active lifestyle is associated with attenuation of hippocampal dysfunction in healthy older adults
Authors: Eisenstein Tamir , Giladi Nir , Hendler Talma , Havakuk Ofer , Lerner Yulia 
Published: May 2021

AbstractAlterations in hippocampal function have been shown in older adults, expressed as changes in hippocampal activity and connectivity. While hippocampal activation during memory demands have been demonstrated to decrease with age, some older individuals present increased activity, or hyperactivity, of the hippocampus which is associated with increased neuropathology and poorer memory function. In addition, lower functional coherence between the hippocampus and core hubs of the default mode network (DMN), namely the posteromedial and medial prefrontal cortices, as well as increased local intrahippocampal connectivity, were also demonstrated in cognitively intact older adults. Aerobic exercise has been shown to elicit neuroprotective effects on hippocampal structure and vasculature in aging, and improvements in maximal aerobic capacity (MAC) have been suggested to mediate these exercise-related effects. However, how these lifestyle factors relate to hippocampal function is not clear. Fifty-two cognitively intact older adults (age 65-80) have been recruited and divided into physically active (n=29) or non-active (n=23) groups based on their aerobic activity lifestyle habits. Participants underwent resting-state as well as task-based fMRI experiments which included an associative memory encoding paradigm followed by a post-scan memory recognition test. In addition, forty-four participants also performed cardiopulmonary exercise tests to evaluate MAC. While both groups demonstrated increased anterior hippocampal activation during memory encoding, physically active lifestyle was associated with significantly lower activity level and higher memory performance in the recognition task. In addition, the physically active group also demonstrated higher functional connectivity of the anterior and posterior hippocampi with the core hubs of the DMN, and lower local intra-hippocampal connectivity within and between hemispheres. MAC was negatively associated with hippocampal activation level and demonstrated positive correlation with hippocampal-DMN connectivity. According to these findings, aerobically active lifestyle may be associated with attenuation of hippocampal dysfunction in cognitively healthy older adults.
Cell type- and region-specific modulation of cocaine seeking by micro-RNA-1 in striatal projection neurons
Authors: Forget Benoit , Garcia Elena Martin , Godino Arthur , Rodriguez Laura Domingo , Kappes Vincent , Poirier Pierre , Andrianarivelo Andry , Marchan Eric Senabre , Allichon Marie-Charlotte , Marias Mélanie , Vanhoutte Peter , Girault Jean-Antoine , Maldonado Rafael , Caboche Jocelyne 
Published: May 2021

ABSTRACTThe persistent and experience-dependent nature of drug addiction may result in part from epigenetic alterations, including non-coding micro-RNAs (miRNAs), which are both critical for neuronal function and modulated by cocaine in the striatum. Two major striatal cell populations, the striato-nigral and striato-pallidal projection neurons, express respectively the D1 (D1-SPNs) and D2 (D2-SPNs) dopamine receptor, and display distinct but complementary functions in drug-evoked responses. However, a cell-type-specific role for miRNAs action has yet to be clarified. Here, we evaluated the expression of a subset of miRNAs proposed to modulate cocaine effects in the nucleus accumbens (NAc) and dorsal striatum (DS) upon sustained cocaine exposure in mice and showed that these selected miRNAs were preferentially up-regulated in the NAc. We then focused on miR-1 considering the important role of some of its predicted mRNA targets, such as fosb and npas4, in the effects of cocaine. We validated these targets in vitro and in vivo and further showed that overexpression of miR-1 in D1-SPNs of the DS reduced cocaine-induced CPP reinstatement, whereas it increased cue-induced reinstatement of cocaine-SA, without affecting other cocaine-mediated adaptive behavior. In addition, miR-1 overexpression in D2-SPNs of the DS reduced the motivation to self-administer cocaine but did not modify other measured behaviors. Together, our results highlight a precise cell-type- and region-specific control of relapse to cocaine-seeking behaviors by miR-1, and illustrate the importance of cell-specific investigations.
The “dark matter” of protein variants carries a distinct DNA signature and predicts damaging variant effects
Authors: Ng Joseph Chi-Fung , Fraternali Franca 
Published: May 2021

AbstractSignatures of DNA motifs associated with distinct mutagenic exposures have been defined for somatic variants, but little is known about the consequences different mutational processes pose to the cell, especially how mutagens exert damage on specific proteins and their three-dimensional structures. Here we identify a DNA mutational signature which corresponds to damaging protein variants. We show that this mutational signature is under-sampled in sequencing data from tumour cohorts, constituting the “dark matter” of the mutational landscape which could only be accessed using deep mutational scanning (DMS) data. By training a set of gradient boosting classifiers, we illustrate that DMS data from only a handful (≈ 10) of experiments can accurately predict variant impact, and that DNA mutational signatures embed information about the protein-level impact of variants. We bridge the gap between DNA sequence variations and protein-level consequences, discuss the significance of this signature in informing protein design and molecular principles of protein stability, and clarify the relationship between disease association and the true impact mutations bring to protein function.
The Skeletal Muscle Circadian Clock Regulates Titin Splicing Through RBM20
Authors: Riley Lance A. , Zhang Xiping , Douglas Collin M. , Mijares Joseph M. , Hammers David W. , Wolff Christopher A. , Wood Neil B. , Olafson Hailey R. , Du Ping , Labeit Siegfried , Previs Michael J. , Wang Eric T. , Esser Karyn A. 
Published: May 2021

AbstractCircadian rhythms are maintained by a cell autonomous, transcriptional-translational feedback loop known as the molecular clock. While previous research suggests a role of the molecular clock in regulating skeletal muscle structure and function, no mechanisms have connected the molecular clock to sarcomere filaments. Utilizing inducible, skeletal muscle specific, Bmal1 knockout (iMSBmal1-/-) mice, we showed that knocking out skeletal muscle clock function alters titin isoform expression using RNAseq, LC-MS, and SDS-VAGE. This alteration in titin’s spring length resulted in sarcomere length heterogeneity. We demonstrate the direct link between altered titin splicing and sarcomere length in vitro using U7 snRNPs that truncate the region of titin altered in iMSBmal1-/- muscle. We identified a mechanism whereby the skeletal muscle clock regulates titin isoform expression through transcriptional regulation of Rbm20, a potent splicing regulator of titin. Lastly, we used an environmental model of circadian rhythm disruption and identified significant down-regulation of Rbm20 expression. Our findings demonstrate the importance of the skeletal muscle circadian clock in maintaining titin isoform through regulation of RBM20 expression. Because circadian rhythm disruption is a feature of many chronic diseases, our results highlight a novel pathway that could be targeted to maintain skeletal muscle structure and function in a range of pathologies.
ZHX2 Promotes HIF1α Oncogenic Signaling in Triple-Negative Breast Cancer
Authors: Fang Wentong , Liao Chengheng , Shi Rachel , Simon Jeremy M. , Ptacek Travis S. , Zurlo Giada , Ye Youqiong , Han Leng , Fan Cheng , Ortiz Christopher Llynard , Lin Hong-Rui , Manocha Ujjawal , Luo Weibo , Kim William Y. , Yang Lee-Wei , Zhang Qing 
Published: May 2021

AbstractTriple-negative breast cancer (TNBC) is an aggressive and highly lethal disease, which warrants the critical need to identify new therapeutic targets. We show that Zinc Fingers And Homeoboxes 2 (ZHX2) is amplified or overexpressed in TNBC cell lines and patients. Functionally, depletion of ZHX2 inhibited TNBC cell growth and invasion in vitro, orthotopic tumor growth and spontaneous lung metastasis in vivo. Mechanistically, ZHX2 bound with hypoxia inducible factor (HIF) family members and positively regulated HIF1α activity in TNBC. Integrated ChIP-Seq and gene expression profiling demonstrated that ZHX2 co-occupied with HIF1α on transcriptionally active promoters marked by H3K4me3 and H3K27ac, thereby promoting gene expression. Furthermore, multiple residues (R491, R581 and R674) on ZHX2 are important in regulating its phenotype, which correspond with their roles on controlling HIF1α activity in TNBC cells. These studies establish that ZHX2 activates oncogenic HIF1α signaling, therefore serving as a potential therapeutic target for TNBC.
Separation of multiple motor memories through implicit and explicit processes
Authors: Dawidowicz Gefen , Shaine Yuval , Mawase Firas 
Published: May 2021

AbstractAcquisition of multiple motor skills without interference is a remarkable ability in sport and daily life. During adaptation to opposing perturbations, a common paradigm to study this ability, each perturbation can be successfully learned when a dynamical contextual cue, such as a follow-through movement, is associated with the direction of the perturbation. It is still unclear, however, to what extent this context-dependent learning engages the cognitive strategy-based explicit process and the implicit process that occurs without conscious awareness. Here, we designed four reaching experiments to untangle the individual contributions of the explicit and implicit components while participants learned opposing visuomotor perturbations, with a second unperturbed follow-through movement that served as a contextual cue. In Exp. 1 we replicated previous adaptation results and showed that follow-through movements also allow learning for opposing visuomotor rotations. For one group of participants in Exp. 2 we isolated strategic explicit learning by inducing a 2-sec time delay between movement and end-point feedback, while for another group we isolated the implicit component using the task-irrelevant error-clamp paradigm, in which participants were firmly instructed to aim their reaches directly to the target. Our data showed that opposing perturbations could be fully learned by explicit strategies; but when strategy was restricted, distinct implicit processes contributed to learning. In Exp.3, we examined whether the learned motor behaviors are influenced by the disparity between the follow-through contexts. We found that the location of follow-through targets had little effect on total learning, yet it led to more instances in which participants failed to learn the task. In Exp. 4, we explored the generalization capability to untrained novel targets. Participants showed near-flat generalization of the implicit and explicit processes to adjacent targets. Overall, our results indicate that follow-through contextual cues influence activity of both implicit and explicit processes during separation of motor memories. Furthermore, the follow-through context might activate, in part, top-down cognitive factors that influence not only the dynamics of the explicit learning but also the implicit process.
Sustained ability of a natural microbial community to remove nitrate from groundwater
Authors: Paradis Charles J. , Miller John I. , Moon Ji-Won , Spencer Sarah J. , Lui Lauren M. , Van Nostrand Joy D. , Ning Daliang , Steen Andrew D. , McKay Larry D. , Arkin Adam P. , Zhou Jizhong , Alm Eric J. , Hazen Terry C. 
Published: May 2021

AbstractMicrobial-mediated nitrate removal from groundwater is widely recognized as the predominant mechanism for nitrate attenuation in contaminated aquifers and is largely dependent on the presence of a carbon-bearing electron donor. The repeated exposure of a natural microbial community to an electron donor can result in the sustained ability of the community to remove nitrate; this phenomenon has been clearly demonstrated at the laboratory scale. However, in situ demonstrations of this ability are lacking. For this study, ethanol (electron donor) was repeatedly injected into a groundwater well (treatment) for six consecutive weeks to establish the sustained ability of a microbial community to remove nitrate. A second well (control) located up-gradient was not injected with ethanol during this time. The treatment well demonstrated strong evidence of sustained ability as evident by concomitant ethanol and nitrate removal and subsequent sulfate removal upon consecutive exposures. Both wells were then monitored for six additional weeks under natural (no injection) conditions. During the final week, ethanol was injected into both treatment and control wells. The treatment well demonstrated sustained ability as evident by concomitant ethanol and nitrate removal whereas the control did not. Surprisingly, the treatment well did not indicate a sustained and selective enrichment of a microbial community. These results suggested that the predominant mechanism(s) of sustained ability likely exist at the enzymatic- and/or genetic-levels. The results of this study demonstrated that the in situ ability of a microbial community to remove nitrate can be sustained in the prolonged absence of an electron donor. Moreover, these results implied that the electron-donor exposure history of nitrate-contaminated groundwater can play an important role nitrate attenuation.Article Impact StatementGroundwater microbes sustain ability to remove nitrate in absence of carbon and energy source.
A Universal Approach to Analyzing Transmission Electron Microscopy with ImageJ
Authors: Lam Jacob , Katti Prasanna , Biete Michelle , Mungai Margaret , AshShareef Salma , Neikirk Kit , Garza Lopez Edgar , Vue Zer , Christensen Trace A. , Beasley Heather K. , Rodman Taylor , Salisbury Jeffrey L. , Glancy Brian , Pereira Renata O. , Abel E. Dale , Hinton Antentor 
Published: May 2021

2ABSTRACTTransmission electron microscopy (TEM) is a scientific research standard for producing nanometer-resolution ultrastructural images of subcellular components within cells and tissues. Mitochondria, endoplasmic reticulum (ER), lysosomes, and autophagosomes are organelles of particular interest to those investigating metabolic disorders. However, there is no clear consensus amongst regarding the best methods for quantifying the features of organelles in TEM images. In this protocol, we propose a standardized approach to accurately measure the morphology of these important subcellular structures using the free program ImageJ, developed by the National Institutes of Health (NIH). Specifically, we detail procedures for obtaining mitochondrial length, width, area, and circularity, in addition to assessing cristae morphology. We further provide methods for measuring interactions between the mitochondria and ER and measuring the length and width of lysosomes and autophagosomes. This standardized method can be used to quantify key features of organelle morphology, allowing investigators to produce accurate and reproducible measurements of organelle structures in their experimental samples.1SUMMARYWe discuss a standardized method for measuring and quantifying organelle features using transmission electron microscopy and accessing for interactions between subcellular structures; organelles of focus include mitochondria, endoplasmic reticulum, lysosomes, and autophagosomes.
Perceptual clustering in auditory streaming
Authors: Larigaldie Nathanael , Yates Tim , Beierholm Ulrik R. 
Published: May 2021

AbstractPerception is dependent on the ability to separate stimuli from different objects and causes in order to perform inference and further processing. We have models of how the human brain can perform such causal inference for simple binary stimuli (e.g., auditory and visual), but the complexity of the models increases dramatically with more than two stimuli. To characterize human perception with more complex stimuli, we developed a Bayesian inference model that takes into account a potentially unlimited number of stimulus sources: it is general enough to factor in any discrete sequential cues from any modality. Because the model employs a non-parametric prior, increased signal complexity does not necessitate the addition of more parameters. The model not only predicts the number of possible sources, but also specifies the source with which each signal is associated. As a test case, we demonstrate that such a model can explain several phenomena in the auditory stream perception literature, that it provides an excellent fit to experimental data, and that it makes novel predictions that we experimentally confirm. These findings have implications not just for human auditory temporal perception, but for a wide range of perceptual phenomena across unisensory and multisensory stimuli.
The Mitochondrial Genome and Epigenome of the Golden Lion Tamarin from Fecal DNA using Nanopore Adaptive Sequencing
Authors: Wanner Nicole , Larsen Peter A. , McLain Adam , Faulk Christopher 
Published: May 2021

AbstractThe golden lion tamarin (Leontopithecus rosalia) is an endangered Platyrrhine primate endemic to the Atlantic coastal forests of Brazil. Despite ongoing conservation efforts, genetic data on this species remains scarce. Complicating factors include limitations on sample collection and a lack of high-quality reference sequences. Here, we used nanopore adaptive sampling to resequence the L. rosalia mitogenome from feces, a sample which can be collected non-invasively. Adaptive sampling doubled the fraction of both host-derived and mitochondrial sequences compared to sequencing without enrichment. 258x coverage of the L. rosalia mitogenome was achieved in a single flow cell by targeting the unfinished genome of the distantly related emperor tamarin (Saguinus imperator) and the mitogenome of the closely related black lion tamarin (Leontopithecus chrysopygus). The L. rosalia mitogenome has a length of 16,597 bp, sharing 99.68% sequence identity with the L. chrysopygus mitogenome. A total of 38 SNPs between them were identified, with the majority being found in the non-coding D-loop region. DNA methylation and hydroxymethylation were directly detected using a neural network model applied to the raw signal from the MinION sequencer. In contrast to prior reports, DNA methylation was negligible in mitochondria in both CpG and non-CpG contexts. Surprisingly, a quarter of the 642 CpG sites exhibited DNA hydroxymethylation greater than 1% and 44 sites were above 5%, with concentration in the 3’ side of several coding regions. Overall, we report a robust new mitogenome assembly for L. rosalia and direct detection of cytosine base modifications in all contexts.
Natural variation at the Drosophila melanogaster Or22 odorant receptor locus is associated with changes in olfactory behaviour
Authors: Shaw Katherine H. , Dent Craig I. , Johnson Travis K. , Anderson Alisha , de Bruyne Marien , Warr Coral G. 
Published: May 2021

AbstractIn insects many critical olfactory behaviours are mediated by the large odorant receptor (Or) gene family, which determine the response properties of different classes of olfactory receptor neurons (ORNs). While ORN responses are generally conserved within and between Drosophila species, variant alleles of the D.melanogaster Or22 locus have previously been shown to the response profiles of an ORN class called ab3A. These alleles show potential clinal variation, suggesting that selection is acting at this locus. Here, we investigated if the changes seen in ab3A responses lead to changes in olfactory-related behaviours. We show that variation at the Or22 locus and in the ab3A neurons are not fully compensated for by other ORNs and lead to overall changes in antennal odorant detection. We further show that this correlates with differences in odorant preference behaviour and with differences in oviposition site preference, with flies that have the chimaeric short allele strongly preferring to oviposit on banana. These findings indicate that variation at the Or22 locus leads to changes in olfactory-driven behaviours that could be under selective pressure, and add support to the idea that the ab3A neurons are of especial importance to the ecology of Drosophila flies.
Revealing conserved mechanisms of neurodegeneration in a colonial chordate
Authors: Anselmi C , Kowarsky MA , Gasparini F , Caicci F , Ishizuka KJ , Palmeri KJ , Sinhar R , Neff N , Quake SR , Weissman IL , Voskoboynik A , Manni L 
Published: May 2021

ABSTRACTLoss of the brain’s functional ability is a common symptom of aging and neurodegenerative diseases1,2. While the genetic and molecular mechanisms underlying human neurodegeneration are studied in-depth3–6, very little is known about the evolutionary origin of these traits and their involvement in loss of nervous system function in aged invertebrate species. Here we study evolutionarily conserved elements of brain degeneration using the colonial chordate model species Botryllus schlosseri. B. schlosseri reproduces both sexually and asexually7, with adult brains regenerating and degenerating multiple times throughout its adult life. Combining microscopy, transcriptomics and behavioral assays, we characterized adult brains from diverse stages and ages. We found that the number of neurons fluctuates each week, reaching a maximum of ∼1000 cells, and thereafter decreasing while the number of immunocytes increases. Comparing the number of neurons in the adult brains of young and old colonies, we found that older brains are smaller and contain fewer cells. Both during weekly degeneration cycles and overall with age, the decrease in neuron number correlates with reduced response to stimuli and with significant changes in the expression of genes with mammalian homologs associated with neural stem cells and neurodegenerative pathways. These results suggest persistent neural stem cell activity across ages and that cellular and molecular mechanisms of neurodegeneration are evolutionary conserved between tunicates and humans.