bluuebunny/crossref_metadata_2025_split huggingface dataset:
V-NeuroStack: 3D Time Stacks for Identifying Patterns in Calcium Imaging Data
Authors: Naik Ashwini G. , Kenyon Robert V. , Taheri Aynaz , Berger-Wolf Tanya , Ibrahim Baher , Llano Daniel A. 
Published: December 2020

AbstractBackgroundUnderstanding functional correlations between the activities of neuron populations is vital for the analysis of neuronal networks. Analyzing large-scale neuroimaging data obtained from hundreds of neurons simultaneously poses significant visualization challenges. We developed V-NeuroStack, a novel network visualization tool to visualize data obtained using calcium imaging of spontaneous activity of cortical neurons in a mouse brain slice.New MethodV-NeuroStack creates 3D time stacks by stacking 2D time frames for a period of 600 seconds. It provides a web interface that enables exploration and analysis of data using a combination of 3D and 2D visualization techniques.Comparison with existing MethodsPrevious attempts to analyze such data have been limited by the tools available to visualize large numbers of correlated activity traces. V-NeuroStack can scale data sets with at least a few thousand temporal snapshots.ResultsV-NeuroStack’s 3D view is used to explore patterns in the dynamic large-scale correlations between neurons over time. The 2D view is used to examine any timestep of interest in greater detail. Furthermore, a dual-line graph provides the ability to explore the raw and first-derivative values of a single neuron or a functional cluster of neurons.ConclusionsV-NeuroStack enables easy exploration and analysis of large spatio-temporal datasets using two visualization paradigms: (a) Space-Time cube (b)Two-dimensional networks, via web interface. It will support future advancements in in vitro and in vivo data capturing techniques and can bring forth novel hypotheses by permitting unambiguous visualization of large-scale patterns in the neuronal activity data.
Concept Recognition as a Machine Translation Problem
Authors: Boguslav Mayla R , Hailu Negacy D , Bada Michael , Baumgartner William A , Hunter Lawrence E 
Published: December 2020

AbstractBackgroundAutomated assignment of specific ontology concepts to mentions in text is a critical task in biomedical natural language processing, and the subject of many open shared tasks. Although the current state of the art involves the use of neural network language models as a post-processing step, the very large number of ontology classes to be recognized and the limited amount of gold-standard training data has impeded the creation of end-to-end systems based entirely on machine learning. Recently, Hailu et al. recast the concept recognition problem as a type of machine translation and demonstrated that sequence-to-sequence machine learning models had the potential to outperform multi-class classification approaches. Here we systematically characterize the factors that contribute to the accuracy and efficiency of several approaches to sequence-to-sequence machine learning.ResultsWe report on our extensive studies of alternative methods and hyperparameter selections. The results not only identify the best-performing systems and parameters across a wide variety of ontologies but also illuminate about the widely varying resource requirements and hyperparameter robustness of alternative approaches. Analysis of the strengths and weaknesses of such systems suggest promising avenues for future improvements as well as design choices that can increase computational efficiency with small costs in performance. Bidirectional Encoder Representations from Transformers for Biomedical Text Mining (BioBERT) for span detection (as previously found) along with the Open-source Toolkit for Neural Machine Translation (OpenNMT) for concept normalization achieve state-of-the-art performance for most ontologies in CRAFT Corpus. This approach uses substantially fewer computational resources, including hardware, memory, and time than several alternative approaches.ConclusionsMachine translation is a promising avenue for fully machine-learning-based concept recognition that achieves state-of-the-art results on the CRAFT Corpus, evaluated via a direct comparison to previous results from the 2019 CRAFT Shared Task. Experiments illuminating the reasons for the surprisingly good performance of sequence-to-sequence methods targeting ontology identifiers suggest that further progress may be possible by mapping to alternative target concept representations. All code and models can be found at:https://github.com/UCDenver-ccp/Concept-Recognition-as-Translation.
Activation of Kiss1 neurons in the preoptic hypothalamus stimulates testosterone synthesis in adult male mice
Authors: Sanz Elisenda , Bean Jonathan C. , Palmiter Richard D. , Quintana Albert , McKnight G. Stanley 
Published: December 2020

ABSTRACTKisspeptin-expressing neurons in the rostral periventricular region of the third ventricle (RP3V) play an essential role in female reproduction. However, adult male mice were reported to have very few Kisspeptin-expressing neurons in the RP3V compared to females. This led to the hypothesis that Kiss1RP3Vneurons are responsible for the ability of females, but not males, to generate a surge of LH, triggering ovulation and steroid synthesis in the female. Using mouse genetics and cell type-specific gene expression analysis, we show that male mice harbor almost as many Kiss1RP3Vneurons as the female and that gene expression in these neurons is very similar. Specific activation of male Kiss1RP3Vneurons expressing viral-encoded hM3Dq caused a surge in serum testosterone levels. These results demonstrate that Kiss1RP3Vneurons are present in the adult male and fully capable of regulating the hypothalamic/pituitary/gonadal axis. We suggest that these neurons may continue to play a role in reproductive behavior in adult male mice.
Design of smart antibody mimetics with photosensitive switches
Authors: He Lian , Tan Peng , Huang Yun , Zhou Yubin 
Published: December 2020

ABSTRACTAs two prominent examples of intracellular single-domain antibodies or antibody mimetics derived from synthetic protein scaffolds, monobodies and nanobodies are gaining wide applications in cell biology, structural biology, synthetic immunology, and theranostics. We introduce herein a generally-applicable method to engineer light-controllable monobodies and nanobodies, designated as moonbody and sunbody, respectively. These engineered antibody-like modular domains enable rapid and reversible antibody-antigen recognition by utilizing light. By paralleled insertion of two LOV2 modules into a single sunbody and the use of bivalent sunbodies, we substantially enhance the range of dynamic changes of photo-switchable sunbodies. Furthermore, we demonstrate the use of moonbodies or sunbodies to precisely control protein degradation, gene transcription, and base editing by harnessing the power of light.
SIX2 and SIX3 coordinately regulate functional maturity and fate of human pancreatic β cells
Authors: Bevacqua Romina J. , Lam Jonathan Y. , Peiris Heshan , Whitener Robert L. , Kim Seokho , Gu Xueying , Friedlander Mollie S.H. , Kim Seung K. 
Published: December 2020

AbstractThe physiological functions of many vital tissues and organs continue to mature after birth, but the genetic mechanisms governing this postnatal maturation remain an unsolved mystery. Human pancreatic β-cells produce and secrete insulin in response to physiological cues like glucose, and these hallmark functions improve in the years after birth. This coincides with expression of the transcription factors SIX2 and SIX3, whose functions in native human β-cells remain unknown. Here, we show that shRNA-mediatedSIX2orSIX3suppression in human pancreatic adult islets impairs insulin secretion. However, transcriptome studies revealed thatSIX2andSIX3regulate distinct targets. Loss ofSIX2markedly impaired expression of genes governing β-cell insulin processing and output, glucose sensing, and electrophysiology, whileSIX3loss led to inappropriate expression of genes normally expressed in fetal β-cells, adult a-cells and other non-β-cells. Chromatin accessibility studies identified genes directly regulated by SIX2. Moreover, β-cells from diabetic humans with impaired insulin secretion also had reducedSIX2transcript levels. Revealing howSIX2andSIX3govern functional maturation and maintain developmental fate in native human β-cells should advance β-cell replacement and other therapeutic strategies for diabetes.
Escape from mitotic catastrophe by actin-dependent nuclear displacement in fission yeast
Authors: Yukawa Masashi , Teratani Yasuhiro , Toda Takashi 
Published: December 2020

SUMMARYProper nuclear positioning is essential for the execution of a wide variety of cellular processes in eukaryotic cells (Gundersen and Worman, 2013; Kopf et al., 2020; Lele et al., 2018). In proliferating mitotic cells, nuclear positioning is crucial for successful cell division. The bipolar spindle, which pulls sister chromatids towards two opposite poles, needs to assemble in the geometrical center of the cell. This ensures symmetrical positioning of the two nuclei that are reformed upon mitotic exit, by which two daughter cells inherit the identical set of the chromosomes upon cytokinesis. In fission yeast, the nucleus is positioned in the cell center during interphase; cytoplasmic microtubules interact with both the nucleus and the cell tips, thereby retaining the nucleus in the medial position of the cell (Daga et al., 2006; Tran et al., 2001). By contrast, how the nucleus is positioned during mitosis remains elusive. Here we show that several cell-cycle mutants that arrest in mitosis all displace the nucleus towards one end of the cell axis. Intriguingly, the actin cytoskeleton, not the microtubule counterpart, is responsible for the asymmetric movement of the nucleus. Time-lapse live imaging indicates that mitosis-specific F-actin cables interact with the nuclear membrane, thereby possibly generating an asymmetrical pushing force. In addition, constriction of the actomyosin ring further promotes nuclear displacement. This nuclear movement is beneficial, because if the nuclei were retained in the cell center, subsequent cell division would impose the lethal cut phenotype (Hirano et al., 1986; Yanagida, 1998), in which chromosomes are intersected by the contractile actin ring and the septum. Thus, fission yeast escapes from mitotic catastrophe by means of actin-dependent nuclear movement.
A meta-analysis on uncertainty monitoring in four non-primate animal species: Pigeons, rats, large-billed crows, and bees
Authors: Qu Zhizhen , Kwok Sze Chai 
Published: December 2020

AbstractHumans have the metacognitive capacity to be aware of what they do and do not know. While uncertainty monitoring has long been regarded as uniquely human, researchers in search of the polygenetic root of this ability have gathered evidence that primate species possess functional features parallel to humans. However, there were no systematic studies that quantitively take into account of extant data for these non-primate animals. Through a meta-analysis, we collected published data reported in 11 articles from 55 individual non-primate animals spanning over four species on the “opt-out” paradigm, the most prevailing paradigms used to test nonhuman animals’ uncertainty monitoring. We used chosen-forced advantage and opt-out rate to quantify animals’ performance results for computing the aggregated effect size for this literature. We found that these four NPA species process a significantly positive effect size for both scores and identified the moderators that have contributed to the inconsistencies across these studies. Implications for theories on metacognition are discussed.
Identification of hippocampal volume as a mediator of the association between APOE4 and dementia
Authors: Brenek Sixtine , Debette Stéphanie , Auriacombe Sophie , Amouyel Philippe , Chouraki Vincent , Meirhaeghe Aline , Damotte Vincent 
Published: December 2020

AbstractObjectiveTo identify any mediating effect of vascular and neurodegenerative risk factors of dementia in the association existing between APOE4 and dementia.Methods1,240 participants from the French Three City Dijon Study without prevalent tumor or dementia were included. Among these participants, 76 developed dementia during the 12 years of follow-up. Using regression and mediation analyses, we studied whether known risk factors for dementia i.e smoking status, body mass index, diabetes mellitus, hypercholesterolemia, hypertension, hippocampal volume, rate of hippocampal volume loss or white matter hyperintensities could mediate the association between APOE4 and dementia. Regression models were adjusted for age, sex, education level (and total intracranial volume when imaging metrics were considered).ResultsHippocampal volume was a partial mediator of the association between APOE4 and dementia (mediation ratio = 6.7%, p=0.03). No mediation effect was found for hypercholesterolemia. No mediation analyses could be undertaken for the others factors due to the lack of their association with APOE4 in our sample.ConclusionsIn this study, the association between APOE4 and dementia was partially mediated by hippocampal volume, confirming a deleterious role of APOE4 in the hippocampus. This result warrants further replication in other cohorts, with higher sample sizes.
Bridging neuronal correlations and dimensionality reduction
Authors: Umakantha Akash , Morina Rudina , Cowley Benjamin R. , Snyder Adam C. , Smith Matthew A. , Yu Byron M. 
Published: December 2020

AbstractTwo commonly used approaches to study interactions among neurons are spike count correlation, which describes pairs of neurons, and dimensionality reduction, applied to a population of neurons. While both approaches have been used to study trial-to-trial correlated neuronal variability, they are often used in isolation and have not been directly related. We first established concrete mathematical and empirical relationships between pairwise correlation and metrics of population-wide covariability based on dimensionality reduction. Applying these insights to macaque V4 population recordings, we found that the previously reported decrease in mean pairwise correlation associated with attention stemmed from three distinct changes in population-wide covariability. Overall, our work builds the intuition and formalism to bridge between pairwise correlation and population-wide covariability and presents a cautionary tale about the inferences one can make about population activity by using a single statistic, whether it be mean pairwise correlation or dimensionality.
Direct activation of RA signaling in cardiomyocytes protects hearts from apoptosis after myocardial infarction in mice
Authors: Da Silva Fabio , Motamedi Fariba Jian , Tison Amelie , Arachchige Lahiru Chamara Weerasinghe , Bradford Stephen T. , Lefebvre Jonathan , Dollé Pascal , Ghyselinck Norbert B. , Wagner Kay Dietrich , Schedl Andreas 
Published: December 2020

ABSTRACTRetinoic acid (RA) is an essential signaling molecule for cardiac development and plays a protective role in the heart after myocardial infarction (MI). In both cases, the effect of RA signaling on cardiomyocytes, the principle cell type of the heart, has been reported to be indirect. Here we have developed an inducible murine transgenic RA-reporter line usingCreERT2technology that permits lineage tracing of RA-responsive cells and faithfully recapitulates endogenous RA activity in multiple organs during embryonic development. Strikingly, we have observed a direct RA response in cardiomyocytes during mid-late gestation and after MI. Ablation of RA signaling through deletion of theAldh1a1/a2/a3genes encoding RA-synthesizing enzymes leads to increased cardiomyocyte apoptosis in adults subjected to MI. RNA sequencing analysis revealsTgm2andAce1, two genes with well-established links to cardiac repair, as potential targets of RA signaling in primary cardiomyocytes, thereby providing novel links between the RA pathway and heart disease.
The effect of pasture management on fire ant,Solenopsis invicta(Hymenoptera: Formicidae), abundance and the relationship to arthropod community diversity
Authors: Schmid Ryan B. , Lundgren Jonathan G. 
Published: December 2020

AbstractThe red imported fire ant,Solenopsis invicta, is one of the most prolific invasive species to the Southeastern U.S. These invaders preferentially colonize highly disturbed land and grassland habitat. Management of livestock in pasture systems can have a profound impact on the level of disturbance in grassland habitats, and we hypothesized that pasture management would have a significant effect onS. invictaabundance in the Southeastern U.S., and arthropod diversity would negatively correlate with this invasive species. We studied the effects that pasture management systems (based on stocking density, rotation frequency, and insecticide application rates) have on fire ant mound abundance and arthropod diversity for the soil, foliar, and dung communities.S. invictamounds were quantified and mound areas were documented along transect lines in six pastures. Soil and foliar arthropod communities were collected along the same transect lines, and dung communities sampled from pats within the pasture system. Pastures managed under adaptive multi-paddock (AMP) practices had 3.35× moreS. invictamounds and 4.64× more mound area than their conventionally managed counterparts. However, arthropod diversity did not correlate withS. invictaabundance for any of the three arthropod communities sampled. This study shows pasture management can have a significant impact onS. invictamound abundance, but arthropod communities in AMP managed pastures did not suffer decreased diversity from increased abundance ofS. invicta. Additionally, this study demonstrates that this invasive species does not necessarily contribute to diversity decline, at least under AMP pasture systems.
Redox protein Memo1 coordinates FGF23-driven signaling and small Rho-GTPases in the mouse kidney
Authors: Bartos Katalin , Ramakrishnan Suresh Krishna , Braga-Lagache Sophie , Hänzi Barbara , Durussel Fanny , Prakash Sridharan Arjun , Zhu Yao , Sheehan David , Hynes Nancy E. , Bonny Olivier , Moor Matthias B. 
Published: December 2020

AbstractMemo1deletion in mice causes premature aging and an unbalanced metabolism partially resemblingFgf23andKlotholoss-of-function animals. We report a role for Memo’s redox function in renal FGF23-Klotho signaling using mice with postnatally induced Memo deficiency in the whole body (cKO). Memo cKO mice showed impaired FGF23-driven renal ERK phosphorylation and transcriptional responses. FGF23 actions involved activation of oxidation-sensitive protein phosphotyrosyl phosphatases (PTP) in the kidney. Redox proteomics revealed excessive thiols of Rho-GDP dissociation inhibitor 1 (Rho-GDI1) in Memo cKO, and we detected a functional interaction between Memo’s redox function and oxidation at Rho-GDI1 Cys79. In isolated cellular systems, Rho-GDI1 did not directly affect FGF23-driven cell signaling, but we detected disturbed Rho-GDI1 dependent small Rho-GTPase protein abundance and activity in the kidney of Memo cKO mice. Collectively, this study reveals previously unknown layers in the regulation of renal FGF23 signaling and connects Memo with the network of small Rho-GTPases.
Comparative analysis of antigen-specific anti-SARS-CoV-2 antibody isotypes in COVID-19 patients
Authors: Fujigaki Hidetsugu , Inaba Masato , Osawa Michiko , Moriyama Saya , Takahashi Yoshimasa , Suzuki Tadaki , Yamase Kenya , Yoshida Yukihiro , Yagura Yo , Oyamada Takayoshi , Takemura Masao , Doi Yohei , Saito Kuniaki 
Published: December 2020

AbstractSerological tests for detection of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in blood are expected to identify individuals who have acquired immunity against SARS-CoV-2 and indication of seroprevalence of SARS-CoV-2 infection. Many serological tests have been developed to detect antibodies against SARS-CoV-2. However, these tests have considerable variations in their specificity and sensitivity, and whether they can predict levels of neutralizing activity is yet to be determined. This study aimed to investigate the kinetics and neutralizing activity of various antigen-specific antibody isotypes against SARS-CoV-2 in serum of coronavirus disease 2019 (COVID-19) patients confirmed via polymerase chain reaction test. We developed IgG, IgM and IgA measurement assays for each antigen, including receptor-binding domain (RBD) of spike (S) protein, S1 domain, full length S protein, S trimer and nucleocapsid (N) domain, based on enzyme-linked immunosorbent assay. The assays of the S protein for all isotypes showed high specificity, while the assays for all isotypes against N protein showed lower specificity. The sensitivity of all antigen-specific antibody isotypes depended on the timing of the serum collection and all of them, except for IgM against N protein, reached more than 90% at 15-21 days post-symptom onset. The best correlation with virus neutralizing activity was found for IgG against RBD (RBD-IgG), and levels of RBD-IgG in sera from four severe COVID-19 patients increased concordantly with neutralizing activity. Our results provide valuable information regarding the selection of serological test for seroprevalence and vaccine evaluation studies.
A secreted endoribonuclease ENDU-2 from the soma protects germline immortality inC. elegans
Authors: Qi Wenjing , Gromoff Erika D v. , Xu Fan , Zhao Qian , Yang Wei , Pfeifer Dietmar , Maier Wolfgang , Long Lijiang , Baumeister Ralf 
Published: December 2020

AbstractMulticellular organisms coordinate tissue specific response to environmental information via both cell-autonomous and non-autonomous mechanisms. In addition to secreted ligands, secreted small RNAs have recently been reported to regulate gene expression across tissue boundaries. Here we show that the conserved poly-U specific endoribonuclease ENDU-2 is secreted from the soma and taken-up by the germline to ensure germline immortality at elevated temperature inC. elegans. ENDU-2 binds to mature mRNAs and negatively regulates mRNA abundance both in the soma and the germline. While ENDU-2 promotes RNA decay in the soma directly via its endoribonuclease activity, ENDU-2 prevents misexpression of soma-specific genes in the germline and preserves germline immortality independent of its RNA-cleavage activity. In summary, our results suggest that the secreted RNase ENDU-2 transmits environmental information across tissue boundaries and contributes to maintenance of stem cell immortality probably via retaining a stem cell specific program of gene expression.
Tissue-specific safety mechanism results in opposite protein aggregation patterns during aging
Authors: Jung Raimund , Lechler Marie C. , Rödelsperger Christian , Röseler Waltraud , Sommer Ralf J. , David Della C. 
Published: December 2020

AbstractDuring aging, proteostasis capacity declines and aggregation-prone proteins become instable, accumulating in protein aggregates both inside and outside cells. Both in disease and during aging, proteins selectively aggregate in certain tissues and not others. Yet, tissue-specific regulation of protein aggregation remains poorly understood. Surprisingly, we found that the inhibition of three core protein quality control systems, i.e. chaperones, proteasome and macroautophagy, leads to lower levels of age-dependent protein aggregation inC. eleganspharyngeal muscles, but higher levels in body-wall muscles. We describe a novel safety mechanism called SAPA that selectively targets newly synthesized aggregation-prone proteins to suppress aggregation and proteotoxicity.vha-12andscav-3mutants reveal that SAPA relies on macroautophagy-independent lysosomal degradation. Furthermore, SAPA involves several previously uncharacterized components of the intracellular pathogen response. We propose that SAPA represents an anti-aggregation machinery targeting aggregation-prone proteins for lysosomal degradation.