bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiological Risk Factors of SARS-CoV-2 Infections
Authors: Barletta William A. 
Published: October 2020

AbstractSince the first recognitions by governments of the pandemic characteristic of the SARS-CoV-2 infections, public health agencies have warned the public about the dangers of the virus to persons with a variety of underlying physical conditions, many of which are more commonly found in persons over 50 years old or in certain ethnic groups. To investigate the statistical, rather than physiological basis of such warnings, this study examines correlations globally on a nation-by-nation basis between the statistical data concerning COVID-19 fatalities among the populations of the ninety-nine countries with the greatest number of SARS-CoV-2 infections plus the statistics of potential co-morbidities that may influence the severity of the infections. It examines reasons that may underlie of the degree to which advanced age increases the risk of mortality of an infection and contrasts the risk factors of SARS-Cov-2 infections with those of influenzas and their associated pneumonias.
Small extracellular vesicles secreted by Candida albicans hyphae have highly diverse protein cargoes that include virulence factors and stimulate macrophages
Authors: Martínez-López Raquel , Hernáez Maria Luisa , Redondo Esther , Calvo Guillermo , Radau Sonja , Gil Concha , Monteoliva Lucía 
Published: October 2020

ABSTRACTExtracellular vesicles (EVs) have been described as mediators of microorganism survival and interaction with the host. InCandida albicans, a relevant commensal fungal pathogen, the dimorphic transition is an important virulence trait in candidiasis. We have analyzed EVs secreted by yeast (YEVs) or hyphal cells (HEVs) fromC. albicans, finding interesting differences in both size distribution and protein loading. In general, HEVs were smaller and carried a much more diverse protein cargo than YEVs, including most of the proteins identified in YEVs, which were mainly cell surface proteins. Virulence factors such as phospholipases, aspartic proteases (Saps), adhesins and invasins, and the precursor protein of candidalysin toxin Ece1p were also detected. HEVs were also enriched in proteasomal and ribosomal proteins, and in enzymes from amino acid biosynthetic pathways, all involved in protein metabolism, as well as proteins related to intracellular protein transport and components of the ESCRT pathway related to exosome biogenesis. Both types of EV presented immune reactivity with human sera from patients suffering invasive candidiasis. In our conditions, only HEVs could elicit the release of TNFα by activated macrophages. This first analysis ofC. albicansHEVs shows their relevance to pathogenesis and possible new diagnostics or treatments.
Variations in the frequency and amplitude of resting-state EEG and fMRI signals in normal adults: The effects of age and sex
Authors: Zhong Xiaole , Chen J. Jean 
Published: October 2020

AbstractFrequency and amplitude features of both resting-state electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are crucial metrics that reveal patterns of brain health in aging. However, the association between these two modalities is still unclear. In this study, we examined the peak frequency and standard deviation of both modalities in a dataset comprising healthy young (35.5±3.4 years, N=134) and healthy old (66.9±4.8 years, N=51) adults. Both age and sex effects were examined using non-parametric analyses of variance (ANOVA) and Tukey’s Honest Significant Difference (HSD) post-hoc comparisons in the cortical and subcortical regions. We found that, with age, EEG power decreases in the low frequency band (1-12 Hz) but increases in the high frequency band (12-30 Hz). Moreover, EEG frequency generally shifts up with aging. For fMRI, fluctuation amplitude is lower but fluctuation frequency is higher in older adults, but in a manner that depends on the fMRI frequency range. Furthermore, there are significant sex effects in EEG power (female > male), but the sex effect is negligible for EEG frequency as well as fMRI power and frequency. We also found that the fMRI-EEG power ratio is higher in young adults than old adults. However, the mediation analysis shows the association between EEG and fMRI parameters in aging is negligible. This is the first study that examines both power and frequency of both resting EEG and fMRI signals in the same cohort. In conclusion, both fMRI and EEG signals reflect age-related and sex-related brain differences, but they likely associate with different origins.
Role for the Na+/K+ATPase pump alpha 3 (ATP1A3) subunit in folding and lamination of the human neocortex
Authors: Smith Richard S. , Florio Marta , Akula Shyam K. , Neil Jennifer E. , Wang Yidi , Hill R. Sean , Goldman Melissa , Mullally Christopher D. , Reed Nora , Bello-Espinosa Luis , Flores-Sarnat Laura , Monteiro Fabiola Paoli , Erasmo Casella B. , e Vairo Filippo Pinto , Morava Eva , Barkovich A. James , Gonzalez-Heydrich Joseph , Brownstein Catherine A. , McCarroll Steven A. , Walsh Christopher A. 
Published: October 2020

ABSTRACTOsmotic equilibrium and membrane potential in animal cells depend on concentration gradients of sodium (Na+) and potassium (K+) ions across the plasma membrane, a function that is catalyzed by the Na,K-ATPase alpha subunit. In vertebrates, four paralogous genes,ATP1A1-4, encode distinct alpha subunit isoforms (a1-a4), three of which (a1, a2, a3) are expressed in the brain, and two (a1, a3) predominantly in neurons. Thea3isoform, encoded byATP1A3, is critical to neuronal physiology, and a growing spectrum of neurological diseases are associated withATP1A3pathogenic variants, with ages of onset ranging from early childhood to adulthood. Here, we describeATP1A3variants encoding dysfunctionala3subunits in children affected by polymicrogyria, a developmental malformation of the cerebral cortex characterized by abnormal folding and laminar organization. To gain cell-biological insights into the spatiotemporal dynamics of prenatalATP1A3expression, we established a transcriptional atlas ofATP1A3expression during cortical development using mRNAin situhybridization and transcriptomic profiling of ~125,000 individual cells with single-cell RNA sequencing (Drop-Seq) from various areas of the midgestational human neocortex. We find that fetal expression ofATP1A3is restricted to a subset of excitatory neurons carrying transcriptional signatures of neuronal activity and maturation characteristic of the developing subplate. Furthermore, by performing Drop-Seq on ~52,000 nuclei from four different areas of an infant human neocortex, we show thatATP1A3expression persists throughout early postnatal development, not only within excitatory neurons across all cortical layers, but also and more predominantly in inhibitory neurons, with specific enrichment in fast-spiking basket cells. In addition, we show thatATP1A3expression, both in fetal and postnatal neurons, tends to be higher in frontal cortical areas than in occipital areas, in a pattern consistent with the rostro-caudal maturation gradient of the human neocortex. Finally, we discover distinct co-expression patterns linking catalytic α subunit isoforms (ATP1A1,2,3) and auxiliary isoforms (ATP1B1,2,3), suggesting the ATPase pump may form non-redundant, cell-type specific α-β combinations. Together, the importance of the developmental phenotypes and dynamic expression patterns ofATP1A3point to a key role fora3in the development and function of human cortex.
Using Touchscreen Equipped Operant Chambers to Study Comparative Cognition. Benefits, Limitations, and Advice
Authors: Seitz BM , McCune KB , MacPherson M , Bergeron L , Blaisdell AP , Logan CJ 
Published: October 2020

AbstractOperant chambers are small enclosures used to test animal behavior and cognition. While traditionally reliant on simple technologies for presenting stimuli (e.g., lights and sounds) and recording responses made to basic manipulanda (e.g., levers and buttons), an increasing number of researchers are beginning to use Touchscreen-equipped Operant Chambers (TOCs). These TOCs have obvious advantages, namely by allowing researchers to present a near infinite number of stimuli as well as increased flexibility in the types of responses that can be made and recorded. Here, we trained wild-caught adult and juvenile great-tailed grackles (Quiscalus mexicanus) to complete experiments using a TOC. We have learned much from these efforts, and outline the advantages and disadvantages of these two approaches. We report data from our training sessions and discuss important modifications we made to facilitate animal engagement and participation in various tasks. Finally, we provide a “training guide” for creating experiments using PsychoPy, a free and open-source software that we have found to be incredibly useful during these endeavors. This article, therefore, should serve as a useful resource to those interested in switching to or maintaining a TOC, or who similarly wish to use a TOC to test the cognitive abilities of non-model species or wild-caught individuals.
In silicocharacterization ofMTP1gene associated with Zn homeostasis across different dicot plant species
Authors: Kabir Ahmad Humayan 
Published: October 2020

ABSTRACTZinc (Zn) is tightly regulated in plants. The MTP1/ZAT (metal tolerance protein) plays a critical role in adjusting Zn homeostasis upon Zn fluctuation in plants. This study characterizes MTP1 homologs with particular emphasis on AtMT1 in various dicot plants. The protein BLAST search was used to identify a total of 21 MTP1 proteins. Generally, all these MTP1 proteins showed around 400 residues long, six transmembrane helices, stable instability index along with cation transmembrane transporter activity (GO:0008324). These physio-chemical features of MTP1 can be utilized as a benchmark in the prediction of Zn uptake and tolerance in plants. These MTP1 homologs were located on chromosomes 2, 7, and 14 with one exon. Motif analysis showed conserved sequences of 41-50 residues belonging to the family of cation efflux, which may be helpful for binding sites targeting and transcription factor analysis. Phylogenetic studies revealed close similarities ofAtZATwithGlycine maxandMedicago trunculatathat may infer a functional relationship in Zn tolerance or uptake across different plant species. Further, interactome analysis suggests that AtZAT is closely linked cadmium/zinc-transporting ATPase and ZIP metal ion transporter, which could provide essential background for functional genomics studies in plants. The network of AtZAT is predominantly connected to cadmium/zinc-transporting ATPase (HMA2, HMA3, HMA4), cation efflux protein (MTP11), and metal tolerance protein C3 (AT4G58060). The Genevestigator platform further predicts the high expression potential of AtMTP1 in root tissue at the germination and grain filling stage. The structural analysis of MTP1 proteins suggests the conserved N-glyco motifs as well as similar hydrophobicity, net charge and nonpolar residues, alpha-helix in all MTP1 proteins. Altogether, thesein silicocharacterization features of MTP1 and its orthologs will provide an essential theoretical background to perform wet-lab experiments and to better understand Zn homeostasis aiming to develop genetically engineered plants.
5-HT2C agonists and antagonists block different components of behavioral responses to potential, distal, and proximal threat in zebrafish
Authors: Xavier do Carmo Silva Rhayra , Gomes do Nascimento Bianca , Gomes Gabriela Cristini Vidal , Holanda da Silva Nadyme Assad , Pinheiro Jéssica Souza , Nayara da Silva Chaves Suianny , Pimentel Ana Flávia Nogueira , Costa Bruna Patrícia Dutra , Herculano Anderson Manoel , Lima-Maximino Monica , Maximino Caio 
Published: October 2020

AbstractSerotonin (5-HT) receptors have been implicated in responses to aversive stimuli in mammals and fish, but its precise role is still unknown. Moreover, since at least seven families of 5-HT receptors exist in vertebrates, the role of specific receptors is still debated. Aversive stimuli can be classified as indicators of proximal, distal, or potential threat, initiating responses that are appropriate for each of these threat levels. Responses to potential threat usually involve cautious exploration and increased alertness, while responses to distal and proximal threat involve a fight-flight-freeze reaction. We exposed adult zebrafish to a conspecific alarm substance (CAS) and observed behavior during (distal threat) and after (potential threat) exposure, and treated with the 5-HT2Creceptor agonists MK-212 or WAY-161503 or with the antagonist RS-102221. The agonists blocked CAS-elicited defensive behavior (distal threat), but not post-exposure increases in defensive behavior (potential threat), suggesting inhibition of responses to distal threat. MK-212 blocked changes in freezing elicited by acute restraint stress, a model of proximal threat, while RS-102221 blocked changes in geotaxis elicited this stressor. We also found that RS-102221, a 5-HT2Creceptor antagonist, produced small effect on behavior during and after exposure to CAS.Preprint:https://www.biorxiv.org/content/10.1101/2020.10.04.324202;Data and scripts:https://github.com/lanec-unifesspa/5-HT-CAS/tree/master/data/5HT2C
CXCL10+peripheral activation niches couple preferred sites of Th1 entry with optimal APC encounter
Authors: Prizant Hen , Patil Nilesh , Negatu Seble , McGurk Alexander , Leddon Scott A. , Hughson Angela , McRae Tristan D. , Gao Yu-Rong , Livingstone Alexandra M , Groom Joanna R , Luster Andrew D , Fowell Deborah J 
Published: October 2020

SUMMARYCorrect positioning of T cells within infected tissues is critical for T cell activation and pathogen control. Upon tissue entry, effector T cells must efficiently locate antigen presenting cells (APC) for peripheral activation. We reveal that tissue entry and initial peripheral activation of Th1 effector T cells are tightly linked to perivascular positioning of chemokine-expressing APCs. Dermal inflammation induced tissue-widede novogeneration of discrete perivascular CXCL10+cell clusters, enriched for CD11c+MHC-II+monocyte-derived dendritic cells. These chemokine clusters were ‘hot spots’ for both Th1 extravasation and activation in the inflamed skin. CXCR3-dependent Th1 localization to the cluster micro-environment prolonged T-APC interactions and boosted function. Both the frequency and range of these clusters were enhanced via a Th1-intrinsic, IFNγ-dependent positive feedback loop. Thus, the perivascular CXCL10+clusters act as initial peripheral activation niches, optimizing controlled activation broadly throughout the tissue by coupling Th1 tissue entry with enhanced opportunities for Th1-APC encounter.
Preneoplastic lesions fimbria pan-proteomic studies establish the fimbriectomy benefit for BRCA1/2 patients and identify early diagnosis markers of HGSC
Authors: Wisztorski Maxence , Saudemont Philippe , Aboulouard Soulaimane , Cardon Tristan , Narducci Fabrice , Robin Yves-Marie , Lemaire Anne-Sophie , Bertin Delphine , Kobeissy Firas , Leblanc Eric , Fournier Isabelle , Salzet Michel 
Published: October 2020

ABSTRACTOvarian cancer is the leading cause of death from gynecologic cancer worldwide; however, the origin of ovarian tumors, particularly for high-grade serous carcinoma (HGSC), is still debated. Accumulated evidence converges towards the involvement of the preneoplastic lesions observed in the fimbriated end of the fallopian tubes. In this study, we propose to carry out an in-depth proteomics analysis of these epithelial lesions (p53 signature, serous tubal intraepithelial carcinoma-STIC and serous tubal intraepithelial lesions-STIL) based on spatially resolved proteomic guided by IHC technique. We identified specific clusters related to each preneoplastic lesions, specific protein mutations based on Cosmic database and a Ghost proteome translated from non-coding RNAs and alternative ORFs, using the OpenProt database. Protein networks have been constructed from each cluster utilizing systems biology platform. Generated data were used to confirm the potentially dormant character of the STIL lesion and the more aggressive profile of the STIC which appears closer to HGSC than other lesions. In summary, our results established the chronological mechanisms and genesis of different ovarian cancer phenotypes but also identified the early diagnostic markers of HCSC guiding an adapted therapy and a better patient care.
Peripheral kappa opioid receptor activation drives noxious cold hypersensitivity in mice
Authors: Madasu Manish K. , Thang Loc V. , Chilukuri Priyanka , Palanisamy Sree , Arackal Joel S. , Sheahan Tayler D. , Foshage Audra M. , Houghten Richard A. , McLaughlin Jay P. , McCall Jordan G. , Al-Hasani Ream 
Published: October 2020

AbstractNoxious cold sensation is commonly associated with peripheral neuropathies, however, there has been limited progress in understanding the mechanism of cold pain. Here we identify a role for kappa opioid receptors (KOR) in driving noxious cold hypersensitivity. First, we show that systemic activation of KOR by the agonist U50,488 (U50), increases the latency to jump and the number of jumps on a cold plate at 3°C, and that the KOR antagonist NorBNI attenuates U50-induced noxious cold hypersensitivity. However, the central administration of NorBNI does not block U50-induced noxious cold hypersensitivity, suggesting that peripheral KOR may modulate this effect. To directly test this, we use the peripherally-restricted KOR agonist, ff(nle)r-NH2 and also show selective activation of peripheral KOR causes noxious cold hypersensitivity. To begin to understand how peripheral KOR drive noxious cold hypersensitivity we investigated whether KOR interact with transient receptor potential ankyrin 1(TRPA1) channels, known to facilitate the perception of noxious cold, in dorsal root ganglion (DRG). Using fluorescentin situhybridization, we show that KOR mRNA colocalizes with the transcripts for the cold-activated TRPA1 channels in DRG. We also show a potentiation in intracellular calcium release in DRG neurons during the simultaneous application of the TRPA1 agonist, mustard oil (MO), and a KOR agonist, U50, when compared to MO alone. Together our data suggest that peripheral KOR may induce noxious cold hypersensitivity through modulation of TRPA1 channels.
Deep Collection of Quantitative Nuclear Division Dynamics Data in RNAi-treatedCaenorhabditis elegansEmbryos
Authors: Kyoda Koji , Okada Hatsumi , Itoga Hiroya , Onami Shuichi 
Published: October 2020

SUMMARYRecent advances in bioimage informatics techniques have yielded quantitative data on multicellular dynamics from microscopy images of animal development. Several such data collections have been created forCaenorhabditis elegansembryos under various gene silencing conditions. However, because of the limited depth of the datasets, it is impractical to apply standard statistical methods to these collections. Here, we created a deep collection of quantitative data on nuclear division dynamics during the first three rounds of cell division inC. elegansembryos, in which 263 essential embryonic genes were silenced individually by RNA-mediated interference. The collection consists of datasets from 33 wild-type and 1142 RNAi-treated embryos, including five or more datasets for 189 genes. Application of a two-samplet-test identified 8660 reproducible RNAi-induced phenotypes for 421 phenotypic characters. Clustering analysis suggested 24 functional processes essential for early embryogenesis. Our collection is a rich resource for understanding animal development mechanisms.In BriefKyoda et al. used bioimage informatics techniques to create a deep collection of quantitative data on nuclear division dynamics in RNAi-treatedC. elegansembryos for 263 essential embryonic genes. Statistical analysis identified 8660 reproducible RNAi phenotypes for 421 phenotypic characters. The collection is a rich resource for understanding animal development.HighlightsBioimage informatics quantified nuclear division dynamics inC. elegansembryosFrom RNAi-silenced embryos we collected 1142 data sets on 263 essential genesStatistical analysis identified 8660 reproducible RNAi phenotypesClustering analysis suggested 24 functional processes inC. elegansembryogenesis
The contribution of PARP1, PARP2 and poly(ADP-ribosyl)ation to base excision repair in the nucleosomal context
Authors: Kutuzov M.M. , Belousova E.A. , Kurgina T.A. , Ukraintsev A.A. , Vasil’eva I.A. , Khodyreva S.N. , Lavrik O.I. 
Published: October 2020

ABSTRACTThe repair processes regulation including base excision repair (BER) is implemented by a cellular signal PARylation catalysed by PARP1 and PARP2. Despite intensive studies, it is far from clear how BER is regulated by PARPs and how the roles are distributed between the PARPs. Here, we investigated the effects of PARP1, PARP2 and PARylation on activities of the main BER enzymes (APE1, Polβ and LigIIIα) in combination with XRCC1 in the nucleosomal context. We constructed nucleosomes with midward- or outward-oriented damage. It was concluded that in most cases, the presence of PARP1 leads to the suppression of the activities of APE1, Polβ, and to a lesser extent LigIIIα. PARylation by PARP1 attenuated this effect to various degrees. PARP2 had an influence predominantly on the last stage of BER: DNA sealing. Nonetheless, PARylation by PARP2 led to Polβ inhibition and to significant stimulation of LigIIIα activities in a NAD+-dependent manner.
TopBP1 assembles nuclear condensates to switch on ATR signalling
Authors: Frattini Camilla , Promonet Alexy , Alghoul Emile , Vidal-Eychenie Sophie , Lamarque Marie , Blanchard Marie-Pierre , Urbach Serge , Basbous Jihane , Constantinou Angelos 
Published: October 2020

AbstractATR checkpoint signalling is crucial for cellular responses to DNA replication impediments. Using an optogenetic platform, we show that TopBP1, the main activator of ATR, self-assembles extensively to yield micron-sized condensates. These opto-TopBP1 condensates are functional entities organized in tightly packed clusters of spherical nano-particles. TopBP1 condensates are reversible, occasionally fuse and co-localise with TopBP1 partner proteins. We provide evidence that TopBP1 condensation is a molecular switch that amplifies ATR activity to phosphorylate checkpoint kinase 1 (Chk1) and slowdown replication forks. Single amino acid substitutions of key residues in the intrinsically disordered ATR-activation domain disrupt TopBP1 condensation and, consequently, ATR/Chk1 signalling. In physiologic salt concentration and pH, purified TopBP1 undergoes liquid-liquid phase separationin vitro. We propose that the actuation mechanism of ATR signalling is the assembly of TopBP1 condensates driven by highly regulated multivalent and cooperative interactions.
Evolution of molecular determinants for SUMO-activating enzyme subcellular localization in plants
Authors: Más Abraham , Castaño-Miquel Laura , Carretero-Paulet Lorenzo , Colomé Núria , Canals Francesc , Lois L. Maria 
Published: October 2020

AbstractPost-translational modification by Small Ubiquitin-related Modifier (SUMO) is an essential regulatory mechanism in eukaryotes. In the cell, SUMO conjugates are highly enriched in the nucleus and, consistently, SUMOylation machinery components are mainly nuclear. Nonetheless, cytosolic SUMO targets also exist and the mechanisms that facilitate SUMO conjugation in the cytosol are unknown. Here, we show that the nuclear localization of the Arabidopsis SUMO activating enzyme large subunit SAE2 is dependent on two nuclear localization signals, the canonical NLS1 and the non-canonical NLS2 identified and validated here. NLS2 is proteolytic processed from SAE2 during seed development, facilitating SAE2 enrichment in the cytosol. Results obtained using transgenic plants expressing different SAE2 proteoforms suggest that SAE2 cytosolic enrichment could constitute a rapid signal for growth arrest. Phylogenetic studies indicated that the Arabidopsis NLS1-NLS2 structural organization is conserved only in seed plants, providing a potential evolutionary role of cytosolic SUMOylation in seed appearance.