bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experience of the COVID-19 pandemic in rural Odisha, India: knowledge, preventative actions, and impacts on daily life
Authors: Bauza Valerie , Sclar Gloria D. , Bisoyi Alokananda , Owens Ajilé , Ghugey Apurva , Clasen Thomas 
Published: November 2020

AbstractWe conducted 131 semi-structured phone interviews with householders in rural Odisha, India to explore participants’ COVID-19 related knowledge, perceptions, and preventative actions, as well as how the pandemic was impacting their daily life, economic and food security, and the village-level response. Interviews were conducted with 73 heads of household, 37 primary caregivers, and 21 members of village water and sanitation committees from 43 rural villages in Ganjam and Gajapati districts in Odisha state. The study took place between May-July 2020 throughout various lockdown restrictions and at a time when many migrant workers were returning to their villages. Most respondents could name at least one correct symptom of COVID-19 (75%), but there was lower knowledge about causes of the disease and high-risk groups, and overall COVID-19 knowledge was lowest among caregivers. Respondents reported high compliance with important preventative measures, including staying home as much as possible (94%), social distancing (91%), washing hands frequently (96%), and wearing a facial mask (95%). Additionally, many respondents reported job loss (31%), financial challenges (93%), challenges related to staying home whether as a preventative measure or due to lockdowns (57%), changes in types and/or amount of food consumed (61%), and adverse emotional effects as a result of the pandemic and lockdown. We also provide detailed summaries of qualitative responses to allow for deeper insights into the lived experience of villagers during this pandemic. Although the research revealed high compliance with preventative measures, the pandemic and associated lockdowns also led to many challenges and hardships faced in daily life particularly around job loss, economic security, food security, and emotional wellbeing. The results underscore the vulnerability of marginalized populations to the pandemic and the need for measures that increase resilience to large-scale shocks.
A CDK-regulated chromatin segregase promoting chromosome replication
Authors: Chacin Erika , Bansal Priyanka , Reusswig Karl-Uwe , Diaz-Santin Luis M. , Ortega Pedro , Vizjak Petra , Gómez-González Belen , Müller-Planitz Felix , Aguilera Andrés , Pfander Boris , Cheung Alan C.M. , Kurat Christoph F. 
Published: November 2020

The replication of chromosomes during S phase is critical for cellular and organismal function. Replicative stress can result in genome instability, which is a major driver of cancer. Yet how chromatin is made accessible during eukaryotic DNA synthesis is poorly understood.Here, we report the identification of a novel class of chromatin remodeling enzyme, entirely distinct from classical SNF2-ATPase family remodelers. Yta7 is a AAA+-ATPase that assembles into ~ 1 MDa hexameric complexes capable of segregating histones from DNA. Yta7 chromatin segregase promotes chromosome replication bothin vivoandin vitro. Biochemical reconstitution experiments using purified proteins revealed that Yta7’s enzymatic activity is regulated by S phase-forms of Cyclin-Dependent Kinase (S-CDK). S-CDK phosphorylation stimulates ATP hydrolysis by Yta7, promoting nucleosome disassembly and chromatin replication.Our results present a novel mechanism of how cells orchestrate chromatin dynamics in co-ordination with the cell cycle machinery to promote genome duplication during S phase.
Likelihood Approximation Networks (LANs) for Fast Inference of Simulation Models in Cognitive Neuroscience
Authors: Fengler Alexander , Govindarajan Lakshmi N. , Chen Tony , Frank Michael J. 
Published: November 2020

AbstractIn cognitive neuroscience, computational modeling can formally adjudicate between theories and affords quantitative fits to behavioral/brain data. Pragmatically, however, the space of plausible generative models considered is dramatically limited by the set of models with known likelihood functions. For many models, the lack of a closed-form likelihood typically impedes Bayesian inference methods. As a result, standard models are evaluated for convenience, even when other models might be superior. Likelihood-free methods exist but are limited by their computational cost or their restriction to particular inference scenarios. Here, we propose neural networks that learn approximate likelihoods for arbitrary generative models, allowing fast posterior sampling with only a one-off cost for model simulations that is amortized for future inference. We show that these methods can accurately recover posterior parameter distributions for a variety of neurocognitive process models. We provide code allowing users to deploy these methods for arbitrary hierarchical model instantiations without further training.
Transmission and protection against re-infection in the ferret model with the SARS-CoV-2 USA-WA1/2020 reference isolate
Authors: Patel Devanshi R. , Field Cassandra J. , Septer Kayla M. , Sim Derek G. , Jones Matthew J. , Heinly Talia A. , McGraw Elizabeth A. , Sutton Troy C 
Published: November 2020

AbstractSARS-CoV-2 has initiated a global pandemic and vaccines are being rapidly developed. Using the reference strain SARS-CoV-2 USA-WA1/2020, we evaluated modes of transmission and the ability of prior infection or vaccine-induced immunity to protect against infection in ferrets. Ferrets were semi-permissive to infection with the USA-WA1/2020 isolate. When transmission was assessed via the detection of vRNA at multiple timepoints, direct contact transmission was efficient to 3/3 and 3/4 contact animals in two respective studies, while respiratory transmission was poor to only 1/4 contact animals. To assess the durability of immunity, ferrets were re-challenged 28 or 56 days post-primary infection. Following viral challenge, no infectious virus was recovered in nasal wash samples. In addition, levels of vRNA in the nasal wash were several orders of magnitude lower than during primary infection, and vRNA was rapidly cleared. To determine if intramuscular vaccination protected ferrets against infection, ferrets were vaccinated using a prime-boost strategy with the S-protein receptor-binding domain formulated with an oil-in-water adjuvant. Upon viral challenge, none of the mock or vaccinated animals were protected against infection, and there were no significant differences in vRNA or infectious virus titers in the nasal wash. Combined these studies demonstrate that in ferrets direct contact is the predominant mode of transmission of the SARS-CoV-2 USA-WA1/2020 isolate and immunity to SARS-CoV-2 is maintained for at least 56 days. Our studies also indicate protection of the upper respiratory tract against SARS-CoV-2 will require vaccine strategies that mimic natural infection or induce site-specific immunity.ImportanceThe SARS-CoV-2 USA-WA1/2020 strain is a CDC reference strain used by multiple research laboratories. Here, we show the predominant mode of transmission of this isolate in ferrets is by direct contact. We further demonstrate ferrets are protected against re-infection for at least 56 days even when levels of neutralizing antibodies are low or undetectable. Last, we show that when ferrets were vaccinated by the intramuscular route to induce antibodies against SARS-CoV-2, ferrets remain susceptible to infection of the upper respiratory tract. Collectively, these studies suggest protection of the upper respiratory tract will require vaccine approaches that mimic natural infection.
Neuromorphological changes following selection for tameness and aggression in the Russian fox-farm experiment
Authors: Hecht Erin E. , Kukekova Anna , Gutman David A. , Acland Greg , Preuss Todd M. , Trut Lyudmila 
Published: November 2020

AbstractThe Russian fox-farm experiment is an unusually long-running and well-controlled study designed to replicate wolf-to-dog domestication. As such, it offers an unprecedented window onto the neural mechanisms governing the evolution of behavior. Here we report adaptations to gray matter morphology resulting from selection for tameness vs. aggressive response toward humans. Contrasting with prior work in other domesticated species, tame foxes did not show reduced brain volume. Rather, gray matter volume in both the tame and aggressive strains was increased relative to foxes bred without selection on behavior. Furthermore, tame- and aggressive-enlarged regions overlapped substantially, including portions of motor, somatosensory, and prefrontal cortex, amygdala, hippocampus, and cerebellum. We also observed differential morphological covariation across distributed gray matter networks. In one prefrontal-hypothalamic network, this covariation differentiated the tame and aggressive foxes together from the conventional strain. These findings indicate that selection for opposite behaviors can influence brain morphology in a similar way.
Crosstalk between repair pathways elicits Double-Strand Breaks in alkylated DNA: implications for the action of temozolomide
Authors: Fuchs Robert P. , Isogawa Asako , Paulo Joao A. , Onizuka Kazumitsu , Takahashi Tatsuro , Amunugama Ravindra , Duxin Julien , Fujii Shingo 
Published: November 2020

AbstractTemozolomide (TMZ), a DNA methylating agent, is the primary chemotherapeutic drug used in glioblastoma treatment. TMZ induces mostly N-alkylation adducts (N7-methylguanine and N3-methyladenine) and some O6-methylguanine (O6mG). Current models propose that during DNA replication, thymine is incorporated across from O6mG, promoting a futile cycle of mismatch repair (MMR) that leads to DNA double strand breaks (DSBs). To revisit the mechanism of O6mG processing, we reacted plasmid DNA with N-Methyl-N-nitrosourea (MNU), a temozolomide mimic, and incubated it in Xenopus egg extracts. We show that in this system, mismatch repair (MMR) proteins are enriched on MNU-treated DNA and we observe robust, MMR-dependent, repair synthesis. Our evidence also suggests that MMR, initiated at O6mG:C sites, is strongly stimulated incisby repair processing of other lesions, such as N-alkylation adducts. Importantly, MNU-treated plasmids display DSBs in extracts, the frequency of which increased linearly with the square of alkylation dose. We suggest that DSBs result from two independent repair processes, one involving MMR at O6mG:C sites and the other involving BER acting at a nearby N-alkylation adducts. We propose a new, replication-independent mechanism of action of TMZ, that operates in addition to the well-studied cell cycle dependent mode of action.
Forensic features and genetic legacy of the Baloch population of Pakistan and the Hazara population across Durand-line revealed by Y chromosomal STRs
Authors: Adnan Atif , Wen Shao-Qing , Rakha Allah , Alghafri Rashed , Nazir Shahid , Rehman Muhammad , Wang Chuan-Chao , Lu Jie 
Published: November 2020

ABSTRACTHazara population across Durand-line has experienced extensive interaction with Central Asian and East Asian populations. Hazara individuals have typical Mongolian facial appearances and they called themselves descendants of Genghis Khan’s army. The people who speak the Balochi language are called Baloch. Previously, a worldwide analysis of Y-chromosomal haplotype diversity for rapidly mutating (RM) Y-STRs and with PowerPlex Y23 System (Promega Corporation Madison, USA) kit was created with collaborative efforts, but Baloch and Hazara population from Pakistan and Hazara population from Afghanistan were missing. A limited data with limited number of markers and samples is available which poorly define these populations. So, in the current study, Yfiler Plus PCR Amplification Kit loci were examined in 260 unrelated Hazara individuals from Afghanistan, 153 Hazara individuals, and 111 Balochi individuals from Baluchistan Pakistan. For the Hazara population from Afghanistan and Pakistan overall, 380 different haplotypes were observed on these 27 Y-STR loci, gene diversities ranged from 0.51288 (DYS389I) to 0.9257 (DYF387S1) and haplotype diversity was 0.9992 +/- 0.0004. For the Baloch population, every individual was unique at 27 Y-STR loci, gene diversity ranged from 0.5718 (DYS460) to 0.9371(DYF387S1). Twelve haplotypes shared between 178 individuals while only two haplotypes among these twelve were shared between 87 individuals in Hazara populations. Rst and Fst pairwise genetic distance analyses, multidimensional scaling (MDS) plot, Neighbor-joining (NJ) tree, linear discriminatory analysis (LDA), and median-joining network (MJNs) were performed, which shed light on the history of Hazara and Baloch populations. Interestingly null alleles were observed at DYS448 with specific mutation patterns in Hazara populations. The results of our study showed that the Yfiler Plus PCR Amplification Kit marker set provided substantially stronger discriminatory power in the Baloch population of Pakistan and the Hazara population across the Durand-line.
Patient-derived Glioblastoma Stem cells transfer mitochondria through Tunneling Nanotubes in Tumor Organoids
Authors: Pinto Giulia , Saenz-de-Santa-Maria Inés , Chastagner Patricia , Perthame Emeline , Delmas Caroline , Toulas Christine , Moyal-Jonathan-Cohen Elizabeth , Brou Christel , Zurzolo Chiara 
Published: November 2020

AbstractGlioblastoma (GBM) is the most aggressive brain cancer and its relapse after surgery, chemo and radiotherapy appears to be led by GBM stem cells (GSLCs). Also, tumor networking and intercellular communication play a major role in driving GBM therapy-resistance. Tunneling Nanotubes (TNTs), thin membranous open-ended channels connecting distant cells, have been observed in several types of cancer, where they emerge to drive a more malignant phenotype. Here, we investigated whether GBM cells are capable to intercommunicate by TNTs. Two GBM stem-like cells (GSLCs) were obtained from the external and infiltrative zone of one GBM from one patient. We show, for the first time, that both GSLCs, grown in classical 2D culture and in 3D-tumor organoids, formed functional TNTs which allowed mitochondria transfer. In the organoid model, recapitulative of several tumor’s features, we observed the formation of a network between cells constituted of both Tumor Microtubes (TMs), previously observedin vivo, and TNTs. In addition, the two GSLCs exhibited different responses to irradiation in terms of TNT induction and mitochondria transfer, although the correlation with the disease progression and therapy-resistance needs to be further addressed. Thus, TNT-based communication is active in different GSLCs derived from the external tumoral areas associated to GBM relapse, and we propose that they participate together with TMs in tumor networking.
Computational cell cycle analysis of single cell RNA-Seq data
Authors: Moussa Marmar , Măndoiu Ion I. 
Published: November 2020

AbstractThe variation in gene expression profiles of cells captured in different phases of the cell cycle can interfere with cell type identification and functional analysis of single cell RNA-Seq (scRNA-Seq) data. In this paper, we introduce SC1CC (SC1 CellCycle analysis tool), a computational approach for clustering and ordering single cell transcriptional profiles according to their progression along cell cycle phases. We also introduce a new robust metric, Gene Smoothness Score (GSS) for assessing the cell cycle based order of the cells. SC1CC is available as part of the SC1 web-based scRNA-Seq analysis pipeline, publicly accessible athttps://sc1.engr.uconn.edu/.
A conserved strategy for inducing appendage regeneration
Authors: Abrams Michael J. , Tan Fayth , Basinger Ty , Heithe Martin , Li Yutian , Raffiee Misha , Leahy Patrick , Dabiri John O. , Gold David A. , Goentoro Lea 
Published: November 2020

AbstractCan limb regeneration be induced? Few have pursued this question, and an evolutionarily conserved strategy has yet to emerge. This study reports a strategy for inducing regenerative response in appendages, which works across three species that span the animal phylogeny. In Cnidaria, the frequency of appendage regeneration in the moon jellyfishAureliawas increased by feeding with the amino acid L-leucine and the growth hormone insulin. In insects, the same strategy induced tibia regeneration in adultDrosophila. Finally, in mammals, L-leucine and sucrose administration induced digit regeneration in adult mice, including dramatically from mid-phalangeal amputation. The conserved effect of L-leucine and insulin/sugar suggests a key role for energetic parameters in regeneration induction. The simplicity by which nutrient supplementation can induce appendage regeneration provides a testable hypothesis across animals.
Correlative transmission electron microscopy and high-resolution hard X-ray fluorescence microscopy of cell sections to measure trace elements concentrations at the organelle level
Authors: Suárez Vanessa Tardillo , Gallet Benoit , Chevallet Mireille , Jouneau Pierre-Henri , Tucoulou Rémi , Veronesi Giulia , Deniaud Aurélien 
Published: November 2020

AbstractMetals are essential to all forms of life and their concentration and distribution in the organisms are tightly regulated. Indeed, in their free form, metal ions are toxic. Therefore, an excess of physiologic metal ions or the uptake of non-physiologic metal ions can be highly detrimental for the organisms. It is thus fundamental to understand metals distribution and dynamics in physiologic or disrupted conditions, for instance in metal-related pathologies or upon environmental exposure to metals. Elemental imaging techniques can serve this purpose, by allowing the visualization and the quantification of metal species in a tissue or down to the interior of a cell. Among these techniques, synchrotron radiation-based X-ray fluorescence (SR-XRF) microscopy is the most sensitive to date, and great progresses were made to reach spatial resolutions as low as 20×20 nm2. Until recently, 2D XRF mapping was used on whole cells, thus summing up the signal from the whole thickness of the cell. In the last two years, we have developed a methodology to work on thin cell sections, in order to analyze the metal content at the level of the organelle. Herein, we propose a correlative method to couple SR-XRF to electron microscopy, with the aim to quantify the elemental content in an organelle of interest. As a proof-of-concept, the technique was applied to the analysis of mitochondria from hepatocytes exposed to silver nanoparticles. It was thus possible to identify mitochondria with higher concentration of Ag(I) ions compared to the surrounding cytosol. The versatility of the method makes it suitable to answer a large panel of biological questions, for instance related to metal homeostasis in biological organisms.
DNA methylation age analysis of rapamycin in common marmosets
Authors: Horvath Steve , Zoller Joseph A. , Haghani Amin , Lu Ake T. , Raj Ken , Jasinska Anna J. , Mattison Julie A. , Salmon Adam B. 
Published: November 2020

AbstractHuman DNA methylation data have previously been used to develop highly accurate biomarkers of aging (“epigenetic clocks”). Subsequent studies demonstrate that similar epigenetic clocks can also be developed for mice and many other mammals. Here, we describe epigenetic clocks for common marmosets (Callithrix jacchus) based on novel DNA methylation data generated from highly conserved mammalian CpGs that were profiled using a custom Infinium array (HorvathMammalMethylChip40). From these, we developed and present here, two epigenetic clocks for marmosets that are applicable to whole blood samples. We find that the human-marmoset clock for relative age exhibits moderately high age correlations in two other non-human primate species: vervet monkeys and rhesus macaques. In a separate cohort of marmosets, we tested whether intervention with rapamycin, a drug shown to extend lifespan in mice, would alter the epigenetic age of marmosets, as measured by the marmoset epigenetic clocks. These clocks did not detect significant effects of rapamycin on the epigenetic age of marmoset blood. The common marmoset stands out from other mammals in that it is not possible to build accurate estimators of sex based on DNA methylation data: the accuracy of a random forest predictor of sex (66%) was substantially lower than that observed for other mammals (which is close to 100%). Overall, the epigenetic clocks developed here for the common marmoset are expected to be useful for age estimation of wild-born animals and for anti-aging studies in this species.
CM1-driven assembly and activation of Yeast γ-Tubulin Small Complex underlies microtubule nucleation
Authors: Brilot Axel F. , Lyon Andrew S. , Zelter Alex , Viswanath Shruthi , Maxwell Alison , MacCoss Michael J. , Muller Eric G. , Sali Andrej , Davis Trisha N. , Agard David A. 
Published: November 2020

ABSTRACTMicrotubule (MT) nucleation is regulated by the γ-tubulin ring complex (γTuRC), conserved from yeast to humans. In Saccharomyces cerevisiae, γTuRC is composed of seven identical γ-tubulin small complex (γTuSC) sub-assemblies which associate helically to template microtubule growth. γTuRC assembly provides a key point of regulation for the MT cytoskeleton. Here we combine cross-linking mass spectrometry (XL-MS), X-ray crystallography and cryo-EM structures of both monomeric and dimeric γTuSCs, and open and closed helical γTuRC assemblies in complex with Spc110p to elucidate the mechanisms of γTuRC assembly. γTuRC assembly is substantially aided by the evolutionarily conserved CM1 motif in Spc110p spanning a pair of adjacent γTuSCs. By providing the highest resolution and most complete views of any γTuSC assembly, our structures allow phosphorylation sites to be mapped, surprisingly suggesting that they are mostly inhibitory. A comparison of our structures with the CM1 binding site in the human γTuRC structure at the interface between GCP2 and GCP6 allows for the interpretation of significant structural changes arising from CM1 helix binding to metazoan γTuRC.