bluuebunny/crossref_metadata_2025_split huggingface dataset:
Yet another lockdown? A large-scale study on people’s unwillingness to be confined during the first 5 months of the COVID-19 pandemic in Spain
Authors: Martinez-Garcia Marina , Rabasa Alejandro , Barber Xavier , Polotskaya Kristina , Roomp Kristof , Oliver Nuria 
Published: May 2021

ABSTRACTPopulation confinements have been one of the most widely adopted non-pharmaceutical interventions (NPIs) implemented by governments across the globe to help contain the spread of the SARS-CoV-2 virus. While confinement measures have been proven to be effective to reduce the number of infections, they entail significant economic and social costs. Thus, different policy makers and social groups have exhibited varying levels of acceptance of this type of measures. In this context, understanding the factors that determine the willingness of individuals to be confined during a pandemic is of paramount importance, particularly, to policy and decision-makers. In this paper, we study the factors that influence the unwillingness to be confined during the COVID-19 pandemic by means of a large-scale, online population survey deployed in Spain. We apply both quantitative (logistic regression) and qualitative (automatic pattern discovery) methods and consider socio-demographic, economic and psychological factors, together with the 14-day cumulative incidence per 100,000 inhabitants. Our analysis of 109,515 answers to the survey covers data spanning over a 5-month time period to shed light on the impact of the passage of time. We find evidence of pandemic fatigue as the percentage of those who report an unwillingness to be in confinement increases over time; we identify significant gender differences, with women being generally less likely than men to be able to sustain long-term confinement of at least 6 months; we uncover that the psychological impact was the most important factor to determine the willingness to be in confinement at the beginning of the pandemic, to be replaced by the economic impact as the most important variable towards the end of our period of study. Our results highlight the need to design gender and age specific public policies, to implement psychological and economic support programs and to address the evident pandemic fatigue as the success of potential future confinements will depend on the population’s willingness to comply with them.
Social inequalities in COVID-19 vaccine acceptance and uptake for children and adolescents in Montreal, Canada: a cross-sectional study
Authors: McKinnon Britt , Quach Caroline , Dubé Ève , Nguyen Cat Tuong , Zinszer Kate 
Published: May 2021

ABSTRACTBackgroundThe success of current and prospective COVID-19 vaccine campaigns for children and adolescents will in part depend on the willingness of parents to accept vaccination. This study examined social determinants of parental COVID-19 vaccine acceptance and uptake for children and adolescents.MethodsWe used cross-sectional data from an ongoing COVID-19 cohort study in Montreal, Canada and included all parents of 2 to 18-year-olds who completed an online questionnaire between May 18 and June 26, 2021 (n=809). We calculated child age-adjusted prevalence estimates of vaccine acceptance by parental education, race/ethnicity, birthplace, household income, and neighbourhood, and used multinomial logistic regression to estimate adjusted prevalence differences (aPD) and ratios (aPR). Social determinants of vaccine uptake were estimated for the vaccine-eligible sample of 12 to 18 year-olds (n=306).ResultsIntention to vaccinate children against COVID-19 was high, with only 12.4% of parents unlikely to have their child vaccinated. Parents with younger children were less likely to accept vaccination, as were those from lower-income households, racialized groups, and those born outside Canada. The percent of parents whose child was vaccinated or very likely to be vaccinated was 18.4 percentage points lower among those with annual household incomes <$100,000 vs. ≥$150,000 (95% CI: 10.1 to 26.7). Racialized parents reported greater unwillingness to vaccinate compared to White parents (aPD=10.3; 95% CI: 1.5, 19.1). Vaccine-eligible adolescents from the most deprived neighbourhood were half as likely to be vaccinated compared to those from the least deprived neighbourhood (aPR = 0.48; 95% CI: 0.18 to 0.77).InterpretationThis study identified marked social inequalities in COVID-19 vaccine acceptance and uptake for children and adolescents. Efforts are needed to reach disadvantaged and marginalized populations with tailored strategies that promote informed decision making and facilitate access to vaccination.
Association of Obesity with COVID-19 Severity and Mortality: A Systemic Review and Meta-Regression
Authors: Singh Romil , Rathore Sawai Singh , Khan Hira , Karale Smruti , Bhurwal Abhishek , Tekin Aysun , Jain Nirpeksh , Mehra Ishita , Anand Sohini , Reddy Sanjana , Sidhu Guneet Singh , Panagopoulos Anastasios , Pattan Vishwanath , Kashyap Rahul , Bansal Vikas 
Published: May 2021

AbstractObjectiveTo estimate the association of obesity with severity (defined as use of invasive mechanical ventilation or intensive care unit admission) and all-cause mortality in coronavirus disease 2019 (COVID-19) patients.Patients and MethodsA systematic search was conducted from inception of COVID-19 pandemic through January 31st, 2021 for full-length articles focusing on the association of increased BMI/ Obesity and outcome in COVID-19 patients with help of various databases including Medline (PubMed), Embase, Science Web, and Cochrane Central Controlled Trials Registry. Preprint servers such as BioRxiv, MedRxiv, ChemRxiv, and SSRN were also scanned. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used for study selection and data extraction. The severity in hospitalized COVID-19 patients, such as requirement of invasive mechanical ventilation and intensive care unit admission with high BMI/ Obesity was the chief outcome. While all-cause mortality in COVID-19 hospitalized patients with high BMI/ Obesity was the secondary outcome.ResultsA total of 576,784 patients from 100 studies were included in this meta-analysis. Being obese was associated with increased risk of severe disease (RR=1.46, 95% CI 1.34-1.60, p<0.001, I2= 92 %). Similarly, high mortality was observed in obese patients with COVID-19 disease (RR=1.12, 95% CI 1.06-1.19, p<0.001, I2= 88%). In a multivariate meta-regression on severity outcome, the covariate of female gender, pulmonary disease, diabetes, older age, cardiovascular diseases, and hypertension was found to be significant and explained R2= 50% of the between-study heterogeneity for severity. Similarly, for mortality outcome, covariate of female gender, proportion of pulmonary disease, diabetes, hypertension, and cardiovascular diseases were significant, these covariates collectively explained R2=53% of the between-study variability for mortality.ConclusionsOur findings suggest that obesity is significantly associated with increased severity and higher mortality among COVID-19 patients. Therefore, the inclusion of obesity or its surrogate body mass index in prognostic scores and streamlining the management strategy and treatment guidelines to account for the impact of obesity in patient care management is recommended.
Emergent population activity in metric-free and metric networks of neurons with stochastic spontaneous spikes and dynamic synapses
Authors: Zendrikov Dmitrii , Paraskevov Alexander 
Published: May 2021

AbstractWe show that networks of excitatory neurons with stochastic spontaneous spiking activity and short-term synaptic plasticity can exhibit spontaneous repetitive synchronization in so-called population spikes. The major reason for this is that synaptic plasticity nonlinearly modulates the interaction between neurons. For large-scale two-dimensional networks, where the connection probability decreases exponentially with increasing distance between the neurons resulting in a small-world network connectome, a population spike occurs in the form of circular traveling waves diverging from seemingly non-stationary nucleation sites. The latter is in drastic contrast to the case of networks with a fixed fraction of steady pacemaker neurons, where the set of a few spontaneously formed nucleation sites is stationary. Despite the spatial non-stationarity of their nucleation, population spikes may occur surprisingly regularly. From a theoretical viewpoint, these findings show that the regime of nearly-periodic population spikes, which mimics respiratory rhythm, can occur strictly without stochastic resonance. In addition, the observed spatiotemporal effects serve as an example of transient chimera patterns.
Dietary restriction andclockdelay eye aging to extend lifespan inD. melanogaster
Authors: Hodge Brian A. , Meyerhof Geoffrey T. , Katewa Subhash D. , Lian Ting , Lau Charles , Bar Sudipta , Leung Nicole , Li Menglin , Li-Kroeger David , Melov Simon , Schilling Birgit , Montell Craig , Kapahi Pankaj 
Published: May 2021

AbstractMany vital processes in the eye are under circadian regulation, and circadian dysfunction has emerged as a potential driver of eye aging. Dietary restriction is one of the most robust lifespan-extending therapies and amplifies circadian rhythms with age. Herein, we demonstrate that dietary restriction extends lifespan inD. melanogasterby promoting circadian homoeostatic processes that protect the visual system from age- and light- associated damage. Disrupting circadian rhythms in the eye by inhibiting the transcription factor, Clock (CLK), or CLK-output genes, accelerated visual senescence, induced a systemic immune response, and shortened lifespan. Flies subjected to dietary restriction were protected from the lifespan-shortening effects of photoreceptor activation. Inversely, photoreceptor inactivation, achieved via mutating rhodopsin or housing flies in constant darkness, primarily extended lifespan in flies reared on a high-nutrient diet. Our findings establish the eye as a diet-sensitive modulator of lifespan and indicate that vision is an antagonistically pleiotropic process that contributes to organismal aging.
Fish diversity in a doubly landlocked country - a description of the fish fauna of Uzbekistan using DNA barcoding
Authors: Sheraliev Bakhtiyor , Peng Zuogang 
Published: May 2021

AbstractUzbekistan is one of two doubly landlocked countries in the world, where all rivers are endorheic basins. Although fish diversity is relatively poor in Uzbekistan compared to other regions, the fish fauna of the region has not yet been fully studied. The aim of this study was to establish a reliable barcoding reference database for fish in Uzbekistan. A total of 666 specimens, belonging to 59 species within 39 genera, 16 families, and 9 orders, were subjected to polymerase chain reaction amplification in the barcode region and sequenced. The length of the 666 barcodes was 682 bp. The average K2P distances within species, genera, and families were 0.22%, 6.33%, and 16.46%, respectively. The average interspecific distance was approximately 28.8 times higher than the mean intraspecific distance. The Barcode Index Number (BIN) discordance report showed that 666 specimens represented 55 BINs, of which five were singletons, 45 were taxonomically concordant, and five were taxonomically discordant. The barcode gap analysis demonstrated that 89.3% of the fish species examined could be discriminated by DNA barcoding. These results provide new insights into fish diversity in the inland waters of Uzbekistan and can provide a basis for the development of further studies on fish fauna.
Permeability profiling of all 13 Arabidopsis PIP aquaporins using a high throughput yeast approach
Authors: Groszmann Michael , De Rosa Annamaria , Chen Weihua , Qiu Jiaen , McGaughey Samantha A , Byrt Caitlin S. , Evans John R 
Published: May 2021

AbstractPlant aquaporins have many more functions than just transporting water. Within the diversity of plant aquaporins are isoforms capable of transporting signaling molecules, nutrients, metalloids and gases. It is established that aquaporin substrate discrimination depends on combinations of factors such as solute size, pore size and polarity, and post-translational protein modifications. But our understanding of the relationships between variation in aquaporin structures and the implications for permeability is limited. High-throughput yeast-based assays were developed to assess diverse substrate permeabilities to water, H2O2, boric acid, urea and Na+. All 13 plasma membrane intrinsic proteins (PIPs) from Arabidopsis (AtPIPs) were permeable to both water and H2O2, although their effectiveness varied, and none were permeable to urea. AtPIP2 isoforms were more permeable to water than AtPIP1s, while AtPIP1s were more efficient at transporting H2O2with AtPIP1;3 and AtPIP1;4 being the most permeable. Among the AtPIP2s, AtPIP2;2 and AtPIP2;7 were also permeable to boric acid and Na+. Linking AtPIP substrate profiles with phylogenetics and gene expression data enabled us to align substrate preferences with known biological roles of AtPIPs and importantly guide towards unidentified roles hidden by functional redundancy at key developmental stages and within tissue types. This analysis positions us to more strategically testin plantaphysiological roles of AtPIPs in order to unravel their complex contributions to the transport of important substrates, and secondly, to resolve links between aquaporin protein structure, substrate discrimination, and transport efficiency.One sentence summaryYeast based high throughput assays were developed to assess the permeability of each Arabidopsis PIP aquaporin isoform to water, H2O2, boric acid, urea and sodium.
Multi-color 4D superresolution light-sheet microscopy reveals organelle interactions at isotropic 100-nm resolution and sub-second timescales
Authors: Zhao Yuxuan , Zhang Meng , Zhang Wenting , Liu Qing , Wang Peng , Chen Rong , Fei Peng , Zhang Yu-Hui 
Published: May 2021

AbstractLong-term visualization of the dynamic organelle-organelle or protein-organelle interactions throughout the three-dimensional space of whole live cells is essential to better understand their functions, but this task remains challenging due to the limitations of existing three-dimensional fluorescence microscopy techniques, such as an insufficient axial resolution, low volumetric imaging rate, and photobleaching. Here, we present the combination of a progressive deep-learning superresolution strategy with a dual-ring-modulated SPIM design capable of visualizing the dynamics of intracellular organelles in live cells for hours at an isotropic spatial resolution of ∼100 nm in three dimensions and a temporal resolution up to ∼17 Hz. With a compelling spatiotemporal resolution, we substantially reveal the complex spatial relationships and interactions between the endoplasmic reticulum (ER) and mitochondria throughout live cells, providing new insights into ER-mediated mitochondrial division. We also localized the motion of Drp1 oligomers in three dimensions and observed Drp1-mediated mitochondrial branching for the first time.
Ariadne: Synthetic Long Read Deconvolution Using Assembly Graphs
Authors: Mak Lauren , Meleshko Dmitry , Danko David C. , Barakzai Waris N. , Maharjan Salil , Belchikov Natan , Hajirasouliha Iman 
Published: May 2021

AbstractSynthetic Long Read (SLR) sequencing techniques such as UST’s TELL-Seq, and Loop Genomics’ LoopSeq combine 3′barcoding with standard short-read sequencing to expand the range of linkage resolution from hundreds to tens of thousands of base-pairs. However, the lack of a 1:1 correspondence between a long fragment and a 3′unique molecular identifier (UMI) confounds the assignment of linkage between short-reads. We introduce Ariadne, a novel assembly graph-based SLR deconvolution algorithm, that can be used to extract single-species read-clouds from SLR datasets to improve the taxonomic classification andde novoassembly of complex populations, such as metagenomes.
Efficient CRISPR/Cas-mediated Targeted Mutagenesis in Spring and Winter Wheat Varieties
Authors: Hahn Florian , Loures Laura Sanjurjo , Sparks Caroline A. , Kanyuka Kostya , Nekrasov Vladimir 
Published: May 2021

AbstractThe CRISPR/Cas technology has recently become a molecular tool of choice for gene function studies in plants as well as crop improvement. Wheat is a globally important staple crop with a well annotated genome and there is plenty of scope for improving its agriculturally important traits using genome editing technologies, such as CRISPR/Cas. As part of this study we targeted three different genes in hexaploid wheat Triticum aestivum: TaBAK1-2 in the spring cultivar Cadenza as well as Ta-eIF4E and Ta-eIF(iso)4E in winter cultivars Cezanne, Goncourt and Prevert. The primary transgenic lines carrying CRISPR/Cas-induced indels were successfully generated for all targeted genes. As winter wheat varieties are generally less amenable to genetic transformation, the successful experimental methodology for transformation and genome editing in winter wheat presented in this study will be of interest to the research community working with this crop.
Can the lack of fibrillar form of alpha-synuclein in Lewy bodies be explained by its catalytic activity?
Authors: Kuznetsov Ivan A. , Kuznetsov Andrey V. 
Published: May 2021

AbstractFinding the causative pathophysiological mechanisms for Parkinson’s disease (PD) is important for developing therapeutic interventions. Until recently, it was believed that Lewy bodies (LBs), the hallmark of PD, are mostly composed of alpha-synuclein (α-syn) fibrils. Recent results (Shahmoradian et al., Lewy pathology in Parkinson’s disease consists of crowded organelles and lipid membranes, Nature Neuroscience 22 (2019) 1099-1109) demonstrated that the fibrillar form of α-syn is lacking from LBs. Here we propose that this surprising observation can be explained by the catalytic activity of the fibrillar form of α-syn. We assumed that α-syn fibrils catalyze the formation of LBs, but do not become part of them. We developed a mathematical model based on this hypothesis. By using the developed model, we investigated the consequences of this hypothesis. In particular, the model suggests that the long incubation time of PD can be explained by a two-step aggregation process that leads to its development: (i) aggregation of monomeric α-syn into α-syn oligomers and fibrils and (ii) clustering of membranebound organelles, which may cause disruption of axonal trafficking and lead to neuron starvation and death. The model shows that decreasing the rate of destruction of α-syn aggregates in somatic lysosomes accelerates the formation of LBs. Another consequence of the model is the prediction that removing α-syn aggregates from the brain after the aggregation of membrane-bound organelles into LBs has started may not stop the progression of PD because LB formation is an autocatalytic process; hence, the formation of LBs will be catalyzed by aggregates of membrane-bound organelles even in the absence of α-syn aggregates. The performed sensitivity study made it possible to establish the hierarchy of model parameters with respect to their effect on the formation of vesicle aggregates in the soma.
Rapid generation of conditional knockout mice using the CRISPR-CAS9 system and electroporation for neuroscience research
Authors: Nishizono Hirofumi , Hayano Yuki , Nakahata Yoshihisa , Ishigaki Yasuhito , Yasuda Ryohei 
Published: May 2021

AbstractThe Cre/Loxp-based conditional knockout technology is a powerful tool for gene function analyses by allowing region-time-specific gene manipulation. However, inserting a pair of LoxP cassettes for generating conditional knock-out can be technically challenging and thus time- and resource-consuming. This study proposes an efficient, low-cost method to generate floxed mice using the in vitro fertilization and the CRISPR-Cas9 system over two consecutive generations. This method allowed us to produce floxed mice targeting exon 5 to exon 6 of CaMK1 in a short period, 125 days, using only 16 mice. The efficiency of generating floxed mice was 10%, significantly higher than the conventional ES cell-based method. We directly edited the genome of C57BL/6N fertilized eggs, our target genetic background, to eliminate additional backcrossing steps. We confirmed that the genome of this floxed mouse is responsive to Cre protein. This low-cost, highly efficient method for generating conditional knock-out will facilitate comprehensive, tissue-specific genome analyses.
Distinct states of proinsulin misfolding in MIDY
Authors: Haataja Leena , Arunagiri Anoop , Hassan Anis , Regan Kaitlin , Tsai Billy , Dhayalan Balamurugan , Weiss Michael A. , Liu Ming , Arvan Peter 
Published: May 2021

AbstractA precondition for efficient proinsulin export from the endoplasmic reticulum (ER) is that proinsulin meets ER quality control folding requirements, including formation of the Cys(B19)-Cys(A20) “interchain” disulfide bond, facilitating formation of the Cys(B7)-Cys(A7) bridge. The third proinsulin disulfide, Cys(A6)-Cys(A11), is not required for anterograde trafficking, i.e., a “lose-A6/A11” mutant [Cys(A6), Cys(A11) both converted to Ser] is well secreted. Nevertheless, an unpaired Cys(A11) can participate in disulfide mispairings, causing ER retention of proinsulin. Among the many missense mutations causing the syndrome of MutantINSgene-induced Diabetes of Youth (MIDY), all seem to exhibit perturbed proinsulin disulfide bond formation. Here we have examined a series of seven MIDY mutants [including G(B8)V, Y(B26)C, L(A16)P, H(B5)D, V(B18)A, R(Cpep+2)C, E(A4)K], six of which are essentially completely blocked in export from the ER in pancreatic β-cells. Three of these mutants, however, must disrupt the Cys(A6)-Cys(A11) pairing to expose a critical unpaired cysteine thiol perturbation of proinsulin folding and ER export, because when introduced into the proinsulin lose-A6/A11 background, these mutants exhibit native-like disulfide bonding and improved trafficking. This maneuver also ameliorates dominant-negative blockade of export of co-expressed wild-type proinsulin. A growing molecular understanding of proinsulin misfolding may permit allele-specific pharmacological targeting for some MIDY mutants.
Inhibition of granuloma triglyceride synthesis imparts control ofMycobacterium tuberculosisthrough curtailed inflammatory responses
Authors: Dawa Stanzin , Menon Dilip , Arumugam Prabhakar , Bhaskar Akash Kumar , Mondal Moumita , Rao Vivek , Gandotra Sheetal 
Published: May 2021

AbstractLipid metabolism plays a complex and dynamic role in host-pathogen interaction duringMycobacterium tuberculosisinfection. While bacterial lipid metabolism is key to the success of the pathogen, the host also offers a lipid rich environment in the form of necrotic caseous granulomas, making this association beneficial for the pathogen. Accumulation of the neutral lipid triglyceride, as lipid droplets at the cellular cuff of necrotic granulomas, is a peculiar feature of pulmonary tuberculosis. The role of triglyceride synthesis in the TB granuloma and its impact on the disease outcome has not been studied in detail. Here, we identified diacylglycerol O-acyltransferase 1 (DGAT1) to be essential for accumulation of triglyceride in necrotic TB granulomas using the C3HeB/FeJ murine model of infection. Treatment of infected mice with a pharmacological inhibitor of DGAT1 (T863) led to reduction in granuloma triglyceride levels and bacterial burden. A decrease in bacterial burden was associated with reduced neutrophil infiltration and degranulation, and a reduction in several pro-inflammatory cytokines including IL1β, TNFα, IL6, and IFNβ. Triglyceride lowering impacted eicosanoid production through both metabolic re-routing and via transcriptional control. Our data suggests that manipulation of lipid droplet homeostasis may offer a means for host directed therapy in Tuberculosis.