bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional traits predict species responses to environmental variation in a California grassland annual plant community
Authors: Kandlikar Gaurav S. , Kleinhesselink Andew R. , Kraft Nathan J.B. 
Published: November 2020

AbstractTurnover in species composition and community-wide functional traits across environmental gradients is a ubiquitous pattern in ecology, and is generally assumed to reflect shifts in trait optima across these gradients. However, the demographic processes that give rise to these trait turnover patterns at the community level remain unclear.We asked whether shifts in the community-weighted means of three key functional traits across an environmental gradient in a southern California grassland reflect variation in the trait-performance relationship across the landscape.We planted seeds of 17 annual plant species in cleared patches with no competitors, and quantified the lifetime seed production of 1360 individuals. We then asked whether models that included trait-environment interactions help explain interspecific variation in demographic responses to the environment. This allowed us to evaluate whether observed shifts in community-weighted mean traits matched the direction of any trait-environment interactions detected in the plant performance experiment.Our results indicate that commonly-measured plant functional traits help explain variation in species responses to the environment – for example, high-SLA species had a demographic advantage in soils with high soil Ca:Mg levels, while low-SLA species had an advantage in low Ca:Mg soils. We also found that shifts in community-weighted mean traits often reflect the direction of these trait-environment interactions, though not all trait-environment relationships at the community level reflect interactive effects of traits and environment on species performance.Our results support the value of plant functional traits for predicting species responses to environmental variation, and highlight a need for more detailed evaluation of how trait-performance relationships change across environments to improve such predictions.
First record of the Australian redclaw crayfishCherax quadricarinatus(von Martens 1868) in Hong Kong, China
Authors: Sze-man YAU , Anthony LAU 
Published: November 2020

AbstractInvasive freshwater crayfish are spreading rapidly across the world. Here, we report the first record of Australian redclaw crayfish,Cherax quadricarinatus(von Martens 1868) in Hong Kong, China. Identification of the captured crayfish was confirmed using external morphological features and molecular analyses. A total of 49 crayfish were captured from a stream pool and a reservoir in Pok Fu Lam Country Park using dip nets and funnel traps. The capturedC. quadricarinatusranged from 17.20 mm to 56.40 mm (mean = 30.70) in carapace length and the sex ratio was 1:1. Since this species is globally recognized as an invasive species, a comprehensive survey on its status and invasion front, an investigation into its potential ecological impacts, as well as the formulation of a monitoring and removal strategy, are warranted.
Circulating tumor fraction analyses with ultra-low pass whole genome sequencing predict response to chemoradiation and recurrence in stage IV small cell carcinoma of the cervix: a longitudinal case study
Authors: Abbas Ata , Gruner Morgan , Karohl Jennifer , Rose Peter G. , Joehlin-Price Amy , Al-Sudani Hussein , Stover Daniel , Mahdi Haider 
Published: November 2020

ABSTRACTNeuroendocrine carcinoma of the cervix is a rare and aggressive form of cervical cancer that presents with frequent metastasis at diagnosis and high recurrence rates. Primary treatment is multimodal, which often includes chemotherapy with or without radiation therapy. There is no data available to guide treatment for recurrence, and second-line therapies are extrapolated from small cell lung carcinoma data. Close monitoring of these patients for recurrence is paramount. Evaluation of circulating tumor DNA (ctDNA) in the peripheral blood is an attractive approach due to its noninvasive nature. Ultra-low pass whole genome sequencing (ULP-WGS) can assess tumor burden, response to therapy, and predict recurrence; however, data are lacking regarding the role of ULP-WGS in small cell carcinoma of the cervix. This study demonstrates a patient whose response to chemotherapy and cancer recurrence was accurately monitored by ctDNA using ULP-WGS testing and confirmed with radiologic imaging findings.
Genome-wide association study of febrile seizures identifies seven new loci implicating fever response and neuronal excitability genes
Authors: Skotte Line , Fadista João , Bybjerg-Grauholm Jonas , Appadurai Vivek , Hildebrand Michael S , Hansen Thomas F , Banasik Karina , Grove Jakob , Climent Clara A , Geller Frank , Bjurström Carmen F , Vilhjálmsson Bjarni J , Coleman Matthew , Damiano John A , Burgess Rosemary , Scheffer Ingrid E , Vesterager Pedersen Ole Birger , Erikstrup Christian , Westergaard David , René Nielsen Kaspar , Sørensen Erik , Bruun Mie Topholm , Liu Xueping , Hjalgrim Henrik , Pers Tune H , Mortensen Preben Bo , Mors Ole , Nordentoft Merete , Dreier Julie W , Børglum Anders , Christensen Jakob , Hougaard David M , Buil Alfonso , Hviid Anders , Melbye Mads , Ullum Henrik , Berkovic Samuel F , Werge Thomas , Feenstra Bjarke 
Published: November 2020

ABSTRACTFebrile seizures represent the most common type of pathological brain activity in young children and are influenced by genetic, environmental, and developmental factors. While usually benign, in a minority of cases, febrile seizures precede later development of epilepsy. Here, we conducted a genome-wide association study of febrile seizures with 7,635 cases and 93,966 controls identifying and replicating seven new loci, all with P < 5 × 10−10. Variants at two loci were functionally related to altered expression of the fever response genes PTGER3 and IL10, and four other loci harbored genes (BSN, ERC2, GABRG2, HERC1) influencing neuronal excitability by regulating neurotransmitter release and binding, vesicular transport or membrane trafficking at the synapse. GABRG2 is a well-established epilepsy gene comprising variants associated with febrile seizures, and overall we found positive genetic correlations with epilepsies (rg = 0.39, P = 1.68 × 10−4). Finally, a polygenic risk score based on all genome-wide significant loci was associated within patients with number of hospital admissions with febrile seizures and age at first admission, suggesting potential clinical utility of improved genetic understanding of febrile seizure genesis.
REACT-1 round 6 updated report: high prevalence of SARS-CoV-2 swab positivity with reduced rate of growth in England at the start of November 2020
Authors: Riley Steven , Ainslie Kylie E. C. , Eales Oliver , Walters Caroline E. , Wang Haowei , Atchison Christina , Fronterre Claudio , Diggle Peter J. , Ashby Deborah , Donnelly Christl A. , Cooke Graham , Barclay Wendy , Ward Helen , Darzi Ara , Elliott Paul 
Published: November 2020

AbstractBackgroundEngland is now in the midst of its second wave of the COVID-19 pandemic. Multiple regions of the country are at high infection prevalence and all areas experienced rapid recent growth of the epidemic during October 2020.MethodsREACT-1 is a series of community surveys of SARS-CoV-2 RT-PCR swab-positivity in England designed to monitor the spread of the epidemic and thus increase situational awareness. Round 6 of REACT-1 commenced swab-collection on 16th October. A prior interim report included data from 16th to 25th October for 85,971 participants. Here, we report data for the entire round on 160,175 participants with swab results obtained up to 2nd November 2020.ResultsOverall weighted prevalence of infection in the community in England was 1.3% or 130 people per 10,000 infected, up from 60 people per 10,000 in the round 5 report (18th September to 5th October 2020), doubling every 24 days on average since the prior round. The corresponding R number was estimated to be 1.2. Prevalence of infection was highest in North West (2.4%, up from 1.2%), followed by Yorkshire and The Humber (2.3% up from 0.84%), West Midlands (1.6% up from 0.60%), North East (1.5% up from 1.1%), East Midlands (1.3% up from 0.56%), London (0.97%, up from 0.54%), South West (0.80% up from 0.33%), South East (0.69% up from 0.29%), and East of England (0.69% up from 0.30%). Rapid growth in the South observed in the first half of round 6 was no longer apparent in the second half of round 6. We also observed a decline in prevalence in Yorkshire and The Humber during this period. Comparing the first and second halves of round 6, there was a suggestion of decline in weighted prevalence in participants aged 5 to 12 years and in those aged 25 to 44 years. While prevalence remained high, in the second half of round 6 there was suggestion of a slight fall then rise that was seen nationally and also separately in both the North and the South.ConclusionThe impact of the second national lockdown in England is not yet known. We provide here a detailed description of swab-positivity patterns at national, regional and local scales for the period immediately preceding lockdown, against which future trends in prevalence can be evaluated.
Quantifying Covid19-Vaccine Location Strategies For Germany
Authors: Leithäuser Neele , Schneider Johanna , Johann Sebastian , Krumke Sven O. , Schmidt Eva , Streicher Manuel , Scholz Stefan 
Published: November 2020

AbstractBackgroundVaccines are an important tool to limit the health and economic damage of the Covid-19 pandemic. Several vaccine candidate already provided promising effectiveness data, but it is crucial for an effective vaccination campaign that people are willing and able to get vaccinated as soon as possible. Taking Germany as an example, we provide insights of using a mathematical approach for the planning and location of vaccination sites to optimally administer vaccines against Covid-19.MethodsWe used mathematical programming for computing an optimal selection of vaccination sites out of a given set (i.e., university hospitals, health department related locations and general practices). Different patient-to-facility assignments and doctor-to-facility assignments and different constraints on the number of vaccinees per site or maximum travel time are used.ResultsIn order to minimize the barriers for people to get vaccinated, i.e., limit the one-way travel journey (airline distance) by around 35 km for 75 % of the population (with a maximum of 70 km), around 80 well-positioned facilities can be enough. If only the 38 university hospitals are being used, the 75 % distance increases to around 50 km (with a maximum of 145 km). Using all 400 health departments or all 56 000 general practices can decrease the journey length significantly, but comes at the price of more required staff and possibly wastage of only partially used vaccine containers.ConclusionsIn the case of free assignments, the number of required physicians can in most scenarios be limited to 2 000, which is also the minimum with our assumptions. However, when travel distances for the patients are to be minimized, capacities of the facilities must be respected, or administrative assignments are prespecified, an increased number of physicians is unavoidable.
Type I PRMTs and PRMT5 Independently Regulate Both snRNP Arginine Methylation and Post-Transcriptional Splicing
Authors: Maron Maxim I. , Burgos Emmanuel S. , Gupta Varun , Casill Alyssa D. , Kosmyna Brian , Chen Hongshan , Gamble Matthew J. , Query Charles C. , Shechter David 
Published: November 2020

AbstractProtein argininemethyltransferases (PRMTs) methylate histones, splicing factors, and many other nuclear proteins. Type I enzymes (PRMT1-4,6,8) catalyze mono- (Rme1/MMA) and asymmetric (Rme2a/ADMA) dimethylation; Type II enzymes (PRMT5,9) catalyze mono- and symmetric (Rme2s/SDMA) dimethylation. Misregulation of PRMTs in multiple types of cancers is associated with aberrant gene expression and RNA splicing. To understand the specific mechanisms of PRMT activity in splicing regulation, we treated cells with the PRMT5 inhibitor GSK591 and the Type I inhibitor MS023 and probed their transcriptomic consequences. We discovered that Type I PRMTs and PRMT5 inversely regulate core spliceosomal Sm protein Rme2s and intron retention. Loss of Sm Rme2s is associated with the accumulation of polyadenylated RNA containing retained introns and snRNPs on chromatin. Conversely, increased Sm Rme2s correlates with decreased intron retention and chromatin-association of intron-containing polyadenylated RNA. Using the newly developed SKaTER-seq model, comprehensive and quantitative analysis of co-transcriptional splicing revealed that either Type I PRMT or PRMT5 inhibition resulted in slower splicing rates. Surprisingly, altered co-transcriptional splicing kinetics correlated poorly with ultimate changes in alternatively spliced mRNA. Quantitation of retained intron decay following inhibition of nascent transcription revealed that Type I PRMTs and PRMT5 reciprocally regulate post-transcriptional splicing efficiency.
Reprogrammed CRISPR-Cas13b suppresses SARS-CoV-2 replication and circumvents its mutational escape through mismatch tolerance
Authors: Fareh Mohamed , Zhao Wei , Hu Wenxin , Casan Joshua ML , Kumar Amit , Symons Jori , Voskoboinik Ilia , Ekert Paul G , Rudraraju Rajeev , Lewin Sharon R , Trapani Joseph A 
Published: November 2020

ABSTRACTMutation-driven evolution of SARS coronavirus-2 (SARS-CoV-2) highlights the need for innovative approaches that simultaneously suppress viral replication and circumvent viral escape routes from host immunity and antiviral therapeutics. Here, we employed genome-wide computational prediction and singlenucleotide resolution screening to reprogram CRISPR-Cas13b against SARS-CoV-2 genomic and subgenomic RNAs. Reprogrammed Cas13b effectors targeting accessible regions of Spike and Nucleocapsid transcripts achieved >98% silencing efficiency in virus free-models. Further, optimized and multiplexed gRNAs suppressed viral replication by up to 90% in mammalian cells infected with replication-competent SARS-CoV-2. Unexpectedly, the comprehensive mutagenesis of guide-target interaction demonstrated that single-nucleotide mismatches do not impair the capacity of a potent single gRNA to simultaneously suppress ancestral and mutated SARS-CoV-2 in infected mammalian cells, including the highly infectious and globally disseminated Spike D614G mutant. The specificity, efficiency and rapid deployment properties of reprogrammed Cas13b described here provide a molecular blueprint of antiviral therapeutics to simultaneously suppress a wide range of SARS-CoV-2 mutants, and is readily adaptable to other emerging pathogenic viruses.
A precise measure of the impact of the first wave of Covid-19 on life expectancy. Regional differentials in Switzerland
Authors: Wanner Philippe 
Published: November 2020

AbstractBased on publicly available data supplied by the Swiss Federal Statistical Office (FSO), we calculated life tables by sex and by week for seven major regions of Switzerland in 2020, up to October 26th. These life tables provide information on the trends of life expectancy at birth and at the age of 65 years during the first wave of the coronavirus disease 2019 (COVID-19) epidemic.The results show a strong cyclical decrease in life expectancy, particularly in Ticino, where this variable has decreased by almost 6 years compared to the 2019 life expectancy, and in the Lake Geneva region. The other regions of Switzerland observed more modest decreases during the first wave, generally not exceeding a 2-year reduction. This decrease can be explained to some extent by seasonal variations in this indicator.In conclusion, the very sharp decrease in the average lifespan observed in the two regions mentioned above suggests that the first wave of the epidemic had a significant impact. It also reflects an unfavourable health situation. The life expectancy at the age of 65 years observed at the end of March 2020 in Ticino corresponded to the average life expectancy observed in Switzerland forty years ago.The calculated indicators have the advantage of accounting for the age structures of the respective populations. They therefore demonstrate their usefulness in monitoring during a pandemic, such as the one occurring currently.
Screening & diagnosing errors in longitudinal measures of body size
Authors: Wills AK 
Published: November 2020

AbstractThis paper presents a novel multi-step automated algorithm to screen for errors in longitudinal height and weight data and describes the frequency and characteristics of errors in three datasets. It also offers a taxonomy of published cleaning routines from a scoping review.Illustrative data are from three Norwegian retrospective cohorts containing 87,792 assessments (birth to 14y) from 8,428 children. Each has different data pipelines, quality control and data structure. The algorithm contains 43 steps split into 3 sections; (a) dates, (b) Identifiable data entry errors, (c) biologically impossible/ implausible change, and uses logic checks, and cross-sectional and longitudinal routines. The WHO cross-sectional approach was also applied as a comparison.Published cleaning routines were taxonomized by their design, the marker used to screen errors, the reference threshold and how threshold was selected. Fully automated error detection was not possible without false positives or reduced sensitivity. Error frequencies in the cohorts were 0.4%, 2.1% and 2.4% of all assessments, and the percentage of children with ≥1 error was 4.1%, 13.4% and 15.3%. In two of the datasets, >2/3s of errors could be classified as inliers (within ±3SD scores). Children with errors had a similar distribution of HT and WT to those without error. The WHO cross-sectional approach lacked sensitivity (range 0-55%), flagged many false positives (range: 7-100%) and biased estimates of overweight and thinness.Elements of this algorithm may have utility for built-in data entry rules, data harmonisation and sensitivity analyses. The reported error frequencies and structure may also help design more realistic simulation studies to test routines. Multi-step distribution-wide algorithmic approaches are recommended to systematically screen and document the wide range of ways in which errors can occur and to maximise sensitivity for detecting errors, naive cross-sectional trimming as a stand-alone method may do more harm than good.
Ultrafast Brownian-ratchet mechanism for protein translocation by a AAA+ machine
Authors: Mazal Hisham , Iljina Marija , Riven Inbal , Haran Gilad 
Published: November 2020

AbstractAAA+ ring-shaped machines, such as ClpB and Hsp104, mediate substrate translocation through their central channel by a set of pore loops. Recent structural studies suggested a universal hand-over-hand translocation mechanism, in which pore loops are moving rigidly in tandem with their corresponding subunits. However, functional and biophysical studies are in discord with this model. Here, we directly measure the real-time dynamics of the pore loops of ClpB and their response to substrate binding, using single-molecule FRET spectroscopy. All pore loops undergo large-amplitude fluctuations on the microsecond timescale, and change their conformation upon interaction with substrate proteins. Pore-loop conformational dynamics are modulated by nucleotides and strongly correlate with disaggregation activity. The differential behavior of the pore loops along the axial channel points to a fast Brownian-ratchet translocation mechanism, which likely acts in parallel to the much slower hand-over-hand process.
Generation of two Multipotent Mesenchymal Progenitor Cell Lines Capable of Osteogenic, Mature Osteocyte, Adipogenic, and Chondrogenic Differentiation
Authors: Prideaux Matthew , Wright Christian S. , Noonan Megan L. , Yi Xin , Clinkenbeard Erica L. , Mevel Elsa , Wheeler Jonathan A. , Byers Sharon , Sankar Uma , White Kenneth E. , Atkins Gerald J. , Thompson William R. 
Published: November 2020

AbstractDifferentiation of multi-potent mesenchymal progenitor cells give rise to several tissue types including bone, cartilage, and adipose. In addition to the complication arising from the numerous spatial, temporal, and hormonal factors that regulate lineage allocation, targeting of these cellsin vivois challenging, making mesenchymal progenitor cell lines valuable tools to study both tissue development and the differentiated cell types. Mesenchymal stem cells (MSCs) can be isolated from humans and animals; however, obtaining homogenous, responsive cells in a reproducible fashion can be problematic. As such, we have developed two novel mesenchymal progenitor cell (MPC) lines, MPC1 and MPC2, which were generated from the bone marrow of male C57BL/6 mice. These cells were immortalized using the temperature sensitive large T-antigen, allowing for thermal control of proliferation and differentiation. Both MPC1 and MPC2 cell lines are capable of osteogenic, adipogenic, and chondrogenic differentiation. Under osteogenic conditions both cell lines formed discrete mineralized nodules, staining for alizarin red and alkaline phosphatase, while expressing high levels of osteogenic genes includingSost,Fgf23, andDmp1.SostandDmp1mRNA levels were drastically reduced with parathyroid hormone, thus recapitulatingin vivoresponses. MPC cells secreted both the intact (iFGF23) andC-terminal (cFGF23) forms of endocrine hormone FGF23, which was upregulated in the presence of 1,25 dihydroxy vitamin D (1,25D). In addition to osteogenic differentiation, both cell lines also rapidly entered the adipogenic lineage, expressing several adipose markers after only 4 days in adipogenic media. MPC cells were also capable of chondrogenic differentiation, displaying increased expression of common cartilage genes including aggrecan, sox9, and cartilage oligomeric matrix protein. With the ability to differentiate into multiple mesenchymal lineages and mimic in vivo responses of key regulatory genes/proteins, MPC cells are a valuable model to study factors that regulate mesenchymal lineage allocation as well as the mechanisms that dictate transcription, protein modification, and secretion of these factors.
The structural mechanism underlying the antithetic effect of homologous RND1 and RhoD GTPases in plexin regulation
Authors: Liu Yanyan , Ke Pu , Kuo Yi-chun , Wang Yuxiao , Zhang Xuewu , Song Chen , Shan Yibing 
Published: November 2020

AbstractPlexins are semaphorin receptors that play essential roles in neuronal axon guidance and in many other important biological processes. Plexin signaling depends on a semaphorin-induced dimerization mechanism, and is modulated by small signaling GTPases of the Rho family, of which RND1 serves as a plexin activator yet its close homolog RhoD an inhibitor. Using molecular dynamics (MD) simulations we showed that RND1 reinforces plexin dimerization interface whereas RhoD destabilizes it due to their differential interaction with cell membrane. Upon binding plexin dimers at the Rho-GTPase binding (RBD) domains, RND1 and RhoD interact differently with the inner leaflet of cell membrane, and exert opposite effects on the dimerization interface via an allosteric network involving the RBD domain, RBD linkers, and a buttress segment adjacent to the dimerization interface. The differential membrane interaction is attributed to the fact that, unlike RND1, RhoD features a short C-terminal tail and a positively-charged membrane interface.