bluuebunny/crossref_metadata_2025_split huggingface dataset:
Draft Genome of the Sea Cucumber Holothuria glaberrima, a model for the study of regeneration
Authors: Medina-Feliciano Joshua G. , Pirro Stacy , García-Arrarás Jose E. , Mashanov Vladimir , Ryan Joseph F. 
Published: May 2020

AbstractRegeneration is one of the most fascinating and yet least understood processes of animals. Echinoderms, one of the closest related invertebrate groups to humans, can contribute to our understanding of the genetic basis of regenerative processes. Amongst echinoderms, sea cucumbers have the ability to grow back most of their body parts following injury, including the intestine and nervous tissue. The cellular and molecular events underlying these abilities in sea cucumbers have been most extensively studied in the speciesHolothuria glaberrima. However, research into the regenerative abilities of this species have been impeded due to the lack of adequate genomic resources. Here, we report the first draft genome assembly ofH. glaberrimaand demonstrate its value for future genetic studies. Using only short sequencing reads, we assembled the genome into 2,960,762 scaffolds totaling 1.5 gigabases with an N50 of 15 kilobases. Our BUSCO assessment of the genome resulted in 882 (90.2%) complete and partial genes from 978 genes queried. We incorporated transcriptomic data from several different life history stages to annotate 41,076 genes in our final assembly. To demonstrate the usefulness of the genome, we fully annotated the melanotransferrin (Mtf)gene family, which have a potential role in regeneration of the sea cucumber intestine. Using these same data, we extracted the mitochondrial genome, which showed high conservation to that of other holothuroids. Thus, these data will be a critical resource for ongoing studies of regeneration and other studies in sea cucumbers.
Proteomic pipeline to identify age-related compositional and structural changes of the human dentin extracellular matrix
Authors: Reis Mariana , Lee Fred , Bedran-Russo Ana K. , Naba Alexandra 
Published: May 2020

AbstractObjectiveDevise a pipeline to investigate the protein composition of the human root dentin extracellular matrix (ECM) from single individuals of different age cohorts.DesignIndividual cervical root dentin of sound human molars from two age brackets, young (18-25 years old; n=3) and old (75-85 years old; n=3), were cut and pulverized. Protein extraction and fractionation were completed by sequential demineralization with EDTA buffer, chaotropic extraction with guanidine hydrochloride, and urea. The resulting protein extracts of differential solubility were digested into peptides and peptides were analyzed by mass spectrometry. Data generated for this study are available via ProteomeXchange, identifier PXD018320.ResultsWe found that protein extracts of different solubilities present distinct biochemical compositions. We further define the matrisome of young (48 proteins) and old (50 proteins) human root dentin and report the identification of compositional and structural differences in ECM proteins from young and old teeth.ConclusionOur study provides a rigorous pipeline, from sample preparation to data analysis, to investigate the ECM composition – or matrisome – of the dentin. This pipeline has the potential to lead to the discovery of biomarkers of tooth aging and health.
Atoh7-independent specification of retinal ganglion cell identity
Authors: Brodie-Kommit Justin , Clark Brian S. , Shi Qing , Shiau Fion , Kim Dong Won , Langel Jennifer , Sheely Catherine , Schmidt Tiffany , Badea Tudor , Glaser Thomas , Zhao Haiqing , Singer Joshua , Blackshaw Seth , Hattar Samer 
Published: May 2020

AbstractRetinal ganglion cells (RGCs), which relay visual information from the eye to the brain, are the first cell type generated during retinal neurogenesis. Loss of function of the transcription factorAtoh7, which is expressed in multipotent early neurogenic retinal progenitor cells, leads to a selective and near complete loss of RGCs.Atoh7has thus been considered essential for conferring competence on progenitors to generate RGCs. However, when apoptosis is inhibited inAtoh7-deficient mice by loss of function ofBax, only a modest reduction in RGC number is observed. Single-cell RNA-Seq ofAtoh7;Bax-deficient retinas shows that RGC differentiation is delayed, but that RGC precursors are grossly normal.Atoh7;Bax-deficient RGCs eventually mature, fire action potentials, and incorporate into retinal circuitry, but exhibit severe axonal guidance defects. This study reveals an essential role forAtoh7in RGC survival, and demonstratesAtoh7-independent mechanisms for RGC specification.
Novel heme-binding enables allosteric modulation in an ancient TIM-barrel glycosidase
Authors: Gamiz-Arco Gloria , Gutierrez-Rus Luis I. , Risso Valeria A. , Ibarra-Molero Beatriz , Hoshino Yosuke , Petrović Dušan , Romero-Rivera Adrian , Seelig Burckhard , Gavira Jose A. , Kamerlin Shina C.L. , Gaucher Eric A. , Sanchez-Ruiz Jose M. 
Published: May 2020

ABSTRACTGlycosidases are phylogenetically widely distributed enzymes that are crucial for the cleavage of glycosidic bonds. Here, we present the exceptional properties of a putative ancestor of bacterial and eukaryotic family-1 glycosidases. The ancestral protein shares the TIM-barrel fold with its modern descendants but displays large regions with greatly enhanced conformational flexibility. Yet, the barrel core remains comparatively rigid and the ancestral glycosidase activity is stable, with an optimum temperature within the experimental range for thermophilic family-1 glycosidases. None of the ~5500 reported crystallographic structures of ~1400 modern glycosidases show a bound porphyrin. Remarkably, the ancestral glycosidase binds heme tightly and stoichiometrically at a well-defined buried site. Heme binding rigidifies this TIM-barrel and allosterically enhances catalysis. Our work demonstrates the capability of ancestral protein reconstructions to reveal valuable but unexpected biomolecular features when sampling distant sequence space. The potential of the ancestral glycosidase as a scaffold for custom catalysis and biosensor engineering is discussed.
Making many out of few: deep generative models for single-cell RNA-sequencing data
Authors: Treppner Martin , Salas-Bastos Adrián , Hess Moritz , Lenz Stefan , Vogel Tanja , Binder Harald 
Published: May 2020

ABSTRACTDeep generative models, such as variational autoencoders (VAEs) or deep Boltzmann machines (DBM), can generate an arbitrary number of synthetic observations after being trained on an initial set of samples. This has mainly been investigated for imaging data but could also be useful for single-cell transcriptomics (scRNA-seq). A small pilot study could be used for planning a full-scale study by investigating planned analysis strategies on synthetic data with different sample sizes. It is unclear whether synthetic observations generated based on a small scRNA-seq dataset reflect the properties relevant for subsequent data analysis steps.We specifically investigated two deep generative modeling approaches, VAEs and DBMs. First, we considered single-cell variational inference (scVI) in two variants, generating samples from the posterior distribution, the standard approach, or the prior distribution. Second, we propose single-cell deep Boltzmann machines (scDBM). When considering the similarity of clustering results on synthetic data to ground-truth clustering, we find that thescVIposteriorvariant resulted in high variability, most likely due to amplifying artifacts of small data sets. All approaches showed mixed results for cell types with different abundance by overrepresenting highly abundant cell types and missing less abundant cell types. With increasing pilot dataset sizes, the proportions of the cells in each cluster became more similar to that of ground-truth data. We also showed that all approaches learn the univariate distribution of most genes, but problems occurred with bimodality. Overall, the results showed that generative deep learning approaches might be valuable for supporting the design of scRNA-seq experiments.
Optimizing high-yield production of SARS-CoV-2 soluble spike trimers for serology assays
Authors: Esposito Dominic , Mehalko Jennifer , Drew Matthew , Snead Kelly , Wall Vanessa , Taylor Troy , Frank Peter , Denson John-Paul , Hong Min , Gulten Gulcin , Sadtler Kaitlyn , Messing Simon , Gillette William 
Published: May 2020

AbstractThe SARS-CoV-2 spike trimer is the primary antigen for several serology assays critical to determining the extent of SARS-CoV-2 exposure in the population. Until stable cell lines are developed to increase the titer of this secreted protein in mammalian cell culture, the low yield of spike protein produced from transient transfection of HEK293 cells will be a limiting factor for these assays. To improve the yield of spike protein and support the high demand for antigens in serology assays, we investigated several recombinant protein expression variables by altering the incubation temperature, harvest time, chromatography strategy, and final protein manipulation. Through this investigation, we developed a simplified and robust purification strategy that consistently yields 5 mg of protein per liter of expression culture for two commonly used forms of the SARS-CoV-2 spike protein. We show that these proteins form well-behaved stable trimers and are consistently functional in serology assays across multiple protein production lots.HighlightsImproved yields of SARS-CoV-2 spike protein through modification of expression and purification parametersYields of greater than 5 mg/l obtained for VRC spike under optimal conditionsSpike protein quality was validated by QC methods to ensure utility in serology assays
Age separation dramatically reduces COVID-19 mortality rate in a computational model of a large population
Authors: Mizrahi Liron , Stern Shani 
Published: May 2020

AbstractCOVID-19 pandemic has caused a global lock down in many countries throughout the world. Faced with a new reality, and until a vaccine or efficient treatment is found, humanity must figure out ways to keep economy going on one hand, yet keep the population safe on the other hand, especially those that are susceptible to this virus. Here we use a network simulation, with parameters that were drawn from what is known about the virus, to explore 5 different scenarios of partial lock down release. We find that separating age groups by reducing interactions between age groups, protects the general population and reduces mortality rates. Furthermore, addition of new connections within the same age group to compensate for the lost connections outside the age group, still has a strong beneficial influence and reduces the total death toll by 66%. While complete isolation from society may be the most protective scenario for the elderly population, it would have an emotional and possibly cognitive impact that might outweigh its benefit. We therefore propose creating age-related social recommendations or even restrictions, thereby allowing social connections but still strong protection for the older population.
Renal function is preserved following Tenofovir Disoproxil Fumarate (TDF) initiation among Rwandan’s living with HIV
Authors: Rwibasira Gallican N. , Kim Hae-Young , Twizere Christella , Hoover Donald R , Shi Qiuhu , Adedimeji Adebola , Ross Jonathan , Murenzi Gad , Sinayobye Jean d’Amour , Anastos Kathryn 
Published: May 2020

ABSTRACTBackgroundTenofovir disoproxil fumarate (TDF) is the antiretroviral drug most commonly associated with renal dysfunction. However, few studies have examined this association in sub-Saharan Africa despite recent scale-up of antiretroviral therapy (ART) to all people living with HIV (Treat All) in this region. We assessed estimated glomerular filtration rate (eGFR) change among HIV infected Rwandan adults following first line TDF-based therapy initiation.MethodsThis prospective, observational study was conducted in 10 Rwandan health centers. Participants were ART-naive adults (≥18 years) living with HIV who initiated TDF-based ART from 1st July 2016 through 30th July 2018. The primary outcome was eGFR change from pre-(within 12 months) to post-TDF initiation (within 6 months).ResultsOf 476 patients with pre- and post-TDF eGFR measurements, 264 (55.5%) were women and mean age was 35.9 years (SD 9.6). Mean pre-TDF eGFR was 92.4 (SD 24.0) and mean post-TDF was 96.0 (SD 21.0) mL/min/1.73m2. Mean pre-to post-TDF change thus increased 3.60 (SD, 26.6) mL/min/1.73m2 (p=0.001).ConclusionWe detected a statistically significant clinically small renal function improvement within 6 months following TDF initiation among 476 ART-naïve patients. This supports continued TDF use for first-line treatment.
How did governmental interventions affect the spread of COVID-19 in European countries?
Authors: Post R.A.J. , Regis M. , Zhan Z. , van den Heuvel E.R. 
Published: May 2020

SummaryBackgroundTo reduce transmission of Coronavirus Disease 2019, European governments have implemented successive measures to encourage social distancing. However, it remained unclear how effectively measures reduced the spread of the virus, due to data complications. We examined how the effective-contact rate (ECR) among European citizens evolved over the period with implemented measures using a new data-oriented approach that is based on an extended Susceptible-Exposed-Infectious-Removed (SEIR) model.MethodsUsing the available data on the confirmed numbers of infections and hospitalizations, we first estimated the daily number of infectious-, exposed- and susceptible individuals and subsequently estimated the ECR with an iterative Poisson regression model, disregarding information on governmental measures. We then studied change points in the daily ECRs to the moments of the governmental measures.FindingsThe change points in the daily ECRs were found to align with the implementation of governmental interventions. At the end of the considered time-window, we found similar ECRs for Italy (0·29), Spain (0·24), and Germany (0·27), while the ECR in the Netherlands (0·34), Belgium (0·35) and the UK (0·37) were somewhat higher. The highest ECR was found for Sweden (0·45).InterpretationThere seemed to be an immediate effect of banning events and closing schools, typically among the first measures taken by the governments. The effect of additionally closing bars and restaurants seemed limited. For most countries a somewhat delayed effect of the full lockdown was observed, and the ECR after a full lockdown was not necessarily lower than an ECR after (only) a gathering ban.
Physical violence during pregnancy in Peru: Proportion, geographical distribution, and associated factors
Authors: Nuñez-Ochoa Mercedes Joselyn , Moquillaza-Alcantara Victor Hugo , Tinoco Clara Margarita Diaz 
Published: May 2020

ABSTRACTObjectiveEstimate the proportion, geographic distribution and sociodemographic factors associated with physical violence during pregnancy between 2016 and 2018.Material and methodsSecondary analysis of the Demographic and Family Health Survey, which included respondents whether they presented physical violence during pregnancy in the last 12 months.ResultsThe proportion of physical violence was 9,9% [95%CI:9,6–10,4%] during 2016, 9,2% [95%CI:8,8–9,6%] during 2017 and 8,6% [95%CI:8,3–8,9%] during 2018, The regions with the highest proportion were Puno, Arequipa and Apurímac during the 3 years. Among the associated factors, the residue in rural areas (RP:0,49; p=0,011) and be “very rich” (RP:0,63; p=0,029) was protective; while they were at risk of not presenting studies (RP:1,87; p=0,014), the cohabiting marital status (RP:1,51; p=0,001), separated (RP:3,56; p<0,001), showing an age between 40 a 49 years (RP:1,79; p=0,012) and that partner drinks alcohol (RP:1,61; p<0,001).ConclusionThe proportion of violence in Peru has been decreasing. The factors that predispose this phenomenon are the wealth index, educational level, marital status, and the age of the pregnant woman.
COVID-19 Lockdown in a Kenyan Informal Settlement: Impacts on Household Energy and Food Security
Authors: Shupler Matthew , Mwitari James , Gohole Arthur , Cuevas Rachel Anderson de , Puzzolo Elisa , Čukić Iva , Nix Emily , Pope Dan 
Published: May 2020

AbstractA COVID-19 lockdown may impact household fuel use and food security for ∼700 million sub-Saharan Africans who rely on polluting fuels (e.g. wood, kerosene) for household energy and typically work in the informal economy. In an informal settlement in Nairobi, surveys administered before (n=474) and after (n=194) a mandatory COVID-19-related community lockdown documented socioeconomic/household energy impacts. During lockdown, 95% of participants indicated income decline or cessation and 88% reported being food insecure. Three quarters of participants cooked less frequently and half altered their diet. One quarter (27%) of households primarily using liquefied petroleum gas (LPG) for cooking before lockdown switched to kerosene (14%) or wood (13%). These results indicate the livelihoods of urban Kenyan families were deleteriously affected by COVID-19 lockdown, with a likely rise in household air pollution from community-level increases in polluting fuel use. To safeguard public health, policies should prioritize enhancing clean fuel and food access among the urban poor.
Causal Impact of Masks, Policies, Behavior on Early Covid-19 Pandemic in the U.S
Authors: Chernozhukov Victor , Kasahara Hiroyuki , Schrimpf Paul 
Published: May 2020

AbstractThe paper evaluates the dynamic impact of various policies adopted by US states on the growth rates of confirmed Covid-19 cases and deaths as well as social distancing behavior measured by Google Mobility Reports, where we take into consideration people’s voluntarily behavioral response to new information of transmission risks in a causal structural model framework. Our analysis finds that both policies and information on transmission risks are important determinants of Covid-19 cases and deaths and shows that a change in policies explains a large fraction of observed changes in social distancing behavior. Our main counterfactual experiments suggest that nationally mandating face masks for employees early in the pandemic could have reduced the weekly growth rate of cases and deaths by more than 10 percentage points in late April and could have led to as much as 19 to 47 percent less deaths nationally by the end of May, which roughly translates into 19 to 47 thousand saved lives. We also find that, without stay-at-home orders, cases would have been larger by 6 to 63 percent and without business closures, cases would have been larger by 17 to 78 percent. We find considerable uncertainty over the effects of school closures due to lack of cross-sectional variation; we could not robustly rule out either large or small effects. Overall, substantial declines in growth rates are attributable to private behavioral response, but policies played an important role as well. We also carry out sensitivity analyses to find neighborhoods of the models under which the results hold robustly: the results on mask policies appear to be much more robust than the results on business closures and stay-at-home orders. Finally, we stress that our study is observational and therefore should be interpreted with great caution. From a completely agnostic point of view, our findings uncover predictive effects (association) of observed policies and behavioral changes on future health outcomes, controlling for informational and other confounding variables.
Non-communicable diseases and inequalities increase risk of death among COVID-19 patients in Mexico
Authors: Gutierrez Juan Pablo , Bertozzi Stefano M. 
Published: May 2020

AbstractBackgroundThe SARS-CoV-2 pandemic compounds Mexico’s pre-existing challenges: very high levels of both non-communicable diseases (NCD) and social inequity.Methods and findingsUsing data from national reporting of SARS-CoV-2 tested individuals, we estimated odds of hospitalization, intubation and death based on pre-existing non-communicable diseases and socioeconomic indicators. We found that obesity, diabetes and hypertension are positively associated with the 3 outcomes in a synergistic manner. The municipal poverty level is also positively associated with hospitalization and death.ConclusionsMexico’s response to COVID-19 is complicated by a synergistic double challenge: raging NCDs and extreme social inequity. The response to the current pandemic must take both of them into account both to be effective and to ensure that the burden of COVID-19 not fall disproportionately on those who are already disadvantaged.
Plasmin cascade mediates thrombolytic events in SARS-CoV-2 infection via complement and platelet-activating systems
Authors: Mukund Kavitha , Mathee Kalai , Subramaniam Shankar 
Published: May 2020

SUMMARYRecently emerged beta-coronavirus, SARS-CoV-2 has resulted in the current pandemic designated COVID-19. COVID-19 manifests as severe illness exhibiting systemic inflammatory response syndrome, acute respiratory distress syndrome (ARDS), thrombotic events, and shock, exacerbated further by co-morbidities and age1–3. Recent clinical reports suggested that the pulmonary failure seen in COVID-19 may not be solely driven by acute ARDS, but also microvascular thrombotic events, likely driven by complement activation4,5. However, it is not fully understood how the SARS-CoV-2 infection mechanisms mediate thrombotic events, and whether such mechanisms and responses are unique to SARS-CoV-2 infection, compared to other respiratory infections. We address these questions here, in the context of normal lung epithelia,in vitroandin vivo, using publicly available data. Our results indicate that plasmin is a crucial mediator which primes interactions between complement and platelet-activating systems in lung epithelia upon SARS-CoV-2 infection, with a potential for therapeutic intervention.
Assessment of Inactivation Procedures for SARS-CoV-2
Authors: Auerswald Heidi , Yann Sokhoun , Dul Sokha , In Saraden , Dussart Philippe , Martin Nicholas J. , Karlsson Erik A. , Garcia-Rivera Jose A. 
Published: May 2020

AbstractSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), presents a challenge to laboratorians and healthcare workers around the world. Handling of biological samples from individuals infected with the SARS-CoV-2 virus requires strict biosafety and biosecurity measures. Within the laboratory, non-propagative work with samples containing the virus requires, at minimum, Biosafety Level-2 (BSL-2) techniques and facilities. Therefore, handling of SARS-CoV-2 samples remains a major concern in areas and conditions where biosafety and biosecurity for specimen handling is difficult to maintain, such as in rural laboratories or austere field testing sites. Inactivation through physical or chemical means can reduce the risk of handling live virus and increase testing ability worldwide. Herein we assess several chemical and physical inactivation techniques employed against SARS-CoV-2 isolates from Cambodian COVID-19 patients. This data demonstrates that all chemical (AVL, inactivating sample buffer and formaldehyde) and heat treatment (56°C and 98°C) methods tested completely inactivated viral loads of up to 5 log10.