bluuebunny/crossref_metadata_2025_split huggingface dataset:
Portable and accurate diagnostics for COVID-19: Combined use of the miniPCR thermocycler and a well-plate reader for SARS-CoV-2 virus detection
Authors: González-González Everardo , Santiago Grissel Trujillo-de , Mayorga Itzel Montserrat Lara- , Martínez-Chapa Sergio Omar , Moisés Alvarez Mario 
Published: April 2020

AbstractThe coronavirus disease 2019 (COVID-19) pandemic has crudely demonstrated the need for massive and rapid diagnostics. By the first week of July, more than 10,000,000 positive cases of COVID-19 have been reported worldwide, although this number could be greatly underestimated. In the case of an epidemic emergency, the first line of response should be based on commercially available and validated resources. Here, we demonstrate the use of the miniPCR, a commercial compact and portable PCR device recently available on the market, in combination with a commercial well-plate reader as a diagnostic system for detecting genetic material of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19. We used the miniPCR to detect and amplify SARS-CoV-2 DNA sequences using the sets of initiators recommended by the World Health Organization (WHO) for targeting three different regions that encode for the N protein. Prior to amplification, samples were combined with a DNA intercalating reagent (i.e., EvaGreen Dye). Sample fluorescence after amplification was then read using a commercial 96-well plate reader. This straightforward method allows the detection and amplification of SARS-CoV-2 nucleic acids in the range of ∼625 to 2×105 DNA copies. The accuracy and simplicity of this diagnostics strategy may provide a cost-efficient and reliable alternative for COVID-19 pandemic testing, particularly in underdeveloped regions where RT-QPCR instrument availability may be limited. The portability, ease of use, and reproducibility of the miniPCR makes it a reliable alternative for deployment in point-of-care SARS-CoV-2 detection efforts during pandemics.
COVID-19 pandemic: Impact of lockdown, contact and non-contact transmissions on infection dynamics
Authors: Roy Shovonlal 
Published: April 2020

AbstractCOVID-19 coronavirus pandemic has virtually locked down the entire world of human population, and through its rapid and unstoppable spread COVID-19 has essentially compartmentalised the population merely into susceptible, exposed, infected and recovered classes. Adapting the classical epidemic modelling framework, two distinct routes of COVID-19 transmission are incorporated into a model: (a) direct person-to-person contact transmission, and (b) indirect airborne and fomites-driven transmission. The indirect non-contact transmission route needs to explored in models of COVID-19 spread, because evidences show that this route of transmission is entirely viable with hugely uncertain level of relative contribution. This theoretical study based on model simulations demonstrates the following: (1) Not incorporating indirect transmission route in the model leads to underestimation of the basic reproduction number, and hence will impact on the COVID-19 mitigation decisions; (2) Lockdown measures can suppress the primary infection peak, but will lead to a secondary peak whose relative strength and time of occurrence depend on the success and duration of the lockdown measures; (3) To make lockdown effective, a considerable level of reduction in both contact and non-contact transmission rates over a long period is required; (4) To bring down the infection cases below any hypothetical health-care capacity, reduction of non-contact transmission rate is key, and hence active measures should be taken to reduce non-contact transmission (e.g., extensive uses of areal and aerosol disinfectant in public spaces to improve contaminated surfaces and air); (5) Any premature withdrawal of lockdown following the sign of a brief retracement in the infection cases can backfire, and can lead to a quicker, sharper and higher secondary peak, due to reactivation of the two transmission routes. Based on these results, this study recommends that any exit policy from lockdown, should take into account the level of transmission reduction in both routes, the absolute scale of which will vary among countries depending on their health-service capacity, but should be computed using accurate time-series data on infection cases and transmission rates.
Control Strategies to Curtail Transmission of COVID-19
Authors: Shah Nita H. , Suthar Ankush H. , Jayswal Ekta N. 
Published: April 2020

AbstractRecently the World Health Organization has declared the outbreak of a severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) as a pandemic, and declared it as Public Health Emergency of International Concern. More than 683,536 positive cases and 32,139 deaths caused by novel corona virus 2019 (COVID-19) has affected 199 countries and territories. This pandemic can transform into an extremely destructive form if we still do not take it seriously. In the present study, we propose a generalized SEIR model of COVID-19 to study the behaviour of its transmission under different control strategies. In the model, all possible cases of human to human transmission are taken care and its reproduction number is formulated to analyse accurate transmission dynamics of the coronavirus outbreak. Optimal control theory is applied in the model to pretend the impact of various intervention strategies, including voluntary quarantine, isolation of infected individuals, improving an individual’s immunity and hospitalisation. Also, effect of the control strategies on model is analysed graphically by simulating the model numerically.
Plasma Metabolomic and Lipidomic Alterations Associated with COVID-19
Authors: Wu Di , Shu Ting , Yang Xiaobo , Song Jian-Xin , Zhang Mingliang , Yao Chengye , Liu Wen , Huang Muhan , Yu Yuan , Yang Qingyu , Zhu Tingju , Xu Jiqian , Mu Jingfang , Wang Yaxin , Wang Hong , Tang Tang , Ren Yujie , Wu Yongran , Lin Shu-Hai , Qiu Yang , Zhang Ding-Yu , Shang You , Zhou Xi 
Published: April 2020

AbstractThe pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. The symptoms of COVID-19 range from mild to severe conditions. However, the physiological changes associated with COVID-19 are barely understood. In this study, we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of COVID-19 patients who had experienced different symptoms. We found the metabolite and lipid alterations exhibit apparent correlation with the course of disease in these COVID-19 patients, indicating that the development of COVID-19 affected whole-body metabolism of the patients. In particular, malic acid of the TCA cycle and carbamoyl phosphate of urea cycle reveal the altered energy metabolism and hepatic dysfunction, respectively. It should be noted that carbamoyl phosphate is profoundly down-regulated in fatal patients compared with mild patients. And more importantly, guanosine monophosphate (GMP), which is mediated by not only GMP synthase but also CD39 and CD73, is significant changed between healthy subjects and COVID-19 patients, as well as between the mild and fatal groups. In addition, the dyslipidaemia was observed in COVID-19 patients. Overall, the disturbed metabolic patterns have been found to align with the progress and severity of COVID-19. This work provides valuable knowledge about plasma biomarkers associated with COVID-19 and potential therapeutic targets, as well as important resource for further studies of COVID-19 pathogenesis.
A hybrid multi-scale model of COVID-19 transmission dynamics to assess the potential of non-pharmaceutical interventions
Authors: Bouchnita Anass , Jebrane Aissam 
Published: April 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that emerged in Wuhan, China in December 2019. It has caused a global outbreak which represents a major threat to global health. Public health resorted to non-pharmaceutical interventions such as social distancing and lockdown to slow down the spread of the pandemic. However, the effect of each of these measures remains hard to quantify. We design a multi-scale model that simulates the transmission dynamics of COVID-19. We describe the motion of individual agents using a social force model. Each agent can be either susceptible, infected, quarantined, immunized or deceased. The model considers both mechanisms of direct and indirect transmission. We parameterize the model to reproduce the early dynamics of disease spread in Italy. We show that panic situations increase the risk of infection transmission in crowds despite social distancing measures. Next, we reveal that pre-symptomatic transmission accelerates the onset of the exponential growth of cases. After that, we demonstrate that the persistence of SARS-CoV-2 on hard surfaces determines the number of cases reached during the peak of the epidemic. Then, we show that the restricted movement of the individuals flattens the epidemic curve. Finally, model predictions suggest that measures stricter than social distancing and lockdown were used to control the epidemic in Wuhan, China.
Primate phageomes are structured by superhost phylogeny and environment
Authors: Gogarten Jan F. , Rühlemann Malte , Archie Elizabeth , Tung Jenny , Akoua-Koffi Chantal , Bang Corinna , Deschner Tobias , Muyembe-Tamfun Jean-Jacques , Robbins Martha M. , Schubert Grit , Surbeck Martin , Wittig Roman M. , Zuberbühler Klaus , Baines John F. , Franke Andre , Leendertz Fabian H. , Calvignac-Spencer Sébastien 
Published: April 2020

AbstractThe evolutionary origins of human-associated bacteriophage communities are poorly understood. To address this question, we examined fecal phageomes of 23 wild non-human primate taxa, including multiple representatives of all the major primate radiations, and find relatives of the majority of human-associated phages. Primate taxa have distinct phageome compositions that exhibit a clear phylosymbiotic signal, and phage-superhost co-divergence is detected for 44 individual phages. Within species, neighboring social groups harbor evolutionarily and compositionally distinct phageomes, structured by superhost social behavior. However, captive non-human primate phageomes are more similar to humans than their wild counterparts, revealing replacement of wild-associated phages with human-associated ones. Together, our results suggest that potentially labile primate-phage associations persisted across millions of years of evolution, potentially facilitated by transmission between groupmates.One Sentence SummaryRelatives of human-associated phages in wild primates reveal ancient but dynamic superhost-phage associations shaped by social transmission.
Single cell plasticity and population coding stability in auditory thalamus upon associative learning
Authors: Taylor James Alexander , Hasegawa Masashi , Benoit Chloé Maëlle , Freire Joana Amorim , Theodore Marine , Ganea Dan Alin , Lu Tingjia , Gründemann Jan 
Published: April 2020

AbstractCortical and limbic brain areas are regarded as centres for learning. However, how thalamic sensory relays participate in plasticity upon associative learning, yet support stable long-term sensory coding remains unknown. Using a miniature microscope imaging approach, we monitor the activity of populations of auditory thalamus (MGB) neurons in freely moving mice upon fear conditioning. We find that single cells exhibit mixed selectivity and heterogeneous plasticity patterns to auditory and aversive stimuli upon learning, which is conserved in amygdala-projecting MGB neurons. In contrast to individual cells, population level encoding of auditory stimuli remained stable across days. Our data identifies MGB as a site for complex neuronal plasticity in fear learning upstream of the amygdala that is in an ideal position to drive plasticity in cortical and limbic brain areas. These findings suggest that MGB’s role goes beyond a sole relay function by balancing experience-dependent, diverse single cell plasticity with consistent ensemble level representations of the sensory environment to support stable auditory perception with minimal affective bias.
MiR-203 inhibits the proliferation, invasion, and migration of pancreatic cancer cells by down-regulating fibroblast growth factor 2
Authors: Fu Xi-Feng , Zhao Hai-Chao , Chen Chang-Zhou , Wang Kang , Gao Fei , Tian Yang-Zhang , Li Hui-Yu , Zhao Hao-Liang 
Published: April 2020

AbstractBackgroundAberrant fibroblast growth factor 2 (FGF2) expression is a major cause of poor prognosis in pancreatic cancer. MiR-203 is a newly discovered microRNA (miRNA) that can affect the biological behavior of tumors. This study investigated whether miR-203 can regulate FGF2 expression and its role in pancreatic cancer cell proliferation, apoptosis, invasion, and migration.MethodsMiR-203 expression in different cell lines was examined by qRT-PCR, followed by the establishment of knockdown and overexpression cell models. We used the CCK-8 assay to examine cell proliferation and the annexin V-APC/7-AAD double-staining method to detect apoptosis. In addition, we used wound healing and transwell assays to investigate the effects of miR-203 on the migration and invasion of pancreatic cancer cells. The effects of miR-203 knockdown and overexpression on FGF2 mRNA expression were detected by qRT-PCR. We also overexpressed FGF2 and examined the effects of FGF2 overexpression on the proliferation, apoptosis, invasion, and migration of pancreatic cancer cells. The binding of miR-203 to FGF2 was assessed by a luciferase reporter assay.ResultsWe found that the miR-203 expression level was significantly down-regulated in pancreatic cancer cells compared to normal pancreatic cells. Functionally, the knockdown of miR-203 inhibited cell proliferation and increased apoptosis. Equally important, miR-203 reduced the migration and invasion of pancreatic cancer cells. In addition, we found that miR-203 overexpression inhibited FGF2 expression in pancreatic cancer cells by qRT-PCR. FGF2 overexpression significantly affected the proliferation, invasion, and metastasis of pancreatic cancer cells. Mechanistically, miR-203 base-paired with the FGF2 mRNA, resulting in the knockdown of the FGF2 mRNA and the down-regulation of the FGF2 protein.ConclusionsMiR-203 inhibits FGF2 expression, regulates the proliferation of pancreatic cancer cells, and inhibits the invasion and metastasis of pancreatic cancer cells.
Knowledge Beacons: Web Service Workflow for FAIR Data Harvesting of Distributed Biomedical Knowledge
Authors: Hannestad Lance M. , Dančík Vlado , Godden Meera , Suen Imelda W. , Huellas-Bruskiewicz Kenneth C. , Good Benjamin M. , Mungall Christopher J. , Bruskiewich Richard M. 
Published: April 2020

AbstractThe continually expanding distributed global compendium of biomedical knowledge is diffuse, heterogeneous and huge, posing a serious challenge for biomedical researchers in knowledge harvesting: accessing, compiling, integrating and interpreting data, information and knowledge. In order to accelerate research towards effective medical treatments and optimizing health, it is critical that efficient and automated tools for identifying key research concepts and their experimentally discovered interrelationships are developed.As an activity within the feasibility phase of a project called “Translator”(https://ncats.nih.gov/translator) funded by the National Center for Advancing Translational Sciences (NCATS) to develop a biomedical science knowledge management platform, we designed a Representational State Transfer (REST) web services Application Programming Interface (API) specification, which we call a Knowledge Beacon. Knowledge Beacons provide a standardized basic workflow for the discovery of concepts, their relationships and associated supporting evidence from distributed online repositories of biomedical knowledge. This specification also enforces the annotation of knowledge concepts and statements to the NCATS endorsed the Biolink Model data model and semantic encoding standards (https://biolink.github.io/biolink-model/). Implementation of this API on top of diverse knowledge sources potentially enables their uniform integration behind client software which will facilitate research access and integration of biomedical knowledge.AvailabilityThe API and associated software is open source and currently available for access athttps://github.com/NCATS-Tangerine/translator-knowledge-beacon.
A rare variant in ANP32B impairs influenza virus replication in human cells
Authors: Staller Ecco , Baillon Laury , Frise Rebecca , Peacock Thomas P. , Sheppard Carol M. , Sancho-Shimizu Vanessa , Barclay Wendy 
Published: April 2020

ABSTRACTViruses require host factors to support their replication, and genetic variation in such factors can affect susceptibility to infectious disease. Influenza virus replication in human cells relies on ANP32 proteins, which are involved in assembly of replication-competent dimeric influenza virus polymerase (FluPol) complexes. Here, we investigate naturally occurring single nucleotide variants (SNV) in the humanAnp32AandAnp32Bgenes. We note that variant rs182096718 inAnp32Bis found at a higher frequency than other variants in either gene. This SNV results in a D130A substitution in ANP32B, which is less able to support FluPol activity than wildtype ANP32B and binds FluPol with lower affinity. Interestingly, ANP32B-D130A exerts a dominant negative effect over wildtype ANP32B and interferes with the functionally redundant paralogue ANP32A. FluPol activity and virus replication are attenuated in CRISPR-edited cells expressing wildtype ANP32A and mutant ANP32B-D130A. We propose a model in which the D130A mutation impairs FluPol dimer formation, thus resulting in compromised replication. We suggest that both homozygous and heterozygous carriers of rs182096718 may have some genetic protection against influenza viruses.
Translational adaptation of human viruses to the tissues they infect
Authors: Hernandez-Alias Xavier , Schaefer Martin H. , Serrano Luis 
Published: April 2020

ABSTRACTViruses need to hijack the translational machinery of the host cell for a productive infection to happen. However, given the dynamic landscape of tRNA pools among tissues, it is unclear whether different viruses infecting different tissues have adapted their codon usage toward their tropism. Here, we collect the coding sequences of over 500 human-infecting viruses and determine that tropism explains changes in codon usage. Using anin silicomodel of translational efficiency, we validate the correspondence of the viral codon usage with the translational machinery of their tropism. In particular, we propose that the improved translational adaptation to the upper respiratory airways of the pandemic agent SARS-CoV-2 coronavirus could enhance its transmissibility. Furthermore, this correspondence is specifically defined in early viral proteins, as upon infection cells undergo reprogramming of tRNA pools that favors the translation of late counterparts.
Characterization of essential eggshell proteins from Aedes aegypti mosquitoes
Authors: Simington Carter J. , Oscherwitz Max E. , Peterson Alyssa J. , Rascón Alberto A. , Massani Brooke B. , Miesfeld Roger L. , Isoe Jun 
Published: April 2020

AbstractUp to 40% of the world population now live in areas where dengue mosquito vectors coexist with humans. Aedes aegypti are vectors for zoonotic diseases that affect hundreds of millions of individuals per year globally. We recently identified the eggshell organizing factor 1 (EOF1) protein using systematic RNA interference (RNAi) screening of mosquito lineage-specific genes. It was shown that eggs deposited by RNAi-EOF1 A. aegypti and A. albopictus mosquitoes were non-melanized, fragile, and contained nonviable embryos. Motivated by this discovery, we performed RNAi screening of eggshell proteins to determine putative downstream target proteins of intracellular EOF1. We identified several eggshell proteins as essential for eggshell formation in A. aegypti and characterized their phenotypes in detail by molecular and biochemical approaches. We found that Nasrat, Closca, and Polehole structural proteins, together with the Nudel serine protease, are indispensable for eggshell melanization and egg viability. While all four proteins are predominantly expressed in ovaries of adult females, Nudel mRNA expression is highly upregulated in response to blood feeding. Furthermore, we identified four secreted eggshell enzymes as important factors for controlling the processes of mosquito eggshell formation and melanization. These enzymes included three dopachrome converting enzymes and one cysteine protease. All eight characterized eggshell proteins were required for intact eggshell formation. However, their surface topologies in response to RNAi did not phenocopy the effect of RNAi-EOF1. Still, it remains unclear how EOF1 influences eggshell formation and melanization. The use of proteomic analysis of eggshell proteins from RNAi-EOF1 assisted in the identification of additional proteins that could be regulated in EOF1 deficient eggshells.
Store Independent Ca2+Entry Regulates the DNA Damage Response in Breast Cancer Cells
Authors: Makena Monish Ram , Ko Myungjun , Mekile Allatah X. , Dang Donna K. , Warrington John , Buckhaults Phillip , Talbot C. Conover , Rao Rajini 
Published: April 2020

SUMMARYAlthough the mainstay of treatment for hormone responsive breast tumors is targeted endocrine therapy, many patients develop de novo or acquired resistance and are treated with chemotherapeutic drugs. The vast majority (80%) of estrogen receptor positive tumors also express wild type p53 protein that is a major determinant of the DNA damage response. Tumors that are ER+ and p53WTrespond poorly to chemotherapy, although the underlying mechanisms are not completely understood. We describe a novel link between store independent Ca2+entry (SICE) and resistance to DNA damaging drugs, mediated by the secretory pathway Ca2+-ATPase, SPCA2. In luminal ER+/PR+ breast cancer subtypes, SPCA2 levels are high and correlate with poor survival prognosis. Independent of ion pump activity, SPCA2 elevates baseline Ca2+levels through SICE and drives cell proliferation. Attenuation of SPCA2 or depletion of extracellular Ca2+increased mitochondrial ROS production, DNA damage and activation of the ATM/ATR-p53 axis leading to G0/G1 phase cell cycle arrest and apoptosis. Consistent with these findings, SPCA2 knockdown confers chemosensitivity to DNA damaging agents including doxorubicin, cisplatin and ionizing radiation. We conclude that elevated SPCA2 expression in ER+ p53WTbreast tumors drives pro-survival and chemotherapy resistance by suppressing the DNA damage response. Drugs that target storeindependent Ca2+entry pathways may have therapeutic potential in treating receptor positive breast cancer.