bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tooth-shape adaptations in aglyphous colubrid snakes inferred from three-dimensional geometric morphometrics and finite element analysis
Authors: Rajabizadeh Mahdi , Van Wassenbergh Sam , Mallet Christophe , Rücklin Martin , Herrel Anthony 
Published: May 2020

AbstractTo date there are few quantitative studies investigating the evolution of tooth shape and function in aglyphous snakes in relation to diet. A considerable evolutionary decrease in body size is observed in whip snakes of the genus Dolichophis and their sister-group Eirenis. This was coupled with a considerable shift in diet from a regime consisting mainly of prey with endoskeleton to prey bearing a hard exoskeleton. Three-dimensional (3D) geometric morphometrics revealed that the maxillary and palatine teeth of E. persicus are blunt and conical in shape, while the same teeth are sharp and elongated in E. punctatolineatus and D. schmidti. Blunt and conically shaped teeth, as observed in E. persicus, seem to be more adapted for biting hard-bodied, arthropod prey. In contrast, the sharp and elongated teeth in Dolichophis and E. punctatolineatus, are likely specialized for puncturing prey with an endoskeleton. The results of a finite element analysis confirms that during the biting of a hard-bodied prey, the generated stresses in E. persicus teeth are well below the von Mises yield criterion, while in D. schmidti the value is roughly two to three times higher, indicating that E. persicus teeth are better suited for biting hard-bodied prey such as arthropods.
Mutation landscape of SARS-CoV-2 reveals five mutually exclusive clusters of leading and trailing single nucleotide substitutions
Authors: Mishra Akhilesh , Pandey Ashutosh Kumar , Gupta Parul , Pradhan Prashant , Dhamija Sonam , Gomes James , Kundu Bishwajit , Vivekanandan Perumal , Menon Manoj B. 
Published: May 2020

AbstractThe COVID-19 pandemic has spread across the globe at an alarming rate. However, unlike any of the previous global outbreaks the availability of a large number of SARS-CoV-2 sequences provides us with a unique opportunity to understand viral evolution in real time. We analysed 1448 full-length (>29000 nt) sequences available and identified 40 single-nucleotide substitutions occurring in >1% of the genomes. Majority of the substitutions were C to T or G to A. We identify C/Gs with an upstream TTT trinucleotide motif as hotspots for mutations in the SARS-CoV-2 genome. Interestingly, three of the 40 substitutions occur within highly conserved secondary structures in the 5’ and 3’ regions of the genomic RNA that are critical for the virus life cycle. Furthermore, clustering analysis revealed unique geographical distribution of SARS-CoV-2 variants defined by their mutation profile. Of note, we observed several co-occurring mutations that almost never occur individually. We define five mutually exclusive lineages (A1, B1, C1, D1 and E1) of SARS-CoV-2 which account for about three quarters of the genomes analysed. We identify lineage-defining leading mutations in the SARS-CoV-2 genome which precede the occurrence of sub-lineage defining trailing mutations. The identification of mutually exclusive lineage-defining mutations with geographically restricted patterns of distribution has potential implications for diagnosis, pathogenesis and vaccine design. Our work provides novel insights on the temporal evolution of SARS-CoV-2.ImportanceThe SARS-CoV-2 / COVID-19 pandemic has spread far and wide with high infectivity. However, the severeness of the infection as well as the mortality rates differ greatly across different geographic areas. Here we report high frequency mutations in the SARS-CoV-2 genomes which show the presence of linage-defining, leading and trailing mutations. Moreover, we propose for the first time, five mutually exclusive clusters of SARS-CoV-2 which account for 75% of the genomes analysed. This will have implications in diagnosis, pathogenesis and vaccine design
Knowledge, attitude and practice of secondary school students toward COVID-19 epidemic in Italy: a cross selectional study
Authors: Souli Dafni , Dilucca Maddalena 
Published: May 2020

AbstractThe coronavirus disease (COVID-19) is a highly transmittable and pathogenic viral infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which emerges in December 2019 in Wuhan, China and spreads around the world at the beginning of 2020. The World Health Organization declares the outbreak a Public Health Emergency of International Concern on the 30th of January, and a pandemic on the 11th of March. On the 4th of March, the Italian government orders the full closure of all schools and universities nationwide.The aim of this study is to investigate the knowledge, practice and attitudes (KAP) of secondary school at the time of COVID-19 pandemic in Italy. In this cross-sectional, web-based survey, conducted among the high school student population with age ranging from 14 to 19 years old, a questionnaire with 19 items regarding the KAP toward COVID-19 is asked. Study participants are recruited from several secondary schools of different areas. Frequencies and histograms are computed for descriptive purposes. Statistical analysis is computed with Chi square test, utilized to depict relevant difference between geender. Among a total of 2380 students who answers the questionnaire, 40.7% are male and 59.3% are female.Level of knowledge about generical characteristics of COVID-19 is quite similar among gender. Students present a good level of knowledge about the clinical presentation of the disease, the basic hygiene principles, the modes of transmission and the method of protection against virus transmission. The knowledge about number of this pandemia and easy scientific correlation with COVID-19 is quite confused. The most frequently reported source of knowledge about COVID-19 is television, whereas the less is the school. Our findings suggest that student population shows appropriate practice, and positive attitude towards COVID-19 at the time of its outbreak.More emphasis should be placed on education of the student partecipants about biological meaning of this infection and relative preventive or future measures.
SARS-CoV-2 activates lung epithelia cell proinflammatory signaling and leads to immune dysregulation in COVID-19 patients by single-cell sequencing
Authors: Chen Huarong , Liu Weixin , Liu Dabin , Zhao Liuyang , Yu Jun 
Published: May 2020

AbstractObjectiveThe outbreak of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection has become a global health emergency. We aim to decipher SARS-CoV-2 infected cell types, the consequent host immune response and their interplay in the lung of COVID-19 patients.DesignWe analyzed single-cell RNA sequencing (scRNA-seq) data of lung samples from 17 subjects (6 severe COVID-19 patients, 3 mild patients who recovered and 8 healthy controls). The expression of SARS-CoV-2 receptors (ACE2 and TMPRSS2) was examined among different cell types in the lung. The immune cells infiltration patterns, their gene expression profiles, and the interplay of immune cells and SARS-CoV-2 target cells were further investigated.ResultsCompared to healthy controls, the overall ACE2 (receptor of SARS-CoV-2) expression was significantly higher in lung epithelial cells of COVID-19 patients, in particular in ciliated cell, club cell and basal cell. Comparative transcriptome analysis of these lung epithelial cells of COVID-19 patients and healthy controls identified that SARS-CoV-2 infection activated pro-inflammatory signaling including interferon pathway and cytokine signaling. Moreover, we identified dysregulation of immune response in patients with COVID-19. In severe COVID-19 patients, significantly higher neutrophil, but lower T and NK cells in lung were observed along with markedly increased cytokines (CCL2, CCL3, CCL4, CCL7, CCL3L1 and CCL4L2) compared with healthy controls as well as mild patients who recovered. The cytotoxic phenotypes were shown in lung T and NK cells of severe patients as evidenced by enhanced ifnγ, Granulysin, Granzyme B and Perforin expression. Moreover, SARS-CoV-2 infection altered the community interplay of lung epithelial cells and immune cells: the interaction between epithelial cells with macrophage, T and NK cell was stronger, but their interaction with neutrophils was lost in COVID-19 patients compared to healthy controls.ConclusionsSARS-CoV-2 infection activates pro-inflammatory signaling in lung epithelial cells expressing ACE2 and causes dysregulation of immune response to release more pro-inflammatory cytokines. Moreover, SARS-CoV-2 infection breaks the interplay of lung epithelial cells and immune cells.
HDAC inhibitors decrease TLR7/9-mediated human plasmacytoid dendritic cell activation by interfering with IRF-7 and NF-κB signaling
Authors: Descalzi-Montoya Dante B. , Dai Jihong , Singh Sukhwinder , Fitzgerald-Bocarsly Patricia 
Published: May 2020

AbstractHistone deacetylase inhibitors (HDACi) are epigenome modulating molecules that target histone and non-histone proteins and have been successfully used to target many types of cancer and immunological disorders. While HDACi’s effects on nuclear histone deacetylases are well characterized, their effect on non-nuclear, cytoplasmic molecules requires further investigation. In the current study we characterized the effects of class I/II HDACi, specifically, TSA, MS-275, and SAHA, on plasmacytoid dendritic cell (pDC) biology upon viral activation via the TLR7/9 pathway. TSA, MS-275, and SAHA, down-modulated the induction of IFN-α and TNF-α upon Influenza A virus (IAV; TLR7 signaling) and Herpes Simplex 1 (HSV-1; TLR9 signaling) stimulation in primary pDC. The HDACi inhibitory effect was more prominent for IAV-mediated responses than for HSV-1. While IFN-α induction was not associated with inhibition of IRF-7 upregulation in the presence of TSA or MS-275, IRF-7 upregulation was affected by SAHA, but only for IAV. Furthermore, TSA, but not MS-275, inhibited TLR7/9-induced expression of maturation markers, CD40, and CD86, but not CD40. In addition, HDACi treatment increased virally-induced shedding of CD62L. Mechanistically, TSA, MS-275, SAHA significantly decreased early IRF-7 and NF-κB nuclear translocation, which was preceded by a decline in phosphorylation of IRF-7 at Ser477/479 and NF-κB p-p65, except for MS-275. In summary, we propose that broad HDACi, but not class I HDACi, treatment can negatively impact early TLR7/9-mediated signaling, namely, the disruption of IRF-7 and NF-κB activation and translocation that lead to deleterious effects on pDC function.
COVID-19 peak estimation and effect of nationwide lockdown in India
Authors: Belfin R V , Bródka Piotr , Radhakrishnan B L , Rejula V 
Published: May 2020

AbstractThere was a fury of the pandemic because of novel coronavirus (2019-nCoV/SARS-CoV-2) that happened in Wuhan, Hubei province, in China in December 2019. Since then, many model predictions on the COVID-19 pandemic in Wuhan and other parts of China have been reported. The first incident of coronavirus disease 2019 (COVID-19) in India was reported on 30 January 2020, which was a student from Wuhan. The number of reported cases has started to increase day by day after 30 February 2020. The purpose of this investigation is to provide a prediction of the epidemic peak for COVID-19 in India by utilizing real-time data from 30 February to 14 April 2020. We apply the well-known epidemic compartmental model “SEIR” to predict the epidemic peak of COVID-19, India. Since we do not have the complete detail of the infective population, using the available infected population data, we identify the R0 by using polynomial regression. By using the third-order polynomial equation, we estimate that the basic reproduction number for the epidemic in India is R0 = 3.3 (95%CI, 3.1–3.5), and the epidemic peak could be reached by September 2020.
Timing of non-pharmaceutical interventions to mitigate COVID-19 transmission and their effects on mobility: A cross-country analysis
Authors: Summan Amit , Nandi Arindam 
Published: May 2020

AbstractNon-pharmaceutical interventions (NPIs) that encourage physical distancing can decrease and delay the transmission of COVID-19. They have been implemented globally during the pandemic, however, the specific NPIs implemented and the timing of interventions has varied widely. We validated two published datasets on the implementation of NPIs globally. The health and socioeconomic factors associated with delay in implementation of NPIs was analyzed using fractional logit and probit models, and beta regression models. The probability of timely NPI implementation by a country was analyzed using a probit model. The effects of these interventions on mobility changes using Google social mobility reports, were analyzed with propensity score matching methods. Three NPIs were analyzed: national school closure, national lockdown, and global travel ban. Countries with higher incomes, larger populations, and better health preparedness measures had greater delays in implementation. Countries with greater population density, more democratic political systems, lower case detection capacity, and later arrival of first cases were more likely to implement NPIs. Implementation of lockdowns significantly reduced physical mobility. Mobility was further reduced when lockdowns were enforced with curfews or fines, or were more strictly defined. National school closures did not significantly change mobility. The implementation of NPIs is a global public good during pandemics, and the international community needs to address constraints and design incentives so countries implement NPIs in a timely manner. Further analysis is needed on the effect of NPI variations on mobility and transmission, and their associated costs.
SARS-CoV-2 receptor networks in diabetic and COVID-19 associated kidney disease
Authors: Menon Rajasree , Otto Edgar A. , Sealfon Rachel , Nair Viji , Wong Aaron K. , Theesfeld Chandra L. , Chen Xi , Wang Yuan , Boppana Avinash S. , Luo Jinghui , Yang Yingbao , Kasson Peter M. , Schaub Jennifer A. , Berthier Celine C. , Eddy Sean , Lienczewski Chrysta C. , Godfrey Bradley , Dagenais Susan L. , Sohaney Ryann , Hartman John , Fermin Damian , Subramanian Lalita , Looker Helen C. , Harder Jennifer L. , Mariani Laura H. , Hodgin Jeffrey B. , Sexton Jonathan Z. , Wobus Christiane E. , Naik Abhijit S. , Nelson Robert G. , Troyanskaya Olga G. , Kretzler Matthias 
Published: May 2020

AbstractCOVID-19 morbidity and mortality is increased in patients with diabetes and kidney disease via unknown mechanisms. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for entry into host cells. Since ACE2 is a susceptibility factor for infection, we investigated how diabetic kidney disease (DKD) and medications alter ACE2 receptor expression in kidneys. Single cell RNA profiling of healthy living donor (LD) and DKD kidney biopsies revealed ACE2 expression primarily in proximal tubular epithelial cells (PTEC). This cell specific localization was confirmed by in situ hybridization. ACE2 expression levels were unaltered by exposures to renin angiotensin aldosterone system inhibitors in DKD. Bayesian integrative analysis of a large compendium of public -omics datasets identified molecular network modules induced in ACE2-expressing PTEC in DKD (searchable at hb.flatironinstitute.org/covid-kidney) that were linked to viral entry, immune activation, endomembrane reorganization, and RNA processing. The DKD ACE2-positive PTEC module overlapped with expression patterns seen in SARS-CoV-2 infected cells. Similar cellular programs were seen in ACE2-positive PTEC obtained from urine samples of 13 COVID-19 patients who were hospitalized, suggesting a consistent ACE2-coregulated PTEC expression program that may interact with the SARS-CoV-2 infection processes. Thus SARS-CoV-2 receptor networks can seed further research into risk stratification and therapeutic strategies for COVID-19 related kidney damage.Translational statementTo understand the overwhelming burden of kidney disease in COVID-19, we mapped the expression of the SARS-CoV-2 receptor, ACE2, in healthy kidney, early diabetic (DKD) and COVID-19 associated kidney diseases. Single cell RNA sequencing of 111035 cells identified ACE2 predominantly in proximal tubular epithelial cells. ACE2 upregulation was observed in DKD, but was not associated with RAAS inhibition, arguing against an increased risk of COVID-19 among patients taking RAAS inhibitors. Molecular network analysis linked ACE2 expression to innate immune response and viral entry machinery, thereby revealing potential therapeutic strategies against COVID-19.
Brazil Health Care System preparation against COVID-19
Authors: Silva Lincoln Luís , de Carvalho Dutra Amanda , Iora Pedro Henrique , Ramajo Guilherme Luiz Rodrigues , Messias Gabriel Antônio Fernandes , Gualda Iago Amado Peres , Scheidt Joao Felipe Hermann Costa , Amaral Pedro Vasconcelos Maia do , Staton Catherine , Rocha Thiago Augusto Hernandes , Andrade Luciano de , Vissoci João Ricardo Nickenig 
Published: May 2020

ABSTRACTBackgroundThe coronavirus disease outbreak from 2019 (COVID-19) is associated with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly contagious virus that claimed thousands of lives around the world and disrupted the health system in many countries. The assessment of emergency capacity in every country is a necessary part of the COVID-19 response efforts. Thus, it is extremely recommended to evaluate the health care system to prepare the country to tackle COVID-19 challenges.Methods and FindingsA retrospective and ecological study was performed with data retrieved from the public national healthcare database (DATASUS). Numbers of intensive care unit and infirmary beds, general or intensivists physicians, nurses, nursing technicians, and ventilators from each Regional Health Unity were extracted, and the beds per health professionals and ventilators per population rates were assessed. The accessibility to health services was also performed using a spatial overlay approach to verify regions that lack assistance. It was found that Brazil lacks equity, integrity, and may struggle to assist with high complexity for the COVID-19 patients in many regions of the country.ConclusionsBrazil’s health system is insufficient to tackle the COVID-19 in some regions of the country where the coronavirus may be responsible for high rates of morbidity and mortality.
Molecular Docking studies of Phytocompounds ofRheum emodiWall with proteins responsible for antibiotic resistance in bacterial and fungal pathogens:In silicoapproach to enhance the bio-availability of antibiotics
Authors: Rolta Rajan , Kumar Vikas , Sourirajan Anuradha , Dev Kamal 
Published: May 2020

AbstractRheum emodiWall. (Himalayan rhubarb) has been used to cure many human diseases. Literature survey demonstrated that it has many pharmacological activities such as antioxidant, antimicrobial, antiviral, anticancer and wound healing. The present study was aimed to understand if major phytocompounds ofRheum emodicould bind proteins responsible for antibiotic resistance in bacterial and fungal pathogens and enhance the potency of antibiotics. The major phytocompounds ofR. emodi(emodin, rhein-13c6 and chrysophenodimethy ether) were retrieved from Pubchem and target proteins were retrieved from RCSB protein data bank. The docking study was performed with Hex 8.0.0 software and molinspiration, swiss ADME servers were used for determination of Lipinski rule of 5, drug-likeness prediction respectively, whereas, admetSAR and Protox-II tools were used for toxicity prediction. Among all the selected phytocompounds, emodin showed the best binding energy of −235.82 Kcal mol-1and −245 Kcal mol-1with cytochrome P450 14 alpha-sterol demethylase (PDB ID: 1EA1) andN-myristoyl transferase (PDB ID: 1IYL) receptors, respectively, which is more than that of fluconazole (−224.12 kcalmol-1and −161.14 kcal mol-1). Similarly, with Penicillin binding protein 3 (PDB ID: 3VSL) receptor, emodin and Chrysophanol dimethyl ether showed highest binding energy of - 216.68 Kcal mol-1and −215.58 kcal mol-1which is comparable to erythromycin (−263.63 kcal mol-1), chloramphanicol (−217.34 kcal mol-1) and tetracycline (−263.63 kcal mol-1). All the selected phytocompounds also fulfill Lipinski rule, non-carcinogenic and non-cytotoxic in nature. These compounds also showed high LD50value showing non-toxicity of these phytocompounds.Graphical abstract
Semi-automatic model revision of Boolean regulatory networks: confronting time-series observations with (a)synchronous dynamics
Authors: Gouveia Filipe , Lynce Inês , Monteiro Pedro T. 
Published: May 2020

AbstractMotivationComplex cellular processes can be represented by biological regulatory networks. Computational models of such networks have successfully allowed the reprodution of known behaviour and to have a better understanding of the associated cellular processes. However, the construction of these models is still mainly a manual task, and therefore prone to error. Additionally, as new data is acquired, existing models must be revised. Here, we propose a model revision approach of Boolean logical models capable of repairing inconsistent models confronted with time-series observations. Moreover, we account for both synchronous and asynchronous dynamics.ResultsThe proposed tool is tested on five well known biological models. Different time-series observations are generated, consistent with these models. Then, the models are corrupted with different random changes. The proposed tool is able to repair the majority of the corrupted models, considering the generated time-series observations. Moreover, all the optimal solutions to repair the models are produced.Contact{filipe.gouveia@tecnico.ulisboa.pt,pedro.tiago.monteiro@tecnico.ulisboa.pt}
Overexpression of Orange (OR) and OR mutant protein inChlamydomonas reinhardtiienhances carotenoid and ABA accumulation and increases resistance to abiotic stress
Authors: Yazdani Mohammad , Croen Michelle G. , Fish Tara L. , Thannhauser Theodore W. , Ahner Beth A. 
Published: May 2020

AbstractThe carotenoid content of plants can be increased by overexpression of the regulatory protein ORANGE (OR) or a mutant variant known as the ‘golden SNP’. In the present study, transgenic lines of the microalgaeChlamydomonas reinhardtiiwere generated to overexpress either wild typeCrOR(CrORWT) or a mutatedCrOR(CrORHis) containing a single histidine substitution for a conserved arginine. Overexpression of bothCrORWTandCrORHisdramatically enhanced the accumulation of several different carotenoids, including β-cartotene, α-carotene, lutein and violaxanthin, inC. reinhardtiiand, in contrast to higher plants, upregulated the transcript abundance of several relevant carotenoid biosynthetic genes. In addition, microscopic analysis revealed that theORtransgenic cells were larger than control cells and exhibited larger chloroplasts with a disrupted morphology. Moreover, bothCrORWTandCrORHiscell lines showed increased tolerance to salt and paraquat stress. The levels of endogenous phytohormone abscisic acid (ABA) were also increased inCrORWTandCrORHislines, not only in normal growth conditions but also in growth medium supplemented with paraquat. Together these results offer new insights regarding the role of the OR protein in regulating carotenoid biosynthesis and accumulation in microalgae, and establish a new functional role forORto modulate oxidative stress tolerance mediated by ABA.