scholarly journals Role of Ecologic ACE I/D Polymorphism Data Towards Prediction of COVID-19 Epidemiology

2021 ◽  
Author(s):  
Ali Amar ◽  
Abdul Rafay Khan ◽  
Madiha Shakoor ◽  
Aiysha Abid ◽  
Shagufta Khaliq
Keyword(s):  
Ecological Study ◽  
Clinical Course ◽  
Predictive Biomarker ◽  
Data Set ◽  
Functional Studies ◽  
Marked Variability ◽  
Specific Manner ◽  
Polymorphism Data ◽  
Underlying Pathogenesis

Abstract COVID-19 displays marked variability in the clinical course as well as regional epidemiology. Abnormalities in RAAS system especially stemming from genetic variability in ACE and ACE2 expression (including ACE I/D polymorphism) have been proposed to explain underlying pathogenesis and variability in SARS-CoV-2 infection. In a meta-regression data set of 30 countries, we found significant associations of ACE I/D ratio and COVID-19 prevalence, deaths and recovery rate but not when adjusted for possible confounders. This ecological study suggests potential of ACE I/D data as predictive biomarker COVID-19 risk and severity in a population specific manner, subject to validation in large genetic epidemiological and functional studies.

Ionic homeostasis and subcellular element compartmentation

1990 ◽  
Vol 48 (2) ◽  
pp. 150-151
Author(s):  
Ann LeFurgey ◽  
Peter Ingram ◽  
J.J. Blum ◽  
M.C. Carney ◽  
L.A. Hawkey ◽  
...  
Keyword(s):  
Leishmania Major ◽  
Ionic Homeostasis ◽  
X Ray ◽  
Functional Studies ◽  
Cell Compartments ◽  
X Ray Imaging ◽  
Resolution Electron ◽  
Multiple Cell ◽  
Role Of Zn

Subcellular compartments commonly identified and analyzed by high resolution electron probe x-ray microanalysis (EPXMA) include mitochondria, cytoplasm and endoplasmic or sarcoplasmic reticulum. These organelles and cell regions are of primary importance in regulation of cell ionic homeostasis. Correlative structural-functional studies, based on the static probe method of EPXMA combined with biochemical and electrophysiological techniques, have focused on the role of these organelles, for example, in maintaining cell calcium homeostasis or in control of excitation-contraction coupling. New methods of real time quantitative x-ray imaging permit simultaneous examination of multiple cell compartments, especially those areas for which both membrane transport properties and element content are less well defined, e.g. nuclei including euchromatin and heterochromatin, lysosomes, mucous granules, storage vacuoles, microvilli. Investigations currently in progress have examined the role of Zn-containing polyphosphate vacuoles in the metabolism of Leishmania major, the distribution of Na, K, S and other elements during anoxia in kidney cell nuclel and lysosomes; the content and distribution of S and Ca in mucous granules of cystic fibrosis (CF) nasal epithelia; the uptake of cationic probes by mltochondria in cultured heart ceils; and the junctional sarcoplasmic retlculum (JSR) in frog skeletal muscle.

Exchange Spin Coupling from Gaussian Process Regression

2020 ◽  
Author(s):  
Marc Philipp Bahlke ◽  
Natnael Mogos ◽  
Jonny Proppe ◽  
Carmen Herrmann
Keyword(s):  
Machine Learning ◽  
Gaussian Process ◽  
Gaussian Process Regression ◽  
Molecular Magnets ◽  
Molecular Structures ◽  
Spin Coupling ◽  
Structure Property ◽  
Data Set ◽  
Uncertainty Estimates

Heisenberg exchange spin coupling between metal centers is essential for describing and understanding the electronic structure of many molecular catalysts, metalloenzymes, and molecular magnets for potential application in information technology. We explore the machine-learnability of exchange spin coupling, which has not been studied yet. We employ Gaussian process regression since it can potentially deal with small training sets (as likely associated with the rather complex molecular structures required for exploring spin coupling) and since it provides uncertainty estimates (“error bars”) along with predicted values. We compare a range of descriptors and kernels for 257 small dicopper complexes and find that a simple descriptor based on chemical intuition, consisting only of copper-bridge angles and copper-copper distances, clearly outperforms several more sophisticated descriptors when it comes to extrapolating towards larger experimentally relevant complexes. Exchange spin coupling is similarly easy to learn as the polarizability, while learning dipole moments is much harder. The strength of the sophisticated descriptors lies in their ability to linearize structure-property relationships, to the point that a simple linear ridge regression performs just as well as the kernel-based machine-learning model for our small dicopper data set. The superior extrapolation performance of the simple descriptor is unique to exchange spin coupling, reinforcing the crucial role of choosing a suitable descriptor, and highlighting the interesting question of the role of chemical intuition vs. systematic or automated selection of features for machine learning in chemistry and material science.

Vocational Development in Emerging Adulthood

2018 ◽  
Author(s):  
Michael W. Pratt ◽  
M. Kyle Matsuba
Keyword(s):  
Turning Point ◽  
Life Stories ◽  
Life Story ◽  
Emerging Adult ◽  
Vocational Development ◽  
Data Set ◽  
The World ◽  
Key Concepts

Chapter 6 reviews research on the topic of vocational/occupational development in relation to the McAdams and Pals tripartite personality framework of traits, goals, and life stories. Distinctions between types of motivations for the work role (as a job, career, or calling) are particularly highlighted. The authors then turn to research from the Futures Study on work motivations and their links to personality traits, identity, generativity, and the life story, drawing on analyses and quotes from the data set. To illustrate the key concepts from this vocation chapter, the authors end with a case study on Charles Darwin’s pivotal turning point, his round-the-world voyage as naturalist for the HMS Beagle. Darwin was an emerging adult in his 20s at the time, and we highlight the role of this journey as a turning point in his adult vocational development.

scholarly journals Actors, Partisan Inclination, and Emotions: An Analysis of Government Shutdown News Stories Shared on Twitter

2021 ◽  
Vol 7 (2) ◽  
pp. 205630512110088
Author(s):  
Colin Agur ◽  
Lanhuizi Gan
Keyword(s):  
Emotional Responses ◽  
The United States ◽  
Online Information ◽  
News Frames ◽  
Data Set ◽  
Political Issues ◽  
News Stories ◽  
News Sharing ◽  
Government Shutdown

Scholars have recognized emotion as an increasingly important element in the reception and retransmission of online information. In the United States, because of existing differences in ideology, among both audiences and producers of news stories, political issues are prone to spark considerable emotional responses online. While much research has explored emotional responses during election campaigns, this study focuses on the role of online emotion in social media posts related to day-to-day governance in between election periods. Specifically, this study takes the 2018–2019 government shutdown as its subject of investigation. The data set shows the prominence of journalistic and political figures in leading the discussion of news stories, the nuance of emotions employed in the news frames, and the choice of pro-attitudinal news sharing.

scholarly journals The RelA hydrolase domain acts as a molecular switch for (p)ppGpp synthesis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Anurag Kumar Sinha ◽  
Kristoffer Skovbo Winther
Keyword(s):  
Active Sites ◽  
Molecular Switch ◽  
Cell Physiology ◽  
Synthetase Activity ◽  
Wild Type ◽  
Functional Studies ◽  
Loop Region ◽  
A Site ◽  
Trna Binding

AbstractBacteria synthesize guanosine tetra- and penta phosphate (commonly referred to as (p)ppGpp) in response to environmental stresses. (p)ppGpp reprograms cell physiology and is essential for stress survival, virulence and antibiotic tolerance. Proteins of the RSH superfamily (RelA/SpoT Homologues) are ubiquitously distributed and hydrolyze or synthesize (p)ppGpp. Structural studies have suggested that the shift between hydrolysis and synthesis is governed by conformational antagonism between the two active sites in RSHs. RelA proteins of γ-proteobacteria exclusively synthesize (p)ppGpp and encode an inactive pseudo-hydrolase domain. Escherichia coli RelA synthesizes (p)ppGpp in response to amino acid starvation with cognate uncharged tRNA at the ribosomal A-site, however, mechanistic details to the regulation of the enzymatic activity remain elusive. Here, we show a role of the enzymatically inactive hydrolase domain in modulating the activity of the synthetase domain of RelA. Using mutagenesis screening and functional studies, we identify a loop region (residues 114–130) in the hydrolase domain, which controls the synthetase activity. We show that a synthetase-inactive loop mutant of RelA is not affected for tRNA binding, but binds the ribosome less efficiently than wild type RelA. Our data support the model that the hydrolase domain acts as a molecular switch to regulate the synthetase activity.

Do the Heterogeneous Determinants of Repayment Affect Differently across Borrowers of Diverse Credit Sources in Rural Assam? A Double Hurdle Approach

2021 ◽  
pp. 245513332110316
Author(s):  
Tiken Das ◽  
Pradyut Guha ◽  
Diganta Das
Keyword(s):  
Rural Areas ◽  
Probit Model ◽  
Original Data ◽  
Community Based ◽  
Data Set ◽  
Brahmaputra Valley ◽  
Double Hurdle ◽  
Instrumental Variable Probit ◽  
Instrumental Variable Probit Model

This study made an attempt to answer the question: Do the heterogeneous determinants of repayment affect the borrowers of diverse credit sources differently? The study is based on data collected from 240 households from three districts in the lower Brahmaputra valley of Assam through a carefully designed primary survey. Besides, the study uses the double hurdle approach and the instrumental variable probit model to reduce possible selection bias. It observes better repayment performance among formal borrowers, followed by semiformal borrowers, while occupation wise it is prominent among organised employees. It has been found that in general, the household characteristics, loan characteristics and location-specific characteristics significantly affect repayment performance of borrowers. However, the nature of impact of the factors influencing repayment performance is remarkably different across credit sources. It ignores the role of traditional community-based organisations in rural Assam while analysing the determinants of repayment performance. The study also recommends for ensuring productive opportunities and efficient market linkages in rural areas of Assam. The study is based on an original data set that has specially been collected to examine question that—do the heterogeneous determinants of repayment affect the borrowers of diverse credit sources differently in the lower Brahmaputra valley of Assam—which has not been studied before.

scholarly journals The role of prophylactic antibiotics in hepatitis B virus-related acute-on-chronic liver failure patients at risk of bacterial infection: a retrospective study

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiao-Qin Liu ◽  
Xue-Yun Zhang ◽  
Yue Ying ◽  
Jian-Ming Zheng ◽  
Jian Sun ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Clinical Course ◽  
Prophylactic Antibiotics ◽  
Third Generation ◽  
Chronic Liver Failure ◽  
Free Survival ◽  
B Virus ◽  
Third Generation Cephalosporins

Abstract Background Acute-on-chronic liver failure (ACLF) is characterized by an excessive systemic inflammatory response and organ failure and has high mortality. Bacterial infections (BIs) worsen the clinical course of ACLF and carry a poor prognosis in ACLF patients. The efficacy of third-generation cephalosporins has been challenged in recent years. The aim of this study was to characterize the difference between ACLF patients with and without BIs and to provide a reference for medical intervention. Methods A total of 140 patients with hepatitis B virus-related ACLF (HBV-ACLF) hospitalized at the Department of Infectious Diseases, Huashan Hospital, Fudan University (Shanghai, China) between May 2013 and January 2020 were enrolled. Mann-Whitney U test was used to compare the baseline characteristics of HBV-ACLF patients with and without BIs. Univariate and multivariate analyses were performed to find predictors of BIs. The characteristics of BIs and the role of prophylactic antibiotics were profiled. Results A total of 97 episodes of BIs occurred in patients during the course of HBV-ACLF. Patients with and without BIs differed in clinical characteristics. The incidence of BIs showed a positive correlation with the ACLF grade (P = 0.003) and the clinical course (P = 0.003). The 90-day transplant-free survival of patients with BIs was lower than those without BIs (P < 0.0001). Patients administered prophylactic antibiotics showed a lower incidence of BIs and had a higher transplant-free survival probability than those who did not (P = 0.046). No statistical differences in antibiotic efficacy between third-generation and other antibiotics were observed (P = 0.108). Conclusions BIs affected the clinical course and prognosis of patients with HBV-ACLF. Prophylactic antibiotics were of potential clinical importance in the prevention of BIs and improving the clinical course and prognosis in HBV-ACLF patients. Third-generation cephalosporins were qualified for use in antibiotic prophylaxis.

scholarly journals Germline variant in REXO2 is a novel candidate gene in familial pheochromocytoma

2020 ◽  
Vol 102 ◽  
Author(s):  
Yael Laitman ◽  
Shay Tzur ◽  
Ruben Attali ◽  
Amit Tirosh ◽  
Eitan Friedman
Keyword(s):  
Allelic Imbalance ◽  
Chromosomal Region ◽  
Cancer Susceptibility ◽  
Functional Studies ◽  
Cancer Susceptibility Genes ◽  
Whole Exome ◽  
Familial Pheochromocytoma ◽  
The Family ◽  
Recombination Processes

Abstract Pheochromocytoma (PCC) is a rare, mostly benign tumour of the adrenal medulla. Hereditary PCC accounts for ~35% of cases and has been associated with germline mutations in several cancer susceptibility genes (e.g., KIF1B, SDHB, VHL, SDHD, RET). We performed whole-exome sequencing in a family with four PCC-affected patients in two consecutive generations and identified a potential novel candidate pathogenic variant in the REXO2 gene that affects splicing (c.531-1G>T (NM 015523.3)), which co-segregated with the phenotype in the family. REXO2 encodes for RNA exonuclease 2 protein and localizes to 11q23, a chromosomal region displaying allelic imbalance in PCC. REXO2 protein has been associated with DNA repair, replication and recombination processes and thus its inactivation may contribute to tumorigenesis. While the study suggests that this novel REXO2 gene variant underlies PCC in this family, additional functional studies are required in order to establish the putative role of the REXO2 gene in PCC predisposition.

scholarly journals WEE1 Inhibitor: Clinical Development

2021 ◽  
Vol 23 (9) ◽  
Author(s):  
Anthony Kong ◽  
Hisham Mehanna
Keyword(s):  
Clinical Trials ◽  
Tp53 Mutation ◽  
Predictive Biomarker ◽  
Concurrent Chemotherapy ◽  
Clinical Development ◽  
Novel Agents ◽  
The Novel ◽  
Grade 3 ◽  
Chemotherapy Agents

Abstract Purpose of Review WEE1 inhibitor has been shown to potential chemotherapy or radiotherapy sensitivity in preclinical models, particularly in p53-mutated or deficient cancer cells although not exclusively. Here, we review the clinical development of WEE1 inhibitor in combination with chemotherapy or radiotherapy with concurrent chemotherapy as well as its combination with different novel agents. Recent Findings Although several clinical trials have shown that WEE1 inhibitor can be safely combined with different chemotherapy agents as well as radiotherapy with concurrent chemotherapy, its clinical development has been hampered by the higher rate of grade 3 toxicities when added to standard treatments. A few clinical trials had also been conducted to test WEE1 inhibitor using TP53 mutation as a predictive biomarker. However, TP53 mutation has not been shown to be the most reliable predictive biomarker and the benefit of adding WEE1 inhibitor to chemotherapy has been modest, even in TP53 biomarker-driven studies. Summary There are ongoing clinical trials testing WEE1 inhibitor with novel agents such as ATR and PAPR inhibitors as well as anti-PDL1 immunotherapy, which may better define the role of WEE1 inhibitor in the future if any of the novel treatment combination will show superior anti-tumor efficacy with a good safety profile compared to monotherapy and/or standard treatment.

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