scholarly journals SARS-CoV-2 NSP-12 mutations survey during the pandemic in the world

2021 ◽  
Author(s):  
Sogol Mazhari ◽  
Helia Alavifard ◽  
Karim Rahimian ◽  
Zohreh Karimi ◽  
Mohammadamin Mahmanzar ◽  
...  
Keyword(s):  
Critical Role ◽  
Reference Sequence ◽  
Structural Protein ◽  
Inclusion Criteria ◽  
The World ◽  
Biochemical Studies ◽  
Severity Of The Disease ◽  
The Stability ◽  
Python Programming

Abstract Background SARS-CoV-2 belongs to the beta coronavirus family responsible for coronavirus disease 2019 (COVID-19), a novel severe acute respiratory syndrome pandemic. The infection first emerged in Wuhan, China, and rapidly spread worldwide. The ongoing outbreak has posed an urgent worldwide health threat due to the rapid transmittable potential and high mortality rate. Due to the critical role of none structural protein − 12 (NSP-12) in COVID-19. This study tries to investigate the link between genotype-phenotype NSP-12 variation and the prevalence of this disease. Methods We analyzed approximately 2 million Nsp12 of SARS-CoV-2 protein sequence from January 2020 until June 2021. Python programming language was utilized to preprocess and apply inclusion criteria on FASTA files to prepare a list of suitable samples for clustering samples. NSP-12 regions were aligned to the reference sequence to compare and identify mutation patterns, categorized based on frequency and continent. Results The rate of ‌NSP-12 mutation in divided geographical areas was different. Based on continental studies, the P227L and G671S mutations have multiplied over time and in European and Asian societies in recent months. According to biochemical studies, the occurrence of G671S mutation increases the stability of the protein. Conclusion We concluded that NSP-12 P227L and G671S mutations in SARS-CoV-2 are increased in recent months. Further studies will be required to investigate whether these mutations impact the severity of the disease.

scholarly journals OVERCROWDED PRISONS IN PAKISTAN: UNDERSTANDING THE CRITICAL ROLE OF PROBATION, PAROLE OFFICERS AND COURTS

2021 ◽  
Vol 03 (01) ◽  
pp. 40-47
Author(s):  
Mukhtyar Nabi ◽  
◽  
Saddam Hussain ◽  
Muhammad Kamran ◽  
◽  
...  
Keyword(s):  
Present Article ◽  
Behavioral Problems ◽  
High Frequency ◽  
Critical Role ◽  
Prison System ◽  
Probation Officers ◽  
Parole Officers ◽  
The World

Prison is a place for rehabilitation of offenders in every country of the world. The present study has tried to explore the present-day situation of the prison system of Pakistan and discuss its overcrowding condition in all four provinces. There are total 120 prisons in the country which hold authorized space for not more than 57,712 prisoners, but the number of inmates is 77,275, which is far away from the authorized space. This congested prison system not only creates hurdles in rehabilitation of prisoners but makes them more criminal by mixing of low and high frequency offenders. It also leads to various health and behavioral problems. Rehabilitation is only possible if there is balance in authorized and available prisoners in the prisons. The present article has come up with some viable suggestion for concerned authorities that can better perform their duty in eradication of this problem. The authors discussed the role of parole and probation officers in the elimination of these numbers in prison. The majority of the prisoners in our prisons are under-trail, thus the role of the judiciary has also been explored in balancing the incarceration ratio in prisons. Keywords: Prison System, Overcrowded Prisons, Parole and Probation, Judiciary, Courts, Pakistan

scholarly journals Relative contribution of non-structural protein 1 in dengue pathogenesis

2020 ◽  
Author(s):  
Pei Xuan Lee ◽  
Donald Heng Rong Ting ◽  
Clement Peng Hee Boey ◽  
Eunice Tze Xin Tan ◽  
Janice Zuo Hui Chia ◽  
...  
Keyword(s):  
Critical Role ◽  
Health Concern ◽  
Structural Protein ◽  
Promising Candidate ◽  
Relative Contribution ◽  
Structural Region ◽  
Strain Dependent ◽  
Pro Inflammatory Cytokines

AbstractDengue is a major public health concern in the tropical and sub-tropical world with no effective treatment. The controversial live attenuated virus vaccine Dengvaxia has boosted the pursuit of sub-unit vaccine approaches, and the non-structural protein 1 (NS1) has recently emerged as a promising candidate. However, we found that NS1 immunization or passive transfer of NS1 antibodies failed to confer protection in symptomatic dengue mouse models using two non mouse-adapted DENV2 strains from the Cosmopolitan genotype that currently circulates in South-East Asia. Furthermore, exogenous administration of purified NS1 did not worsen in vivo vascular leakage in sub-lethally infected mice, thereby supporting that NS1 does not play a critical role in the pathogenesis of these DENV2 strains. Virus chimerization approaches indicated that the prME structural region, but not NS1, plays a critical role in driving in vivo fitness and virulence of the virus, through induction of key pro-inflammatory cytokines. This work highlights that the pathogenic role of NS1 is DENV strain-dependent, which warrants re-evaluation of NS1 as a universal dengue vaccine candidate.

Role of miRNAs In Cancer Diagnostics And Therapy: A Recent Update

2021 ◽  
Vol 27 ◽  
Author(s):  
Adil A. Sayyed ◽  
Piyush Gondaliya ◽  
Palak Bhat ◽  
Mukund Mali ◽  
Neha Arya ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Tumor Invasion ◽  
Cancer Metastasis ◽  
Critical Role ◽  
Delivery Systems ◽  
Cancer Diagnostics ◽  
Disease Monitoring ◽  
The Stability ◽  
Diagnostics And Therapy

: The discovery of miRNAs has been one of the revolutionary developments and has led to the advent of new diagnostic and therapeutic opportunities for the management of cancer. In this regard, miRNA dysregulation has been shown to play a critical role in various stages of tumorigenesis, including tumor invasion, metastasis as well as angiogenesis. Therefore, miRNA profiling can provide accurate fingerprints for the development of diagnostic and therapeutic platforms. This review discusses the recent discoveries of miRNA-based tools for early detection of cancer as well as disease monitoring in cancers that are common, like breast, lung, hepatic, colorectal, oral and brain cancer. Based on the involvement of miRNA in different cancers as oncogenic miRNA or tumor suppressor miRNA, the treatment with miRNA inhibitors or mimics is recommended. However, the stability and targeted delivery of miRNA remain the major limitations of miRNA delivery. In relation to this, several nanoparticle-based delivery systems have been reported which have effectively delivered the miRNA mimics or inhibitors and showed the potential for transforming these advanced delivery systems from bench to bedside in the treatment of cancer metastasis and chemoresistance. Based on this, we attempted to uncover recently reported advanced nanotherapeutic approaches to deliver the miRNAs in the management of different cancers.

scholarly journals The Central Role of Non-Structural Protein 1 (NS1) in Influenza Biology and Infection

2020 ◽  
Vol 21 (4) ◽  
pp. 1511 ◽  
Author(s):  
Nícia Rosário-Ferreira ◽  
António J. Preto ◽  
Rita Melo ◽  
Irina S. Moreira ◽  
Rui M. M. Brito
Keyword(s):  
Viral Disease ◽  
Influenza Viruses ◽  
World Health ◽  
World Population ◽  
Structural Protein ◽  
Human Respiratory Tract ◽  
Host Interactions ◽  
The World ◽  
Health Organization

Influenza (flu) is a contagious viral disease, which targets the human respiratory tract and spreads throughout the world each year. Every year, influenza infects around 10% of the world population and between 290,000 and 650,000 people die from it according to the World Health Organization (WHO). Influenza viruses belong to the Orthomyxoviridae family and have a negative sense eight-segment single-stranded RNA genome that encodes 11 different proteins. The only control over influenza seasonal epidemic outbreaks around the world are vaccines, annually updated according to viral strains in circulation, but, because of high rates of mutation and recurrent genetic assortment, new viral strains of influenza are constantly emerging, increasing the likelihood of pandemics. Vaccination effectiveness is limited, calling for new preventive and therapeutic approaches and a better understanding of the virus–host interactions. In particular, grasping the role of influenza non-structural protein 1 (NS1) and related known interactions in the host cell is pivotal to better understand the mechanisms of virus infection and replication, and thus propose more effective antiviral approaches. In this review, we assess the structure of NS1, its dynamics, and multiple functions and interactions, to highlight the central role of this protein in viral biology and its potential use as an effective therapeutic target to tackle seasonal and pandemic influenza.

Is there a role for extraretinal factors in the maintenance of stability in a structured environment?

1994 ◽  
Vol 17 (2) ◽  
pp. 258-258 ◽  
Author(s):  
Eugene Chekaluk
Keyword(s):  
Eye Movements ◽  
The World ◽  
Calibration Solution ◽  
The Stability ◽  
Perceptual Factors

The calibration solution to the stability of the world despite eye movements depends, according to Bridgeman et al., upon a combination of three factors which presumably all need to operate to achieve the goal of stability. Although the authors admit (sect. 4.3, para. 5) that the relative contributions of retinal and extraretinal factors will depend on the particular viewing situation, Figure 5 (sect. 4.3) makes it clear in its representation that the role of perceptual factors is relatively minor compared to extraretinal ones. It is with this representation that this commentary wishes to take issue, believing that it occurs as a result of some assumptions about terminology that may be ambiguous, as well as some misconceptions about the circumstances in which there is a need for stability.

scholarly journals Viperin catalyzes methionine oxidation to promote protein expression and function of helicases

2019 ◽  
Vol 5 (8) ◽  
pp. eaax1031 ◽  
Author(s):  
Lei Bai ◽  
Jiazhen Dong ◽  
Zhenqiu Liu ◽  
Youliang Rao ◽  
Pinghui Feng ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Methionine Oxidation ◽  
Biological Processes ◽  
Loss Of Function ◽  
Rna Helicases ◽  
Dna And Rna ◽  
Biochemical Studies ◽  
The Stability ◽  
And Function

Helicases play pivotal roles in fundamental biological processes, and posttranslational modifications regulate the localization, function, and stability of helicases. Here, we report that methionine oxidation of representative helicases, including DNA and RNA helicases of viral (ORF44 of KSHV) and cellular (MCM7 and RIG-I) origin, promotes their expression and functions. Cellular viperin, a major antiviral interferon-stimulated gene whose functions beyond host defense remain largely unknown, catalyzes the methionine oxidation of these helicases. Moreover, biochemical studies entailing loss-of-function mutations of helicases and a pharmacological inhibitor interfering with lipid metabolism and, hence, decreasing viperin activity indicate that methionine oxidation potently increases the stability and enzyme activity of these helicases that are critical for DNA replication and immune activation. Our work uncovers a pivotal role of viperin in catalyzing the methionine oxidation of helicases that are implicated in diverse fundamental biological processes.

scholarly journals May the force be with you: Transfer of healthy mitochondria from stem cells to stroke cells

2018 ◽  
Vol 39 (2) ◽  
pp. 367-370 ◽  
Author(s):  
Cesar V Borlongan ◽  
Hung Nguyen ◽  
Trenton Lippert ◽  
Eleonora Russo ◽  
Julian Tuazon ◽  
...  
Keyword(s):  
United States ◽  
Stem Cells ◽  
Therapeutic Option ◽  
Critical Role ◽  
The United States ◽  
Brain Disorders ◽  
Mitochondrial Dysfunctions ◽  
Limited Therapeutic Option ◽  
The World

Stroke is a major cause of death and disability in the United States and around the world with limited therapeutic option. Here, we discuss the critical role of mitochondria in stem cell-mediated rescue of stroke brain by highlighting the concept that deleting the mitochondria from stem cells abolishes the cells’ regenerative potency. The application of innovative approaches entailing generation of mitochondria-voided stem cells as well as pharmacological inhibition of mitochondrial function may elucidate the mechanism underlying transfer of healthy mitochondria to ischemic cells, thereby providing key insights in the pathology and treatment of stroke and other brain disorders plagued with mitochondrial dysfunctions.

scholarly journals Mutational Analysis of VIM-2 Reveals an Essential Determinant for Metallo-β-Lactamase Stability and Folding

2010 ◽  
Vol 54 (8) ◽  
pp. 3197-3204 ◽  
Author(s):  
Luisa Borgianni ◽  
Julie Vandenameele ◽  
André Matagne ◽  
Luca Bini ◽  
Robert A. Bonomo ◽  
...  
Keyword(s):  
Mutational Analysis ◽  
Critical Role ◽  
Kinetic Studies ◽  
Amino Acid Position ◽  
Structural Knowledge ◽  
Saturation Mutagenesis ◽  
Biochemical Analyses ◽  
The Stability ◽  
Substrate Hydrolysis

ABSTRACT Metallo-β-lactamase (MBL)-producing bacteria are emerging worldwide and represent a formidable threat to the efficacy of relevant β-lactams, including carbapenems, expanded-spectrum cephalosporins, and β-lactamase inactivator/β-lactam combinations. VIM-2 is currently the most widespread MBL and represents a primary target for MBL inhibitor research, the clinical need for which is expected to further increase in the future. Using a saturation mutagenesis approach, we probed the importance of four residues (Phe-61, Ala-64, Tyr-67, and Trp-87) located close to the VIM-2 active site and putatively relevant to the enzyme activity based on structural knowledge of the enzyme and on structure-activity relationships of the subclass B1 MBLs. The ampicillin MIC values shown by the various mutants were affected very differently depending on the randomized amino acid position. Position 64 appeared to be rather tolerant to substitution, and kinetic studies showed that the A64W mutation did not significantly affect substrate hydrolysis or binding, representing an important difference from IMP-type enzymes. Phe-61 and Tyr-67 could be replaced with several amino acids without the ampicillin MIC being significantly affected, but in contrast, Trp-87 was found to be critical for ampicillin resistance. Further kinetic and biochemical analyses of W87A and W87F variants showed that this residue is apparently important for the structure and proper folding of the enzyme but, surprisingly, not for its catalytic activity. These data support the critical role of residue 87 in the stability and folding of VIM-2 and might have strong implications for MBL inhibitor design, as this residue would represent an ideal target for interaction with small molecules.

scholarly journals Public Health Literacy for Lawyers

2003 ◽  
Vol 31 (4) ◽  
pp. 701-713 ◽  
Author(s):  
Wendy E. Parmet ◽  
Anthony Robbins
Keyword(s):  
Public Health ◽  
Health Professionals ◽  
Critical Role ◽  
The Public ◽  
Health Measures ◽  
Public Health Professionals ◽  
The World ◽  
Key Issues ◽  
Public Health Literacy

Public health professionals recognize the critical role the law plays in determining the success of public health measures. Even before September 11, 2001, public health experience with tobacco use, HIV, industrial pollution and other potent threats to the health of the public demonstrated that laws can assist or thwart public health efforts. The new focus on infectious threats and bioterrorism, starting with the anthrax attacks through the mail and continuing with SARS, has highlighted the important role of law.For lawyers to serve as effective partners in public health, they should have a basic familiarity with public health: how public health professionals see the world and the key issues they tackle. A practical grasp of public health can be acquired, and often is acquired, “on the job.”

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