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Severe acute respiratory syndrome coronavirus‐2 natural animal reservoirs and experimental models: systematic review
Dergi Makalesi

Dergi Makalesi
Kaynak :
Wiley Online Library
Dergi:
Reviews in Medical Virology
Yazar(lar) :
Salma Younes , Nadin Younes , Farah Shurrab , Gheyath K. Nasrallah
Konu :
Virology, Infectious Diseases
Yıl :
2020
Salma Younes
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Tam Metin
Kaydet Alıntıla
The current severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) outbreak has been rapidly spreading worldwide, causing serious global concern. The role that animal hosts play in disease transmission is still understudied and researchers wish to find suitable animal models for fundamental research and drug discovery. In this systematic review, we aimed to compile and discuss all articles that describe experimental or natural infections with SARS‐CoV‐2, from the initial discovery of the virus in December 2019 through to October 2020. We systematically searched four databases (Scopus, PubMed, Science Direct and Web of Science). The following data were extracted from the included studies: type of infection (natural or experimental), age, sample numbers, dose, route of inoculation, viral replication, detection method, clinical symptoms and transmission. Fifty‐four studies were included, of which 34 were conducted on animal reservoirs (naturally or experimentally infected), and 20 involved models for testing vaccines and therapeutics. Our search revealed that Rousettus aegyptiacus (fruit bats), pangolins, felines, mink, ferrets and rabbits were all susceptible to SARS‐CoV‐2, while dogs were weakly susceptible and pigs, poultry, and tree shrews were not. In addition, virus replication in mice, mink, hamsters and ferrets resembled subclinical human infection, so these animals might serve as useful models for future studies to evaluate vaccines or antiviral agents and to study host‐pathogen interactions. Our review comprehensively summarized current evidence on SARS‐CoV‐2 infection in animals and their usefulness as models for studying vaccines and antiviral drugs. Our findings may direct future studies for vaccine development, antiviral drugs and therapeutic agents to manage SARS‐CoV‐2‐caused diseases.
DOI : 10.1002/rmv.2196
ISSN: 1052-9276

2
Genetic polymorphisms associated with obesity in the Arab world: a systematic review
Dergi Makalesi

Dergi Makalesi
Kaynak :
Springer Nature
Dergi:
International Journal of Obesity
Yayıncı:
Springer Science and Business Media LLC
Yazar(lar) :
Salma Younes , Amal Ibrahim , Rana Al-Jurf , Hatem ZayedSalma Younes , Amal Ibrahim , Rana Al-Jurf , Hatem Zayed
Yıl :
2021
Salma Younes
Yayıncı Web Sitesi
Tam Metin
Kaydet Alıntıla
Abstract\n Background\n Obesity, one of the most common chronic health conditions worldwide, is a multifactorial disease caused by complex genetic and environmental interactions. Several association studies have revealed a considerable number of candidate loci for obesity; however, the genotype–phenotype correlations remain unclear. To date, no comprehensive systematic review has been conducted to investigate the genetic risk factors for obesity among Arabs.\n \n Objectives\n This study aimed to systematically review the genetic polymorphisms that are significantly associated with obesity in Arabs.\n \n Methods\n We searched four literature databases (PubMed, Science Direct, Scopus, and Google Scholar) from inception until May 2020 to obtain all reported genetic data related to obesity in Arab populations. Quality assessment and data extraction were performed individually by three investigators.\n \n Results\n In total, 59 studies comprising a total of 15,488 cases and 9,760 controls were included in the systematic review. A total of 76 variants located within or near 49 genes were reported to be significantly associated with obesity. Among the 76 variants, two were described as unique to Arabs, as they have not been previously reported in other populations, and 19 were reported to be distinctively associated with obesity in Arabs but not in non-Arab populations.\n \n Conclusions\n There appears to be a unique genetic and clinical susceptibility profile of obesity in Arab patients.\n
DOI : 10.1038/s41366-021-00867-6
ISSN: 0307-0565
Sayı: 9
Cilt: 45
Sayfa: 1899-1913
3
Drosophila as a Model Organism in Host–Pathogen Interaction Studies
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
Frontiers in Cellular and Infection Microbiology
Yazar(lar) :
Salma Younes , Asma Al-Sulaiti , Elham Abdulwahab Ahmed Nasser , Hoda Najjar , Layla Kamareddine
Yıl :
2020
Salma Younes
Yayıncı Web Sitesi
 Piri Tam Metin Bulucu
Kaydet Alıntıla
Owing to the genetic similarities and conserved pathways between a fruit fly and mammals, the use of the Drosophila model as a platform to unveil novel mechanisms of infection and disease progression has been justified and widely instigated. Gaining proper insight into host–pathogen interactions and identifying chief factors involved in host defense and pathogen virulence in Drosophila serves as a foundation to establish novel strategies for infectious disease prevention and control in higher organisms, including humans.
DOI : 10.3389/fcimb.2020.00214
Anahtar Kelimeler : Drosophila, hostu2013pathogen interactions, host defense factors, pathogen virulence factors, disease control, disease progression
ISSN: 2235-2988
Cilt: 10
Sınıflandırma :
4
Dysregulation of Signaling Pathways Due to Differentially Expressed Genes From the B-Cell Transcriptomes of Systemic Lupus Erythematosus Patients – A Bioinformatics Approach
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
Frontiers in Bioengineering and Biotechnology
Yazar(lar) :
S. Udhaya Kumar , D. Thirumal Kumar , R. Siva , C. George Priya Doss , Salma Younes , Nadin Younes , Mariem Sidenna , Hatem Zayed
Yıl :
2020
Salma Younes
Yayıncı Web Sitesi
 Piri Tam Metin Bulucu
Kaydet Alıntıla
Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disorder that is clinically complex and has increased production of autoantibodies. Via emerging technologies, researchers have identified genetic variants, expression profiling of genes, animal models, and epigenetic findings that have paved the way for a better understanding of the molecular and genetic mechanisms of SLE. Our current study aimed to illustrate the essential genes and molecular pathways that are potentially involved in the pathogenesis of SLE. This study incorporates the gene expression profiling data of the microarray dataset GSE30153 from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) between the B-cell transcriptomes of SLE patients and healthy controls were screened using the GEO2R web tool. The identified DEGs were subjected to STRING analysis and Cytoscape to explore the protein–protein interaction (PPI) networks between them. The MCODE (Molecular Complex Detection) plugin of Cytoscape was used to screen the cluster subnetworks that are highly interlinked between the DEGs. Subsequently, the clustered DEGs were subjected to functional annotation with ClueGO/CluePedia to identify the significant pathways that were enriched. For integrative analysis, we used GeneGo MetacoreTM, a Cortellis Solution software, to exhibit the Gene Ontology (GO) and enriched pathways between the datasets. Our study identified 4 upregulated and 13 downregulated genes. Analysis of GO and functional enrichment using ClueGO revealed the pathways that were statistically significant, including pathways involving T-cell costimulation, lymphocyte costimulation, negative regulation of vascular permeability, and B-cell receptor signaling. The DEGs were mainly enriched in metabolic networks such as the phosphatidylinositol-3,4,5-triphosphate pathway and the carnitine pathway. Additionally, potentially enriched pathways, such as the signaling pathways induced by oxidative stress and reactive oxygen species (ROS), chemotaxis and lysophosphatidic acid signaling induced via G protein-coupled receptors (GPCRs), and the androgen receptor activation pathway, were identified from the DEGs that were mainly associated with the immune system. Four genes (EGR1, CD38, CAV1, and AKT1) were identified to be strongly associated with SLE. Our integrative analysis using a multitude of bioinformatics tools might promote an understanding of the dysregulated pathways that are associated with SLE development and progression. The four DEGs in SLE patients might shed light on the pathogenesis of SLE and might serve as potential biomarkers in early diagnosis and as therapeutic targets for SLE.
DOI : 10.3389/fbioe.2020.00276
Anahtar Kelimeler : systemic lupus erythematosus, proteinu2013protein interactions, Metacore, microarray and bioinformatics, expression profiling data, biomarkers
ISSN: 2296-4185
Cilt: 8
Sınıflandırma :
5
Enhanced production of anthraquinones by gamma-irradiated cell cultures of Rubia cordifolia in a bioreactor
Dergi Makalesi

Dergi Makalesi
Kaynak :
Science Direct
Dergi:
Industrial Crops and Products
Yayıncı:
Elsevier
Yazar(lar) :
Mariadoss A , Ramesh Satdive , Devanand P. Fulzele , Siva Ramamoorthy , George Priya Doss C , Hatem Zayed , Salma Younes , Rajasekaran C
Yıl :
2020
Salma Younes
Yayıncı Web Sitesi
Tam Metin
Kaydet Alıntıla
The aim of this study was to obtain high-yielding cell cultures of Rubia cordifolia by applying gamma irradiation and subsequently scaling up for anthraquinone production in a bioreactor. Calli cultured on MS medium was irradiated at variable doses between 2 Gy and 30 Gy. The callus cultures that were irradiated at 8 Gy accumulated a maximum alizarin level of 26.86 mg g-1 DW and a purpurin level of 44.85 mg g-1 DW during the M1T4 (fourth sub-cultures after gamma irradiation treatment) subculture, which was 6-fold and 11-fold higher than those of the nonirradiated callus cultures, respectively. Suspension cultures that originated from high-yielding callus cultures irradiated at 8 Gy were scaled up in an 8-L stirred bioreactor equipped with different impellers. The callus cultures in a bioreactor using a helical ribbon for homogenous mixing synthesized 63.58 % more anthraquinones than those in the bioreactor equipped with a Rushton disc turbine. This is the first report on the production of alizarin and purpurin in a bioreactor.
DOI : 10.1016/j.indcrop.2019.111987
ISSN: 0926-6690
Cilt: 145
Sayfa: 111987
Sınıflandırma :
6
Challenges in Laboratory Diagnosis of the Novel Coronavirus SARS-CoV-2
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak 1:
MDPI
Kaynak 2:
Directory of Open Access Journals (DOAJ)
Dergi:
Viruses
Yayıncı:
MDPI AG
Yazar(lar) :
Nadin Younes , Duaa W. Al-Sadeq , Hadeel AL-Jighefee , Salma Younes , Ola Al-Jamal , Hanin I. Daas , Hadi. M. Yassine , Gheyath K. Nasrallah
Yıl :
2020
Salma Younes
Tam Metin
Kaydet Alıntıla
The recent outbreak of the Coronavirus disease 2019 (COVID-19) has quickly spread worldwide since its discovery in Wuhan city, China in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, clinical treatment, and development of vaccines, is urgently needed to win the battle against COVID-19. The past three unprecedented outbreaks of emerging human coronavirus infections at the beginning of the 21st century have highlighted the importance of readily available, accurate, and rapid diagnostic technologies to contain emerging and re-emerging pandemics. Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) based assays performed on respiratory specimens remain the gold standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging with high sensitivity and specificity as well. Even though excellent techniques are available for the diagnosis of symptomatic patients with COVID-19 in well-equipped laboratories; critical gaps still remain in screening asymptomatic people who are in the incubation phase of the virus, as well as in the accurate determination of live viral shedding during convalescence to inform decisions for ending isolation. This review article aims to discuss the currently available laboratory methods and surveillance technologies available for the detection of COVID-19, their performance characteristics and highlight the gaps in current diagnostic capacity, and finally, propose potential solutions. We also summarize the specifications of the majority of the available commercial kits (PCR, EIA, and POC) for laboratory diagnosis of COVID-19.
DOI : 10.3390/v12060582
ISSN: 1999-4915
Sayı: 6
Cilt: 12
Sayfa: 582
Sınıflandırma :
7
Molecular dynamics, residue network analysis, and cross-correlation matrix to characterize the deleterious missense mutations in GALE causing galactosemia III
Dergi Makalesi

Dergi Makalesi
Kaynak :
Springer Link
Dergi:
Cell Biochemistry and Biophysics
Yazar(lar) :
S. Udhaya Kumar , Srivarshini Sankar , D. Thirumal Kumar , Salma Younes , Nadin Younes , R. Siva , C. George Priya Doss , Hatem Zayed
Konu :
Cell Biology, Biochemistry, General Medicine, Biophysics
Yıl :
2021
Salma Younes
Yayıncı Web Sitesi
Tam Metin
Kaydet Alıntıla
Epimerase-deficiency galactosemia (EDG) is caused by mutations in the UDP-galactose 4’-epimerase enzyme, encoded by gene GALE. Catalyzing the last reaction in the Leloir pathway, UDP-galactose-4-epimerase catalyzes the interconversion of UDP-galactose and UDP-glucose. This study aimed to use in-depth computational strategies to prioritize the pathogenic missense mutations in GALE protein and investigate the systemic behavior, conformational spaces, atomic motions, and cross-correlation matrix of the GALE protein. We searched four databases (dbSNP, ClinVar, UniProt, and HGMD) and major biological literature databases (PubMed, Science Direct, and Google Scholar), for missense mutations that are associated with EDG patients, our search yielded 190 missense mutations. We applied a systematic computational prediction pipeline, including pathogenicity, stability, biochemical, conservational, protein residue contacts, and structural analysis, to predict the pathogenicity of these mutations. We found three mutations (p.K161N, p.R239W, and p.G302D) with a severe phenotype in patients with EDG that correlated with our computational prediction analysis; thus, they were selected for further structural and simulation analyses to compute the flexibility and stability of the mutant GALE proteins. The three mutants were subjected to molecular dynamics simulation (MDS) with native protein for 200 ns using GROMACS. The MDS demonstrated that these mutations affected the beta-sheets and helical region that are responsible for the catalytic activity; subsequently, affects the stability and flexibility of the mutant proteins along with a decrease and more deviations in compactness when compared to that of a native. Also, three mutations created major variations in the combined atomic motions of the catalytic and C-terminal regions. The network analysis of the residues in the native and three mutant protein structures showed disturbed residue contacts occurred owing to the missense mutations. Our findings help to understand the structural behavior of a protein owing to mutation and are intended to serve as a platform for prioritizing mutations, which could be potential targets for drug discovery and development of targeted therapeutics.
DOI : 10.1007/s12013-020-00960-z
Anahtar Kelimeler : GALE, Mutation, Galactose epimerase deficiency, Molecular dynamics simulation, Residue contacts, Residue networks
ISSN: 1085-9195 1559-0283
Sayı: 2
Cilt: 79
Sayfa: 201-219
8
Whole-exome sequencing analysis of NSCLC reveals the pathogenic missense variants from cancer-associated genes
Dergi Makalesi

Dergi Makalesi
Kaynak :
Science Direct
Dergi:
Computers in Biology and Medicine
Yayıncı:
Elsevier BV
Yazar(lar) :
Udhaya Kumar S , Ambritha Balasundaram , Hephzibah Cathryn R , Rinku Polachirakkal Varghese , Siva R , Gnanasambandan R , Salma Younes , Hatem Zayed , George Priya Doss C
Yıl :
2022
Salma Younes
Yayıncı Web Sitesi
Tam Metin
Kaydet Alıntıla
Background Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. NSCLC accounts for 84% of all lung cancer cases. In recent years, advances in pathway understanding, methods for discovering novel genetic biomarkers, and new drugs designed to inhibit the signaling cascades has enabled clinicians to personalize therapy for NSCLC. The primary aim of this study is to identify the genes associated with NSCLC that harbor pathogenic variants that could be causative for NSCLC. The second aim is to investigate their roles in different pathways that lead to NSCLC. Methods We examined exome-sequencing datasets from 54 NSCLC patients to characterize the variants associated with NSCLC. Results Our findings revealed that 17 variants in 14 genes were considered highly pathogenic, including CDKN2A, ERBB2, FOXP1, IDH1, JAK3, KMT2D, K-Ras, MSH3, MSH6, POLE, RNF43, TCF7L2, TP53, and TSC1. Gene set enrichment analysis revealed the involvement of transmembrane receptor protein tyrosine kinase activity, protein binding, ATP binding, phosphatidylinositol-4,5-bisphosphate 3-kinase, and Ras guanyl-nucleotide exchange factor activity. Pathway analysis of these genes yielded different cancer-related pathways, including colorectal, prostate, endometrial, pancreatic, PI3K-Akt signaling pathways, and signaling pathways regulating pluripotency of stem cells. Module 1 from protein-protein interactions (PPIs) identified genes that harbor pathogenic SNPs. Three of the most deleterious SNPs are ERBB2 (rs1196929947), K-Ras (rs121913529), and POLE (rs751425952). Interestingly, one patient has a pathogenic K-Ras variant (rs121913529) co-occurred with the missense variant (rs752054698) inTSC1 gene. Conclusion This study maps highly pathogenic variants associated with NSCLC and investigates their contributions to the pathogenesis of NSCLC. This study sheds light on the potential applications of precision medicine in patients with NSCLC.
DOI : 10.1016/j.compbiomed.2022.105701
Anahtar Kelimeler : Non-small cell lung cancer, Whole-exome sequencing, Non-synonymous single nucleotide polymorphisms, Pathogenic variants, PPI network, Pathway enrichment analysis, Precision medicine
ISSN: 0010-4825
Sayfa: 105701
9
Description of PTPRG genetic variants identified in a cohort of Chronic Myeloid Leukemia patients and their ability to influence response to Tyrosine kinase Inhibitors
Dergi Makalesi

Dergi Makalesi
Kaynak :
Science Direct
Yazar(lar) :
Mohamed.A. Ismail , Gheyath K. Nasrallah , Maria Monne , Ali AlSayab , Mohamed A. Yassin , Govindarajulu Varadharaj , Salma Younes , Claudio Sorio , Richard Cook , Helmout Modjtahedi , Nader I. Al-Dewik
Yıl :
2021
Salma Younes
Yayıncı Web Sitesi
Tam Metin
Kaydet Alıntıla
Tyrosine kinase inhibitors (TKIs) have remarkably transformed Ph+ chronic myeloid leukemia (CML) management; however, TKI resistance remains a major clinical challenge. Mutations in BCR-ABL1 are well studied but fail to explain 20–40% of resistant cases, suggesting the activation of alternative, BCR-ABL1-independent pathways. Protein Tyrosine Phosphatase Receptor Gamma (PTPRG), a tumor suppressor, was found to be well expressed in CML patients responsive to TKIs and remained at low level in resistant patients. In this study, we aimed to identify genetic variants in PTPRG that could potentially modulate TKIs response in CML patients. DNA was extracted from peripheral blood samples collected from two CML cohorts (Qatar and Italy) and targeted exome sequencing was performed. Among 31 CML patients, six were TKI-responders and 25 were TKI-non-responsive. Sequencing identified ten variants, seven were annotated and three were novel SNPs (c.1602_1603insC, c.85+14412delC, and c.2289-129delA). Among them, five variants were identified in 15 resistant cases. Of these, one novel exon variant (c.1602_1603insC), c.841-29C>T (rs199917960) and c.1378-224A>G (rs2063204) were found to be significantly different between the resistant cases compared to responders. Our findings suggest that PTPRG variants may act as an indirect resistance mechanism of BCR-ABL1 to affect TKI treatment.
DOI : 10.1016/j.gene.2021.146101
Anahtar Kelimeler : CML Chronic Myeloid Leukemia, Chronic Myeloid Leukemia, TKIs Tyrosine Kinase Inhibitors, Tyrosine Kinase Inhibitors, BCR-ABL1 Breakpoint cluster region- ABL Proto-Oncogene 1, Breakpoint cluster region- ABL Proto-Oncogene 1, PTPRG Protein Tyrosine Phosphatase Receptor Gamma, Protein Tyrosine Phosphatase Receptor Gamma, DNA Deoxyribonucleic Acid, Deoxyribonucleic Acid, SNP Single Nucleotide Polymorphisms, Single Nucleotide Polymorphisms, Ph Philadelphia Chromosome, Philadelphia Chromosome, CDK1 cyclin-Dependent Kinase 1, cyclin-Dependent Kinase 1, CDC2 Cell Division Cycle protein 2 homolog, Cell Division Cycle protein 2 homolog, ATP Adenosine Triphosphate, Adenosine Triphosphate, IM Imatinib Mesylate, Imatinib Mesylate, KD Kinase Domain, Kinase Domain, ELN European LeukemiaNet, European LeukemiaNet, PTP Protein Tyrosine Phosphatase, Protein Tyrosine Phosphatase, EDTA Ethylenediamine Tetraacetic Acid, Ethylenediamine Tetraacetic Acid, PGM Personal Genome Machine, Personal Genome Machine, OR Odds Ratio, Odds Ratio, CI Confidence Interval, Confidence Interval, QGP Qatar Genome Program, Qatar Genome Program, Chronic Myeloid Leukemia, Protein Tyrosine Phosphatase Receptor Type G, BCR-ABL1, Single Nucleotide Polymorphisms, Tyrosine Kinase Inhibitors, Therapeutic Modalities
ISSN: 0378-1119
Sayfa: 146101
10
A review of novel coronavirus disease (COVID-19): based on genomic structure, phylogeny, current shreds of evidence, candidate vaccines, and drug repurposing
Dergi Makalesi

Dergi Makalesi
Kaynak :
Springer Link
Dergi:
3 Biotech
Yazar(lar) :
S. Udhaya Kumar , N. Madhana Priya , S. R. Nithya , Priyanka Kannan , Nikita Jain , D. Thirumal Kumar , R. Magesh , Salma Younes , Hatem Zayed , C. George Priya Doss
Konu :
Agricultural and Biological Sciences (miscellaneous), Environmental Science (miscellaneous), Biotechnology
Yıl :
2021
Salma Younes
Yayıncı Web Sitesi
Tam Metin
Kaydet Alıntıla
Coronavirus disease (COVID-19) pandemic is instigated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of March 13, 2021, more than 118.9 million cases were infected with COVID-19 worldwide. SARS-CoV-2 is a positive-sense single-stranded RNA beta-CoV. Most COVID-19 infected individuals recover within 1–3 weeks. Nevertheless, approximately 5% of patients develop acute respiratory distress syndrome and other systemic complications, leading to death. Structural genetic analyses of SARS-CoV-2 have shown genomic resemblances but a low evolutionary correlation to SARS-CoV-1 responsible for the 2002–2004 outbreak. The S glycoprotein is critical for cell adhesion and the entrance of the virus into the host. The process of cell entry uses the cellular receptor named angiotensin-converting enzyme 2. Recent evidence proposed that the CD147 as a SARS-CoV-2′s potential receptor. The viral genome is mainly held by two non-structural proteins (NSPs), ORF1a and ORF1ab, along with structural proteins. Although NSPs are conserved among the βCoVs, mutations in NSP2 and NSP3 may play critical roles in transmitting the virus and cell tropism. To date, no specific/targeted anti-viral treatments exist. Notably, more than 50 COVID-19 candidate vaccines in clinical trials, and a few being administered. Preventive precautions are the primary strategy to limit the viral load transmission and spread, emphasizing the urgent need for developing significant drug targets and vaccines against COVID-19. This review provides a cumulative overview of the genomic structure, transmission, phylogeny of SARS-CoV-2 from Indian clusters, treatment options, updated discoveries, and future standpoints for COVID-19.
DOI : 10.1007/s13205-021-02749-0
Anahtar Kelimeler : COVID-19, Drug repurposing, SARS-CoV-2, SARS-CoV-2 genome, COVID-19 therapeutics, Vaccines, COVID-19 molecular diagnosis, Remdesivir, Hydroxychloroquine, Protease, India
ISSN: 2190-572X 2190-5738
Sayı: 4
Cilt: 11

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