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  1. Article ; Online: Assessing the evolution of SARS-CoV-2 lineages and the dynamic associations between nucleotide variations.

    Gupta, Asmita / Basu, Reelina / Bashyam, Murali Dharan

    Access microbiology

    2023  Volume 5, Issue 7

    Abstract: Despite seminal advances towards understanding the infection mechanism of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), it continues to cause significant morbidity and mortality worldwide. Though mass immunization programmes have been ... ...

    Abstract Despite seminal advances towards understanding the infection mechanism of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), it continues to cause significant morbidity and mortality worldwide. Though mass immunization programmes have been implemented in several countries, the viral transmission cycle has shown a continuous progression in the form of multiple waves. A constant change in the frequencies of dominant viral lineages, arising from the accumulation of nucleotide variations (NVs) through favourable selection, is understandably expected to be a major determinant of disease severity and possible vaccine escape. Indeed, worldwide efforts have been initiated to identify specific virus lineage(s) and/or NVs that may cause a severe clinical presentation or facilitate vaccination breakthrough. Since host genetics is expected to play a major role in shaping virus evolution, it is imperative to study the role of genome-wide SARS-CoV-2 NVs across various populations. In the current study, we analysed the whole genome sequence of 3543 SARS-CoV-2-infected samples obtained from the state of Telangana, India (including 210 from our previous study), collected over an extended period from April 2020 to October 2021. We present a unique perspective on the evolution of prevalent virus lineages and NVs during this period. We also highlight the presence of specific NVs likely to be associated favourably with samples classified as vaccination breakthroughs. Finally, we report genome-wide intra-host variations at novel genomic positions. The results presented here provide critical insights into virus evolution over an extended period and pave the way to rigorously investigate the role of specific NVs in vaccination breakthroughs.
    Language English
    Publishing date 2023-07-20
    Publishing country England
    Document type Journal Article
    ISSN 2516-8290
    ISSN (online) 2516-8290
    DOI 10.1099/acmi.0.000513.v3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: To β or Not to β: Lack of Correlation Between APC Mutation and β-Catenin Nuclear Localization in Colorectal Cancer.

    Bala, Pratyusha / Kavadipula, Padmavathi / Sarkar, Sanjana / Bashyam, Murali Dharan

    Journal of gastrointestinal cancer

    2022  Volume 54, Issue 4, Page(s) 1181–1184

    Abstract: Purpose: Colorectal cancer (CRC) appears to arise from sequential genetic lesions in tumor suppressor genes (APC, SMAD4, and TP53) and oncogenes (KRAS) leading to the classical adenoma to carcinoma progression. Biallelic APC inactivating genetic ... ...

    Abstract Purpose: Colorectal cancer (CRC) appears to arise from sequential genetic lesions in tumor suppressor genes (APC, SMAD4, and TP53) and oncogenes (KRAS) leading to the classical adenoma to carcinoma progression. Biallelic APC inactivating genetic aberrations are detected in about 70% of early microadenomas implicating APC inactivation as the first genetic hit in CRC. APC is an essential protein of the Wnt 'destruction complex'; APC inactivation is believed to cause disruption of the complex allowing stabilization and nuclear translocation of β-catenin, resulting in transcriptional activation of cancer-promoting genes.
    Methods: β-catenin nuclear localization and APC mutation were validated from serial FFPE sections representing the same tumor regions, using immunohistochemistry and Sanger sequencing, respectively.
    Results: Here, we provide evidence for a surprising lack of correlation between APC mutation and β-catenin nuclear localization in early-onset sporadic rectal cancer samples. Several factors including status of KRAS mutation could not explain this anomaly. The lack of correlation was validated in CRC cell lines harboring various APC mutations.
    Conclusion: Our results provide evidence directly from tumor samples for possible non-canonical role(s) for mutant APC.
    MeSH term(s) Humans ; beta Catenin/genetics ; beta Catenin/metabolism ; Colorectal Neoplasms/pathology ; Proto-Oncogene Proteins p21(ras)/genetics ; Proto-Oncogene Proteins p21(ras)/metabolism ; Wnt Signaling Pathway/genetics ; Mutation ; Adenomatous Polyposis Coli Protein/genetics ; Adenomatous Polyposis Coli Protein/metabolism
    Chemical Substances beta Catenin ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; Adenomatous Polyposis Coli Protein
    Language English
    Publishing date 2022-12-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2452514-5
    ISSN 1941-6636 ; 1559-0739 ; 1941-6628 ; 1537-3649
    ISSN (online) 1941-6636 ; 1559-0739
    ISSN 1941-6628 ; 1537-3649
    DOI 10.1007/s12029-022-00886-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Monitoring SARS-CoV-2 genome evolution in a localized population

    Gupta, Asmita / Basu, Reelina / Bashyam, Murali Dharan

    medRxiv

    Abstract: Despite seminal advances towards understanding its infection mechanism, SARS-CoV-2 continues to cause significant morbidity and mortality worldwide. Though mass immunization programs have been implemented in several countries, the viral transmission ... ...

    Abstract Despite seminal advances towards understanding its infection mechanism, SARS-CoV-2 continues to cause significant morbidity and mortality worldwide. Though mass immunization programs have been implemented in several countries, the viral transmission cycle has shown a continuous progression in the form of multiple waves. A constant change in the frequencies of dominant viral lineages, arising from the accumulation of nucleotide variations (NVs) through favourable selection, is understandably expected to be a major determinant of disease severity and possible vaccine escape. Indeed, worldwide efforts have been initiated to identify specific virus lineage(s) and/or NVs that may cause a severe clinical presentation or facilitate vaccination breakthrough. Since host genetics is expected to play a major role in shaping virus evolution, it is imperative to study role of genome-wide SARS-CoV-2 NVs across various populations. In the current study, we analysed the whole genome sequence of 3543 SARS-CoV-2 infected samples obtained from the state of Telangana, India (including 210 from our previous study), collected over an extended period from April, 2020 to October, 2021. We present a unique perspective on the evolution of prevalent virus lineages and NVs during this time period. We also highlight presence of specific NVs likely to be associated favourably with samples classified as vaccination breakthroughs. Finally, we report genome-wide intra-host variations (iSNVs) at novel genomic positions. The results presented here provide critical insights into virus evolution over an extended time period within a geographically restricted area and pave the way to rigorously investigate the role of specific NVs in vaccination breakthroughs.
    Keywords covid19
    Language English
    Publishing date 2022-01-21
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2022.01.19.22269572
    Database COVID19

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  4. Article ; Online: Aberrant cytoplasmic localization of ARID1B activates ERK signaling and promotes oncogenesis.

    Animireddy, Srinivas / Kavadipula, Padmavathi / Kotapalli, Viswakalyan / Gowrishankar, Swarnalata / Rao, Satish / Bashyam, Murali Dharan

    Journal of cell science

    2021  Volume 134, Issue 4

    Abstract: The ARID1B (BAF250b) subunit of the human SWI/SNF chromatin remodeling complex is a canonical nuclear tumor suppressor. We ... ...

    Abstract The ARID1B (BAF250b) subunit of the human SWI/SNF chromatin remodeling complex is a canonical nuclear tumor suppressor. We employed
    MeSH term(s) Carcinogenesis/genetics ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; DNA-Binding Proteins/metabolism ; Humans ; MAP Kinase Signaling System ; Protein Phosphatase 1 ; Signal Transduction ; Transcription Factors/genetics ; beta Catenin/genetics ; beta Catenin/metabolism
    Chemical Substances ARID1B protein, human ; DNA-Binding Proteins ; Transcription Factors ; beta Catenin ; PPP1CA protein, human (EC 3.1.3.16) ; Protein Phosphatase 1 (EC 3.1.3.16)
    Language English
    Publishing date 2021-02-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2993-2
    ISSN 1477-9137 ; 0021-9533
    ISSN (online) 1477-9137
    ISSN 0021-9533
    DOI 10.1242/jcs.251637
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Novel EDA mutations cause X-linked hypohidrotic ectodermal dysplasia: the first study from Venezuela.

    Cammarata-Scalisi, Francisco / Callea, Michele / Chaudhary, Ajay Kumar / Tadich, Antonio Cárdenas / Castillo, Maykol Araya / Morabito, Antonino / Bellacchio, Emanuele / Pisaneschi, Elisa / Novelli, Antonio / Willoughby, Colin E / Bashyam, Murali Dharan

    Clinical and experimental dermatology

    2023  Volume 48, Issue 12, Page(s) 1409–1413

    MeSH term(s) Humans ; Ectodermal Dysplasia 1, Anhidrotic/genetics ; Venezuela ; Ectodermal Dysplasia/genetics ; Ectodysplasins/genetics ; Mutation ; Pedigree
    Chemical Substances Ectodysplasins
    Language English
    Publishing date 2023-06-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 195504-4
    ISSN 1365-2230 ; 0307-6938
    ISSN (online) 1365-2230
    ISSN 0307-6938
    DOI 10.1093/ced/llad218
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Exome sequencing identifies ARID2 as a novel tumor suppressor in early-onset sporadic rectal cancer.

    Bala, Pratyusha / Singh, Anurag Kumar / Kavadipula, Padmavathi / Kotapalli, Viswakalyan / Sabarinathan, Radhakrishnan / Bashyam, Murali Dharan

    Oncogene

    2020  Volume 40, Issue 4, Page(s) 863–874

    Abstract: Early-onset sporadic rectal cancer (EOSRC) is a unique and predominant colorectal cancer (CRC) subtype in India. In order to understand the tumorigenic process in EOSRC, we performed whole-exome sequencing of 47 microsatellite stable EOSRC samples. ... ...

    Abstract Early-onset sporadic rectal cancer (EOSRC) is a unique and predominant colorectal cancer (CRC) subtype in India. In order to understand the tumorigenic process in EOSRC, we performed whole-exome sequencing of 47 microsatellite stable EOSRC samples. Signature 1 was the predominant mutational signature in EOSRC, as previously shown in other CRC exome studies. More importantly, we identified TP53, KRAS, APC, PIK3R1, SMAD4 and ZNF880 as significantly mutated (q < 0.1) and ARID1A and ARID2 as near-significantly mutated (restricted hypothesis testing; q < 0.1) candidate drivers. Unlike the other candidates, the tumorigenic potential of ARID2, encoding a component of the SWI/SNF chromatin remodeling complex, is largely unexplored in CRC. shRNA-mediated ARID2 knockdown performed in different CRC cell lines resulted in significant alterations in transcript levels of cancer-related target genes. More importantly, ARID2 knockdown promoted several tumorigenic features including cell viability, proliferation, ability to override contact inhibition of growth, and migration besides significantly increasing tumor formation ability in nude mice. The observed gain in tumorigenic features was rescued upon ectopic expression of wild type but not mutant ARID2. Analyses of the TCGA pan-cancer dataset revealed several modes of ARID2 inactivation and of the CRC dataset revealed poorer survival in patients with ARID2 alterations. We therefore propose ARID2 as a novel tumor suppressor in CRC.
    MeSH term(s) Adult ; Animals ; Cell Line, Tumor ; Female ; Genes, p53 ; Humans ; Male ; Mice ; Middle Aged ; Mutation ; Proto-Oncogene Proteins p21(ras)/genetics ; Rectal Neoplasms/genetics ; Transcription Factors/physiology ; Tumor Suppressor Proteins/physiology ; Whole Exome Sequencing/methods
    Chemical Substances ARID2 protein, human ; KRAS protein, human ; Transcription Factors ; Tumor Suppressor Proteins ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
    Language English
    Publishing date 2020-12-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639046-8
    ISSN 1476-5594 ; 0950-9232
    ISSN (online) 1476-5594
    ISSN 0950-9232
    DOI 10.1038/s41388-020-01537-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Apico-basal polarity complex and cancer.

    Khursheed, Mohammed / Bashyam, Murali Dharan

    Journal of biosciences

    2014  Volume 39, Issue 1, Page(s) 145–155

    Abstract: Apico-basal polarity is a cardinal molecular feature of adult eukaryotic epithelial cells and appears to be involved in several key cellular processes including polarized cell migration and maintenance of tissue architecture. Epithelial cell polarity is ... ...

    Abstract Apico-basal polarity is a cardinal molecular feature of adult eukaryotic epithelial cells and appears to be involved in several key cellular processes including polarized cell migration and maintenance of tissue architecture. Epithelial cell polarity is maintained by three well-conserved polarity complexes, namely, PAR, Crumbs and SCRIB. The location and interaction between the components of these complexes defines distinct structural domains of epithelial cells. Establishment and maintenance of apico-basal polarity is regulated through various conserved cell signalling pathways including TGF beta, Integrin and WNT signalling. Loss of cell polarity is a hallmark for carcinoma, and its underlying molecular mechanism is beginning to emerge from studies on model organisms and cancer cell lines. Moreover, deregulated expression of apico-basal polarity complex components has been reported in human tumours. In this review, we provide an overview of the apico-basal polarity complexes and their regulation, their role in cell migration, and finally their involvement in carcinogenesis.
    MeSH term(s) Carcinoma/physiopathology ; Cell Movement/genetics ; Cell Polarity/physiology ; Epithelial Cells/cytology ; Gene Expression Regulation, Neoplastic/physiology ; Humans ; Membrane Proteins/metabolism ; Models, Biological ; Multiprotein Complexes/metabolism ; Neoplasm Proteins/metabolism ; Signal Transduction/physiology ; Tumor Suppressor Proteins/metabolism
    Chemical Substances JTB protein, human ; Membrane Proteins ; Multiprotein Complexes ; Neoplasm Proteins ; SCRIB protein, human ; Tumor Suppressor Proteins
    Language English
    Publishing date 2014-02-06
    Publishing country India
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 756157-x
    ISSN 0973-7138 ; 0250-5991
    ISSN (online) 0973-7138
    ISSN 0250-5991
    DOI 10.1007/s12038-013-9410-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: The Yin and Yang of cancer genes

    Bashyam, Murali Dharan / Animireddy, Srinivas / Bala, Pratyusha / Naz, Ashmala / George, Sara Anisa

    Gene. 2019 July 01, v. 704

    2019  

    Abstract: Cancer is caused by malfunctioning of genes that normally regulate cardinal processes including various nuclear functions, cell division and survival, cell surface to nucleus signaling cascades, etc. Cancer associated genes are often classified as ... ...

    Abstract Cancer is caused by malfunctioning of genes that normally regulate cardinal processes including various nuclear functions, cell division and survival, cell surface to nucleus signaling cascades, etc. Cancer associated genes are often classified as oncogenes (OCGs) or tumor suppressor genes (TSGs) depending on whether they promote or suppress tumorigenesis, respectively. Such strict classification of cancer genes may however be an over-simplification. Several studies have highlighted a dual role for cancer genes, often impacting the same facet of tumorigenesis. Knowledge of a possible dichotomy of a cancer gene (particularly an OCG) is imperative when evaluating its possible utility as a therapeutic target. Though previous studies have extensively evaluated specific examples of cancer genes exhibiting a dual nature, efforts to unravel the molecular basis for such contrasting functions have been fewer. The current review is an attempt to delineate molecular events underlying the functional dichotomy of cancer genes at the DNA (mutations, gene fusions, etc.), RNA (alternative splicing, regulation through non-coding RNAs, etc.) and protein (isoforms, mis-localisation, post-translational modifications, proteolytic cleavage, etc.) levels.
    Keywords DNA ; alternative splicing ; carcinogenesis ; cell division ; mutation ; neoplasms ; non-coding RNA ; oncogenes ; post-translational modification ; proteolysis ; therapeutics ; tumor suppressor genes
    Language English
    Dates of publication 2019-0701
    Size p. 121-133.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 391792-7
    ISSN 1879-0038 ; 0378-1119
    ISSN (online) 1879-0038
    ISSN 0378-1119
    DOI 10.1016/j.gene.2019.04.025
    Database NAL-Catalogue (AGRICOLA)

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  9. Article: Apico-basal polarity complex and cancer

    Khursheed, Mohammed / Bashyam, Murali Dharan

    Journal of biosciences. 2014 Mar., v. 39, no. 1

    2014  

    Abstract: Apico-basal polarity is a cardinal molecular feature of adult eukaryotic epithelial cells and appears to be involved in several key cellular processes including polarized cell migration and maintenance of tissue architecture. Epithelial cell polarity is ... ...

    Abstract Apico-basal polarity is a cardinal molecular feature of adult eukaryotic epithelial cells and appears to be involved in several key cellular processes including polarized cell migration and maintenance of tissue architecture. Epithelial cell polarity is maintained by three well-conserved polarity complexes, namely, PAR, Crumbs and SCRIB. The location and interaction between the components of these complexes defines distinct structural domains of epithelial cells. Establishment and maintenance of apico-basal polarity is regulated through various conserved cell signalling pathways including TGFβ, Integrin and WNT signalling. Loss of cell polarity is a hallmark for carcinoma, and its underlying molecular mechanism is beginning to emerge from studies on model organisms and cancer cell lines. Moreover, deregulated expression of apico-basal polarity complex components has been reported in human tumours. In this review, we provide an overview of the apico-basal polarity complexes and their regulation, their role in cell migration, and finally their involvement in carcinogenesis.
    Keywords adults ; carcinogenesis ; carcinoma ; cell communication ; cell movement ; cell polarity ; epithelial cells ; humans ; integrins ; photosynthetically active radiation ; transforming growth factor beta
    Language English
    Dates of publication 2014-03
    Size p. 145-155.
    Publishing place Springer-Verlag
    Document type Article
    ZDB-ID 756157-x
    ISSN 0973-7138 ; 0250-5991
    ISSN (online) 0973-7138
    ISSN 0250-5991
    DOI 10.1007/s12038-013-9410-z
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: The Yin and Yang of cancer genes.

    Bashyam, Murali Dharan / Animireddy, Srinivas / Bala, Pratyusha / Naz, Ashmala / George, Sara Anisa

    Gene

    2019  Volume 704, Page(s) 121–133

    Abstract: Cancer is caused by malfunctioning of genes that normally regulate cardinal processes including various nuclear functions, cell division and survival, cell surface to nucleus signaling cascades, etc. Cancer associated genes are often classified as ... ...

    Abstract Cancer is caused by malfunctioning of genes that normally regulate cardinal processes including various nuclear functions, cell division and survival, cell surface to nucleus signaling cascades, etc. Cancer associated genes are often classified as oncogenes (OCGs) or tumor suppressor genes (TSGs) depending on whether they promote or suppress tumorigenesis, respectively. Such strict classification of cancer genes may however be an over-simplification. Several studies have highlighted a dual role for cancer genes, often impacting the same facet of tumorigenesis. Knowledge of a possible dichotomy of a cancer gene (particularly an OCG) is imperative when evaluating its possible utility as a therapeutic target. Though previous studies have extensively evaluated specific examples of cancer genes exhibiting a dual nature, efforts to unravel the molecular basis for such contrasting functions have been fewer. The current review is an attempt to delineate molecular events underlying the functional dichotomy of cancer genes at the DNA (mutations, gene fusions, etc.), RNA (alternative splicing, regulation through non-coding RNAs, etc.) and protein (isoforms, mis-localisation, post-translational modifications, proteolytic cleavage, etc.) levels.
    MeSH term(s) Animals ; Cell Transformation, Neoplastic/genetics ; Databases, Genetic ; Gene Expression Regulation, Neoplastic ; Genes, Neoplasm ; Genes, Tumor Suppressor/physiology ; Humans ; Mutation ; Neoplasms/genetics ; Neoplasms/pathology ; Oncogenes/physiology
    Language English
    Publishing date 2019-04-11
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 391792-7
    ISSN 1879-0038 ; 0378-1119
    ISSN (online) 1879-0038
    ISSN 0378-1119
    DOI 10.1016/j.gene.2019.04.025
    Database MEDical Literature Analysis and Retrieval System OnLINE

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