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1.
PLoS One ; 19(6): e0304039, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38865327

RESUMO

Methylglyoxal (MG) is a highly cytotoxic molecule produced in all biological systems, which could be converted into non-toxic D-lactate by an evolutionarily conserved glyoxalase pathway. Glutathione-dependent glyoxalase I (GLYI) and glyoxalase II (GLYII) are responsible for the detoxification of MG into D-lactate in sequential reactions, while DJ-1 domain containing glyoxalase III (GLYIII) catalyzes the same reaction in a single step without glutathione dependency. Afterwards, D-lactate dehydrogenase (D-LDH) converts D-lactate into pyruvate, a metabolically usable intermediate. In the study, a comprehensive genome-wide investigation has been performed in one of the important vegetable plants, tomato to identify 13 putative GLYI, 4 GLYII, 3 GLYIII (DJ-1), and 4 D-LDH genes. Expression pattern analysis using microarray data confirmed their ubiquitous presence in different tissues and developmental stages. Moreover, stress treatment of tomato seedlings and subsequent qRT-PCR demonstrated upregulation of SlGLYI-2, SlGLYI-3, SlGLYI-6A, SlGLYII-1A, SlGLYII-3B, SlDJ-1A, SlDLDH-1 and SlDLDH-4 in response to different abiotic stresses, whereas SlGLYI-6B, SlGLYII-1B, SlGLYII-3A, SlDJ-1D and SlDLDH-2 were downregulated. Expression data also revealed SlGLYII-1B, SlGLYI-1A, SlGLYI-2, SlDJ-1D, and SlDLDH-4 were upregulated in response to various pathogenic infections, indicating the role of MG detoxifying enzymes in both plant defence and stress modulation. The functional characterization of each of these members could lay the foundation for the development of stress and disease-resistant plants promoting sustainable agriculture and production.


Assuntos
Regulação da Expressão Gênica de Plantas , Aldeído Pirúvico , Solanum lycopersicum , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Solanum lycopersicum/crescimento & desenvolvimento , Aldeído Pirúvico/metabolismo , Perfilação da Expressão Gênica , Genoma de Planta , Filogenia , Evolução Molecular , Família Multigênica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Tioléster Hidrolases/genética , Tioléster Hidrolases/metabolismo , Lactoilglutationa Liase/genética , Lactoilglutationa Liase/metabolismo , Estresse Fisiológico/genética
2.
Virus Res ; 341: 199323, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38237808

RESUMO

Virion infectivity factor (Vif), an accessory protein of HIV-1 (human immunodeficiency virus type 1), antagonizes host APOBEC3 protein (apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3) or A3 via proteasomal degradation, facilitating viral replication. HLA (Human leukocyte antigens) alleles, host restriction factors, and error-prone reverse transcription contribute to the global polymorphic dynamics of HIV, impacting effective vaccine design. Our computational analysis of over 50,000 HIV-1 M vif sequences from the Los Alamos National Laboratory (LANL) database (1998-2021) revealed positive selection pressure on the vif gene (nonsynonymous to synonymous ratio, dn/ds=1.58) and an average entropy score of 0.372 in protein level. Interestingly, over the years (1998-2021), a decreasing trend of dn/ds (1.68 to 1.47) and an increasing trend of entropy (0.309 to 0.399) was observed. The predicted mutational frequency against Vif consensus sequence decreased over time (slope = -0.00024, p < 0.0001). Sequence conservation was observed in Vif functional motifs F1, F2, F3, G, BC box, and CBF ß binding region, while variability was observed mainly in N- and C- terminal and Zinc finger region, which were dominantly under immune pressure by host HLA-I-restricted CD8+ T cell. Computational analysis of ∆∆Gstability through protein stability prediction tools suggested that missense mutation may affect Vif stability, especially in the Vif-A3 binding interface. Notably, mutations R17K and Y44F in F1 and G box were predicted to destabilize the Vif-A3 binding interface by altering bond formations with adjacent amino acids. Therefore, our analysis demonstrates Vif adaptation with host physiology by maintaining sequence conservation, especially in A3 interacting functional motifs, highlighting important therapeutic candidate regions of Vif against HIV-1 infections.


Assuntos
Infecções por HIV , HIV-1 , Humanos , Produtos do Gene vif do Vírus da Imunodeficiência Humana/genética , Produtos do Gene vif do Vírus da Imunodeficiência Humana/química , Produtos do Gene vif do Vírus da Imunodeficiência Humana/metabolismo , Mutação de Sentido Incorreto , Polimorfismo Genético , Ligação Proteica , Citidina Desaminase/genética , Citidina Desaminase/metabolismo
3.
Sci Rep ; 13(1): 18644, 2023 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-37903828

RESUMO

The identification of deleterious mutations in different variants of SARS-CoV-2 and their roles in the morbidity of COVID-19 patients has yet to be thoroughly investigated. To unravel the spectrum of mutations and their effects within SARS-CoV-2 genomes, we analyzed 5,724 complete genomes from deceased COVID-19 patients sourced from the GISAID database. This analysis was conducted using the Nextstrain platform, applying a generalized time-reversible model for evolutionary phylogeny. These genomes were compared to the reference strain (hCoV-19/Wuhan/WIV04/2019) using MAFFT v7.470. Our findings revealed that SARS-CoV-2 genomes from deceased individuals belonged to 21 Nextstrain clades, with clade 20I (Alpha variant) being the most predominant, followed by clade 20H (Beta variant) and clade 20J (Gamma variant). The majority of SARS-CoV-2 genomes from deceased patients (33.4%) were sequenced in North America, while the lowest percentage (0.98%) came from Africa. The 'G' clade was dominant in the SARS-CoV-2 genomes of Asian, African, and North American regions, while the 'GRY' clade prevailed in Europe. In our analysis, we identified 35,799 nucleotide (NT) mutations throughout the genome, with the highest frequency (11,402 occurrences) found in the spike protein. Notably, we observed 4150 point-specific amino acid (AA) mutations in SARS-CoV-2 genomes, with D614G (20%) and N501Y (14%) identified as the top two deleterious mutations in the spike protein on a global scale. Furthermore, we detected five common deleterious AA mutations, including G18V, W45S, I33T, P30L, and Q418H, which play a key role in defining each clade of SARS-CoV-2. Our novel findings hold potential value for genomic surveillance, enabling the monitoring of the evolving pattern of SARS-CoV-2 infection, its emerging variants, and their impact on the development of effective vaccination and control strategies.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiologia , Glicoproteína da Espícula de Coronavírus/genética , Aminoácidos , Mutação , Filogenia
4.
Ann Med Surg (Lond) ; 85(6): 3213-3217, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37363468

RESUMO

Dengue virus infection, a highly prominent health concern, has caused many health complications, positive cases, and deaths in Bangladesh in previous years. However, the prevalence of this infection and fatality rates in 2022 has shattered all prior records. The dengue virus vector, mosquitoes, found a high prevalence of infection due to the weather's favorable conditions for breeding in the months of June and July. While there is presently no particular vaccination for dengue infection, awareness of its epidemiology, pathogenesis, signs, and symptoms may aid in the development of improved diagnostic and treatment strategies. The government should also improve the infrastructure of cities to make prevent mosquito breeding and the spread of dengue infection.

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