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1.
J Cancer Res Clin Oncol ; 150(5): 226, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38696003

RESUMEN

High-linear energy transfer (LET) radiation is a promising alternative to conventional low-LET radiation for therapeutic gain against cancer owing to its ability to induce complex and clustered DNA lesions. However, the development of radiation resistance poses a significant barrier. The potential molecular mechanisms that could confer resistance development are translesion synthesis (TLS), replication gap suppression (RGS) mechanisms, autophagy, epithelial-mesenchymal transition (EMT) activation, release of exosomes, and epigenetic changes. This article will discuss various types of complex clustered DNA damage, their repair mechanisms, mutagenic potential, and the development of radiation resistance strategies. Furthermore, it highlights the importance of careful consideration and patient selection when employing high-LET radiotherapy in clinical settings.


Asunto(s)
Transferencia Lineal de Energía , Neoplasias , Tolerancia a Radiación , Humanos , Neoplasias/radioterapia , Neoplasias/patología , Daño del ADN/efectos de la radiación , Reparación del ADN/efectos de la radiación , Animales
2.
Front Microbiol ; 15: 1389074, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38605710

RESUMEN

The co-protease activity in the RecA-ssDNA complex cleaves the autorepressor LexA, resulting in the derepression of a large number of genes under LexA control. This process is called the SOS response, and genes that are expressed in response to DNA damage are called SOS genes. The proteins encoded by the SOS genes are involved in both DNA repair and maintaining the functions of crucial cell division proteins (e.g., FtsZ) under check until the damaged DNA is presumably repaired. This mechanism of SOS response is the only known mechanism of DNA damage response and cell cycle regulation in bacteria. However, there are bacteria that do not obey this rule of DNA damage response and cell cycle regulation, yet they respond to DNA damage, repair it, and survive. That means such bacteria would have some alternate mechanism(s) of DNA damage response and cell cycle regulation beyond the canonical pathway of the SOS response. In this study, we present the perspectives that bacteria may have other mechanisms of DNA damage response and cell cycle regulation mediated by bacterial eukaryotic type Ser/Thr protein kinases as an alternate to the canonical SOS response and herewith elaborate on them with a well-studied example in the radioresistant bacterium Deinococcus radiodurans.

3.
J Bacteriol ; 206(4): e0000624, 2024 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-38445859

RESUMEN

Bacterial biofilms are intricate ecosystems of microbial communities that adhere to various surfaces and are enveloped by an extracellular matrix composed of polymeric substances. Within the context of bacterial biofilms, extracellular DNA (eDNA) originates from cell lysis or is actively secreted, where it exerts a significant influence on the formation, stability, and resistance of biofilms to environmental stressors. The exploration of eDNA within bacterial biofilms holds paramount importance in research, with far-reaching implications for both human health and the environment. An enhanced understanding of the functions of eDNA in biofilm formation and antibiotic resistance could inspire the development of strategies to combat biofilm-related infections and improve the management of antibiotic resistance. This comprehensive review encapsulates the latest discoveries concerning eDNA, encompassing its origins, functions within bacterial biofilms, and significance in bacterial pathogenesis.


Asunto(s)
Biopelículas , Ecosistema , Humanos , ADN Bacteriano/genética , Bacterias/genética , Matriz Extracelular
4.
Appl Environ Microbiol ; 90(2): e0194823, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38193676

RESUMEN

Deinococcus radiodurans exhibits remarkable survival under extreme conditions, including ionizing radiation, desiccation, and various DNA-damaging agents. It employs unique repair mechanisms, such as single-strand annealing (SSA) and extended synthesis-dependent strand annealing (ESDSA), to efficiently restore damaged genome. In this study, we investigate the role of the natural transformation-specific protein DprA in DNA repair pathways following acute gamma radiation exposure. Our findings demonstrate that the absence of DprA leads to rapid repair of gamma radiation-induced DNA double-strand breaks primarily occur through SSA repair pathway. Additionally, our findings suggest that the DprA protein may hinder both the SSA and ESDSA repair pathways, albeit in distinct manners. Overall, our results highlight the crucial function of DprA in the selection between SSA and ESDSA pathways for DNA repair in heavily irradiated D. radiodurans.IMPORTANCEDeinococcus radiodurans exhibits an extraordinary ability to endure and thrive in extreme environments, including exposure to radiation, desiccation, and damaging chemicals, as well as intense UV radiation. The bacterium has evolved highly efficient repair mechanisms capable of rapidly mending hundreds of DNA fragments in its genome. Our research indicates that natural transformation (NT)-specific dprA genes play a pivotal role in regulating DNA repair in response to radiation. Remarkably, we found that DprA is instrumental in selecting DNA double-strand break repair pathways, a novel function that has not been reported before. This unique regulatory mechanism highlights the indispensable role of DprA beyond its native function in NT and underscores its ubiquitous presence across various bacterial species, regardless of their NT proficiency. These findings shed new light on the resilience and adaptability of Deinococcus radiodurans, opening avenues for further exploration into its exceptional survival strategies.


Asunto(s)
Proteínas Bacterianas , Deinococcus , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Reparación del ADN , Roturas del ADN de Doble Cadena , ADN/metabolismo , Daño del ADN , Deinococcus/genética , Deinococcus/metabolismo , ADN Bacteriano/genética , ADN Bacteriano/metabolismo
5.
Clin Pediatr (Phila) ; : 99228231214887, 2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38062742

RESUMEN

Childhood hypertension (HTN) is becoming one of the most important health concerns in children, and it is the most important predictor of adult HTN. The objective was to assess the level of knowledge and to develop and validate questionnaires about childhood HTN among final-year medical students. This facility-based cross-sectional study was conducted from January 2018 to September 2018 in 5 teaching hospitals of Central India. A total of 383 interviews were conducted by non-probability purposive sampling using a validated tool. Exploratory factor analysis was used to assess the validity of the questionnaire, and internal consistency of items was assessed with Cronbach α. A total of 26 items were finalized through consensus. The Kaiser-Meyer-Olkin (KMO) measure of sample adequacy was measures of sampling adequacy (MSA) = 0.83, and Bartlett's test of sphericity was (x2 = 15.89, P = .014). This study shows that the tool developed had acceptable validity and reliability to assess the knowledge about childhood HTN among undergraduate medical students.

6.
J Obstet Gynaecol India ; 72(4): 299-306, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35923506

RESUMEN

Purpose: Preeclampsia (PE) affects 5-7% of the pregnancies worldwide, and is one of the most dreaded disorders of pregnancy contributing to maternal and neonatal mortality. PE is mostly presented in the third trimester of pregnancy. Here, we used serum placental growth factor (PIGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) to develop a model for predicting PE in Indian women in early second trimester. Methods: In this case-control study, a total 1452 healthy pregnant women were recruited. Blood samples were collected at the following gestational weeks (GWs), 12-20 (GW1), 21-28 (GW2) and 29-term (GW3), and post-delivery. Body mass index (BMI) was calculated by anthropometric measurements. Serum sFlt-1, PIGF and VEGF were analyzed by ELISA. A predictive model for PE was developed using multivariable logistic regression analysis. Results: In PE cases, serum PlGF and VEGF levels were significantly lower at each GW, while serum sFlt-1 was lower only at GW1, relative to age-matched controls, (n = 132/group). Age-matched comparison between PE cases and controls indicated that sFlt-1 was associated with decreased PE outcome (Odds ratio. OR = 0.988, CI = 0.982-0.993), whereas sFlt-1/PlGF ratio (OR = 1.577, CI = 1.344-1.920) and BMI (OR = 1.334, CI = 1.187-1.520) were associated with increased PE outcome. Logistic regression was used to develop a predictive model for PE at GW1. Using testing dataset, model was externally validated which resulted in 88% accuracy in predicting PE cases at 0.5 probability cutoff. Conclusion: Prediction model using sFlt-1, sFlt-1/PlGF ratio and BMI may be useful to predict PE as early as 12-20 weeks in women with optimal sensitivity and specificity.

7.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-22277718

RESUMEN

ObjectivesTo determine association of biomarkers high sensitivity C-reactive protein (hsCRP), D-dimer, interleukin-6 (IL-6), lactic dehydrogenase (LDH), ferritin and neutrophil-lymphocyte ratio (NLR) at hospital admission with clinical features and outcomes in Covid-19. MethodsSuccessive virologically confirmed Covid-19 patients hospitalized from April 2020 to July 2021 were recruited in a prospective registry. Details of clinical presentation, investigations, management and outcomes were recorded. All the biomarkers were divided into tertiles to determine associations with clinical features and outcomes. Numerical data are presented in median and interquartile range (IQR 25-75). Univariate and multivariate (age, sex, risk factor, comorbidity adjusted) odds ratio (OR) and 95% confidence intervals (CI) were calculated to determine association of deaths with each biomarker. ResultsWe identified 3036 virologically confirmed Covid-19 patients during the study period, 1215 were hospitalized and included in the present study. Men were 70.0%, aged >60y 44.8%, hypertension 44.8% diabetes 39.6% and cardiovascular disease 18.9%. Median symptom duration was 5 days (IQR 4-7) and SpO2 95% (90-97). Total white cell count was 6.9x103/{micro}l, (5.0-9.8), neutrophils 79.2% (68.1-88.2) and lymphocytes 15.8% (8.7-25.5). Medians (IQR) for biomarkers were hsCRP 6.9 mg/dl (2.2-18.9), D-dimer 464 ng/dl (201-982), IL-6 20.1 ng/dl (6.5-60.4), LDH 284 mg/dl (220-396) and ferritin 351 mg/dl (159-676). Oxygen support at admission was in 38.6%, and non-invasive or invasive ventilatory support in 11.0% and 11.6% respectively. 173 (13.9%) patients died and 15 (1.2%) transferred to hospice care. For each biomarker, those in the second and third tertiles, compared to the first, had worse clinical and laboratory abnormalities, and greater oxygen and ventilatory support. Multivariate adjusted OR (95% CI) for deaths in second and third vs first tertiles, respectively, were for hsCRP 2.29(1.14-4.60) and 13.39(7.23-24.80); D-dimer 3.26(1.31-7.05) and 13.89(6.87-28.27); IL-6 2.61(1.31-5.18) and 10.96(5.88-20.43); ferritin 3.19(1.66-6.11) and 9.13(4.97-16.78); LDH 1.85(0.87-3.97) and 10.51(5.41-20.41); and NLR 3.34(1.62-6.89) and 17.52(9.03-34.00) (p<0.001). ConclusionsIn Covid-19, high levels of biomarkers-hsCRP, D-dimer, IL-6, LDH, ferritin and NLR are associated with more severe illness and significantly greater in-hospital mortality. NLR, a simple, widely available and inexpensive investigation provides prognostic information similar to the more expensive biomarkers.

8.
Water Sci Technol ; 85(2): 562-577, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35100139

RESUMEN

In the present study a coagulation process was used as a pretreatment for a reverse osmosis (RO) membrane with turbid raw water collected from Bisalpur dam, Rajasthan, India. To optimize the coagulation performance, three kinds of coagulant, namely, alum (commercially available), synthesized inorganic polymeric coagulant-medium basicity (IPC-M), and inorganic polymeric coagulant-ultrahigh basicity (IPC-UH) were examined for turbidity removal with varying operating parameters. It was observed that in the optimum pH range of 6-7, the IPC-UH was the best performing coagulant with a 0.99 mg/L equivalent Al2O3 dose, revealing 2 NTU residual turbidity and residual aluminium of 0.001 mg/L. Moreover, the Langelier saturation index and Ryznar stability index values were evaluated at optimum conditions for all the three coagulants providing negligible scaling potential. Furthermore, the coagulant-treated water (100 L) was fed to the RO membrane, and the performance was noted in terms of flux, pressure, and total dissolved solids. It was observed that IPC-UH had the lowest reduction in permeate flux of 0.78 L/min/m2 compared with the commercially available coagulant alum (0.90 L/min/m2). Also, an increased feed pressure was observed for all the coagulant-treated waters with the lowest value of 2.3 kg/cm2 for IPC-UH, which was 2.5 kg/cm2 for alum (commercially available coagulant). Therefore, integration of coagulation before the RO system resulted in effective pretreatment of turbid water with very minute scaling.


Asunto(s)
Purificación del Agua , Agua , Filtración , India , Ósmosis
9.
Sci Total Environ ; 807(Pt 1): 150601, 2022 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-34597567

RESUMEN

Fluoride contamination has become a considerable threat to our society worldwide. Fluoride in drinking water is primarily due to rich fluoride soil, volcanic activity, forage, grasses and grains, and anthropogenic reasons. World Health Organization has regulated the upper limit for fluoride in drinking water to be 1.5 mg/L while different countries have set their standards according to their circumstances. Excess amounts of fluoride ions in drinking water can cause dental fluorosis, skeletal fluorosis, arthritis, bone damage, osteoporosis, muscular damage, fatigue, joint-related problems, and chronicle issues. In extreme conditions, it could adversely damage the heart, arteries, kidney, liver, endocrine glands, neuron system, and several other delicate parts of a living organism, briefed in the present article. Moreover, a comprehensive scenario for the situations in countries like, China, Canada, Mexico, United States, Yemen, Pakistan, Saudi Arabia, South Korea, Sri Lanka, Indonesia, Iran, Turkey, Australia, and India affected with high fluoride levels in ground water has been described. To analyze the presence of fluoride molecule, out of different detections methods, ion selective and colorimetric method has been adopted for real situation in the field of water application. Also, different methods to remove fluoride from water like reverse osmosis, nano filtration, adsorption, ion-exchange, and precipitation/coagulation with their removal mechanism were highlighted in the review. Moreover, the applicability of the approach with the prospect of country's economic status has been discussed, due to high cost and maintenance the membrane technology is not popular in developing countries like India, Senegal, Tanzania, and Kenya which employ adsorption and coagulation-precipitation for fluoride removal. It is noticeable from literature study that different approaches show unique potential for defluoridation. Some key parameters and mechanistic adaptations which could pave the defluoridation methods to newer horizons have been put forward.


Asunto(s)
Agua Potable , Fluorosis Dental , Agua Subterránea , Contaminantes Químicos del Agua , Purificación del Agua , Fluoruros/efectos adversos , Fluoruros/análisis , Humanos , Contaminantes Químicos del Agua/análisis
10.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21263091

RESUMEN

Background & ObjectiveCovid-19 pandemic has led to multiple waves secondary to mutations in SARS-CoV-2 and emergence of variants of concern (VOC). Clinical characteristics of delta (B.1.617.2) VOC are not well reported. To compare demographic, clinical and laboratory features and outcomes in the second Covid-19 wave in India (delta VOC) with the previous wave we performed a registry-based study. MethodsSuccessive SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed Covid-19 patients presenting to our Advanced Covid Care hospital were prospectively recruited. In the first phase (wave) from March-December 2020, 1395 of 7476 (18.7%) suspected patients tested positive and 863 (61.89%) hospitalized, while in second wave from January-July 2021 out of 1641 confirmed cases out of 8680 (19.4%) suspected 388 (23.6%) were hospitalized. Details of clinical and laboratory features at admission to hospital, management and outcomes in the two waves have been compared. ResultsIn both cohorts, majority were men and 20% less than 40 years. Prevalence of hypertension, diabetes and cardiovascular diseases was more than 20%. Second wave patients had similar pre-hospitalization symptom duration but had significantly greater cough, fever and shortness of breath and lower SpO2 at presentation with greater lymphopenia, C-reactive proteins, interleukin-6, ferritin, lactic dehydrogenase and transaminases. In the second vs first wave patients, requirement of supplementary oxygen (47.9% vs 34.3%), prone positioning (89.2 vs 38.6%), high flow nasal oxygen(15.7 vs 9.1%), non-invasive ventilation (14.4 vs 9.5%), invasive ventilation (16.2 vs 9.5%), steroids (94.1 vs 85.9%), remdesivir (91.2 vs 76.0%) and anticoagulants (94.3 vs 76.0%) was greater (p<0.001). Median (IQR) length of stay [8 (6-10) vs 7 (5-10) days] as well as ICU stay [9 (5-13) vs 6 (2-10) days] was more in second wave (p<0.001). In-hospital deaths occurred in 173 patients (13.9%) and were significantly more in the second wave, 75 (19.3%), compared to the first, 98 (11.5%); unadjusted odds ratio (95% CI) 1.84 (1.32-2.55) which did not change significantly with adjustment for age and sex (2.03, 1.44-2.86), and age, sex and comorbidities (2.09, 1.47-2.95). Greater disease severity at presentation was associated with mortality in both the waves. ConclusionsCovid-19 patients hospitalized during the second wave of the epidemic (delta variant) had more severe disease with greater dyspnea, hypoxia, hematological and biochemical abnormalities compared to first wave patients. They had greater length of stay in intensive care unit, oxygen requirement, non-invasive and invasive ventilatory support. The in-hospital mortality in the second wave was double of the first.

11.
Front Cell Dev Biol ; 9: 636178, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33959605

RESUMEN

DrRecA and PprA proteins function are crucial for the extraordinary resistance to γ-radiation and DNA strand break repair in Deinococcus radiodurans. DrRecA mediated homologous recombination help in DNA strand break repair and cell survival, while the PprA protein confers radio-resistance via its roles in DNA repair, genome maintenance, and cell division. Genetically recA and pprA genes interact and constitute an epistatic group however, the mechanism underlying their functional interaction is not clear. Here, we showed the physical and functional interaction of DrRecA and PprA protein both in solution and inside the cells. The absence of the pprA gene increases the recombination frequency in gamma-irradiated D. radiodurans cells and genomic instability in cells growing under normal conditions. PprA negatively regulates the DrRecA functions by inhibiting DrRecA mediated DNA strand exchange and ATPase function in vitro. Furthermore, it is shown that the inhibitory effect of PprA on DrRecA catalyzed DNA strand exchange was not due to sequestration of homologous dsDNA and was dependent on PprA oligomerization and DNA binding property. Together, results suggest that PprA is a new member of recombination mediator proteins (RMPs), and able to regulate the DrRecA function in γ-irradiated cells by protecting the D. radiodurans genome from hyper-recombination and associated negative effects.

12.
Environ Sci Pollut Res Int ; 28(4): 3897-3905, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32535825

RESUMEN

Excess fluoride (F) ion of drinking water is a major problem in many areas of India and causes harmful effects such as dental and skeletal fluorosis. The World Health Organization (WHO 2004) recommends an upper limit of 1.5 mg/L fluoride in drinking water, and the concentration of fluoride in groundwater has been found 10-20 times higher in many of the States in India. In this study, the performance of inorganic polymeric coagulant (IPC) named as IPC-23, IPC-13, IPC-17, and alum for fluoride removal from drinking water was investigated. The amount of IPC was decided according to the Al2O3 amount present in the alum dose recommended in the batch Nalgonda defluoridation technique. The effects of coagulant dosage (IPC) at different pH and initial concentrations of fluoride on fluoride removal have been studied. The synthetic sample having a fluoride concentration of 2 to 6 mg/L was treated at the optimized dosage and residual fluoride was reduced to 1.0 to 1.2 ppm with IPC-17. Residual aluminum in treated water was well within WHO norms (< 200 µg/L) for drinking water. Optimum pH for fluoride removal was 6.5, and there was deterioration in the performance of IPC at both lower and higher pH.


Asunto(s)
Agua Potable , Fluorosis Dental , Agua Subterránea , Contaminantes Químicos del Agua , Purificación del Agua , Fluoruros/análisis , Humanos , India , Contaminantes Químicos del Agua/análisis
13.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20232223

RESUMEN

ObjectiveTo describe the clinical profile and factors leading to increased mortality in coronavirus disease (COVID-19) patients admitted to a group of hospitals in India. DesignA records-based study of the first 1000 patients with a positive result on real-time reverse transcriptase-polymerase-chain-reaction assay for SARS-CoV-2 admitted to our facilities. Various factors such as demographics, presenting symptoms, co-morbidities, ICU admission, oxygen requirement and ventilator therapy were studied. ResultsOf the 1000 patients, 24 patients were excluded due to lack of sufficient data. Of the remaining 976 in the early phase of the epidemic, males were admitted twice as much as females (67.1% and 32.9%, respectively). Mortality in this initial phase was 10.6% and slightly higher for males and steeply higher for older patients. More than 8% reported no symptoms and the most common presenting symptoms were fever (78.3%), productive cough (37.2%), and dyspnea (30.64%). More than one-half (53.6%) had no co-morbidity. The major co-morbidities were hypertension (23.7%), diabetes without (15.4%), and with complications (9.6%). The co-morbidities were associated with higher ICU admissions, greater use of ventilators as well as higher mortality. A total of 29.9% were admitted to the ICU, with a mortality rate of 32.2%. Mortality was steeply higher in those requiring ventilator support (55.4%) versus those who never required ventilation (1.4%). The total duration of hospital stay was just a day longer in patients admitted to the ICU than those who remained in wards. ConclusionMale patients above the age of 60 and with co-morbidities faced the highest rates of mortality. They should be admitted to the hospital in early stage of the disease and given aggressive treatment to help reduce the morbidity and mortality associated with COVID-19.

14.
Preprint en Inglés | bioRxiv | ID: ppbiorxiv-162560

RESUMEN

SARS-CoV-2 pandemic resulted in 92 million cases in a span of one year. The study focuses on understanding population specific variations attributing its high rate of infections in specific geographical regions particularly in USA. Rigorous phylogenomic network analysis of complete SARS-CoV-2 genomes (245) inferred five central clades named a (ancestral), b, c, d and e (subtype e1 & e2). The clade d & e2 were found exclusively comprising of USA. Clades were distinguished by 10 co-mutational combinations in Nsp3, ORF8, Nsp13, S, Nsp12, Nsp2 and Nsp6. Our analysis revealed that only 67.46% of SNP mutations were at amino acid level. T1103P mutation in Nsp3 was predicted to increase protein stability in 238 strains except 6 strains which were marked as ancestral type; whereas co-mutation (P409L & Y446C) in Nsp13 were found in 64 genomes from USA highlighting its 100% co-occurrence. Docking highlighted mutation (D614G) caused reduction in binding of Spike proteins with ACE2, but it also showed better interaction with TMPRSS2 receptor contributing to high transmissibility among USA strains. We also found host proteins, MYO5A, MYO5B, MYO5C had maximum interaction with viral proteins (N, S, M). Thus, blocking the internalization pathway by inhibiting MYO5 proteins which could be an effective target for COVID-19 treatment. The functional annotations of the HPI network were found to be closely associated with hypoxia and thrombotic conditions confirming the vulnerability and severity of infection. We also screened CpG islands in Nsp1 & N conferring ability of SARS-CoV-2 to enter and trigger ZAP activity inside host cell. ImportanceIn the current study we presented a global view of mutational pattern observed in SARS-CoV-2 virus transmission. This provided a who-infect-whom geographical model since the early pandemic. This is hitherto the most comprehensive comparative genomics analysis of full-length genomes for co-mutations at different geographical regions specially in USA strains. Compositional structural biology results suggested that mutations have balance of contrary forces effect on pathogenicity suggesting only few mutations to effective at translation level but not all. Novel HPI analysis and CpG predictions elucidates the proof of concept of hypoxia and thrombotic conditions in several patients. Thus, the current study focuses the understanding of population specific variations attributing high rate of SARS-CoV-2 infections in specific geographical regions which may eventually be vital for the most severely affected countries and regions for sharp development of custom-made vindication strategies.

15.
Preprint en Inglés | bioRxiv | ID: ppbiorxiv-006213

RESUMEN

The Coronavirus Disease-2019 (COVID-19) that started in Wuhan, China in December 2019 has spread worldwide emerging as a global pandemic. The severe respiratory pneumonia caused by the novel SARS-CoV-2 has so far claimed more than 60,000 lives and has impacted human lives worldwide. However, as the novel SARS-CoV-2 displays high transmission rates, their underlying genomic severity is required to be fully understood. We studied the complete genomes of 95 SARS-CoV-2 strains from different geographical regions worldwide to uncover the pattern of the spread of the virus. We show that there is no direct transmission pattern of the virus among neighboring countries suggesting that the outbreak is a result of travel of infected humans to different countries. We revealed unique single nucleotide polymorphisms (SNPs) in nsp13-16 (ORF1b polyprotein) and S-Protein within 10 viral isolates from the USA. These viral proteins are involved in RNA replication, indicating highly evolved viral strains circulating in the population of USA than other countries. Furthermore, we found an amino acid addition in nsp16 (mRNA cap-1 methyltransferase) of the USA isolate (MT188341) leading to shift in amino acid frame from position 2540 onwards. Through the construction of SARS-CoV-2-human interactome, we further revealed that multiple host proteins (PHB, PPP1CA, TGF-{beta}, SOCS3, STAT3, JAK1/2, SMAD3, BCL2, CAV1 & SPECC1) are manipulated by the viral proteins (nsp2, PL-PRO, N-protein, ORF7a, M-S-ORF3a complex, nsp7-nsp8-nsp9-RdRp complex) for mediating host immune evasion. Thus, the replicative machinery of SARS-CoV-2 is fast evolving to evade host challenges which need to be considered for developing effective treatment strategies.

16.
J Biomol Struct Dyn ; 38(1): 114-123, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-30688163

RESUMEN

Deinococcus RecA (DrRecA) protein is a key repair enzyme and contributes to efficient DNA repair of Deinococcus radiodurans. Phosphorylation of DrRecA at Y77 (tyrosine 77) and T318 (threonine 318) residues modifies the structural and conformational switching that impart the efficiency and activity of DrRecA. Dynamics comparisons of DrRecA with its phosphorylated analogues support the idea that phosphorylation of Y77 and T318 sites could change the dynamics and conformation plasticity of DrRecA. Furthermore, docking studies showed that phosphorylation increases the binding preference of DrRecA towards dATP versus ATP and for double-strand DNA versus single-strand DNA. This work supporting the idea that phosphorylation can modulate the crucial functions of this protein and having good concordance with the experimental data. AbbreviationsDrRecADeinococcus RecADSBDNA double-strand breakshDNAheteroduplex DNASTYPKserine/threonine/tyrosine protein kinaseT318threonine 318Y77tyrosine 77Communicated by Ramaswamy H. Sarma.


Asunto(s)
Deinococcus/enzimología , Deinococcus/efectos de la radiación , Tolerancia a Radiación , Rec A Recombinasas/química , Rec A Recombinasas/metabolismo , Aminoácidos/química , Aminoácidos/metabolismo , Daño del ADN , Reparación del ADN , ADN de Cadena Simple , Modelos Moleculares , Fosforilación , Relación Estructura-Actividad
17.
Viruses ; 11(12)2019 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-31771194

RESUMEN

Foamy viruses (FVs) are nonpathogenic retroviruses that infect various animals including bovines, felines, nonhuman primates (NHPs), and can be transmitted to humans through zoonotic infection. Due to their non-pathogenic nature, broad tissue tropism and relatively safe integration profile, FVs have been engineered as novel vectors (foamy virus vector, FVV) for stable gene transfer into different cells and tissues. FVVs have emerged as an alternative platform to contemporary viral vectors (e.g., adeno associated and lentiviral vectors) for experimental and therapeutic gene therapy of a variety of monogenetic diseases. Some of the important features of FVVs include the ability to efficiently transduce hematopoietic stem and progenitor cells (HSPCs) from humans, NHPs, canines and rodents. We have successfully used FVV for proof of concept studies to demonstrate safety and efficacy following in-vivo delivery in large animal models. In this review, we will comprehensively discuss FVV based in-vivo gene therapy approaches established in the X-linked severe combined immunodeficiency (SCID-X1) canine model.


Asunto(s)
Terapia Genética , Vectores Genéticos , Spumavirus/genética , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/veterinaria , Animales , Gatos , Bovinos , Modelos Animales de Enfermedad , Perros , Células Madre Hematopoyéticas/fisiología , Humanos , Células Madre/fisiología , Transducción Genética/veterinaria , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/genética , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/terapia
18.
Indian J Thorac Cardiovasc Surg ; 35(1): 115-117, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33060988

RESUMEN

Thymolipoma is a rarely seen benign pathological entity of anterior mediastinum and constitutes of around 2-7% of thymic tumors. They usually present as soft tissue mass composed of mature adipose tissue and thymic tissue, which are clinically silent most of the time, i.e., the reason they reach to a larger dimension before diagnosis. Preoperaative diagnosis is always challenging for the thymolipoma. We wish to report a case of the soft tissue mass of anterior mediastinum in a young male, which on surgical exploration and final histopathological examination was diagnosed as thymolipoma.

19.
Indian J Surg Oncol ; 9(4): 477-482, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30538375

RESUMEN

The aim of this observational prospective study was to determine the technical feasibility, safety, and adequacy of robotic hemithyroidectomy. From April 2015 to May 2016, 16 patients with solitary thyroid lesion underwent robotic hemithyroidectomy using the Da Vinci® Si Surgical system. Patients were observed and data were recorded on surgical time, blood loss, complications, and functional outcome of the patients. A total of 16 patients (3 males and 13 females; mean age 39.9 years) underwent robotic hemithyroidectomy after evaluation for solitary thyroid nodule with a mean nodule size of 2.2 ± 0.3 cm. Fiber-optic laryngoscopy (FOL) was normal in all cases pre-operatively. Five patients were operated by transaxillary approach, the rest by retroauricular (facelift) approach. Mean pocket dissection time was 42 min for transaxillary and 40 min for retroauricular approach. Mean operative console time was 59.4 min for transaxillary and 52.6 min for retroauricular approach. Average blood loss was 45 ml. Mean hospital stay was 1.5 days. None of the patients had any post-operative complication on follow-up. One patient had restricted left vocal cord mobility which improved in 3 months. Mean pain score was 0.25 ± 0.4 and average speech score was 0.5 ± 0.2 at 3 months. Post-operatively, all patients had adequate swallowing with no episode of aspiration. Robotic hemithyroidectomy is a safe, feasible, and oncologically safe procedure. It has benefits in terms of better scar cosmesis than open surgery.

20.
Head Neck ; 40(10): 2263-2270, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29947144

RESUMEN

BACKGROUND: With the introduction of new American Joint Committee on Cancer (AJCC) classifications for head and neck cancers few cases are upgraded from T2 to T3 based only on depth of invasion. The role of adjuvant therapy in this particular subset of patients is still not defined. METHODS: This is a retrospective analysis of data from 2009 to 2015, of patients with histopathology of pT1, T2, and N0. A total of 375 patients were subdivided into 3 groups per the new AJCC classification depth of invasion <5 mm, 6 to 10 mm, and >10 mm. Survival analyses of patients receiving adjuvant therapy and those who did not were compared with specific emphasis on patients who were upstaged from T2 to T3 based on depth of invasion. RESULTS: Depth of invasion is a poor prognostic factor and addition of adjuvant therapy based on depth of invasion did not have significant survival benefits. CONCLUSION: Addition of adjuvant therapy based on depth of invasion does not influence survival in patients with early carcinoma of the tongue.


Asunto(s)
Neoplasias de la Lengua , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Supervivencia sin Enfermedad , Femenino , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/epidemiología , Pronóstico , Radioterapia Adyuvante , Estudios Retrospectivos , Neoplasias de la Lengua/mortalidad , Neoplasias de la Lengua/patología , Neoplasias de la Lengua/terapia
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