Publications by authors named "K S Bose"

361 Publications

Remodelling structure-based drug design using machine learning.

Emerg Top Life Sci 2021 Apr 7. Epub 2021 Apr 7.

Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India.

To keep up with the pace of rapid discoveries in biomedicine, a plethora of research endeavors had been directed toward Rational Drug Development that slowly gave way to Structure-Based Drug Design (SBDD). In the past few decades, SBDD played a stupendous role in identification of novel drug-like molecules that are capable of altering the structures and/or functions of the target macromolecules involved in different disease pathways and networks. Unfortunately, post-delivery drug failures due to adverse drug interactions have constrained the use of SBDD in biomedical applications. However, recent technological advancements, along with parallel surge in clinical research have led to the concomitant establishment of other powerful computational techniques such as Artificial Intelligence (AI) and Machine Learning (ML). These leading-edge tools with the ability to successfully predict side-effects of a wide range of drugs have eventually taken over the field of drug design. ML, a subset of AI, is a robust computational tool that is capable of data analysis and analytical model building with minimal human intervention. It is based on powerful algorithms that use huge sets of 'training data' as inputs to predict new output values, which improve iteratively through experience. In this review, along with a brief discussion on the evolution of the drug discovery process, we have focused on the methodologies pertaining to the technological advancements of machine learning. This review, with specific examples, also emphasises the tremendous contributions of ML in the field of biomedicine, while exploring possibilities for future developments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1042/ETLS20200253DOI Listing
April 2021

Ethnic heterogeneity in body composition patterning and CVD risk factors: a multi-ethnic study of Asian Indian Tribes.

Ethn Health 2021 Apr 5:1-24. Epub 2021 Apr 5.

Department of Anthropology, Vidyasagar University, Midnapore, West Bengal, India.

Background: . Indian subcontinent exhibits considerable degree of ethnic heterogeneity in cardiovascular disease (CVD) risks. Given the importance of ethnicity, the present multi-ethnic study was conducted to find out the differences in body composition patterning and its influence on CVD risk variables.

Objective: . Owing to considerable ethnic heterogeneity among Asian Indians the study was performed to determine the association of variability between body composition and CVD risk factors at the micro-level among different tribes by sex, province, and generation.

Methods.: Nine tribes from three different states (provinces) were considered. Anthropometric measurements, body composition, adiposity, blood pressure, and fasting blood glucose was measured using standard technique. Body composition was measured using BIA method by means of body fat monitor. Mean differences of the body composition measures were analysed by ANOVA. Stepwise multiple regressions were done with CVD risk variables as dependent and body composition profiles as independent variables to find out the significant predictors. Those were then loaded for principal component factor analyses (PCFA).

Results: . Tribal subjects of both sexes and from both younger and older generations in Gujarat had significantly higher percentage body fat, subcutaneous fat-whole body, and subcutaneous fat-trunk as compared to tribal subjects of Odisha, and West Bengal, as well as significantly lower skeletal mass-whole body and skeletal mass-trunk. PCFA showed two components: (i) percentage body fat with muscle mass; and (ii) visceral fat with resting metabolism. These two components cumulatively explained 80-90% of the total variance associated with CVD risk variables, across the nine tribes.

Conclusion: . Tribal subjects of Gujarat had higher CVD risks with significantly higher fat mass and lower muscle mass followed by the tribal subjects of Odisha, and West Bengal respectively. The younger generation are equally at risk as their older counterparts. The CVD risks are developing at a much faster rate resulting in a serious public health threat, even in traditional societies. Body composition measures could be considered as a better non-invasive technique for early intervention and proper risk management among the Asian Indians in general and tribal populations in particular.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13557858.2021.1910626DOI Listing
April 2021

The effect of a natural disaster on handgrip strength in prepubertal Indian children exposed to a severe cyclone during the prenatal and early postnatal growth.

Sci Rep 2021 Apr 2;11(1):7473. Epub 2021 Apr 2.

Department of Anthropology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.

Natural disasters (NDs) experienced by women and their children during prenatal and infant growth may have long-lasting effects on offspring's development. Handgrip strength (HGS) is one of the measures of muscular strength and an indicator of health status. This study compared HGS in children exposed to cyclone Aila in India during their prenatal and infant growth compared to a control group from a non-affected, adjacent area. The total sample involved 444 boys and 423 girls aged 7-9 years, categorised into 3 groups: prenatally exposed to Aila, exposed to Aila in infancy, and the control group, non-exposed to Aila. Results revealed that prenatally exposed children of both sexes had significantly lower HGS than the controls (at least, p < 0.001 in boys; p < 0.05 in girls). On the other hand, the postnatally exposed boys, but not the girls, showed lower HGS than the controls. A significant effect of a group factor (ND exposure) on HGS was observed even after controlling for confounding variables (age, height, BMI, birth weight, gestational age; at least, p < 0.05). Our findings indicate that prenatal or early postnatal experience of a ND may have association with impaired HGS in prepubertal children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-86845-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018953PMC
April 2021

[Chronic kidney injury in patients with liver diseases - Reappraising pathophysiology and treatment options].

Z Gastroenterol 2021 Mar 16. Epub 2021 Mar 16.

Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland.

Acute and chronic kidney disease concurs commonly with liver disease and is associated with a wide array of complications including dialysis dependency and increased mortality. Patients with liver disease or liver cirrhosis show a higher prevalence of chronic kidney disease. This is attributed to concomitant comorbidities, such as metabolic syndrome, chronic inflammation, hypercoagulability, hyperfibrinolysis, diabetes mellitus and dyslipidaemias. But chronic progressive kidney disease is not always due to hepatorenal syndrome. Beyond that, other diseases or disease entities should be considered. Among them are diabetic nephropathy, secondary IgA nephropathy, hepatitis C -associated membranoproliferative Glomerulonephritis (MPGN) and hepatitis B-associated membranous nephropathy.Coexisting diseases, similar underlying pathophysiologic mechanisms, or simultaneously concurring pathophysiological processes and overlapping clinical manifestations, impede the etiologic diagnosis and corresponding treatment of chronic kidney disease in the setting of chronic liver disease. In this review, we focus on common and rare pathologies, which can lead to chronic kidney disease in this particular patient group and try to summarize the most recent therapeutic modalities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1402-1502DOI Listing
March 2021

Loss of GSK-3β mediated phosphorylation in HtrA2 contributes to uncontrolled cell death with Parkinsonian phenotype.

Int J Biol Macromol 2021 Mar 12;180:97-111. Epub 2021 Mar 12.

Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India; Homi Bhabha National Institute, BARC Training School Complex, Anushaktinagar, Mumbai 400094, India. Electronic address:

HtrA2, a proapoptotic mitochondrial serine protease, promotes cellular protection against oxidative damage. Literature reports show positive correlation between loss of HtrA2 protease activity and Parkinson's Disease (PD) susceptibility. Homozygous loss-of-function mutations in murine-HtrA2, and when they rarely occur in humans result in severe neurodegeneration and infantile death. Here, we report a novel heterozygous pathogenic HTRA2 variant, c.725C > T (p.T242M) in Indian PD patients. Although, this mutation exhibits no significant conformational changes compared to the wild-type, functional studies with HtrA2-T242M transfected neurons reveal common features of PD pathogenesis such as dysfunction, altered morphology and mitochondrial membrane depolarization. Despite exhibiting two-fold decrease in enzyme activity, observation of excessive cell-death due to over-expression of the mutant has been correlated with it being constitutively active. This interesting behavioral anomaly has been attributed to the loss of phosphorylation-mediated regulatory checkpoint at the T242M mutation site that is otherwise controlled by glycogen synthase kinase-3β (GSK-3β). This study, with seamless amalgamation of biophysical and biomedical research unravels a mechanistic pathway of HtrA2 regulation and delineates its biological role in PD. Therefore, this investigation will not only prove beneficial toward devising therapeutic strategies against HtrA2-associated diseases mediated by GSK-3β but also suggest new avenues for treatment of Parkinsonian phenotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2021.03.040DOI Listing
March 2021