Chaperone-like activity of tubulin

Tubulin, a ubiquitous protein of eukaryotic cytoskeleton, is a building block unit of microtubule. Although several cellular processes are known to be mediated through the tubulin-microtubule system, the participation of tubulin or microtubule in protein folding pathway has not yet been reported. Here we show that goat brain tubulin has some functions and features similar to many known molecular chaperones. Substoichiometric amounts of tubulin can suppress the non-thermal and thermal aggregation of a number of unrelated proteins such as insulin, equine liver alcohol dehydrogenase, and soluble eye lens proteins containing β- and γ-crystallins. This chaperone-like activity of tubulin becomes more pronounced as temperature increases. Aging of tubulin solution at 37° C also enhances its chaperone-like activity. Tubulin loses its chaperone-like activity upon removal of its flexible hydrophilic C-terminal tail. These results suggest that both electrostatic and hydrophobic interactions are important in substrate binding by tubulin and that the negatively charged C-terminal tails play a crucial role for its chaperone-like activity

Multi-OMICS and Molecular Biology Perspective in Buffalo Genome

The bovine species buffalo was domesticated from its wild strain Bubalus arnee and is widely used livestock in southern Asia. There are two distinct types of Buffalo- the swamp buffalo (B. bubalis kerebau) and the river buffalo (B. bubalis bubalis), which diverged from the wild Asian water buffalo and then evolved in separate geographical regions. Several research studies performed on buffalo, like- characterization of trait-specific Single Nucleotide Polymorphism (SNP), genetic and phenotypic diversity, gene prediction and function annotation, mapping of the draft genome, have helped our understanding of the buffalo genome. Some advanced discovery as identification of Single Nucleotide Variant (SNVs), Simple Sequence Repeats (SSR) marker and their association with various phenotypic traits, MicroRNA's expression profiling, whole-genome sequencing, etc. have also enabled us to track the chromosomal evolution, physiological processes, and gene expression of buffalo. Proper enhancement of these traits can lead us to apply multi-omics-based tools for better animal health and production. Recent advancement in genomic research on buffalo is being accelerated with the association of modern tools like- Genome-Wide Association Study (GWAS), genotyping by sequencing, epigenomic screening, microRNA's expression profiling, microarray technology, and whole-genome sequencing. All these tools bear great significance in breed up-gradation, identification of the phylogenetic relationship between species in proteome and genomic level, study gene expression level, diagnose diseases or developmental stages, phenotypic diversity, etc. All this knowledge paved the way for better optimization of production efficiency, product quality, and resistance to certain health hazards

Optimized Hydrophobic Interactions and Hydrogen Bonding at the Target-Ligand Interface Leads the Pathways of Drug-Designing

Weak intermolecular interactions such as hydrogen bonding and hydrophobic interactions are key players in stabilizing energetically-favored ligands, in an open conformational environment of protein structures. However, it is still poorly understood how the binding parameters associated with these interactions facilitate a drug-lead to recognize a specific target and improve drugs efficacy. To understand this, comprehensive analysis of hydrophobic interactions, hydrogen bonding and binding affinity have been analyzed at the interface of c-Src and c-Abl kinases and 4-amino substituted 1H-pyrazolo [3, 4-d] pyrimidine compounds.In-silico docking studies were performed, using Discovery Studio software modules LigandFit, CDOCKER and ZDOCK, to investigate the role of ligand binding affinity at the hydrophobic pocket of c-Src and c-Abl kinase. Hydrophobic and hydrogen bonding interactions of docked molecules were compared using LigPlot program. Furthermore, 3D-QSAR and MFA calculations were scrutinized to quantify the role of weak interactions in binding affinity and drug efficacy.The in-silico method has enabled us to reveal that a multi-targeted small molecule binds with low affinity to its respective targets. But its binding affinity can be altered by integrating the conformationally favored functional groups at the active site of the ligand-target interface. Docking studies of 4-amino-substituted molecules at the bioactive cascade of the c-Src and c-Abl have concluded that 3D structural folding at the protein-ligand groove is also a hallmark for molecular recognition of multi-targeted compounds and for predicting their biological activity. The results presented here demonstrate that hydrogen bonding and optimized hydrophobic interactions both stabilize the ligands at the target site, and help alter binding affinity and drug efficacy

Minimising disparity in distribution for unsupervised domain adaptation by preserving the local spatial arrangement of data

Domain adaptation is used for machine learning tasks, when the distribution of the training (obtained from source domain) set differs from that of the testing (referred as target domain) set. In the work presented in this study, the problem of unsupervised domain adaptation is solved using a novel optimisation function to minimise the global and local discrepancies between the transformed source and the target domains. The dissimilarity in data distributions is the major contributor to the global discrepancy between the two domains. The authors propose two techniques to preserve the local structural information of source domain: (i) identify closest pair of instances in source domain and minimise the distances between these pairs of instances after transformation; (ii) preserve the naturally occurring clusters present in source domain during transformation. This cost function and constraints yield a non‐linear optimisation problem, used to estimate the weight matrix. An iterative framework solves the optimisation problem, providing a sub‐optimal solution. Next, using orthogonality constraint, an optimisation task is formulated in the Stiefel manifold. Performance analysis using real‐world datasets show that the proposed methods perform better than a few recently published state‐of‐the‐art methods

Assessing land-use changes driven by river dynamics in chronically flood affected Upper Brahmaputra plains, India, using RS-GIS techniques

This work documents land-use changes driven by river dynamics along two tributaries in the chronically flood affected Upper Brahmaputra floodplain which supports a population of more than half a million. Planform changes for a period of 40 years are documented using topographical map and Landsat data, and the associated land-use change is assessed by utilising hybrid classification in GIS environment. Quantification of bankline migration shows that the river courses are unstable. A reversal in the rate of erosion and deposition is also observed. Hybrid classification of Landsat images yielded a higher level of accuracy as evident from the confusion matrixes. Overall, the accuracy of land-use classification ranged between 88.5% and 96.25%. Land-use change shows that there is an increase in settlement and agriculture and a decrease in the grassland. The area affected by erosion–deposition and river migration comprises primarily of the agricultural land. Effect of river dynamics on settlements is also evident. Loss of agricultural land and homestead led to the loss of livelihood and internal migration in the floodplains. The observed pattern of river dynamics and the consequent land-use change in the recent decades have thrown newer environmental challenges at a pace and magnitude way beyond the coping capabilities of the dwellers

A Study to Assess Changes in Cortisol Level and Heart Rate Variability between Fixed Duty and Shift Duty Health Care Providers in a Tertiary Care Hospital- A Cross-Sectional Study

Introduction: Increased demand of service 24 hours around the clock has divided the workers into 2 domains as “Fixed duty” and “Shift duty”. Personals associated with shift duty are increasing in numbers day by day. Shift duty or more specifically night duty is associated with increased stress which results in high morbidity and decrease in work efficiency. Cortisol hormone and Heart Rate Variability (HRV) are useful parameters to determine the effects of stress. Aim: To find any change in cortisol levels, HRV, Athens score among the fixed duty and shift duty healthcare providers. Materials and Methods: A descriptive cross-sectional comparative study was conducted in a tertiary care hospital at Kolkata between July, 15th to Sept, 15th 2021. Predesigned and pretested questionnaire was made and ethical clearance was taken from institutional IEC. Then after taking consent total 120 (60 fixed duty and 60 shift duty) healthcare providers were recruited for the study. Subjects of the study filled up a questionnaire {including Athens Insomnia Scale (AIS)}. After applying exclusion criteria (any cardiovascular, neurological, psychological, sleep disorder) 120 health individuals were taken five minutes short-term HRV (time and frequency domain) recording in supine posture and 4 PM blood sample (for cortisol) were obtained from the participants which was further analysed in Chemiluminescence Immunoassay (CLI). Data was analysed in SPSS version 20.0. Statistical tests like student t-test, Cron bach’s alpha and chi-square tests were applied significant p<0.05 (95% CI). Results: After analysis, shift duty workers showed a significant (p6) than fixed duty workers. Blood test showed that shift duty workers had significantly high evening cortisol level than fixed duty workers (p= 0.036). The time domain of HRV showed that the parameters like Standard Deviation all NN interval (SDNN) (p=0.001), Mean HR (p=0.037), RMSSD (p <0.001), NN50 (p=0.006), pNN50 (p=0.002) were significantly different in the two groups. Whereas the frequency domain of HRV showed that HF power was lower and LF power (p=0.002), LF/HF ratio (p <0.001) were significantly higher in shift duty workers. Conclusion: The study showed that shift duty workers had comparatively higher stress levels resulting in significantly high sympathetic drive and increased risk of insomnia. This can be associated with morbidity and ill health in the shifting duty workers

Lipid profile abnormalities & 10 yr risk of CVD assessment among adult in North East India: A cross-sectional study

Background & objectives: In India, lifestyle changes have contributed to increase in the number of people suffering from lipid profile abnormalities, which is a major risk factor for coronary artery diseases. The present study was aimed to estimate the prevalence of lipid profile abnormalities and 10 yr risk of cardiovascular disease (CVD) among the adult population in west Tripura district and to study the association of lipid profile abnormalities and increased CVD risk with sociodemography, body mass index (BMI), hypertension, random blood sugar (RBS) and haemoglobin level. Methods: This cross-sectional study was conducted amongst 445 adults of 20 to 60 yr of age from a randomly selected block in west Tripura district. The 10 yr risk of CVD was estimated using the Framingham Risk Assessment Tool. Results: The study revealed that overall 83.4 per cent adult population had lipid profile abnormalities, with 22.2, 42 and 70.3 per cent of participants having hypercholesterolaemia, hypertriglyceridaemia and low high-density lipoprotein level, respectively. Gender (P=0.02) and BMI (P<0.001) were the significant determinants of dyslipidaemia. Only 3.8 per cent of participants had intermediate or high risk of CVD, with all of them being males. Gender, age, occupation and RBS were significantly associated with increased CVD risk. Interpretation & conclusions: The study revealed a high burden of lipid profile abnormalities in the study population, with males having more risk of CVD. Hence, periodic screening of lipid profile abnormalities and risk of CVD should be incorporated at the primary care level to combat the CVD epidemic in India

Mechanistic studies on the oxidation of pyruvic acid by an oxo-bridged diiron(III,III) complex in aqueous acidic media

In aqueous solution [Fe2(μ-O)(phen)4(H2O)2]4+ (1, phen = 1,10-phenanthroline) equilibrates with its conjugate bases [Fe2(μ-O)(phen)4(H2O)(OH)]3+ (2) and [Fe2(μ-O)(phen)4(OH)2]2+ (3). In the presence of excess phen and in the pH range 2.5-5.5, the dimer quantitatively oxidizes pyruvic acid to acetic acid and carbon dioxide, the end iron species being ferroin, [Fe(phen)3]2+. The observed reaction rate shows a bell-shaped curve as pH increases, but is independent of added phen. Kinetic analysis shows that (3) is non-reactive and (1) has much higher reactivity than (2) in oxidizing pyruvic acid. The basicity of the bridging oxygen increases with deprotonation of the aqua ligands. The reaction rate decreases significantly in media enriched with D2O in comparison to that in H2O, with a greater retardation at higher pH, suggesting the occurrence of proton coupled electron transfer (PCET; 1e, 1H+), which possibly drags the energetically unfavorable reaction to completion in presence of excess phen. © 2009 Elsevier Ltd. All rights reserved