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Basu, C.

Publications and source records attributed to Basu, C..

5 recordsLinked to original sources

Nox4 Mediates Diastolic Function in a Genetic Model of Pitx2 Haploinsufficiency

Heart failure with preserved ejection fraction (HFpEF) commonly coexists with atrial fibrillation (AF), but shared mechanisms remain unclear. In this study, we hypothesized that Pitx2, a transcription factor located near the strongest genetic locus associated with AF in humans, increases susceptibility to HFpEF-like remodeling. We also sought to understand pathways that might be central to this increased risk. Male and female Pitx2+/- mice and wild-type littermates received 3-week subcutaneous osmotic pump infusion of saline or angiotensin II (Ang II; 500 ng/kg/min). Cardiac structure and function were assessed by echocardiography and catheterization, and functional capacity by exercise treadmill. RNA transcriptomic profiling was performed to identify candidate pathways. In a separate cohort, Ang II-treated mice were randomized to oral GKT136901 (30 mg/kg/day) or vehicle during infusion. After Ang II infusion, Pitx2+/- mice developed exaggerated HFpEF-like changes, including greater left ventricular hypertrophy, left atrial enlargement, diastolic dysfunction, elevated left ventricular end-diastolic pressure, and reduced treadmill performance. RNA-seq showed enrichment of metabolic and stress-response pathways with selective upregulation of Nox4, confirmed by RT-qPCR. GKT136901 attenuated structural remodeling, diastolic dysfunction indices, elevated filling pressures, and cardiomyocyte hypertrophy, but did not improve endurance. These findings implicate redox signaling, including Nox4, in AF genetic susceptibility-HFpEF interactions.

cell biology↗

In vitro investigation and evaluation of the antidiabetic potential of the ethanolic extract of Asparagus racemosus using starch digestion, glucose diffusion, glucose uptake, and DPPH assays

Asparagus racemosus commonly known as Shatamull, is a medicinal plant with pharmacological applications documented in both Indian and British Pharmacopoeias and various traditional medicinal practices. Previous studies have reported that A. racemosus reduces hyperglycemia by enhancing insulin secretion. The aim of the current study was to assess the antihyperglycemic actions and explore the underlying mechanisms of action of A. racemosus utilizing in vitro carbohydrate digestion, glucose diffusion, glucose uptake, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and preliminary phytochemical screening. The inhibition of carbohydrate digestion was assessed using -amylase and -glucosidase enzyme assays. The effect on glucose diffusion was evaluated using cellulose ester dialysis tube. Subsequently, glucose uptake was measured in a yeast cell model at different glucose concentrations, and the antioxidant potential was evaluated by measuring DPPH radical scavenging activity. A. racemosus significantly reduced (p<0.05- 0.01) glucose release during in vitro starch digestion by 21.11%, whereas glucose absorption decreased by 22.75% (p<0.05-0.001). The most significant enhancement (p<0.05-0.001) in glucose uptake by 65.03%, was observed at 5 mM glucose concentration. Furthermore, it showed significant antioxidant activity by scavenging DPPH (p<0.05, 0.001) radicals by 42.46%. Preliminary phytoconstituent screening indicated the existence of flavonoids, tannins, steroids, glycosides and saponins. In conclusion, A. racemosus shows an inhibitory effect on carbohydrate digestion and absorption, enhances glucose uptake and demonstrates significant DPPH radical scavenging activity, potentially due to the presence of naturally occurring phytochemicals. Thus, A. racemosus may contribute as a promising antidiabetic drug for the treatment of diabetes mellitus. More investigations are needed to determine the active compounds in A. racemosus that contribute to its antidiabetic effects.

pharmacology and toxicology↗

A sneak peek at the high altitude adaptation of the Ladakh populations

The physiological response to high-altitude stress (for individuals living at 2,400m and above sea level) has been evident. However, recent advances in genomics have allowed us to explore the molecular genetic basis of these adaptive responses and their relationship with physiological responses. In the current study, we focused on thirteen biological parameters to understand the adaptive response to the high altitude of populations living across regions of Sakti, Korzok, Hanle, Aryan and Zanskar valleys of Ladakh and to understand the variation between and across individuals. Interestingly, we found a negative correlation between haemoglobin levels and partial oxygen pressure, thereby testifying to higher haemoglobin levels as an adaptive response in these individuals. The lipid profiles, including cholesterol, triglyceride, LDL and HDL levels, varied significantly across the five regions studied. Notably, individuals from Sakti Valley showed higher LDL (>140) and cholesterol values. These variations in health parameters and lipid profiles may be attributed to diet and altitude adaptations specific to the region. Overall, the study provides valuable insights into the adaptations of highlanders living at different altitudes in the Ladakh region. The findings can have implications for better understanding the molecular mechanism of physiological responses of humans to high-altitude environments.

evolutionary biology↗

Low effective mechanical advantage of giraffes' limbs during walking reveals trade-off between limb length and locomotor performance

Giraffes (Giraffa camelopardalis) possess specialised locomotor morphology, namely elongate and gracile distal limbs. Whilst this contributes to their overall height (and enhanced feeding behaviour), we propose that the combination of long limb segments and modest muscle lever arms results in low effective mechanical advantage (EMA, the ratio of in-lever to out-lever moment arms), when compared with other cursorial mammals. To test this, we used a combination of experimentally measured kinematics and ground rection forces (GRFs), musculoskeletal modelling, and inverse dynamics to calculate giraffe forelimb EMA during walking. Giraffes walk with an EMA of 0.34 ({+/-}0.05 S.D.), with no evident association with speed within their walking gait. Giraffe EMA was markedly below the expectations extrapolated from other mammals ranging from 0.03 - 297 kg, and provides further evidence that EMA plateaus or even diminishes in mammals exceeding horse size. We further tested the idea that limb segment length is a factor which determines EMA, by modelling the GRF and muscle moment arms in the extinct giraffid Sivatherium giganteum and the other extant giraffid Okapia johnstoni. Giraffa and Okapia shared similar EMA, despite a 4-6 fold difference in body mass (Okapia EMA = 0.38). In contrast Sivatherium, sharing a similar body mass to Giraffa, had greater EMA (0.59), which we propose reflects behavioural differences, such athletic performance. Our modelling approach suggests that limb length is a determinant of GRF moment arm magnitude, and that unless muscle moment arms scale isometrically with limb length, tall mammals are prone to low EMA. Significance StatementGiraffes are the tallest living animals - using their height to access food unavailable to their competitors. It is not clear how their specialized anatomy impacts their athletic ability. We made musculoskeletal models of the forelimbs from a giraffe and two close relatives, and used motion-capture and forceplate data to measure how efficient they are when walking in a straight line. A horse for example, uses just 1 unit of muscle force to oppose 1 unit of force on the ground. Giraffe limbs however are comparatively disadvantaged - their muscles must develop 3 units of force to oppose 1 unit of force at the ground. This explains why giraffes walk and run at relatively slow speeds.

biophysics↗

Cambium-specific Transcriptome Analysis of Paulownia to Study the Molecular Impacts of Winter and Spring Seasons on Tree Growth

Paulownia (Paulownia elongata) is a fast-growing, multipurpose deciduous hardwood species that grows in a wide range of temperatures from -30 {degrees}C to 45 {degrees}C. Seasonal cues influence the secondary growth of tree stems, including cambial activity, wood chemistry, and transition to latewood formation. In this study, a de novo transcriptome approach was conducted to identify the transcripts expressed in vascular cambial tissue from senescent winter and actively growing spring seasons. Illumina paired-end sequenced cambial transcriptome generated 297,049,842 clean reads which finally yielded 61,639 annotated unigenes. Based on non- redundant protein database analyses, Paulownia cambial unigenes shared highest homology (64.8%) with Erythranthe guttata. A total of 35,471 unigenes resulted from KEGG annotation that were mapped to 128 pathways with metabolic pathways dominated among all. Additionally, DEG analysis showed that 2,688 and 7,411 genes were significantly upregulated and downregulated, respectively in spring compared to winter. Interestingly, quite a number of transcripts belonging to heat shock proteins were upregulated in spring season. RT-qPCR expression results of fifteen wood-forming candidate genes involved in hemicellulose, cellulose, lignin, auxin and cytokinin pathways showed that the hemicellulose genes (CSLC4, FUT1, AXY4, GATL1, and IRX19) were significantly upregulated in spring season tissues when compared to winter tissues. In contrast, lignin pathway genes CCR1 and CAD1 were upregulated in winter cambium. Finally, a transcriptome-wide marker analysis identified 11,338 Simple Sequence Repeat (SSRs). The AG/CT dinucleotide repeat predominately represented all SSRs. Altogether, the cambial transcriptomic analysis reported here highlights the molecular events of wood formation during winter and spring. The identification of candidate genes involved in the cambial growth provides a roadmap of wood formation in Paulownia and other trees for the seasonal growth variation.

plant biology↗