Biomedical subjects

Vivek Kumar

Publications and source records attributed to Vivek Kumar.

8 recordsLinked to original sources

PubMed2025

Decoding nitrogen uptake efficiency in maize and sorghum: insights from comparative gene regulatory networks.

Nitrogen (N) is an essential macronutrient for plant growth and yield, yet optimizing nitrogen use efficiency remains a challenge in agriculture. To better understand the regulatory basis of plant responses to N availability, we constructed a maize-specific nitrogen uptake efficiency gene regulatory network (mNUEGRN) comprising 1625 protein-DNA interactions (PDI) between 70 promoters and 301 transcription factors using enhanced yeast one-hybrid assays. We also projected a sorghum NUE GRN (spNUEGRN) based on maize orthologs and analyzed N-responsive subnetworks in both species using transcriptome profiling under N stress of early deprivation and recovery. Cross-species comparison with an existing Arabidopsis GRN revealed about 18% conserved interaction, corresponding to 11% of the mNUEGRN, particularly within the nitrate assimilation pathways. Notably, bZIP18 and bZIP30 emerged as central regulators in mNUEGRN, forming highly connected feed-forward loops (FFLs). From our time series data, we identified 19 236 and 23 864 differentially expressed genes in maize and sorghum, respectively. Gini correlation analysis uncovered 764 and 638 FFLs in mNUEGRN and spNUEGRN, respectively, of which 22 FFLs in maize and 35 in sorghum were identified in both leaf and root for each species. These FFLs may represent candidate regulatory motifs that contribute to modulating transcriptional responses under fluctuating N conditions, but their potential roles require further investigation. Together, our findings reveal evolutionarily conserved and species-specific regulatory strategies that mediate early N responsiveness, offering a foundation for engineering crops with improved NUE.

Sorghum↗

PubMed2003

A solid-phase synthetic strategy for labeled peptides: synthesis of a biotinylated derivative of the delta opioid receptor antagonist TIPP (Tyr-Tic-Phe-Phe-OH).

A general solid-phase synthetic strategy for labeled peptides was developed and used to prepare a biotinylated derivative of the delta opioid receptor antagonist TIPP (Tyr-Tic-Phe-Phe-OH). A monoprotected hydrophilic diamine linker was attached to an aldehyde-containing solid-phase resin by reductive amination, followed by introduction of biotin and peptide synthesis to yield Tyr-Tic-Phe-Phe-Asp-NH(CH(2)CH(2)O)(2)CH(2)CH(2)NH-biotin (2). The high delta receptor affinity and selectivity of 2 demonstrate the applicability of this design approach for labeled peptide derivatives.

Aldehydes↗

PubMed2003

Recent developments in the management of detrusor overactivity.

PURPOSE OF REVIEW: Detrusor overactivity is a relatively common yet embarrassing symptom complex with significant impact on quality of life. The mainstay of current pharmacological treatment involves use of muscarinic receptor antagonists, but their therapeutic efficacy is limited by their troublesome side effects resulting in the non-continuance of treatment in a significant number of patients. Therefore, the development of new drugs can proceed by targeting alternative pathways affecting detrusor overactivity. In this article, the pharmacological basis for the current therapeutic alternatives for managing detrusor overactivity and possible future developments are discussed. RECENT FINDINGS: It is clear that far from being a passive container for urine, the urothelium is a crucial part of the bladder. Its functions are complex, dynamic and important, and only now becoming understood. The release of ATP from urothelium in response to distension and its action on P2X receptors resulting in activating both motor and sensory neurons is being increasingly recognised. In the normal bladder, muscarinic receptor stimulation produces the main part of detrusor contraction. However, in functionally abnormal bladders, a non-cholinergic activation via the purinergic receptors may occur. The central nervous mechanisms controlling the micturition reflex have also recently attracted attention. SUMMARY: Recent research has suggested that several transmitters may modulate voiding. However, few drugs with clinical benefits have been developed so far. Present treatments for overactive bladders have significant non-compliance rates. Hopefully, future research will lead to drugs with greater therapeutic benefits and better tolerance.

Adrenergic beta-Agonists↗

PubMed2003

Annexin II is present on renal epithelial cells and binds calcium oxalate monohydrate crystals.

Attachment of newly formed crystals to renal epithelial cells appears to be a critical step in the development of kidney stones. The current study was undertaken to identify potential calcium oxalate monohydrate (COM) crystal-binding proteins on the surface of renal tubular cells. Apical membranes were prepared from confluent monolayers of renal epithelial cells (MDCKI line), and COM crystal affinity was used to isolate crystal-binding proteins that were then subjected to electrophoresis and electroblotting. Microsequencing of the most prominent COM crystal-binding protein (M(r) of 37 kD) identified it as annexin II (Ax-II). When exposed proteins on the surface of intact monolayers were biotinylated and then isolated using streptavidin agarose beads, Ax-II was detected, suggesting that at least a portion is exposed on the apical cell surface. Ax-II was not completely extracted by 0.1 M Na(2)CO(3), suggesting that at least a portion of cellular Ax-II is an intrinsic membrane-bound protein. Using confocal immunofluorescence microscopy, Ax-II was visualized together with Caveolin-1 (Cav-1) on the apical membrane of intact MDCKI cells. Cells pretreated with a monoclonal anti-Ax-II antibody bound significantly fewer COM crystals, whereas anti-LDL receptor antibody did not decrease COM binding, further suggesting a functional role for Ax-II during adhesion of crystals to intact cells. These results suggest that Ax-II avidly binds COM crystals and is present on the apical surface of MDCKI cells. Therefore, in the intact nephron, Ax-II could mediate adhesion of COM crystals to cells, and altered exposure of Ax-II on the surface of renal tubular cells could promote crystal retention and possibly kidney stone formation.

Animals↗

PubMed2003

Whole urinary proteins coat calcium oxalate monohydrate crystals to greatly decrease their adhesion to renal cells.

PURPOSE: Adhesion of urinary crystals to renal tubular cells could be a critical event that triggers a cascade of responses ending in kidney stone formation. We clarified the role of urinary macromolecules during calcium oxalate monohydrate (COM) crystal adhesion to cells. MATERIALS AND METHODS: To assess COM crystal binding to cells in the presence of whole urine and fractions thereof we used monolayer cultures of distal nephron derived Madin-Darby canine kidney, type I cells as a model system. RESULTS: COM crystal adhesion to cells was decreased in the presence of whole urine compared with an ultrafiltrate prepared by passing urine through a 10 kDa cutoff membrane. Supplementing the ultrafiltrate with urinary concentrate containing proteins greater than 10 kDa returned crystal adhesion to low levels, similar to whole urine. Macromolecules in whole urine acted to decrease binding to cells by coating crystals and 4 proteins previously implicated in the pathogenesis of nephrolithiasis were detected on coated crystals (bikunin, osteopontin, prothrombin fragment 1 + 2 and Tamm-Horsfall glycoprotein). Crystals precipitated and grown in whole urine also bound less avidly to cells than crystals precipitated in artificial urine. CONCLUSIONS: This study confirms that macromolecules present in whole urine can coat crystals and, thereby, block their adhesion to renal tubular cells. Preventing crystal retention in the kidney could be an important mechanism whereby these macromolecules protect against kidney stones.

Adult↗

PubMed2002

Solid phase synthesis and evaluation of Tyr-Tic-Phe-Phe(p-NHCOCH(2)Br) ([Phe(p-bromoacetamide)(4)]TIPP), a potent affinity label for delta opioid receptors.

Derivatives of the delta opioid receptor selective peptide Tyr-Tic-Phe-Phe-OH (TIPP) containing a p-bromoacetamide moiety on the phenyl ring of Phe(3) or Phe(4) were prepared by solid phase synthesis. [Phe(p-NHCOCH(2)Br)(4)]TIPP exhibited high affinity for cloned delta receptors (IC(50) = 5.4 nM), and incubation with only 2.5 nM resulted in 85% wash resistant inhibition of radioligand binding to delta receptors. Therefore, this peptide is a potent affinity label for further study of delta opioid receptors.

Affinity Labels↗

PubMed2002

Molecular basis of renal handling of calcium in response to thyroid hormone status of rat.

We investigated the effect of thyroid hormone status on renal handing of Ca2+. Further, like kinetics of Ca2+ transport across brush-border membrane (BBM) and basolateral membrane (BLM) of renal epithelial cells was carried out. FE(Ca) was decreased in hyperthyroid (Hyper-T) rats and increased in hypothyroid (Hypo-T) rats as compared to euthyroid (Eu-T) rats. Ca2+ uptake into renal brush-border membrane vesicles (BBMV) was increased in Hyper-T rats and decreased in Hypo-T rats as compared to Eu-T rats. K(m) was lower in Hyper-T rats and higher in Hypo-T rats as compared to Eu-T rats whereas, V(max) remained unaltered. The transition temperature for calcium uptake varied inversely with the thyroid hormone status. Renal BBM of Hyper-T rats showed decreased anisotropy and polarisation of DPH as compared to EU-T rats whereas these values were increased in Hypo-T rats. Thus, the altered BBM fluidity appears to modulate Ca2+ transport across BBM. Na+/Ca2+ exchange activity of renal cells was increased in Hyper-T and decreased in Hypo-T rats as compared to Eu-T rats. V(max) for Na+/Ca2+ exchange was increased in Hyper-T rats and deceased in Hypo-T rats as compared to Eu-T rats, whereas, [Na+](0.5) was similar in all three groups. The c-AMP levels of renal cortex of Hyper-T rats was increased and that of Hypo-T rats decreased as compared to Eu-T rats. Thus, thyroid hormones increased Ca2+ reabsorption in the kidney of rat. Thyroid hormone-mediated modulation of BBM fluidity appears to stimulate Ca2+ uptake into renal BBMV. Thyroid hormones possibly activated the Na+/Ca2+ exchanger through cAMP-dependent pathway.

Animals↗

PubMed2002

Transcription corepressor CtBP is an NAD(+)-regulated dehydrogenase.

Transcriptional repression is based on the selective actions of recruited corepressor complexes, including those with enzymatic activities. One well-characterized developmentally important corepressor is the C-terminal binding protein (CtBP). Although intriguingly related in sequence to D2 hydroxyacid dehydrogenases, the mechanism by which CtBP functions remains unclear. We report here biochemical and crystallographic studies which reveal that CtBP is a functional dehydrogenase. In addition, both a cofactor-dependent conformational change, with NAD(+) and NADH being equivalently effective, and the active site residues are linked to the binding of the PXDLS consensus recognition motif on repressors, such as E1A and RIP140. Together, our data suggest that CtBP is an NAD(+)-regulated component of critical complexes for specific repression events in cells.

Alcohol Oxidoreductases↗