Data mining of transcriptional biomarkers at different cotton fiber developmental stages

Functional & Integrative Genomics - Advancement of the gene expression study provides comprehensive information on pivotal genes at different cotton fiber development stages. For the betterment...     

Cerebroprotective effects of hydrogen sulfide in homocysteine-induced neurovascular permeability: Involvement of oxidative stress,arginase, and matrix metalloproteinase-9

An elevated level of homocysteine (Hcy) leads to hyperhomocysteinemia (HHcy), which results in vascular dysfunction and pathological conditions identical to stroke symptoms. Hcy increases oxidative stress and leads to increase in blood–brain barrier permeability and leakage. Hydrogen sulfide (H₂S) production during the metabolism of Hcy has a cerebroprotective effect, although its effectiveness in Hcy-induced neurodegeneration and neurovascular permeability is less explored. Therefore, the current study was designed to perceive the neuroprotective effect of exogenous H ₂S against HHcy, a cause of neurodegeneration. To test this hypothesis, we used four groups of mice: control, Hcy, control + sodium hydrosulfide hydrate (NaHS), and Hcy + NaHS, and an HHcy mice model in Swiss albino mice by giving a dose of 1.8 g of dl -Hcy/L in drinking for 8–10 weeks. Mice that have 30 µmol/L Hcy were taken for the study, and a H ₂S supplementation of 20 μmol/L was given for 8 weeks to all groups of mice. HHcy results in the rise of the levels of superoxide and nitrite, although a concomitant decrease in the level of superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, and arginase in oxidative stress and a concomitant decrease in the endogenous level of H ₂S. Although H ₂S supplementation ameliorated, the effect of HHcy and the levels of H ₂S returned to the average level in HHcy animals supplemented with H ₂S. Interestingly, H ₂S supplementation ameliorated neurovascular remodeling and neurodegeneration. Thus, our study suggested that H ₂S could be a beneficial therapeutic candidate for the treatment of Hcy-associated neurodegeneration, such as stroke and neurovascular disorders.     

Habitat occupancy of sloth bear Melursus ursinus in Chitwan National Park,Nepal

Mammals have experienced a massive decline in their populations and geographic ranges worldwide. The sloth bear, Melursus ursinus (Shaw, 1791), is one of many species facing conservation threats. Despite being endangered in Nepal, decades of inattention to the situation have hindered their conservation and management. We assessed the distribution and patterns of habitat use by sloth bears in Chitwan National Park (CNP), Nepal. We conducted sign surveys from March to June, 2020, in 4 × 4 km grids (n = 45). We collected detection/non‐detection data along a 4‐km trail that was divided into 20 continuous segments of 200 m each. We obtained environmental, ecological, and anthropogenic covariates to understand determinants of sloth bear habitat occupancy. The data were analyzed using the single‐species single‐season occupancy method, with a spatially correlated detection. Using repeated observations, these models accounted for the imperfect detectability of the species to provide robust estimates of habitat occupancy. The model‐averaged occupancy estimate for the sloth bear was 69% and the detection probability was 0.25. The probability of habitat occupancy by sloth bears increased with the presence of termites and fruits and in rugged, dry, open, undisturbed habitats. Our results indicate that the sloth bear is elusive, functionally unique, and widespread in CNP. Future conservation interventions and action plans aimed at sloth bear management must adequately consider their habitat requirements.     

Nephrotoxicity after radionuclide therapies

Radioligand therapies have opened new treatment avenues for cancer patients. They offer precise tumor targeting with a favorable efficacy-to-toxicity profile. Specifically, the kidneys, once regarded as the critical organ for radiation toxicity, also show excellent tolerance to radiation doses as high as 50–60 Gy in selected cases. However, the number of nephrons that form the structural and functional units of the kidney is determined before birth and is fixed. Thus, loss of nephrons secondary to any injury may lead to an irreversible decline in renal function over time. Our primary understanding of radiation-induced nephropathy is derived from the effects of external beam radiation on the renal tissue. With the growing adoption of radionuclide therapies, considerable evidence has been gained with regard to the occurrence of renal toxicity and its associated risk factors. In this review, we discuss the radionuclide therapies associated with the risk of nephrotoxicity, the present understanding of the factors and mechanisms that contribute to renal injury, and the current and potential methods for preventing, identifying, and managing nephrotoxicity, specifically acute onset nephropathies.     

Sacituzumab govitecan in metastatic triple negative breast cancer (TNBC): Four design features in the ASCENT trial potentially favored the experimental arm

The ASCENT trial reports impressive results with a median overall survival (OS) increased from 6.7 months to 12.1 months with sacituzumab govitecan over single-agent chemotherapy, in metastatic triple negative breast cancer (TNBC) patients in second and subsequent line of therapy.We described design features in the ASCENT trial casting doubt on the extrapolation of the reported results to real world patients. First, the open-label design may exaggerate the effect of the experimental arm. Second, the choice of progression-free-survival (PFS) as a primary endpoint, debatable in metastatic TNBC, can lead to biases: early stopping rules may exaggerate efficacy results and informative censoring can bias PFS results interpretation. Third, the control arm was not a complete “physician''s choice”: it was restricted, preventing from using effective agents in this setting, and leading to a substandard control arm. Fourth and lastly, dose reduction and supportive care recommendations for the experimental drug were different between the trial protocol and the FDA labels, and favored the experimental arm as compared with the control arm.In conclusion, we described four design features in the ASCENT trial having the potential to favor the experimental arm or to penalize the control arm. It thus remains uncertain in which extent the reported outcomes will translate in the real world. Efforts should be made to avoid trial biases that will eventually prevent to conclude about their true impact in patients when applied broadly.     

Genistein: A Potent Anti-Breast Cancer Agent

Genistein is an isoflavonoid present in high quantities in soybeans. Possessing a wide range of bioactives, it is being studied extensively for its tumoricidal effects. Investigations into mechanisms of the anti-cancer activity have revealed many pathways including induction of cell proliferation, suppression of tyrosine kinases, regulation of Hedgehog-Gli1 signaling, modulation of epigenetic activities, seizing of cell cycle and Akt and MEK signaling pathways, among others via which the cancer cell proliferation can be controlled. Notwithstanding, the observed activities have been time- and dose-dependent. In addition, genistein has also shown varying results in women depending on the physiological parameters, such as the early or post-menopausal states.     

Bombesin-like peptides stimulate phosphatidylinositol turnover in rat brain slices

The ability of bombesin (BN)-like peptides to stimulate phosphatidylinositol turnover in rat brain slices was investigated. BN (1 μM) significantly stimulated inositol-1-phosphate (IP₁) but not inositol-4,5-biphosphate (IP₂) or inositol-1,4,5-trisphosphate (IP₃) production using frontal cortex slices in the presence of LiCl (7.5 mM); BN had no effect on cAMP or cGMP levels. BN and the structurally-related gastrin releasing peptide (GRP) elevated IP₁ levels in a dose-dependent manner. Similarly, nanomolar concentrations of the GRP fragment (Ac-GRP^20–27) significantly elevated IP₁ levels, whereas micromolar concentrations of the inactive GRP^1–16 did not. BN significantly elevated IP₁ levels in those brain regions enriched in BN receptors such as the olfactory bulb, hippocampus, striatum, thalamus and frontal cortex, whereas IP₁ levels were not significantly increased in areas which have a low density of BN receptors such as the cerebellum, medulla/pons and midbrain. These data suggest that CNS BN receptors may utilize phosphatidylinositol as a second messenger.     

Ultrastructural studies on nodules induced by pyrimidine auxotrophs of Sinorhizobium meliloti

Twenty three pyrimidine auxotrophs of Sinorhizobium meliloti Rmd201 were generated by random mutagenesis with transposon Tn5. On the basis of biochemical characters these auxotrophic mutants were classified into car, pyrC and pyrE/pyrF categories. All auxotrophs induced white nodules which were ineffective in nitrogen fixation. Light and electron microscopic studies revealed that the nodules induced by pyrC mutants were more developed than the nodules of car mutants. Similarly the nodules induced by pyrE/pyrF mutants had more advanced structural features than the nodules of pyrC mutants. The nodule development in case of pyrE/pyrF mutants was not to the extent observed in the parental strain. These results indicated that some of the intermediates and/or enzymes of pyrimidine biosynthetic pathway of S. meliloti play a key role in bacteroidal transformation and nodule development.