Vegf signaling between Müller glia and vascular endothelial cells is regulated by immune cells and stimulates retina regeneration.

In the zebrafish retina, Müller glia (MG) can regenerate retinal neurons lost to injury or disease. Even though zebrafish MG share structure and function with those of mammals, only in zebrafish do MG function as retinal stem cells. Previous studies suggest dying neurons, microglia/macrophage, and T cells contribute to MG's regenerative response [White et al.

A zebrafish model of congenital nephrotic syndrome of the Finnish type.

Nephrotic syndrome (NS) is a disease characterized by proteinuria and subsequent hypoalbuminemia, hyperlipidemia and edema due to the defective renal glomerular filtration barrier (GFB). Mutations of NPHS1, encoding NEPHRIN, a podocyte protein essential for normal GFB, cause congenital nephrotic syndrome (CNS) of the Finnish type (CNF), which accounts for about 50% of CNS cases. We generated zebrafish nphs1 mutants by using CRISPR/Cas9.

Health-care-associated bloodstream and urinary tract infections in a network of hospitals in India: a multicentre, hospital-based, prospective surveillance study.

Background: Health-care-associated infections (HAIs) cause significant morbidity and mortality globally, including in low-income and middle-income countries (LMICs). Networks of hospitals implementing standardised HAI surveillance can provide valuable data on HAI burden, and identify and monitor HAI prevention gaps. Hospitals in many LMICs use HAI case definitions developed for higher-resourced settings, which require human resources and laboratory and imaging tests that are often not available.

Clinical Characterization and Genomic Analysis of Samples from COVID-19 Breakthrough Infections during the Second Wave among the Various States of India.

From March to June 2021, India experienced a deadly second wave of COVID-19, with an increased number of post-vaccination breakthrough infections reported across the country. To understand the possible reason for these breakthroughs, we collected 677 clinical samples (throat swab/nasal swabs) of individuals from 17 states/Union Territories of the country who had received two doses ( = 592) and one dose ( = 85) of vaccines and tested positive for COVID-19. These cases were telephonically interviewed and clinical data were analyzed.

Notch signaling via Hey1 and Id2b regulates Müller glia's regenerative response to retinal injury.

Zebrafish Müller glia (MG) respond to retinal injury by suppressing Notch signaling and producing progenitors for retinal repair. A certain threshold of injury-derived signal must be exceeded in order to engage MG in a regenerative response (MG's injury-response threshold). Pan-retinal Notch inhibition expands the zone of injury-responsive MG at the site of focal injury, suggesting that Notch signaling regulates MG's injury-response threshold.

Assessment of core capacities for antimicrobial stewardship practices in indian hospitals: Report from a multicentric initiative of global health security agenda.

Introduction: Antimicrobial-resistant HAI (Healthcare associated infection) are a global challenge due to their impact on patient outcome. Implementation of antimicrobial stewardship programmes (AMSP) is needed at institutional and national levels. Assessment of core capacities for AMSP is an important starting point to initiate nationwide AMSP.

Glycine Amidinotransferase (GATM), Renal Fanconi Syndrome, and Kidney Failure.

For many patients with kidney failure, the cause and underlying defect remain unknown. Here, we describe a novel mechanism of a genetic order characterized by renal Fanconi syndrome and kidney failure. We clinically and genetically characterized members of five families with autosomal dominant renal Fanconi syndrome and kidney failure.

Evidence for a retroviral insertion in TRPM1 as the cause of congenital stationary night blindness and leopard complex spotting in the horse.

Leopard complex spotting is a group of white spotting patterns in horses caused by an incompletely dominant gene (LP) where homozygotes (LP/LP) are also affected with congenital stationary night blindness. Previous studies implicated Transient Receptor Potential Cation Channel, Subfamily M, Member 1 (TRPM1) as the best candidate gene for both CSNB and LP. RNA-Seq data pinpointed a 1378 bp insertion in intron 1 of TRPM1 as the potential cause.

Metabotropic glutamate receptor 6 signaling enhances TRPM1 calcium channel function and increases melanin content in human melanocytes.

Mutations in TRPM1, a calcium channel expressed in retinal bipolar cells and epidermal melanocytes, cause complete congenital stationary night blindness with no discernible skin phenotype. In the retina, TRPM1 activity is negatively coupled to metabotropic glutamate receptor 6 (mGluR6) signaling through Gαo and TRPM1 mutations result in the loss of responsiveness of TRPM1 to mGluR6 signaling. Here, we show that human melanocytes express mGluR6, and treatment of melanocytes with L-AP4, a type III mGluR-selective agonist, enhances Ca(2+) uptake.

Interactions between GIPC-APPL and GIPC-TRP1 regulate melanosomal protein trafficking and melanogenesis in human melanocytes.

By virtue of the presence of multiple protein-protein interaction and signaling domains, PDZ proteins play important roles in assembling protein complexes that participate in diverse cell biological processes. GIPC is a versatile PDZ protein that binds a variety of target proteins in different cell types. In previous studies we showed that, in epidermal melanocytes, GIPC interacts with newly synthesized melanosomal protein TRP1 in the Golgi region and proposed that this interaction may facilitate intracellular trafficking of TRP1.

Oncogenic BRAFV600E induces expression of neuronal differentiation marker MAP2 in melanoma cells by promoter demethylation and down-regulation of transcription repressor HES1.

MAP2 is a neuron-specific microtubule-associated protein that binds and stabilizes dendritic microtubules. Previously, we showed that MAP2 expression is (a) activated in cutaneous primary melanoma and (b) inversely associated with melanoma tumor progression. We also showed that ectopic expression of MAP2 in metastatic melanoma cells inhibits cell growth by inducing mitotic spindle defects and apoptosis.

Calcium homeostasis in human melanocytes: role of transient receptor potential melastatin 1 (TRPM1) and its regulation by ultraviolet light.

Transient receptor potential melastatin (TRPM) is a subfamily of ion channels that are involved in sensing taste, ambient temperature, low pH, osmolarity, and chemical ligands. Melastatin 1/TRPM1, the founding member, was originally identified as melanoma metastasis suppressor based on its expression in normal pigment cells in the skin and the eye but not in aggressive, metastasis-competent melanomas. The role of TRPM1 and its regulation in normal melanocytes and in melanoma progression is not understood.

Effect of anti-oxidant treatment on hyperhomocysteinemia-induced myocardial fibrosis and diastolic dysfunction.

Background: Recent studies demonstrate that hyperhomocysteinemia is a risk factor for heart failure. Oxidant stress is a major mediator of the pathogenic effects of hyperhomocysteinemia.

Methods: We utilized a rat model of diet-induced hyperhomocysteinemia to examine whether treatment with an anti-oxidant vitamin (C&E) combination will prevent hyperhomocysteinemia-induced myocardial fibrosis.

Effect of long-term hyperhomocysteinemia on myocardial structure and function in hypertensive rats.

Background: Postulated mechanisms of hyperhomocysteinemia (Hhe) overlap with proposed mechanisms of adverse cardiac remodeling such as altered collagen metabolism and oxidant stress. Hence we examined the hypothesis that Hhe would promote myocardial fibrosis and systolic dysfunction.

Methods: Three-month-old spontaneously hypertensive rats (SHRs) were divided into three groups: (1) control, given amino-acid defined diet for 20 weeks; (2) Hhe group, given Hhe-inducing diet for 20 weeks; and (3) combined diet group, which were given Hhe-inducing diet for 10 weeks (which leads to myocardial fibrosis and diastolic dysfunction as shown in our prior studies) and subsequently returned to amino acid-defined diet for 10 more weeks.

Protective role of mast cells in homocysteine-induced cardiac remodeling.

Recent reports including those from our laboratories indicate that hyperhomocysteinemia (Hhe) is an independent risk factor for cardiac dysfunction and clinical heart failure. Mast cell accumulation is a prominent feature in our model of Hhe-induced cardiac dysfunction. Because mast cell-derived mediators can potentially attenuate cardiac remodeling, we investigated the possible protective role of mast cells in Hhe-induced cardiac remodeling using a mast cell-deficient rat model that in our recent report did not demonstrate any adverse cardiac function at younger age (6 mo) than mast cell-competent control animals.

The evaluation of the acute toxicity and long term safety of hydroalcoholic extract of Sapthaparna (Alstonia scholaris) in mice and rats.

The acute and sub-acute toxic effects of various doses of hydroalcoholic extract of Alstonia scholaris (ASE) was studied in mice and rats. The acute toxicity in mice depended on the season of collection of plant. The highest acute toxicity was observed in the ASE prepared from the summer collection followed by winter.

Hyperhomocysteinemia leads to pathological ventricular hypertrophy in normotensive rats.

A recent report indicated that hyperhomocysteinemia (Hhe), in addition to its atherothrombotic effects, exacerbates the adverse cardiac remodeling seen in response to hypertension, a powerful stimulus for pathological ventricular hypertrophy. The present study was undertaken to determine whether Hhe has a direct effect on ventricular remodeling and function in the absence of other hypertrophic stimuli. Male Wistar-Kyoto rats were fed either an amino acid-defined control diet or an intermediate Hhe-inducing diet.