The role of Xin in skeletal muscle regeneration

Adult skeletal muscle has the remarkable capacity of regenerating in response to stressors, such as overuse, injury, or myopathic conditions. A fundamental contributor to the regenerative process is satellite cells, which are the primary stem cells of skeletal muscle. Uncovering factors involved in satellite cell function will greatly improve their therapeutic potential, especially for patients suffering from myopathic diseases. The protein Xin was previously identified as being highly upregulated in damaged skeletal muscle and localized to the satellite cell population, however its purpose there has not been elucidated. Therefore the overall goal of this study was to determine the role of Xin during skeletal muscle regeneration and within its resident stem cell population. This was approached using Xin knockdown (Xin shRNA) and knockout (Xin-/- mice) models, whereby any deficits or changes in the regenerative process can be attributed to the lack/absence of Xin. The results of the following studies reveal that when Xin expression is reduced or absent, muscle regeneration is impaired, satellite cell activation is altered, and muscle fiber morphology moves towards a myopathic state. Furthermore, since Xin has been shown to be upregulated during regeneration, it was interesting to study the expression of Xin in human myopathic muscle which is in a constant state of regeneration. It was observed that Xin expression correlates with degree of damage in myopathic muscle, regardless of disease diagnosis. Therefore, these data have improved our understanding of muscle regeneration, satellite cell function, and suggest a clinical marker for defining muscle damage severity.Master of Science (MSc

Role of Calcium in Vomiting

Cisplatin-like chemotherapeutics cause vomiting via calcium (Ca2+)-dependent release of multiple neurotransmitters/mediators (dopamine, serotonin, substance P, prostaglandins and leukotrienes) from the gastrointestinal enterochromaffin cells and/or the brainstem. Intracellular Ca2+ signaling is triggered by activation of diverse emetic receptors (including neurokininergic NK1, serotonergic 5-HT3, dopaminergic D2, cholinergic M1, or histaminergic H1), whose stimulation in vomit-competent species evokes emesis. Other emetogens such as cisplatin, rotavirus NSP4 protein, and bacterial toxins can also induce intracellular Ca2+ elevation. Our findings demonstrate that application of the L-type Ca2+ channel (LTCC) agonist FPL 64176 and the intracellular Ca2+ mobilizing agent thapsigargin (a sarco/endoplasmic reticulum Ca2+-ATPase inhibitor) cause vomiting in the least shrew. On the other hand, blockade of LTCCs by corresponding antagonists (nifedipine or amlodipine) not only provide broad-spectrum antiemetic efficacy against diverse agents that specifically activate emetogenic receptors such as 5-HT3, NK1, D2, and M1 receptors, but can also potentiate the antiemetic efficacy of palonosetron against the nonspecific emetogen, cisplatin. In this review, we will provide an overview of Ca2+ involvement in the emetic process; discuss the relationship between Ca2+ signaling and the prevailing therapeutics in control of vomiting; highlight the current evidence for Ca2+-signaling blockers/inhibitors in suppressing emetic behavior and also draw attention to the clinical benefits of Ca2+-signaling blockers/inhibitors for the treatment of nausea and vomiting

Tourist Flow and Tourism Potential Regions of Gulmarg in Kashmir Himalayas

Gulmarg has a rich and diverse touristic product that holds the potential to be one of the most attractive tourist destinations for both leisure and sports tourism across the whole Kashmir Himalayan region The place owes its importance mainly to its beautiful geo-environmental setup and unique climate The destination has a history of tourism activities for more than five centuries The resort has been a great attraction for several British officials posted in India and their families made Gulmarg their home for the summer months This his to-geographical personality of the place has resulted in the development of tourist regions of interest to a range of tastes especially for holiday makers and sports and adventure tourists Therefore present study aims at identification and delineation of the different tourist potential regions of the place which would help in proper marketing of the tourist product management of tourist flow optimization of economic returns and management of the environmental health of the destination for sustainable tourism development in the regio

BIOACTIVITY-GUIDED PHYTOCHEMICAL INVESTIGATIONS OF ARTEMISIA MARITIMA: ISOLATION AND CHARACTERIZATION OF CHEMICAL CONSTITUENTS

Objective: In the present study, the extracts (petroleum ether and methanolic extract) of plant Artemisia maritima were subjected to bioactivity evaluation and compound isolation and characterization.Methods: Antioxidant activity was carried out using ferric reducing power and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The anticancer activity was evaluated by MTT assay using three different human cancer cell lines: Embryonic kidney cancer cell (HEK), lung adenocarcinoma epithelial cell (A-549), and human colon cancer cell (HCT), and isolated compounds were characterized using nuclear magnetic resonance (1HNMR), 13CNMR, DEPT, infrared, and mass spectroscopic techniques.Results: The petroleum ether extract of the plant displayed significant antioxidant and cytotoxic effects, which on phytochemical analysis led to the isolation of two bioactive sesquiterpene lactone compounds. These phytochemicals were identified using different spectral techniques in the light of literature. All the compounds displayed significant cytotoxic activity; however, compound-1 exhibited potent anticancer activity with inhibitory concentration value of 17.3 μg/mL. The isolated compounds also displayed significant antioxidant potential.Conclusion: Artemisia maritima, a rich source of sesquiterpene lactone which may be responsible for significant anticancer potential and it also possess remarkable antioxidant activity and hence may be of immense importance to food Chemistry

Watershed Based Drainage Morphometric Analysis of Lidder Catchment in Kashmir Valley Using Geographical Information System

The quantitative analysis of drainage system is an important aspect of characterization of watersheds. Using watershed as a basic unit in morphometric analysis is the most logical choice because all hydrologic and geomorphic processes occur within the watershed. Lidder catchment which constitutes a segment of the western Himalayas with an area of 1159.38 km2 (10% of the river Jhelum catchment) has been selected as the study area. Various linear and areal aspects of the catchment were computed at watershed level. This was achieved using GIS to provide digital data that can be manipulated for different calculations. The analysis has revealed that the total number as well as total length of stream segments is maximum in first order streams and decreases as the stream order increases. Horton’s laws of stream numbers and stream lengths also hold good. The bifurcation ratio between different successive orders is almost constant. The drainage density values of the different watersheds exhibit high degree of positive correlation (0.97) with the stream frequency suggesting that there is an increase in stream population with respect to increasing drainage density and vice versa

Combined T2 and diffusion-weighted MR Imaging with template prostate biopsies in men suspected with prostate cancer but negative transrectal ultrasound-guided biopsies

PURPOSE: Transperineal template prostate (TPB) biopsy has been shown to improve prostate cancer detection in men with rising PSA and previous negative TRUS biopsies. Diagnostic performance of this approach especially MR imaging and using reliable reference standard remains scantly reported. MATERIALS AND METHODS: A total of 200 patients, who were previously TRUS biopsy negative, were recruited in this study. All the participants had at least 28-core TPB under general anesthetic within 8 weeks of previous negative TRUS biopsies. In 15 men undergoing laparoscopic radical prostatectomy, prostate specimens were sectioned using custom-made molds and analyzed by experienced pathologist as a feasibility study. RESULTS: In total, 120 of 200 patients (60 %) had positive TPB biopsy results. All of these men had at least one negative biopsy from transrectal route. T2 diffusion-weighted MR imaging showed no lesion in almost one-third of these men (61/200; 30.5 %). Out of these, 33 (33/61; 54 %) showed malignancy on TPB including high-grade tumors (>Gleason 7). Out of 15 patients underwent surgery with a total of 52 lesions (mean 3.5) on radical prostatectomy histology analyses, TPB detected 36 (70 %) lesions only. Some of these lesions were Gleason 7 and more mostly located in the posterior basal area of prostate. CONCLUSIONS: Transperineal template biopsy technique is associated with significantly high prostate cancer detection rate in men with previous negative TRUS biopsies, however compared to radical prostatectomy histology map, a significant number of lesions can still be missed in the posterior and basal area of prostate

Knowledge and Adoption of Commercial Vegetable Growers in District Budgam, J&K

The study was conducted on 250 vegetable growers selected from ten villages of Budgam district of Jammu and Kashmir. The basic objective of the study was to ascertain the knowledge possessed and adoption level of growers as well as the economic status of vegetable growers. The result revealed that 50.80 per cent of the respondents had medium level of knowledge, 48.40 per cent of respondents belonged to medium adoption category and majority of 60.80 per cent of the vegetable growers belong to the middle economic status group

Air layering in nutmeg (Myristica fragrans Houtt.)

Nutmeg is an important perennial spice crop, which is dioecious in nature. Vegetative propagation is the norm in commercial propagation of the tree. The existing practice of propagation is grafting and budding which needs good skill and expertise for reasonable success. As an alternative to these two methods, air layering was attempted in matured trees for the first time in the country. Air layering was successful in plagiotropic and orthotropic shoots with 100 per cent survival. This method is cost effective and is easy for adoption

Transcriptomics-based drug repurposing approach identifies novel drugs against sorafenib-resistant hepatocellular carcinoma

Objective: Hepatocellular carcinoma (HCC) is frequently diagnosed in patients with late-stage disease who are ineligible for curative surgical therapies. The majority of patients become resistant to sorafenib, the only approved first-line therapy for advanced cancer, underscoring the need for newer, more effective drugs. The purpose of this study is to expedite identification of novel drugs against sorafenib resistant (SR)-HCC. Methods: We employed a transcriptomics-based drug repurposing method termed connectivity mapping using gene signatures from in vitro-derived SR Huh7 HCC cells. For proof of concept validation, we focused on drugs that were FDA-approved or under clinical investigation and prioritized two anti-neoplastic agents (dasatinib and fostamatinib) with targets associated with HCC. We also prospectively validated predicted gene expression changes in drug-treated SR Huh7 cells as well as identified and validated the targets of Fostamatinib in HCC. Results: Dasatinib specifically reduced the viability of SR-HCC cells that correlated with up-regulated activity of SRC family kinases, its targets, in our SR-HCC model. However, fostamatinib was able to inhibit both parental and SR HCC cells in vitro and in xenograft models. Ingenuity pathway analysis of fostamatinib gene expression signature from LINCS predicted JAK/STAT, PI3K/AKT, ERK/MAPK pathways as potential targets of fostamatinib that were validated by Western blot analysis. Fostamatinib treatment reversed the expression of genes that were deregulated in SR HCC. Conclusion: We provide proof of concept evidence for the validity of this drug repurposing approach for SR-HCC with implications for personalized medicine