PCB153-Induced Overexpression of ID3 Contributes to the Development of Microvascular Lesions

Microvascular lesions resulting from endothelial cell dysfunction are produced in the brain, lung, kidney, and retina of patients of complex chronic diseases. The environmental and molecular risk factors which may contribute in the development of microvascular damage are unclear. The mechanism(s) responsible for initiating microvascular damage remain poorly defined, although several inciting factors have been proposed, including environmental toxicants-induced oxidative stress. Enhanced neovascularization has been implicated in either the development or progression of proliferative vascular lesions. Here, we present evidence for how PCB-induced ROS may contribute to the development of a neovascular phenotype with the aim of elucidating the role of environmental toxicants in endothelial dysfunction with a specific focus on the inhibitor of differentiation protein ID3. We used a combination of phenotype and immunohistochemical analysis followed by validating with protein expression and post-translational modifications with Western Blot and MALDI-TOF/TOF analysis. We also looked for a correlation between ID3 expression in vascular tissue. Our results showed that PCB-induced ROS mediated a highly tube branched neovascular phenotype that also depended on ID3 and Pyk2; and PCB153 treatment increased the size of endothelial spheroids under conditions typically used for clonal selection of stem cell spheroids. High ID3 protein expression correlated with a greater degree of malignancy and oxidative DNA damage marker 8-OHdG in blood vessels from human subjects. PCB153 treatment increased both serine and tyrosine phosphorylation of endothelial ID3. Stable ID3 overexpression increased cell survival of human microvascular endothelial cell line hCMEC/D3. In summary, our data provide evidence that ID3 may play a critical role in regulating vascular endothelial cell survival and development of microvascular lesions induced by persistent environmental pollutants such as PCB153. Findings of this study are important because they provide a new paradigm by which PCBs may contribute to the growth of microvascular lesions

Microvascular lesions by estrogen-induced ID3: its implications in cerebral & cardiorenal vascular disease

Severe symptoms of cerebral and cardiorenal vascular diseases can be triggered when cerebral, coronary, or glomerular arterioles grow inappropriately as a result of abnormal cell proliferation. The risk factor(s) and molecular mechanisms responsible for microvascular lesion formation are largely unknown. Although controversial, both animal and epidemiological studies have shown that estrogen increases the risk of stroke which may be due to microvascular lesions. Since microvascular diseases are characterized by excessive vessel growth, it is plausible that estrogen-induced neovascularization contributes to the growth of microvascular lesions. We present evidence for how ID3 overexpression in endothelial cells contributes to the development of an estrogen-induced neovascular phenotype with an additional focus on Pyk2 kinase. Our data showed that ID3 overexpression increased neovascularization, cell migration, and spheroid growth of human cerebral microvascular endothelial cells, hCMEC/D3. ID3 overexpressing cells showed significant estrogen-induced G2/M phase transition. Estrogen treatment increased both ID3 phosphorylation and total protein that was inhibited by tamoxifen; and Pyk2 mediated estrogen-induced ID3 mRNA expression. These findings suggest that Pyk2 signals ID3 expression and ID3 is necessary for estrogen-induced neovascularization in hCMEC/D3 cells. A better understanding of how microvascular lesions depend on ID3 may open new avenues for prevention and treatment of neurological diseases

Out of Pocket expenditure among beneficiaries of Janani Shishu Suraksha Karyakaram

Background: About 67,000 women in India die every year (MoHFW, 2011), due to pregnancy related complications. Similarly, every year more than 13 lacs infants die, within 1 year of the birth and out of these approximately 9 lacs i.e. 2/3rd of the infant deaths take place within the first four weeks of life (1).Out of these, approximately 7 lacs i.e. 75% of the deaths take place within a week of the birth and a majority of these occur in the first two days after birth (1). In view of the difficulty being faced by the pregnant women and parents of sick new-born (MoHFW,2011), along with high out-of-pocket expenses incurred by them on delivery and treatment of sick new-born, Ministry of Health and Family Welfare has taken a major initiative, to provide completely free and cashless services to pregnant women including normal deliveries and caesarean operations and sick new born (up to 30 days after birth) in Government health institutions in both rural & urban areas. Material & Methods: In this community based descriptive cross-sectional study, data was collected from 100 mothers, who had delivered in last one year at District Hospital Maternal Wing situated at Morar Block of Gwalior District M.P and MO, ANM’s, ASHA’s, using Semi structured close ended Interview schedule and an open ended questionnaire respectively. Data were compared by using SPSS (ver. 22.0) Result: Expenses were divided under two heads, medical and non-medical. 15% of the total beneficiaries incurred the medical expenses in the form of medicines, diagnostics etc. and almost 99% of all the respondents incurred the non-medical expenses in the form of transport, food etc. Conclusion: Based on the outcome of the study the overall impression was that 59% of the beneficiaries were not aware of the JSSK scheme. Only during pregnancies through the initiatives of the ASHAs the beneficiaries came to know about the free entitlements of the scheme. There was unavailability of ambulance when required and delay in the services

ID3 Contributes to the Acquisition of Molecular Stem Cell-Like Signature in Microvascular Endothelial Cells: Its implication for understanding microvascular diseases

While significant progress has been made to advance our knowledge of microvascular lesion formation, yet the investigation of how stem-like cells may contribute to the pathogenesis of microvascular diseases is still in its infancy. We assessed whether the inhibitor of DNA binding and differentiation 3 (ID3) contributes to the acquisition of a molecular stem cell-like signature in microvascular endothelial cells. The effects of stable ID3 overexpression and SU5416 treatment — a chemical inducer of microvascular lesions, had on the stemness signature was determined by flow cytometry, immunoblot, and immunohistochemistry. Continuous ID3 expression produced a molecular stemness signature consisting of CD133+ VEGFR3+ CD34+ cells. Cells exposed to SU5416 showed positive protein expression of ID3, VEGFR3, CD34 and increased expression of pluripotent transcription factors Oct-4 and Sox-2. ID3 overexpressing cells supported the formation of a 3-D microvascular lesion co-cultured with smooth muscle cells. In addition, in vivo microvascular lesions from SuHx rodent model showed an increased expression of ID3, VEGFR3, and Pyk2 similar to SU5416 treated human endothelial cells. Further investigations into how normal and stem-like cells utilize ID3 may open up new avenues for a better understanding of the molecular mechanisms which are underlying the pathological development of microvascular diseases

Frequency Dependent Viscosity Near the Critical Point: The Scale to Two Loop Order

The recent accurate measurements of Berg, Moldover and Zimmerli of the viscoelastic effect near the critical point of xenon has shown that the scale factor involved in the frequency scaling is about twice the scale factor obtained theoretically. We show that this discrepancy is a consequence of using first order perturbation theory. Including two loop contribution goes a long way towards removing the discrepancy.Comment: No of pages:7,Submitted to PR-E(Rapid Communication),No of EPS files:

Endophytes: A Treasure House of Bioactive Compounds of Medicinal Importance

Endophytes are an endosymbiotic group of microorganisms that colonize in plants and microbes that can be readily isolated from any microbial or plant growth medium. They act as reservoirs of novel bioactive secondary metabolites, such as alkaloids, phenolic acids, quinones, steroids, saponins, tannins, and terpenoids that serve as a potential candidate for antimicrobial, anti-insect, anticancer and many more properties. While plant sources are being extensively explored for new chemical entities for therapeutic purposes, endophytic microbes also constitute an important source for drug discovery. This review aims to comprehend the contribution and uses of endophytes as an impending source of drugs against various forms of diseases and other possible medicinal use

Critical Viscosity Exponent for Fluids: What Happend to the Higher Loops

We arrange the loopwise perturbation theory for the critical viscosity exponent $x_{\eta}$, which happens to be very small, as a power series in $x_{\eta}$ itself and argue that the effect of loops beyond two is negligible. We claim that the critical viscosity exponent should be very closely approximated by $x_{\eta}=\frac{8}{15 \pi^2}(1+\frac{8}{3 \pi^2})\simeq 0.0685$.Comment: 9 pages and 3 figure