Degradation of Internalized αvβ5 Integrin Is Controlled by uPAR Bound uPA: Effect on β1 Integrin Activity and α-SMA Stress Fiber Assembly

Myofibroblasts (Mfs) that persist in a healing wound promote extracellular matrix (ECM) accumulation and excessive tissue contraction. Increased levels of integrin αvβ5 promote the Mf phenotype and other fibrotic markers. Previously we reported that maintaining uPA (urokinase plasminogen activator) bound to its cell-surface receptor, uPAR prevented TGFβ-induced Mf differentiation. We now demonstrate that uPA/uPAR controls integrin β5 protein levels and in turn, the Mf phenotype. When cell-surface uPA was increased, integrin β5 levels were reduced (61%). In contrast, when uPA/uPAR was silenced, integrin β5 total and cell-surface levels were increased (2–4 fold). Integrin β5 accumulation resulted from a significant decrease in β5 ubiquitination leading to a decrease in the degradation rate of internalized β5. uPA-silencing also induced α-SMA stress fiber organization in cells that were seeded on collagen, increased cell area (1.7 fold), and increased integrin β1 binding to the collagen matrix, with reduced activation of β1. Elevated cell-surface integrin β5 was necessary for these changes after uPA-silencing since blocking αvβ5 function reversed these effects. Our data support a novel mechanism by which downregulation of uPA/uPAR results in increased integrin αvβ5 cell-surface protein levels that regulate the activity of β1 integrins, promoting characteristics of the persistent Mf

Complete Phenotypic Recovery of an Alzheimer's Disease Model by a Quinone-Tryptophan Hybrid Aggregation Inhibitor

The rational design of amyloid oligomer inhibitors is yet an unmet drug development need. Previous studies have identified the role of tryptophan in amyloid recognition, association and inhibition. Furthermore, tryptophan was ranked as the residue with highest amyloidogenic propensity. Other studies have demonstrated that quinones, specifically anthraquinones, can serve as aggregation inhibitors probably due to the dipole interaction of the quinonic ring with aromatic recognition sites within the amyloidogenic proteins. Here, using in vitro, in vivo and in silico tools we describe the synthesis and functional characterization of a rationally designed inhibitor of the Alzheimer's disease-associated β-amyloid. This compound, 1,4-naphthoquinon-2-yl-L-tryptophan (NQTrp), combines the recognition capacities of both quinone and tryptophan moieties and completely inhibited Aβ oligomerization and fibrillization, as well as the cytotoxic effect of Aβ oligomers towards cultured neuronal cell line. Furthermore, when fed to transgenic Alzheimer's disease Drosophila model it prolonged their life span and completely abolished their defective locomotion. Analysis of the brains of these flies showed a significant reduction in oligomeric species of Aβ while immuno-staining of the 3rd instar larval brains showed a significant reduction in Aβ accumulation. Computational studies, as well as NMR and CD spectroscopy provide mechanistic insight into the activity of the compound which is most likely mediated by clamping of the aromatic recognition interface in the central segment of Aβ. Our results demonstrate that interfering with the aromatic core of amyloidogenic peptides is a promising approach for inhibiting various pathogenic species associated with amyloidogenic diseases. The compound NQTrp can serve as a lead for developing a new class of disease modifying drugs for Alzheimer's disease

<span style="font-size:11.0pt;mso-bidi-font-size: 10.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:AR-SA" lang="EN-US">Validation of indigenous knowledge on edibility of b<span style="mso-bidi-font-weight: bold">aby clam, <i>Katylesia opima</i> from the Ratnagiri coast of Maharashtra</span></span>

149-153<span style="font-size:11.0pt;mso-bidi-font-size: 10.0pt;font-family:" times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="" lang="EN-US">Indigenous knowledge can be judiciously blended with modern scientific knowledge and its benefit to the fishers can be greatly improved. Bivalve fishery is traditionally practiced along the estuarine ecosystems in coastal district of Ratnagiri in Maharashtra. Fishermen, by virtue of their intricate association with coastal environment and daily observations of natural resources possess rich indigenous knowledge (IK). In present study, an attempt was made to validate the indigenous knowledge of fishermen related to the seasonal edibility of Baby clam (Katylesia opima) with respect to season-wise variation in the quantity of meat. Data on edibility of clams was collected from 50 fishermen using semi-structured schedules. For validation of the indigenous knowledge, laboratory data on percentage edibility, lipid, protein, ash and glycogen were collected and analyzed. In clams, all the variables tested only the lipid content and percentage edibility (PE) returned significant results (p < 0.05). The summer season displayed the median value, while monsoon the highest and winter the lowest for both the variables. Further, PE and lipid varied significantly during monsoon and winter season (p<0.05). An important aspect of IK that lowest edibility is associated with winter is validated by the study.</span

Assessment of indigenous knowledge on edibility of oyster, <em>Crassostrea madrasensis</em> from the Ratnagiri coast of Maharashtra

204-208Indigenous knowledge (IK) can be broadly defined as the knowledge that an indigenous community accumulates over generations of living in a particular environment whose scientific validity is not proven. Oysters are highly esteemed sea food and considered a delicacy throughout the world. Fishers from Ratnagiri district traditionally practice oyster fishing along the estuarine ecosystems. The daily observations of fishers on the resources and fishing environment result in possessing rich indigenous knowledge.In present study, an attempt was made to validate the indigenous knowledge of fishermen related to the seasonal edibility of oyster, Crassostrea madrasensis with respect to seasonal variation in the quality and quantity of meat. Primary data were collected through semi-structured interview schedule, focus group discussions and observation.Rationality and effectiveness of the indigenous knowledge were assessed. The protein content and percentage edibility (PE) were estimated for the overall edibility of oyster. The summer season displayed the median value, while monsoon the highest and winter the lowest for both the variables. Further PE and protein varied significantly during monsoon and winter season (p < 0.05). An important aspect of IK that the lowest edibility is associated with winter is validated by the study

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Not AvailableBackground: The present study assessed the growth and mortality parameters of the white sardine, Escualosa thoracata which is having high local demand. The white sardine gained importance due to its taste, and high demand in domestic markets as compared to the oil sardine necessitated a study on this resource to know the present status of exploitation level along the central west coast of India. Results: A total of 3026 individuals of different size groups of E. thoracata were randomly collected from the Burondi fish landing center of the Ratnagiri district of Maharashtra. The asymptotic length (L∞) and growth coefficient (K) were estimated to be 115 mm and 1.9 year−1, respectively, by ELEFAN-I and 135 mm and 1.2 year−1 by the scattergram. The value of t0 by von Bertalanffy plot was estimated to be −0.000012 year. The fish attained a length of 65 mm, 94 mm, and 114 mm at the end of 0.5, 1, and 1.5 years of its life, respectively. The instantaneous rate of total mortality (Z), natural mortality (M), and fishing mortality (F) were estimated to be 8.07 year−1, 2.55 year−1, and 5.52 year−1, respectively. The exploitation rate (U) was calculated as 0.65, and the exploitation ratio (E) was 0.68. Conclusion: The growth, mortality, and other population parameters observed in the present study will help to understand the current stock status, which is pointing toward the over-fishing condition (E ˃ 0.50) of the white sardine in the study area. Therefore, the present investigation suggests reducing the fishing pressure on E. thoracata along the central west coast of India for the sustainability of the resource.Not Availabl