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The retinal pigment epithelium (RPE) supports the health and function of retinal photoreceptors and is essential for normal vision. RPE cells are post-mitotic, terminally differentiated, and polarized epithelial cells. In pathological conditions, however, they lose their epithelial integrity, become dysfunctional, even dedifferentiate, and ultimately die. The integrity of epithelial cells is maintained, in part, by adherens junctions, which are composed of cadherin homodimers and p120-, β-, and α-catenins linking to actin filaments. While E-cadherin is the major cadherin for forming the epithelial phenotype in most epithelial cell types, it has been reported that cadherin expression in RPE cells is different from other epithelial cells based on results with cultured RPE cells. In this study, we revisited the expression of cadherins in the RPE to clarify their relative contribution by measuring the absolute quantity of cDNAs produced from mRNAs of three classical cadherins (E-, N-, and P-cadherins) in the RPE in vivo. We found that P-cadherin (CDH3) is highly dominant in both mouse and human RPE in situ. The degree of dominance of P-cadherin is surprisingly large, with mouse Cdh3 and human CDH3 accounting for 82–85% and 92–93% of the total of the three cadherin mRNAs, respectively. We confirmed the expression of P-cadherin protein at the cell-cell border of mouse RPE in situ by immunofluorescence. Furthermore, we found that oxidative stress induces dissociation of P-cadherin and β-catenin from the cell membrane and subsequent translocation of β-catenin into the nucleus, resulting in activation of the canonical Wnt/β-catenin pathway. This is the first report of absolute comparison of the expression of three cadherins in the RPE, and the results suggest that the physiological role of P-cadherin in the RPE needs to be reevaluated. [ABSTRACT FROM AUTHOR]

Two members of the signal transducer and activator of transcription (STAT) factor family, STAT1 and STAT3 are activated in fibroblasts in response to H2O2. The activation is sensitive to antioxidants and does not need protein synthesis. The activity of STAT kinases JAK2 and TYK2 is also stimulated by H2O2. Moreover, reactive oxygen species has a significant role in the activation of STATs by platelet-derived growth factor.

Banking sector is a fast growing sector of India. With swift expansion in the number of branches and the new functions assigned to them, banks are beginning to feel a new pressure on their organizational abilities i.e. the processes of recruitment, placement, training, promotion and appraisal, in order to ensure that the right number of staff with the right capacities are available at the right time and for the right places. Appraisal is one of the key factors of organizational ability which is also the focus of this study. In simple words we can say that performance appraisal is an analysis of employee's recent successes and failures, personal strengths and weaknesses, and suitability for promotion or further training. [ABSTRACT FROM AUTHOR]

Small-scale entrepreneurship plays a significant role in the economic development of a developing country. Therefore, the development of motivation in individuals is a crucial input to entrepreneurship. Basically, entrepreneurship is a result of one's motivation to achieve specific goals in life which is supported by other environmental factors. Motivation causes goal-directed behavior. A motivated person is likely to have broader vision which helps him/ her to make life more meaningful. Motivation is an index belief in one's own resourcefulness to take up challenging tasks like entrepreneurship. In this context, this paper examines the motives of women entrepreneurs in starting a small-scale enterprise in the socioeconomic milieu of Varanasi district. The sample units were selected randomly resulting in a sample size of 150 units. The data were collected through a structured questionnaire and informal interviews. The conclusions drawn from the empirical study show that the direct support from their family members (in the form finance) encouraged them to start their new ventures, which is a healthy signal for economic development of the country. [ABSTRACT FROM AUTHOR]

Vibrio cholerae-derived zonula occludins toxin (Zot) is a multifunctional protein that reversibly disassembles intestinal tight junctions (tjs). Zot structure- function analysis has mapped this activity to aa 288-293, named AT1002. AT1002 reduced transepithelial electrical resistance across rat small intestine, ex vivo, as did Zot and its processed mature form, ΔG. AT1002 increased in vivo permeability to sugar tracers, whereas scrambled control peptides did not. Binding and barrier assays in proteinase activated receptor (PAR)2-expressing and PAR2- null cells established AT1002 activity to be PAR5, dependent. Coincident with the increased intestinal permeability, confocal microscopy of AT1002-exposed rat intestinal IEC6 cells revealed displacement of ZO-1 and occludin from intercellular boundaries. In coimmunoprecipitation assays, AT1002 decreased ZO-1-occludin and ZO-1- claudin 1 interactions coincident with PKCα-dependent ZO-1 serine/threonine phosphorylation. Further, AT1002 increased serine phosphorylation of myosin 1C and, at the same time, transiently diminished its association with ZO- 1. The COOH-terminal domain of ZO-1 was required for its association with myosin 1C. These data indicate that the NH2-terminal portion of active Zot contains a PAR2-activating motif, FCIGRL, that increases PKCα- dependent ZO-1 and myosin 1C serine/threonine phosphorylation. These modifications provoke selective disengagement of ZO-1 from its binding partners, occludin, claudin 1, and myosin 1C, coincident with opening of tjs. [ABSTRACT FROM AUTHOR]

Glaucoma is the leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is one of the major risk factors for glaucoma onset and progression, and available pharmaceutical interventions are exclusively targeted at IOP lowering. However, degeneration of retinal ganglion cells (RGCs) may continue to progress despite extensive lowering of IOP. A complementary strategy to IOP reduction is the use of neuroprotective agents that interrupt the process of cell death by mechanisms independent of IOP. Here, we describe an ion complexation approach for formulating microcrystals containing ~50% loading of a protein kinase inhibitor, sunitinib, to enhance survival of RGCs with subconjunctival injection. A single subconjunctival injection of sunitinib-pamoate complex (SPC) microcrystals provided 20 weeks of sustained retina drug levels, leading to neuroprotection in a rat model of optic nerve injury. Furthermore, subconjunctival injection of SPC microcrystals also led to therapeutic effects in a rat model of corneal neovascularization. Importantly, therapeutically relevant retina drug concentrations were achieved with subconjunctival injection of SPC microcrystals in pigs. For a chronic disease such as glaucoma, a formulation that provides sustained therapeutic effects to complement IOP lowering therapies could provide improved disease management and promote patient quality of life. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about the article "Managing Customers As Investments" by Usha Kiran Rai in a 2007 issue of the journal, as well as a response by the editor-in-chief regarding the decision to cancel the paper.

Retinal pigment epithelium (RPE) is essential for the survival of retinal photoreceptors. To study retinal degeneration, sodium iodate (NaIO 3 ) has been used to cause oxidative stress-induced RPE death followed by photoreceptor degeneration. However, analyses of RPE damage itself are still limited. Here, we characterized NaIO 3 -induced RPE damage, which was divided into three regions: periphery with normal-shaped RPE, transitional zone with elongated cells, and center with severely damaged or lost RPE. Elongated cells in the transitional zone exhibited molecular characteristics of epithelial-mesenchymal transition. Central RPE was more susceptible to stresses than peripheral RPE. Under stresses, SIRT6, an NAD + -dependent protein deacylase, rapidly translocated from the nucleus to the cytoplasm and colocalized with stress granule factor G3BP1, leading to nuclear SIRT6 depletion. To overcome this SIRT6 depletion, SIRT6 overexpression was induced in the nucleus in transgenic mice, which protected RPE from NaIO 3 and partially preserved catalase expression. These results demonstrate topological differences of mouse RPE and warrant further exploring SIRT6 as a potential target for protecting RPE from oxidative stress-induced damage., (© 2023 Yang et al.)

Oxidative stress of the retinal pigment epithelium (RPE) is a major risk factor for age-related macular degeneration (AMD). As a dry AMD model via oxidative stress, sodium iodate (NaIO 3 ), which is primarily toxic to the RPE, has often been used at a high dose to cause RPE death for studying photoreceptor degeneration. Thus, characterization of RPE damage by a low dose of NaIO 3 is still limited. To quantify RPE damage caused by NaIO 3 in mice, we recently developed a morphometric method using RPE flat-mounts. Here, we report that NaIO 3 has a narrow range of dose-effect correlation at 11-18 mg/kg body weight in male C57BL/6J mice. We evaluated the usefulness of our quantification method in two experimental settings. First, we tested the effect of NF-κB inhibition on NaIO 3 -induced RPE damage in male C57BL/6J mice. IKKβ inhibitor BAY 651942 suppressed upregulation of NF-κB targets and protected the RPE from oxidative stress. Second, we tested sex-specific differences in NaIO 3 -induced RPE damage in C57BL/6J mice using a low dose near the threshold. NaIO 3 caused more severe RPE damage in female mice than in male mice. These results demonstrate the usefulness of the quantification method and the importance of fine-tuning of the NaIO 3 dose. The results also show the therapeutic potential of IKKβ inhibition for oxidative stress-related RPE diseases, and reveal previously-unrecognized sex-specific differences in RPE susceptibility to oxidative stress.