Inhibition of apoptotic Bax translocation to the mitochondria is a central function of parkin

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, affecting 1–3% of the population over 65. Mutations in the ubiquitin E3 ligase parkin are the most common cause of autosomal recessive PD. The parkin protein possesses potent cell-protective properties and has been mechanistically linked to both the regulation of apoptosis and the turnover of damaged mitochondria. Here, we explored these two functions of parkin and the relative scale of these processes in various cell types. While biochemical analyses and subcellular fractionation were sufficient to observe robust parkin-dependent mitophagy in immortalized cells, higher resolution techniques appear to be required for primary culture systems. These approaches, however, did affirm a critical role for parkin in the regulation of apoptosis in primary cultured neurons and all other cells studied. Our prior work demonstrated that parkin-dependent ubiquitination of endogenous Bax inhibits its mitochondrial translocation and can account for the anti-apoptotic effects of parkin. Having found a central role for parkin in the regulation of apoptosis, we further investigated the parkin-Bax interaction. We observed that the BH3 domain of Bax is critical for its recognition by parkin, and identified two lysines that are crucial for parkin-dependent regulation of Bax translocation. Last, a disease-linked mutation in parkin failed to influence Bax translocation to mitochondria after apoptotic stress. Taken together, our data suggest that regulation of apoptosis by the inhibition of Bax translocation is a prevalent physiological function of parkin regardless of the kind of cell stress, preventing overt cell death and supporting cell viability during mitochondrial injury and repair

Sourcing complexity factors on contractual relationship: Chinese suppliers’ perspective

To reduce cost and gain competitive advantage, original equipment manufacturers (OEMs) around the world have continued their aggressive sourcing from China. However, sourcing in China has never been a straightforward process and OEMs face both tangible and intangible sourcing complexities with significant negative impact on both expected positive benefits and their contractual relationships with the Chinese suppliers. We developed sourcing complexity model using comprehensive literature review and multiple case studies in various industries to understand the suppliers’ views on sourcing complexity in China. We employed Analytic hierarchy process technique to prioritise identified complexity factors and to derive managerial insights. Our results indicate that tangible complexity factors highly influence the Chinese suppliers’ contractual relationship with OEM’s. Number of suppliers available to OEM’s to procure a component is identified as a primary dominating tangible factor, while differentiation in technical capabilities and operational practices between OEMs and suppliers represents the second biggest issue for Chinese suppliers in establishing contractual relationship with OEM’s

Farmer Assistant Android App

In India most of the population is depending on agriculture and Farmer is the backbone of the Indian economy. The system consists of smartphone applications. The System can be used by farmers on the android application on mobile devices. The paper proposes the utilization of information mining to give suggestions to ranchers to crops, crop data, and distinguishing proof of suitable manure. The smart-phone is used very commonly by everyone who is educated or non-educated. This application can provide different languages, which is Hindi and English this language commonly used and easy to use on the system.

The impact of changes in stakeholder salience on CSR activities in Russian energy firms: a contribution to the divergence / convergence debate

This empirical paper examines the drivers underpinning changes to socially-responsible behaviours in the Russian energy sector. Responding to recent requests to contextualise CSR research, we focus on the changing set of stakeholders and developments in their saliency as reflected in corporations’ CSR activities. Based on interviews with more than thirty industry professionals, our findings suggest that Russian energy companies’ CSR is strongly stakeholder driven, and organisations adapt their activities according to their dependence on the resources that these salient stakeholders possess. We challenge the proposition that CSR in Russia arises from purely endogenous, historical, paternalism or neo-paternalism. We identify stakeholders that now shape CSR in the Russian energy sector, both endogenous (institutional and contextual forces relevant to the national business system) and exogenous (relating to the organisational field of the energy industry - international by nature). We thereby contribute to the convergence / divergence debate within CSR theory by demonstrating that both national business systems and the organisational field must be taken into account when analysing the forces that shape CSR strategies in any one country

Sounds of Silence : The Reflexivity, Self-decentralization, and Transformation Dimensions of Silence at Work

This article explores silence as a phenomenon and practice in the workplace through a Buddhist-enacted lens where silence is intentionally encouraged. It brings forward a reconsideration of the roles of silence in organizations by proposing emancipatory dimensions of silence—reflexivity, self-decentralization, and transformation. Based on 54 interviews with employees and managers in a Vietnamese telecommunications organization, we discuss the dynamic nature of silence, and the possible coexistence of the constructive and the oppressive aspects of silence in a workplace spirituality context. Instead of studying silence as one-dimensional, we call for an integrated view and argue that studying silence requires consideration of the multiplicity of its interconnected dimensions. By considering silence as a relational and emerging processes constructed around its vagueness and uncertainties, our study reveals the many possible ways silence is organized and organizes and sheds light on silence as a marker of the complexities and paradoxes of organizational life

Possible association between ABCC8 C49620T polymorphism and type 2 diabetes in a Nigerian population

The association between ABCC8 gene C49620T polymorphism and type 2 diabetes (T2D) in populations of diverse ethnic backgrounds has been reported. However, such occurrence in an African population is yet to be established. This case-control study involving 73 T2D and 75 non-diabetic (ND) patients investigated the occurrence of this polymorphism among T2D patients in Nigeria and assessed its relationship with body lipids of patients. Demographic and clinical characteristics of patients were collected and lipid profile indices including total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL) were assayed. Restriction fragment length polymorphism-PCR (RFLP-PCR) was employed to genotype the ABCC8-C49620T polymorphism using PstI restriction enzyme. This study revealed significantly (p 0.05) of T2D for the unadjusted codominant, dominant and recessive models. Following age adjustment, the mutant genotypes (CT and TT) showed significant (p<0.05) risk of T2D for all the models with the recessive model presenting the greatest risk of T2D (OR: 2.39, 95% CI: 1.16-4.91, p<0.018). The TT genotype significantly (p<0.05) associated with high level of HDL and reduced levels of TC, TG and LDL in non-diabetic patients but was not associated with any of the demographic and clinical characteristics among T2D patients. ABCC8 C49620T polymorphism showed possible association with T2D marked by predominance of the mutant TT genotype in T2D patients. However, the relationship between TT genotype and lipid abnormalities for possible beneficial effect on people suffering from T2D is unclear

L'India contemporanea. Dinamiche culturali e politiche, trasformazioni economiche e mutamento sociale

Frutto di uno studio interdisciplinare realizzato da tre grandi centri di ricerca indiani, il volume rende con sapienza la vivacità delle dinamiche sociali e della complessa evoluzione culturale in corso nella società indiana.- Indice #5- Introduzione #9- Correnti culturali e versioni indiane della modernità. Le tradizioni e il futuro della democrazia, Ashis Nandy #13- Caste e classi in India: realtà sociale e rappresentazioni politiche, Dhirubhai L. Sheth #33- Religione e politica in India. Cultura politica, revivalismo, fondamentalismo e secolarismo, Triloki N. Madan #61- Comunitarismo e integrazione nello stato nazionale. Tolleranza e secolarismo, Shail Mayaram #79- Il ruolo delle scuole e delle università nel promuovere una cultura comune e lo sviluppo sociale nelle città e nelle aree rurali, Suma Chitnis #101- I partiti e il processo elettorale in India. Nodi centrali nel dibattito politico corrente, Peter R. de Souza #127- Pluralismo centrale e istituzioni politiche. Lo stato federale indiano e il suo futuro, Ajit Mozoomdar #149- Società civile, movimenti sociali e stato in India: le politiche del cambiamento sociale, Shobha Raghuram #183- Geostrategia e geopolitica dell’India. Sviluppi recenti, sfide contemporanee e prospettive future, Jasjit Singh #209- La demografia e le sue implicazioni economiche, Vishvanath A. Pai Panandiker #235- L’economia dell’India e le sue prospettive, Isher J. Ahluwalia #255- Diseguaglianze nella distribuzione del reddito e del patrimonio in India, Nilakantha Rath #279- Il ruolo dello stato e del mercato nell’economia indiana, Eswaran Sridharan #317- La posizione geoeconomica dell’India. Relazioni internazionali e prospettive dell’integrazione regionale, con particolare riferimento all’ASEAN, Charan D. Wadhva #34

Mapping subnational HIV mortality in six Latin American countries with incomplete vital registration systems

Background: Human immunodeficiency virus (HIV) remains a public health priority in Latin America. While the burden of HIV is historically concentrated in urban areas and high-risk groups, subnational estimates that cover multiple countries and years are missing. This paucity is partially due to incomplete vital registration (VR) systems and statistical challenges related to estimating mortality rates in areas with low numbers of HIV deaths. In this analysis, we address this gap and provide novel estimates of the HIV mortality rate and the number of HIV deaths by age group, sex, and municipality in Brazil, Colombia, Costa Rica, Ecuador, Guatemala, and Mexico. Methods: We performed an ecological study using VR data ranging from 2000 to 2017, dependent on individual country data availability. We modeled HIV mortality using a Bayesian spatially explicit mixed-effects regression model that incorporates prior information on VR completeness. We calibrated our results to the Global Burden of Disease Study 2017. Results: All countries displayed over a 40-fold difference in HIV mortality between municipalities with the highest and lowest age-standardized HIV mortality rate in the last year of study for men, and over a 20-fold difference for women. Despite decreases in national HIV mortality in all countries—apart from Ecuador—across the period of study, we found broad variation in relative changes in HIV mortality at the municipality level and increasing relative inequality over time in all countries. In all six countries included in this analysis, 50% or more HIV deaths were concentrated in fewer than 10% of municipalities in the latest year of study. In addition, national age patterns reflected shifts in mortality to older age groups—the median age group among decedents ranged from 30 to 45 years of age at the municipality level in Brazil, Colombia, and Mexico in 2017. Conclusions: Our subnational estimates of HIV mortality revealed significant spatial variation and diverging local trends in HIV mortality over time and by age. This analysis provides a framework for incorporating data and uncertainty from incomplete VR systems and can help guide more geographically precise public health intervention to support HIV-related care and reduce HIV-related deaths

Search for an invisible Z′Z^\prime in a final state with two muons and missing energy at Belle II

The $L_{\mu}-L_{\tau}$ extension of the standard model predicts the existence of a lepton-flavor-universality-violating $Z^{\prime}$ boson that couples only to the heavier lepton families. We search for such a $Z^\prime$ through its invisible decay in the process $e^+ e^- \to \mu^+ \mu^- Z^{\prime}$. We use a sample of electron-positron collisions at a center-of-mass energy of 10.58GeV collected by the Belle II experiment in 2019-2020, corresponding to an integrated luminosity of 79.7fb$^{-1}$. We find no excess over the expected standard-model background. We set 90$\%$-confidence-level upper limits on the cross section for this process as well as on the coupling of the model, which ranges from $3 \times 10^{-3}$ at low $Z^{\prime}$ masses to 1 at $Z^{\prime}$ masses of 8$GeV/c^{2}$