Substrate recruitment via eIF2γ enhances catalytic efficiency of a holophosphatase that terminates the integrated stress response.

Dephosphorylation of pSer51 of the α subunit of translation initiation factor 2 (eIF2αP) terminates signaling in the integrated stress response (ISR). A trimeric mammalian holophosphatase comprised of a protein phosphatase 1 (PP1) catalytic subunit, the conserved C-terminally located ~70 amino acid core of a substrate-specific regulatory subunit (PPP1R15A/GADD34 or PPP1R15B/CReP) and G-actin (an essential cofactor) efficiently dephosphorylate eIF2αP in vitro. Unlike their viral or invertebrate counterparts, with whom they share the conserved 70 residue core, the mammalian PPP1R15s are large proteins of more than 600 residues. Genetic and cellular observations point to a functional role for regions outside the conserved core of mammalian PPP1R15A in dephosphorylating its natural substrate, the eIF2 trimer. We have combined deep learning technology, all-atom molecular dynamics simulations, X-ray crystallography, and biochemistry to uncover binding of the γ subunit of eIF2 to a short helical peptide repeated four times in the functionally important N terminus of human PPP1R15A that extends past its conserved core. Binding entails insertion of Phe and Trp residues that project from one face of an α-helix formed by the conserved repeats of PPP1R15A into a hydrophobic groove exposed on the surface of eIF2γ in the eIF2 trimer. Replacing these conserved Phe and Trp residues with Ala compromises PPP1R15A function in cells and in vitro. These findings suggest mechanisms by which contacts between a distant subunit of eIF2 and elements of PPP1R15A distant to the holophosphatase active site contribute to dephosphorylation of eIF2αP by the core PPP1R15 holophosphatase and to efficient termination of the ISR in mammals.

Intimate Partner Violence in Khaliji Women: A Review of the Frequency and Related Factors.

The Gulf Cooperation Council (GCC), locally known as Khaliji, is a group of six Arab nations, including Saudi Arabia, Bahrain, Kuwait, Oman, Qatar, and the United Arab Emirates (UAE). Intimate partner violence (IPV) is a significant public health concern in the aforementioned region, but research that synthesises this trend has remained scarce. The present narrative review examines existing research on the prevalence and frequency of IPV among Khaliji women who inhabit the GCC nations. This review synthesised studies on physical and sexual violence, emotional abuse, and controlling behaviours perpetrated by an intimate partner. The prevalence rates of IPV among Khaliji women were observed to be high: women reported facing different types of abuse from their partners, namely physical (7-71%), sexual (3.7-81%), financial (21.3-26%), and psychological (7.5-89%), which is a culmination of controlling behaviour (36.8%), emotional violence (22-69%), and social violence (34%). Existing studies in the GCC region suggest that the most endorsed IPV was psychological abuse (89%), followed by sexual violence (81%). Qualitative analysis of the content of associated factors resulted in four significant descriptors, such as victim demographics, sociocultural factors, socioeconomic factors, and perpetrator-related issues. Research on IPV is still in its nascent stages, with very few studies emanating from the GCC region. The way forward will require developing culturally appropriate interventions that address the unique risk factors for IPV among the Khaliji population, strengthening institutional responses, and increasing awareness and social support for victims of IPV.

Post-Stroke Psychiatric and Cognitive Symptoms in West Asia, South Asia and Africa: A Systematic Review and Meta-Analysis.

Recent research has shown that the prevalence of stroke incidents and the number of survivors in developing countries surpass those from developed countries. This study aimed to enumerate the prevalence of post-stroke psychiatric and cognitive symptoms among stroke survivors from West and South Asia and Africa through a systematic review and meta-analysis. Data from each country was systematically acquired from five major databases (PsycINFO, Web of Science, Scopus, PubMed/Medline, and Google Scholar (for any missing articles and grey literature)). Meta-analytic techniques were then used to estimate the prevalence of various post-stoke psychiatric and cognitive symptoms. A total of 36 articles were accrued from 11 countries, of which 25 were evaluated as part of the meta-analysis. The pooled prevalence of post-stroke depression as per the Hospital Anxiety and Depression Scale (HADS), Hamilton Depression Rating Scale, Patient Health Questionnaire, Schedules for Clinical Assessment in Neuropsychiatry (SCAN), Geriatric Depression Scale, and the Montgomery-Asberg Depression Rating Scale ranged from 28.00 to 50.24%. Pooled prevalence of post-stroke anxiety based on the HADS and SCAN was 44.19% and 10.96%, respectively. The pooled prevalence of post-stroke cognitive impairment as per the Mini-Mental Status Examination was 16.76%. This present review has suggested that both psychiatric and cognitive symptoms are common among stroke survivors. Concerted efforts are needed to institute robust studies using culturally sensitive measures to contemplate mechanisms that address the unmet needs of this vulnerable population.