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Pettersson Henningsen posted an update 10 months, 3 weeks ago
Government must replace highly conditional benefit systems by something like a universal basic income. All economic and social policies must be subjected to a legally binding mental health audit. This may sound unfeasibly expensive, but the social and economic costs, not to mention the costs in personal and community suffering, though often invisible, are far greater.Tropomyosins are coiled-coil proteins that regulate the stability and / or function of actin cytoskeleton in muscle and non-muscle cells through direct binding of actin filaments. Recently, using the fission yeast, we discovered a new mechanism by which phosphorylation of serine 125 of tropomyosin (Cdc8), reduced its affinity for actin filaments thereby providing access for the actin severing protein Adf1/Cofilin to actin filaments causing instability of actin filaments. Here we use a genetic code expansion strategy to directly examine this conclusion. We produced in Escherichia coli Cdc8-tropomyosin bearing a phosphate group on Serine-125 (Cdc8 PS125), using an orthogonal tRNA-tRNA synthetase pair that directly incorporates phosphoserine into proteins in response to a UAG codon in the corresponding mRNA. We show using total internal reflection (TIRF) microscopy that, whereas E.coli produced Cdc8 PS125 does not bind actin filaments, Cdc8 PS125 incubated with lambda phosphatase binds actin filaments. This work directly demonstrates that a phosphate moiety present on serine 125 leads to decreased affinity of Cdc8-tropomyosin for actin filaments. We also extend the work to demonstrate the usefulness of the genetic code expansion approach in imaging actin cytoskeletal components.The author, a child and adolescent psychoanalytic psychotherapist working in the UK NHS, discusses the varied impacts of ‘lockdown’ on adolescents, their parents and the psychotherapists who work with them, during the COVID-19 pandemic, in this short observational paper that contributes to the Waiting in Pandemic Times Wellcome Collection in response to COVID-19. She asks, particularly, how psychological therapies are positioned during such a crisis, and whether the pressures of triage and emergency can leave time and space for sustained emotional and psychological care. She wonders how psychoanalytic time with its containing rhythm can be held onto in the face of the need for triage on the one hand and the flight to online and telephone delivery on the other. Above all, the author questions how the apparent suspension of time during lockdown is belied by the onward pressure of adolescent time, and how this can be understood by, and alongside, troubled adolescents.Background n-Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyses the NAD +-dependent oxidative phosphorylation of n-glyceraldehyde-3-phosphate to 1,3-diphospho-n-glycerate and its reverse reaction in glycolysis and gluconeogenesis. Methods Four distinct crystal structures of human n-Glyceraldehyde-3-phosphate dehydrogenase ( HsGAPDH) have been determined from protein purified from the supernatant of HEK293F human epithelial kidney cells. Results X-ray crystallography and mass-spectrometry indicate that the catalytic cysteine of the protein ( HsGAPDH Cys152) is partially oxidised to cysteine S-sulfonic acid. The average occupancy for the Cys152-S-sulfonic acid modification over the 20 crystallographically independent copies of HsGAPDH across three of the crystal forms obtained is 0.31±0.17. Conclusions The modification induces no significant structural changes on the tetrameric enzyme, and only makes aspecific contacts to surface residues in the active site, in keeping with the hypothesis that the oxidising conditions of the secreted mammalian cell expression system result in HsGAPDH catalytic cysteine S-sulfonic acid modification and irreversible inactivation of the enzyme.A coordinated system of disease surveillance will be critical to effectively control the coronavirus disease 2019 (Covid-19) pandemic. AICAR Such systems enable rapid detection and mapping of epidemics and inform allocation of scarce prevention and intervention resources. Although many lower- and middle-income settings lack infrastructure for optimal disease surveillance, health and demographic surveillance systems (HDSS) provide a unique opportunity for epidemic monitoring. This protocol describes a surveillance program at the Africa Health Research Institute’s Population Intervention Platform site in northern KwaZulu-Natal. The program leverages a longstanding HDSS in a rural, resource-limited setting with very high prevalence of HIV and tuberculosis to perform Covid-19 surveillance. Our primary aims include describing the epidemiology of the Covid-19 epidemic in rural KwaZulu-Natal; determining the impact of the Covid-19 outbreak and non-pharmaceutical control interventions (NPI) on behaviour and wellbeing; determining the impact of HIV and tuberculosis on Covid-19 susceptibility; and using collected data to support the local public-sector health response. The program involves telephone-based interviews with over 20,000 households every four months, plus a sub-study calling 750 households every two weeks. Each call asks a household representative how the epidemic and NPI are affecting the household and conducts a Covid-19 risk screen for all resident members. Any individuals screening positive are invited to a clinical screen, potential test and referral to necessary care – conducted in-person near their home following careful risk minimization procedures. In this protocol we report the details of our cohort design, questionnaires, data and reporting structures, and standard operating procedures in hopes that our project can inform similar efforts elsewhere.Checklists are pivotal in the systematic assessment of critically ill patients, pre-operative assessments and for patients with multisystem involvements. Management of tuberculous meningitis is challenging due to prolonged hospital stay, multiple neurological complications like seizures, stroke, raised intracranial tension, stroke, neurosurgical interventions, multiple invasive procedures, health-care-associated sepsis, and ventilation. All these complications are managed by separate checklists to avoid treatment-related errors. The current manuscript aims to ensure completeness of inpatient care addressing issues addressing diagnostic issues, supportive care, and intensive care related issues.