Novel Schizophrenia Risk Gene TCF4 Influences Verbal Learning and Memory Functioning in Schizophrenia Patients

Background: Recently, a role of the transcription factor 4 (TCF4) gene in schizophrenia has been reported in a large genome-wide association study. It has been hypothesized that TCF4 affects normal brain development and TCF4 has been related to different forms of neurodevelopmental disorders. Schizophrenia patients exhibit strong impairments of verbal declarative memory (VDM) functions. Thus, we hypothesized that the disease-associated C allele of the rs9960767 polymorphism of the TCF4 gene led to impaired VDM functioning in schizophrenia patients. Method: The TCF4 variant was genotyped in 401 schizophrenia patients. VDM functioning was measured using the Rey Auditory Verbal Learning Test (RAVLT). Results: Carriers of the C allele were less impaired in recognition compared to those carrying the AA genotype (13.76 vs. 13.06; p = 0.049). Moreover, a trend toward higher scores in patients with the risk allele was found for delayed recall (10.24 vs. 9.41; p = 0.088). The TCF4 genotype did not influence intelligence or RAVLT immediate recall or total verbal learning. Conclusion: VDM function is influenced by the TCF4 gene in schizophrenia patients. However, the elevated risk for schizophrenia is not conferred by TCF4-mediated VDM impairment. Copyright (C) 2011 S. Karger AG, Base

People of the British Isles: preliminary analysis of genotypes and surnames in a UK control population

There is a great deal of interest in fine scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to play a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. Here we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK control population that can be used as a resource by the research community as well as providing fine scale genetic information on the British population. So far, some 4,000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3,865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1,057 samples demonstrates the value of these samples for investigating fine scale population structure within the UK, and shows how this can be enhanced by the use of surnames

Restaurant cooking trends and increased risk for Campylobacter infection

In the United Kingdom, outbreaks of Campylobacter infection are increasingly attributed to undercooked chicken livers, yet many recipes, including those of top chefs, advocate short cooking times and serving livers pink. During 2015, we studied preferences of chefs and the public in the United Kingdom and investigated the link between liver rareness and survival of Campylobacter. We used photographs to assess chefs’ ability to identify chicken livers meeting safe cooking guidelines. To investigate the microbiological safety of livers chefs preferred to serve, we modeled Campylobacter survival in infected chicken livers cooked to various temperatures. Most chefs correctly identified safely cooked livers but overestimated the public’s preference for rareness and thus preferred to serve them more rare. We estimated that 19%-52% of livers served commercially in the United Kingdom fail to reach 70°C and that predicted Campylobacter survival rates are 48%-98%. These findings indicate that cooking trends are linked to increasing Campylobacter infections

Adverse Childhood Experiences: Roads to Recovery

THE ALL-PARTY PARLIAMENTARY GROUP AND THE WORKING GROUP The Working Group that produced this Report is a sub-group of the All-Party Parliamentary Group on a Fit and Healthy Childhood. The purpose of the APPG is to promote evidence-based discussion and produce reports on all aspect of childhood health and wellbeing including obesity, to inform policy decisions and public debate relating to childhood; and to enable communications between interested parties and relevant parliamentarians. Group details are recorded on the Parliamentary website at: https://publications.parliament.uk/pa/cm/cmallparty/190911/fit-and-healthychildhood.htm The Working Group is chaired by Helen Clark, a member of the APPG secretariat. Working Group members are volunteers from the APPG membership with an interest in this subject area. Those that have contributed to the work of the Working Group are listed on the previous page. The Report is divided into themed subject chapters with recommendations that we hope will influence active Government policy

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

miR-22 represses cancer progression by inducing cellular senescence

The microRNA miR-22 targets CDK6, SIRT1, and Sp1—genes involved in regulation of the senescence program—to suppress cell growth and proliferation

Expression of the phosphorylated MEK5 protein is associated with TNM staging of colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Activation of MEK5 in many cancers is associated with carcinogenesis through aberrant cell proliferation. In this study, we determined the level of phosphorylated MEK5 (pMEK5) expression in human colorectal cancer (CRC) tissues and correlated it with clinicopathologic data.</p> <p>Methods</p> <p>pMEK5 expression was examined by immunohistochemistry in a tissue microarray (TMA) containing 335 clinicopathologic characterized CRC cases and 80 cases of nontumor colorectal tissues. pMEK5 expression of 19 cases of primary CRC lesions and paired with normal mucosa was examined by Western blotting. The relationship between pMEK5 expression in CRC and clinicopathologic parameters, and the association of pMEK5 expression with CRC survival were analyzed respectively.</p> <p>Results</p> <p>pMEK5 expression was significantly higher in CRC tissues (185 out of 335, 55.2%) than in normal tissues (6 out of 80, 7.5%; <it>P </it>< 0.001). Western blotting demonstrated that pMEK5 expression was upregulated in 12 of 19 CRC tissues (62.1%) compared to the corresponding adjacent nontumor colorectal tissues. Overexpression of pMEK5 in CRC tissues was significantly correlated to the depth of invasion (<it>P </it>= 0.001), lymph node metastasis (<it>P </it>< 0.001), distant metastasis (<it>P </it>< 0.001) and high preoperative CEA level (<it>P </it>< 0.001). Consistently, the pMEK5 level in CRC tissues was increased following stage progression of the disease (<it>P </it>< 0.001). Analysis of the survival curves showed a significantly worse 5-year disease-free (<it>P </it>= 0.002) and 5-year overall survival rate (<it>P </it>< 0.001) for patients whose tumors overexpressed pMEK5. However, in multivariate analysis, pMEK5 was not an independent prognostic factor for CRC (DFS: <it>P </it>= 0.139; OS: <it>P </it>= 0.071).</p> <p>Conclusions</p> <p>pMEK5 expression is correlated with the staging of CRC and its expression might be helpful to the TNM staging system of CRC.</p

Response to the Novel Corona Virus (COVID-19) Pandemic Across Africa: Successes, Challenges, and Implications for the Future

Background: The COVID-19 pandemic has already claimed considerable lives. There are major concerns in Africa due to existing high prevalence rates for both infectious and non-infectious diseases and limited resources in terms of personnel, beds and equipment. Alongside this, concerns that lockdown and other measures will have on prevention and management of other infectious diseases and non-communicable diseases (NCDs). NCDs are an increasing issue with rising morbidity and mortality rates. The World Health Organization (WHO) warns that a lack of nets and treatment could result in up to 18 million additional cases of malaria and up to 30,000 additional deaths in sub-Saharan Africa. Objective: Document current prevalence and mortality rates from COVID-19 alongside economic and other measures to reduce its spread and impact across Africa. In addition, suggested ways forward among all key stakeholder groups. Our Approach: Contextualise the findings from a wide range of publications including internet-based publications coupled with input from senior-level personnel. Ongoing Activities: Prevalence and mortality rates are currently lower in Africa than among several Western countries and the USA. This could be due to a number of factors including early instigation of lockdown and border closures, the younger age of the population, lack of robust reporting systems and as yet unidentified genetic and other factors. Innovation is accelerating to address concerns with available equipment. There are ongoing steps to address the level of misinformation and its consequences including fines. There are also ongoing initiatives across Africa to start addressing the unintended consequences of COVID-19 activities including lockdown measures and their impact on NCDs including the likely rise in mental health disorders, exacerbated by increasing stigma associated with COVID-19. Strategies include extending prescription lengths, telemedicine and encouraging vaccination. However, these need to be accelerated to prevent increased morbidity and mortality. Conclusion: There are multiple activities across Africa to reduce the spread of COVID-19 and address misinformation, which can have catastrophic consequences, assisted by the WHO and others, which appear to be working in a number of countries. Research is ongoing to clarify the unintended consequences given ongoing concerns to guide future activities. Countries are learning from each other

Ataxia, Dementia, and Hypogonadotropism Caused by Disordered Ubiquitination

In recent years, we have seen great advances in the elucidation of genetic causes of cerebellar ataxia, with newly identified genes regulating a wide spectrum of cellular functions, including intracellular signaling, tau regulation, and mitochondrial function.1 However, a genetic defect cannot be found in approximately 40% of patients with ataxia,1 including those in whom ataxia is associated with reproductive endocrine failure, a syndrome first reported by Gordon Holmes in 1908.2 Most patients with this syndrome have a hypogonadotropic condition, with defective secretion of gonadotropins by the pituitary gland.3-12 Strikingly, genes associated with ataxia have little functional overlap with genes associated with hypogonadotropic hypogonadism, which encode proteins involved in the biologic function of the neurons that secrete gonadotropin-releasing hormone (GnRH).13 A decade ago, we described a consanguineous family with a syndrome of cerebellar ataxia, dementia, and hypogonadotropic hypogonadism.12 Here we report the results of whole-exome and targeted sequencing performed to identify mutations that underlie the syndrome in this kindred and in unrelated patients