Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies

DNA methylation (DNAm)-based biomarkers of aging have been developed for many tissues and organs. However, these biomarkers have sub-optimal accuracy in fibroblasts and other cell types used in ex vivo studies. To address this challenge, we developed a novel and highly robust DNAm age estimator (based on 391 CpGs) for human fibroblasts, keratinocytes, buccal cells, endothelial cells, lymphoblastoid cells, skin, blood, and saliva samples. High age correlations can also be observed in sorted neurons, glia, brain, liver, and even bone samples. Gestational age correlates with DNAm age in cord blood. When used on fibroblasts from Hutchinson Gilford Progeria Syndrome patients, this age estimator (referred to as the skin & blood clock) uncovered an epigenetic age acceleration with a magnitude that is below the sensitivity levels of other DNAm-based biomarkers. Furthermore, this highly sensitive age estimator accurately tracked the dynamic aging of cells cultured ex vivo and revealed that their proliferation is accompanied by a steady increase in epigenetic age. The skin & blood clock predicts lifespan and it relates to many age-related conditions. Overall, this biomarker is expected to become useful for forensic applications (e.g. blood or buccal swabs) and for a quantitative ex vivo human cell aging assay

Recovered memories, satanic abuse, Dissociative Identity Disorder and false memories in the UK: a survey of Clinical Psychologists and Hypnotherapists

An online survey was conducted to examine psychological therapists’ experiences of, and beliefs about, cases of recovered memory, satanic / ritualistic abuse, Multiple Personality Disorder / Dissociative Identity Disorder, and false memory. Chartered Clinical Psychologists (n=183) and Hypnotherapists (n=119) responded. In terms of their experiences, Chartered Clinical Psychologists reported seeing more cases of satanic / ritualistic abuse compared to Hypnotherapists who, in turn, reported encountering more cases of childhood sexual abuse recovered for the first time in therapy, and more cases of suspected false memory. Chartered Clinical Psychologists were more likely to rate the essential accuracy of reports of satanic / ritualistic abuse as higher than Hypnotherapists. Belief in the accuracy of satanic / ritualistic abuse and Multiple Personality Disorder / Dissociative Identity Disorder reports correlated negatively with the belief that false memories were possible

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Tannin sensitivity in larvae of Malacosoma disstria (Lepidoptera): Roles of the peritrophic envelope and midgut oxidation

Final-instar Malacosoma disstria fed artificial diets containing tannic acid develop lethal pupal deformities. We examined some of the factors potentially underlying tannin sensitivity in this species, including the permeability of the peritrophic envelope to tannic acid and the chemical fate of tannic acid in the gut. Tannic acid does not penetrate the peritrophic envelope of M. disstria , demonstrating that the containment of tannic acid within the endoperitrophic space is not sufficient to protect an insect herbivore from the adverse effects of ingested tannins. Ingested tannic acid undergoes extensive chemical modification in the midgut. Only 19–21 % of the high molecular weight components of the tannic acid ingested was recovered in the frass. Of two possible chemical fates of ingested tannic acid, oxidation is the predominant chemical transformation, whereas little hydrolysis occurs. Measurements of gut redox parameters showed that conditions in the midgut favor the oxidation of phenols. However, similar conditions occur in the midguts of Orgyia leucostigma , in which no oxidation occurs. Therefore, oxidizing gut redox conditions do not necessarily lead to polyphenol oxidation in lepidopteran larvae. We conclude that the sensitivity of M. disstria to ingested tannins is a consequence of their oxidation in the midgut.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44887/1/10886_2005_Article_BF02066238.pd