Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis

Background A non-invasive method to grade the severity of steatohepatitis and liver fibrosis is magnetic resonance imaging (MRI) based corrected T1 (cT1). We aimed to identify genetic variants influencing liver cT1 and use genetics to understand mechanisms underlying liver fibroinflammatory disease and its link with other metabolic traits and diseases. Methods First, we performed a genome-wide association study (GWAS) in 14,440 Europeans in UK Biobank with liver cT1 measures. Second, we explored the effects of the cT1 variants on liver blood tests, and a range of metabolic traits and diseases. Third, we used Mendelian randomisation to test the causal effects of 24 predominantly metabolic traits on liver cT1 measures. Results We identified six independent genetic variants associated with liver cT1 that reached GWAS significance threshold (p<5x10-8). Four of the variants (rs75935921 in SLC30A10, rs13107325 in SLC39A8, rs58542926 in TM6SF2, rs738409 in PNPLA3) were also associated with elevated transaminases and had variable effects on liver fat and other metabolic traits. Insulin resistance, type 2 diabetes, non-alcoholic fatty liver and BMI were causally associated with elevated cT1 whilst favourable adiposity (instrumented by variants associated with higher adiposity but lower risk of cardiometabolic disease and lower liver fat) was found to be protective. Conclusion The association between two metal ion transporters and cT1 indicates an important new mechanism in steatohepatitis. Future studies are needed to determine whether interventions targeting the identified transporters might prevent liver disease in at risk individuals

Do many-particle neutrino interactions cause a novel coherent effect?

We investigate whether coherent flavor conversion of neutrinos in a neutrino background is substantially modified by many-body effects, with respect to the conventional one-particle effective description. We study the evolution of a system of interacting neutrino plane waves in a box. Using its equivalence to a system of spins, we determine the character of its behavior completely analytically. We find that, if the neutrinos are initially in flavor eigenstates, no coherent flavor conversion is realized, in agreement with the effective one-particle description. This result does not depend on the size of the neutrino wavepackets and therefore has a general character. The validity of the several important applications of the one-particle formalism is thus confirmed.Comment: 25 pages, 1 figur

Neutrino oscillations in the early universe: How large lepton asymmetry can be generated?

The lepton asymmetry that could be generated in the early universe through oscillations of active to sterile neutrinos is calculated (almost) analytically for small mixing angles, sin 2\theta < 10^{-2}. It is shown that for a mass squared difference, \delta m^2=-1 eV^2 it may rise at most by 6 orders of magnitude from the initial ``normal'' value of 10^{-10}, since the back-reaction from the refraction index terminates this rise while the asymmetry is still small. Only for very large mass differences, \delta m^2 about 10^9 eV^2, the lepton asymmetry could reach a significant magnitude exceeding 0.1.Comment: 25 pages, LaTeX (5 graphs

Cationic lipid-based nanoparticles mediate functional delivery of acetate to tumor cells in vivo leading to significant anticancer effects

Metabolic reengineering using nanoparticle delivery represents an innovative therapeutic approach to normalizing the deregulation of cellular metabolism underlying many diseases, including cancer. Here, we demonstrated a unique and novel application to the treatment of malignancy using a short-chain fatty acid (SCFA)-encapsulated lipid-based delivery system – liposome-encapsulated acetate nanoparticles for cancer applications (LITA-CAN). We assessed chronic in vivo administration of our nanoparticle in three separate murine models of colorectal cancer. We demonstrated a substantial reduction in tumor growth in the xenograft model of colorectal cancer cell lines HT-29, HCT-116 p53+/+ and HCT-116 p53-/-. Nanoparticle-induced reductions in histone deacetylase gene expression indicated a potential mechanism for these anti-proliferative effects. Together, these results indicated that LITA-CAN could be used as an effective direct or adjunct therapy to treat malignant transformation in vivo

The Frailty In Residential Sector over Time (FIRST) study: methods and baseline cohort description

Published online: 03 February 2021Background: The Frailty In Residential Sector over Time (FIRST) Study is a 3-year prospective cohort study investigating the health of residents living in residential aged care services (RACS) in South Australia. The study aims to examine the change in frailty status and associated health outcomes. Methods: This interim report presents data from March 2019–October 2020. The study setting is 12 RACS from one organisation across metropolitan and rural South Australia involving 1243 residents. All permanent (i.e. respite or transition care program excluded) residents living in the RACS for at least 8 weeks were invited to participate. Residents who were deemed to be medically unstable (e.g. experiencing delirium), have less than 3 months to live, or not fluent in English were excluded. Data collected included frailty status, medical diagnoses, medicines, pain, nutrition, sarcopenia, falls, dementia, anxiety and depression, sleep quality, quality of life, satisfaction with care, activities of daily living, and life space use at baseline and 12-months. Data Linkage will occur over the 3 years from baseline. Results: A total of 561 permanent residents (mean age 87.69 ± 7.25) were included. The majority of residents were female (n = 411, 73.3%) with 95.3% (n = 527) being classified as either frail (n = 377, 68.2%) or most-frail (n = 150, 27.1%) according to the Frailty Index (FI). Most residents were severely impaired in their basic activities of daily living (n = 554, 98.8%), and were at-risk of malnutrition (n = 305, 55.0%) and at-risk of sarcopenia (n = 492, 89.5%). Most residents did not experience pain (n = 475, 85.4%), had normal daytime sleepiness (n = 385, 69.7%), and low anxiety and depression scores (n = 327, 58.9%). Conclusion: This study provides valuable information on the health and frailty levels of residents living in RACS in South Australia. The results will assist in developing interventions that can help to improve the health and wellbeing of residents in aged care services. Trial registration: Prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN1261 9000500156).Agathe Daria Jadczak, Leonie Robson, Tina Cooper, J. Simon Bell, Renuka Visvanathan, on behalf of the FIRST Study Collaborator

Representation theory of super Yang-Mills algebras

We study in this article the representation theory of a family of super algebras, called the \emph{super Yang-Mills algebras}, by exploiting the Kirillov orbit method \textit{\`a la Dixmier} for nilpotent super Lie algebras. These super algebras are a generalization of the so-called \emph{Yang-Mills algebras}, introduced by A. Connes and M. Dubois-Violette in \cite{CD02}, but in fact they appear as a "background independent" formulation of supersymmetric gauge theory considered in physics, in a similar way as Yang-Mills algebras do the same for the usual gauge theory. Our main result states that, under certain hypotheses, all Clifford-Weyl super algebras \Cliff_{q}(k) \otimes A_{p}(k), for $p \geq 3$, or $p = 2$ and $q \geq 2$, appear as a quotient of all super Yang-Mills algebras, for $n \geq 3$ and $s \geq 1$. This provides thus a family of representations of the super Yang-Mills algebras

Link between increased gut hormones signaling satiety and reduced food reward following gastric bypass surgery for obesity

CONTEXT: Roux-en-Y gastric bypass (RYGB) surgery is an effective long-term intervention for weight loss maintenance, reducing appetite, and also food reward, via unclear mechanisms. OBJECTIVE: To investigate the role of elevated satiety gut hormones after RYGB, we examined food hedonic-reward responses after their acute post-prandial suppression. DESIGN: These were randomized, placebo-controlled, double-blind, crossover experimental medicine studies. PATIENTS: Two groups, more than 5 months after RYGB for obesity (n = 7-11), compared with nonobese controls (n = 10), or patients after gastric banding (BAND) surgery (n = 9) participated in the studies. INTERVENTION: Studies were performed after acute administration of the somatostatin analog octreotide or saline. In one study, patients after RYGB, and nonobese controls, performed a behavioral progressive ratio task for chocolate sweets. In another study, patients after RYGB, and controls after BAND surgery, performed a functional magnetic resonance imaging food picture evaluation task. MAIN OUTCOME MEASURES: Octreotide increased both appetitive food reward (breakpoint) in the progressive ratio task (n = 9), and food appeal (n = 9) and reward system blood oxygen level-dependent signal (n = 7) in the functional magnetic resonance imaging task, in the RYGB group, but not in the control groups. RESULTS: Octreotide suppressed postprandial plasma peptide YY, glucagon-like peptide-1, and fibroblast growth factor-19 after RYGB. The reduction in plasma peptide YY with octreotide positively correlated with the increase in brain reward system blood oxygen level-dependent signal in RYGB/BAND subjects, with a similar trend for glucagon-like peptide-1. CONCLUSIONS: Enhanced satiety gut hormone responses after RYGB may be a causative mechanism by which anatomical alterations of the gut in obesity surgery modify behavioral and brain reward responses to food

Neutrino oscillations in the early universe. Resonant case

Lepton asymmetry generated in the early universe by neutrino oscillations into sterile partners is calculated. Kinetic equations are analytically reduced to a simple form that permits an easy numerical treatment. Asymptotic values of the asymmetry are at the level of 0.2-0.3 and are reasonably close to those obtained by other groups, though the approach to asymptotics in some cases is noticeably slower. No chaoticity is observed.Comment: 25 pages, late

Primordialists and Constructionists: a typology of theories of religion

This article adopts categories from nationalism theory to classify theories of religion. Primordialist explanations are grounded in evolutionary psychology and emphasize the innate human demand for religion. Primordialists predict that religion does not decline in the modern era but will endure in perpetuity. Constructionist theories argue that religious demand is a human construct. Modernity initially energizes religion, but subsequently undermines it. Unpacking these ideal types is necessary in order to describe actual theorists of religion. Three distinctions within primordialism and constructionism are relevant. Namely those distinguishing: a) materialist from symbolist forms of constructionism; b) theories of origins from those pertaining to the reproduction of religion; and c) within reproduction, between theories of religious persistence and secularization. This typology helps to make sense of theories of religion by classifying them on the basis of their causal mechanisms, chronology and effects. In so doing, it opens up new sightlines for theory and research