90th Anniversary Commentary: Consumption of Sweetened Beverages Predicts the Occurrence of Type 2 Diabetes

Carbohydrate and sugar are recurring themes in the history of diet and disease. After the agricultural revolution 10,000 y ago, nutrition changed from a hunter-gatherer way of life to one in which food could be grown in one locale, avoiding the challenges of continuing to move to find food. The domestication of animals and the development of many grains and other crops allowed civilizations to develop and reduced most effects of seasonality on food supplies for many countries. The agricultural revolution also led to the growth of cities and, with it, a group of infectious diseases that dominated the health of people for thousands of years and led to the continued development of many new caloric foods and beverages over the last 10,000–12,000 y

Critical behavior of the two-dimensional N-component Landau-Ginzburg Hamiltonian with cubic anisotropy

We study the two-dimensional N-component Landau-Ginzburg Hamiltonian with cubic anisotropy. We compute and analyze the fixed-dimension perturbative expansion of the renormalization-group functions to four loops. The relations of these models with N-color Ashkin-Teller models, discrete cubic models, planar model with fourth order anisotropy, and structural phase transition in adsorbed monolayers are discussed. Our results for N=2 (XY model with cubic anisotropy) are compatible with the existence of a line of fixed points joining the Ising and the O(2) fixed points. Along this line the exponent $\eta$ has the constant value 1/4, while the exponent $\nu$ runs in a continuous and monotonic way from 1 to $\infty$ (from Ising to O(2)). For N\geq 3 we find a cubic fixed point in the region $u, v \geq 0$, which is marginally stable or unstable according to the sign of the perturbation. For the physical relevant case of N=3 we find the exponents $\eta=0.17(8)$ and $\nu=1.3(3)$ at the cubic transition.Comment: 14 pages, 9 figure

Imetelstat-mediated alterations in fatty acid metabolism to induce ferroptosis as a therapeutic strategy for acute myeloid leukemia

Telomerase enables replicative immortality in most cancers including acute myeloid leukemia (AML). Imetelstat is a first-in-class telomerase inhibitor with clinical efficacy in myelofibrosis and myelodysplastic syndromes. Here, we develop an AML patient-derived xenograft resource and perform integrated genomics, transcriptomics and lipidomics analyses combined with functional genetics to identify key mediators of imetelstat efficacy. In a randomized phase II-like preclinical trial in patient-derived xenografts, imetelstat effectively diminishes AML burden and preferentially targets subgroups containing mutant NRAS and oxidative stress-associated gene expression signatures. Unbiased, genome-wide CRISPR/Cas9 editing identifies ferroptosis regulators as key mediators of imetelstat efficacy. Imetelstat promotes the formation of polyunsaturated fatty acid-containing phospholipids, causing excessive levels of lipid peroxidation and oxidative stress. Pharmacological inhibition of ferroptosis diminishes imetelstat efficacy. We leverage these mechanistic insights to develop an optimized therapeutic strategy using oxidative stress-inducing chemotherapy to sensitize patient samples to imetelstat causing substantial disease control in AML

Transpiração e crescimento foliar de crisântemo em função da fração de água transpirável no substrato

The objective of this work was to evaluate the response of transpiration and leaf growth of chrysanthemum (Dendranthema grandiflorum) cultivars to available water in the substrate, represented by the fraction of transpirable substrate water (FTbSW). The experiments were performed in two periods, in a completely randomized design, with four chrysanthemum cultivars (Cherie White, Bronze Repin, Yoapple Valley, and Calabria), under two substrate water conditions (with or without water stress), with 10 replicates. Plants were grown in a greenhouse, in 2.8-L pots with substrate. FTSbW, transpiration, and leaf growth were measured daily, during the period of water deficit. The average threshold FTSbW, indicating that transpiration and leaf growth began to be affected, was respectively 0.63 and 0.68 for 'Cherie White', 0.60 and 0.69 for 'Bronze Repin', 0.53 and 0.59 for 'Yoapple Valley', and 0.51 and 0.54 for 'Calabria'. Available water decrease in the substrate reduces leaf growth before restricting transpiration. The Cherie White and Bronze Repin cultivars are more tolerant to water deficit by closing the stomata earlier and retaining more water in the substrate than the Yoapple Valley and Calabria cultivars.O objetivo deste trabalho foi avaliar a resposta da transpiração e do crescimento foliar de cultivares de crisântemo (Dendranthema grandiflorum) ao conteúdo de água disponível no substrato, representado pela fração de água transpirável no substrato (FATSb). Os experimentos foram realizados em dois períodos, em delineamento inteiramente casualizado, com quatro cultivares de crisântemo (Cherie White, Bronze Repin, Yoapple Valley e Calabria), em duas condições hídricas (com ou sem deficiência hídrica), com 10 repetições. As plantas foram cultivadas em casa de vegetação, em vasos de 2,8 L preenchidos com substrato. A FATSb, a transpiração e o crescimento foliar foram determinados diariamente durante o período de deficiência hídrica. As FATSb críticas médias, indicativas de que a transpiração e o crescimento foliar começam a ser afetados, foram respectivamente de 0,63 e 0,68 para 'Cherie White', 0,60 e 0,69 para 'Bronze Repin', 0,53 e 0,59 para 'Yoapple Valley', e 0,51 e 0,54 para 'Calabria'. A diminuição da água disponível no substrato provoca a redução do crescimento foliar antes de restringir a transpiração. As cultivares Cherie White e Bronze Repin são mais tolerantes ao deficit hídrico por fechar os estômatos antes e conservar mais a água no substrato do que as cultivares Yoapple Valley e Calabria

FTO genotype and weight loss: systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials

Objective To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. Design Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. Data sources Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015. Eligibility criteria for study selection Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual participant data from all studies included in this review, using allele dose coding for genetic effects and a common set of covariates. Study level interactions were combined using random effect models. Metaregression and subgroup analysis were used to assess sources of study heterogeneity. Results We identified eight eligible randomised controlled trials for the systematic review and meta-analysis (n=9563). Overall, differential changes in body mass index, body weight, and waist circumference in response to weight loss intervention were not significantly different between FTO genotypes. Sensitivity analyses indicated that differential changes in body mass index, body weight, and waist circumference by FTO genotype did not differ by intervention type, intervention length, ethnicity, sample size, sex, and baseline body mass index and age category. Conclusions We have observed that carriage of the FTO minor allele was not associated with differential change in adiposity after weight loss interventions. These findings show that individuals carrying the minor allele respond equally well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions. Systematic review registration PROSPERO CRD42015015969