Intermittent fasting （IF）, a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the ...underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor （VEGF） expression in white adipose tissue （WAT）. Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders.
Abstract
This study assessed the experiences of elite aquatic athletes with coronavirus disease 2019 (COVID-19) during the first World Championship conducted without social distancing and an ...isolation “bubble”. An online questionnaire was completed by 812 athletes (22.7 ± 5.9 years, 467 females) to provide data on demographics, sports activity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates, symptoms, reinfection, vaccination status, and psychological aspects. The answers revealed that 49.4% of athletes had experienced SARS-CoV-2 infection. The infection rates varied significantly across different aquatic sports, with open water swimmers having the lowest (28%) and water polo players (67%) and artistic swimmers (61%) having the highest infection rates (p < 0.0001). The majority reported mild (51%) or moderate (27%) symptoms, while 16% remained asymptomatic. Reinfection occurred in 13%, and 10% of initial infections led to long COVID, with fatigue (65%) and shortness of breath (48%) being the most common long-term symptoms. Significantly, 92% of athletes received at least two vaccine doses and reported a positive vaccination experience (median score of 8 out of 10 for each shot). Mood changes and subjective performance drops significantly correlated with the overall experience scores (rho: 0.617, p < 0.0001, and rho: 0.466, p < 0.0001, respectively). In conclusion, most athletes experienced a benign disease course despite a relatively high infection rate. This study provides valuable insights into the COVID-19 experiences of elite aquatic athletes. The findings emphasize the importance of vaccination initiatives, monitoring psychological well-being and the need to fortify athletes’ resilience in the face of future health challenges.
We describe the dynamic process of abdominal segment generation in the milkweed bug
We present detailed morphological measurements of the growing germband throughout segmentation. Our data are ...complemented by cell division profiles and expression patterns of key genes, including
and
as markers for different stages of segment formation. We describe morphological and mechanistic changes in the growth zone and in nascent segments during the generation of individual segments and throughout segmentation, and examine the relative contribution of newly formed versus existing tissue to segment formation. Although abdominal segment addition is primarily generated through the rearrangement of a pool of undifferentiated cells, there is nonetheless proliferation in the posterior. By correlating proliferation with gene expression in the growth zone, we propose a model for growth zone dynamics during segmentation in which the growth zone is functionally subdivided into two distinct regions: a posterior region devoted to a slow rate of growth among undifferentiated cells, and an anterior region in which segmental differentiation is initiated and proliferation inhibited.
Characterization of the aromatic ammonia–lyase from Loktanella atrilutea (LaAAL) revealed reduced activity towards canonical AAL substrates: l‐Phe, l‐Tyr, and l‐His, contrasted by its pronounced ...efficiency towards 3,4‐dimethoxy‐l‐phenylalanine. Assessing the optimal conditions, LaAAL exhibited maximal activity at pH 9.5 in the ammonia elimination reaction route, distinct from the typical pH ranges of most PALs and TALs. Within the exploration of the ammonia source for the opposite, synthetically valuable ammonia addition reaction, the stability of LaAAL exhibited a positive correlation with the ammonia concentration, with the highest stability in 4 M ammonium carbamate of unadjusted pH of ~9.5. While the enzyme activity increased with rising temperatures yet, the highest operational stability and highest stationary conversions of LaAAL were observed at 30 °C. The substrate scope analysis highlighted the catalytic adaptability of LaAAL in the hydroamination of diverse cinnamic acids, especially of meta‐substituted and di‐/multi–substituted analogues, with structural modelling exposing steric clashes between the substrates’ ortho–substituents and catalytic site residues. LaAAL showed a predilection for ammonia elimination, while classifying as a tyrosine ammonia–lyase (TAL) among the natural AAL classes. However, its distinctive attributes, such as genomic context, unique substrate specificity and catalytic fingerprint, suggest a potential natural role beyond those of known AAL classes.
The aromatic ammonia–lyase from Loktanella atrilutea (LaAAL) displays a high activity towards 3,4‐dimethoxy trans–cinnamic acid, with a surprisingly diminished activity towards natural AAL substrates. Under the optimal reaction conditions LaAAL exhibited versatility for the transformation of various cinnamic acids. While LaAAL might be classified as a tyrosine ammonia‐lyase (TAL, E.C. 4.3.1.23), its strongly distinctive attributes argue for an elemental role in the transformation of non‐natural phenylalanines.
Abstract Today, sweet corn is considered an important vegetable due to its high sugar content and low starch content. Cluster analysis and variance analysis showed that hybrids had variations in ...yield indices. GB, DE and GS hybrids had similar performance on indices. SE hybrid that has significant performance on zeaxanthin. Biplot showed that fructose, glucose, sucrose and potassium had stability value on hybrids. All the hybrids had the best performance on fructose, glucose, sucrose and potassium factors. Factor biplot positively correlated with yield indices, including calcium, iron, zinc, magnesium, α-Carotene, 9Z-β-Carotene, phosphorus, and β-carotene. On the other hand, there is a positive correlation with fructose, glucose, potassium, lutein, sucrose, β-Cryptoxanthin, and zeaxanthin. So, to evaluate or increase lutein and zeaxanthin, the other parameters like sugar content (fructose, glucose, and sucrose) are important factors and have an effect together. Factor analysis and biplot showed that ME hybrid had a maximum performance on the first factor of yield indices. Also, the second factor of yield indices had a maxi-mum effect on NO hybrids. SE hybrids had maximum performance in zeaxanthin and GS hybrid had maximum performance in zinc, phosphorus, and iron. The dry matter had stability on DB hybrid.
Resumo Hoje, o milho doce é considerado uma hortaliça importante devido ao seu alto teor de açúcar e baixo teor de amido. A análise de agrupamento e a análise de variância mostraram que os híbridos apresentaram variações nos índices de produtividade. Os híbridos GB, DE e GS tiveram desempenho semelhante nos índices. Híbrido SE que apresenta desempenho significativo sobre a zeaxantina. Biplot mostrou que frutose, glicose, sacarose e potássio apresentaram valor de estabilidade em híbridos. Todos os híbridos tiveram o melhor desempenho nos fatores frutose, glicose, sacarose e potássio. O fator biplot correlacionou-se positivamente com os índices de rendimento, incluindo cálcio, ferro, zinco, magnésio, α-caroteno, 9Z-β-caroteno, fósforo e β-caroteno. Por outro lado, há correlação positiva com frutose, glicose, potássio, luteína, sacarose, β-criptoxantina e zeaxantina. Assim, para avaliar ou aumentar a luteína e a zeaxantina, outros parâmetros como o teor de açúcares (frutose, glicose e sacarose) são fatores importantes e atuam em conjunto. A análise fatorial e o biplot mostraram que o híbrido ME apresentou desempenho máximo no primeiro fator de índices de produtividade. Além disso, o segundo fator de índices de produtividade teve um efeito máximo nos híbridos de NO. Os híbridos SE tiveram desempenho máximo em zeaxantina e o híbrido GS teve desempenho máximo em zinco, fósforo e ferro. A matéria seca apresentou estabilidade no híbrido DB.
The ground-breaking work of Yamanaka and Thomson showed that forced expression of just four transcription factors can reprogram mouse and human somatic cells to pluripotency, leading to the discovery ...of the so-called induced pluripotent stem cells (iPSCs). Similar to embryonic stem cells (ESCs), iPSCs have the ability to permanently self-renew and also give rise to multiple cell types once differentiated. These cells opened up the opportunity to develop human disease models in vitro , drug and toxicity screening tools, as well as a continuous autologous cell source for future cell-based therapies. Therefore, it is not surprising that the methods for generating iPSCs have significantly evolved over the past few years. To date the reprogramming methods include the use of various transfection/transduction systems, small molecules to enhance the reprogramming process, and to adapt to a multitude of different cell type sources. We are now able to convert essentially any somatic cell type into iPSCs with increased efficiency and at higher quality when compared to ESCs. More recently, this field has been expanded to direct reprogramming of one cell type to another, including lineage-specific progenitors. Here, we provide a concise review of methods to generate induced pluripotent stem cells, and discuss the most recent strategies augmenting the reprogramming process and increasing the quality of iPSCs.
Reprogramming of somatic cells to induced pluripotent stem cells involves a dynamic rearrangement of the epigenetic landscape. To characterize this epigenomic roadmap, we have performed MethylC-seq, ...ChIP-seq (H3K4/K27/K36me3) and RNA-Seq on samples taken at several time points during murine secondary reprogramming as part of Project Grandiose. We find that DNA methylation gain during reprogramming occurs gradually, while loss is achieved only at the ESC-like state. Binding sites of activated factors exhibit focal demethylation during reprogramming, while ESC-like pluripotent cells are distinguished by extension of demethylation to the wider neighbourhood. We observed that genes with CpG-rich promoters demonstrate stable low methylation and strong engagement of histone marks, whereas genes with CpG-poor promoters are safeguarded by methylation. Such DNA methylation-driven control is the key to the regulation of ESC-pluripotency genes, including Dppa4, Dppa5a and Esrrb. These results reveal the crucial role that DNA methylation plays as an epigenetic switch driving somatic cells to pluripotency.
Nanomedicine provides a promising platform for manipulating dendritic cells (DCs) and the ensuing adaptive immune response. For the induction of regulatory responses, DCs can be targeted
with ...nanoparticles incorporating tolerogenic adjuvants and auto-antigens or allergens.
Here, we investigated the tolerogenic effect of different liposome formulations loaded with vitamin D3 (VD3). We extensively phenotyped monocyte-derived DCs (moDCs) and skin DCs and assessed DC-induced regulatory CD4+ T cells in coculture.
Liposomal VD3 primed-moDCs induced the development of regulatory CD4+ T cells (Tregs) that inhibited bystander memory T cell proliferation. Induced Tregs were of the FoxP3+ CD127low phenotype, also expressing TIGIT. Additionally, liposome-VD3 primed moDCs inhibited the development of T helper 1 (Th1) and T helper 17 (Th17) cells. Skin injection of VD3 liposomes selectively stimulated the migration of CD14+ skin DCs.
These results suggest that nanoparticulate VD3 is a tolerogenic tool for DC-mediated induction of regulatory T cell responses.
A new class of accelerating, exact and explicit solutions of relativistic hydrodynamics is found—more than 50 years after the previous similar result, the Landau–Khalatnikov solution. Surprisingly, ...the new solutions have a simple form, that generalizes the renowned, but accelerationless, Hwa–Bjorken solution. These new solutions take into account the work done by the fluid elements on each other, and work not only in one temporal and one spatial dimensions, but also in arbitrary number of spatial dimensions. They are applied here for an advanced estimation of initial energy density and life-time of the reaction in ultra-relativistic heavy ion collisions. New formulas are also conjectured, that yield further important increase of the initial energy density estimate and the measured life-time of the reaction if the value of the speed of sound is in the realistic range.
In adults, visceral fat accumulation is associated with insulin resistance and dyslipidemia. The cause-and-effect nature of these relationships is not clear. The objective of the present study was to ...determine if similar relationships exist in prepubertal children. Specifically, we determined whether visceral fat was associated with fasting insulin, insulin sensitivity (Si), serum triglyceride (TG) concentration, or serum HDL cholesterol (HDL-C) concentration; whether visceral fat or Si was independently related to lipids; and whether ethnicity influenced the relationship between visceral fat and risk factors. Subjects were 61 prepubertal African-American and Caucasian children. Total body fat was determined by dual-energy X-ray absorptiometry, visceral fat by computed tomography, and insulin sensitivity by the tolbutamide-modified, frequently sampled intravenous glucose tolerance test with minimal modeling. In multiple linear regression analysis (adjusting for total fat, sex, and ethnicity), visceral fat was independently related to TG (P < 0.05) and fasting insulin (P < 0.001), but not Si (P = 0.425). Total body fat was independently related to Si (P < 0.001). Si was independently related to fasting insulin (P < 0.001) but not to TG or HDL-C (P = 0.941 and 0.201, respectively). Si in African-Americans was 42% lower than in Caucasians (0.50 +/- 0.05 vs. 0.86 +/- 0.11 x 10(-5) min(-1) x pmol(-1) x l, mean +/- SE after adjusting for total fat, P < 0.001). Nonetheless, ethnicity was not independently related to either TG or HDL-C (P = 0.075 and 0.619, respectively, after adjusting for total and visceral fat and sex). The slopes of the relationships of total and visceral fat with risk factors did not differ with ethnicity. In conclusion, visceral fat appears metabolically unique in children, being independently associated with elevated TG and insulin but not Si. Obese children and African-American children were more insulin resistant, independent of visceral fat accumulation. Lower Si was associated with higher, faster insulin, but not dyslipidemia. Thus, obesity, visceral fat accumulation, and ethnicity in children may confer negative, but independent, health risks.
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