Hepcidin: A Critical Regulator of Iron Metabolism during Hypoxia

Iron status affects cognitive and physical performance in humans. Recent evidence indicates that iron balance is a tightly regulated process affected by a series of factors other than diet, to include hypoxia. Hypoxia has profound effects on iron absorption and results in increased iron acquisition and erythropoiesis when humans move from sea level to altitude. The effects of hypoxia on iron balance have been attributed to hepcidin, a central regulator of iron homeostasis. This paper will focus on the molecular mechanisms by which hypoxia affects hepcidin expression, to include a review of the hypoxia inducible factor (HIF)/hypoxia response element (HRE) system, as well as recent evidence indicating that localized adipose hypoxia due to obesity may affect hepcidin signaling and organismal iron metabolism

Vitamin D status in female military personnel during combat training

Vitamin D is an essential nutrient for maintaining bone health. Recent data suggest that vitamin D and calcium supplementation might affect stress fracture incidence in military personnel. Although stress fracture is a health risk for military personnel during training, no study has investigated changes in vitamin D status in Soldiers during United States (US) Army basic combat training (BCT). This longitudinal study aimed to determine the effects of BCT on 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) levels in female Soldiers. Serum 25(OH)D and PTH were assessed in 74 fasted Soldier volunteers before and after an 8-week BCT course conducted between August and October in Columbia, South Carolina. In the total study population, 25(OH)D levels decreased (mean ± SD) from 72.9 ± 30.0 to 63.3 ± 19.8 nmol/L (P < 0.05) and PTH levels increased from 36.2 ± 15.8 to 47.5 ± 21.2 pg/mL (P < 0.05) during BCT. Ethnicity affected changes in vitamin D status (ethnicity-by-time interaction, P < 0.05); 25(OH)D decreased (P < 0.05) in both Hispanic and non-Hispanic whites, but did not change in non-Hispanic blacks. Ethnicity did not affect BCT-induced changes in PTH. These data indicate that vitamin D status in female Soldiers may decline during military training in the late summer and early autumn months in the Southeastern US. Future studies should strive to determine the impact of military clothing and seasonality on vitamin D status, as well as the functional impact of declining vitamin D status on bone health

Higher Protein Density Diets Are Associated With Greater Diet Quality and Micronutrient Intake in Healthy Young Adults

Objective: This study characterized habitual dietary protein intake in healthy young adults entering military service and explored whether diet protein density is associated with diet quality and micronutrient intake.Methods: An FFQ was used to estimate habitual dietary intake and calculate HEI scores in 276 males [mean(SD), age:21.1y(3.8)] and 254 females [age:21.2y(3.7)]. Multivariate-adjusted MANCOVA and ANCOVA models were used to identify associations between protein density quartiles and HEI scores and micronutrient intake. Higher HEI components scores for sodium, refined grains, and empty calories indicate lower intake; higher scores for all other components indicate higher intakes.Results: Mean(SD) energy-adjusted protein intakes were 29.3(3.2), 36.0(1.4), 40.8(1.3), and 47.9(3.9) g/1,000 kcal for protein density quartiles 1–4, respectively. For males, empty calorie scores as well as dark green and orange vegetable scores were higher in quartiles 3 and 4 than 1 and 2 (all, p &lt; 0.05). Scores for total vegetable, dairy, and total protein foods were lower in quartile 1 vs. quartiles 2, 3, and 4 (all, p &lt; 0.05). Sodium scores decreased as quartiles increased (p &lt; 0.001). Total HEI, fruit, whole grains, seafood and plant protein, fatty acids, and refined grain scores did not differ. For females, total HEI, vegetable, and total protein foods scores were higher in quartiles 3 and 4 than 1 and 2 (all, p &lt; 0.05). Empty calorie scores increased as quartile increased (p &lt; 0.05). Dairy scores were higher in quartiles 2, 3, and 4 than 1 (p &lt; 0.05). Whole fruit scores were lowest in quartile 1 (p &lt; 0.05). Whole grain as well as seafood and plant protein scores were higher in quartile 4 vs. 1 (both, p &lt; 0.05). Sodium scores decreased as quartile increased (p &lt; 0.001). Fatty acids scores did not differ. For males and females, micronutrient intakes progressively increased across quartiles with the exception of calcium and vitamin C, (all, p &lt; 0.05). Intakes remained nearly the same when controlled for fruit and vegetable intake.Conclusion: These cross-sectional data suggest that habitually consuming a higher protein density diet is associated with better scores for some, but not all, diet quality components in males, better overall diet quality scores in females, and greater intakes of micronutrients in both male and female healthy, young adults entering military service

Mediterranean diet - promotion and dissemination of healthy eating: proceedings of an exploratory seminar at the Radcliffe institute for advanced study.

The traditional Mediterranean diet is considered the world's most evidence-based eating pattern for promoting health and longevity. However, institutional food environments and their busy consumers often sacrifice health benefits for the convenience of faster and cheaper foods that generally are of lower quality and are more processed, and thus, contribute to the current epidemics of obesity and diabetes. Expert consensus has even identified the Mediterranean diet as the easiest to follow among healthy eating patterns. Nonetheless, fewer American families cook at home and many food services have been slow to implement healthier food options compatible with the Mediterranean diet. In September 2019, we convened a group of thought leaders at an exploratory seminar entitled: "Mediterranean Diet: Promotion and Dissemination of Healthy Eating", hosted by the Radcliffe Institute for Advanced Studies at Harvard University. The multidisciplinary faculty discussed best practices for translating traditional Mediterranean lifestyle principles to modern society

Evolutionary relationships among barley and <i>Arabidopsis</i> core circadian clock and clock-associated genes

The circadian clock regulates a multitude of plant developmental and metabolic processes. In crop species, it contributes significantly to plant performance and productivity and to the adaptation and geographical range over which crops can be grown. To understand the clock in barley and how it relates to the components in the Arabidopsis thaliana clock, we have performed a systematic analysis of core circadian clock and clock-associated genes in barley, Arabidopsis and another eight species including tomato, potato, a range of monocotyledonous species and the moss, Physcomitrella patens. We have identified orthologues and paralogues of Arabidopsis genes which are conserved in all species, monocot/dicot differences, species-specific differences and variation in gene copy number (e.g. gene duplications among the various species). We propose that the common ancestor of barley and Arabidopsis had two-thirds of the key clock components identified in Arabidopsis prior to the separation of the monocot/dicot groups. After this separation, multiple independent gene duplication events took place in both monocot and dicot ancestors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00239-015-9665-0) contains supplementary material, which is available to authorized users

PFKFB3-Mediated Glycolysis Rescues Myopathic Outcomes in the Ischemic Limb

Compromised muscle mitochondrial metabolism is a hallmark of peripheral arterial disease, especially in patients with the most severe clinical manifestation — critical limb ischemia (CLI). We asked whether inflexibility in metabolism is critical for the development of myopathy in ischemic limb muscles. Using Polg mtDNA mutator (D257A) mice, we reveal remarkable protection from hind limb ischemia (HLI) due to a unique and beneficial adaptive enhancement of glycolytic metabolism and elevated ischemic muscle PFKFB3. Similar to the relationship between mitochondria from CLI and claudicating patient muscles, BALB/c muscle mitochondria are uniquely dysfunctional after HLI onset as compared with the C57BL/6 (BL6) parental strain. AAV-mediated overexpression of PFKFB3 in BALB/c limb muscles improved muscle contractile function and limb blood flow following HLI. Enrichment analysis of RNA sequencing data on muscle from CLI patients revealed a unique deficit in the glucose metabolism Reactome. Muscles from these patients express lower PFKFB3 protein, and their muscle progenitor cells possess decreased glycolytic flux capacity in vitro. Here, we show supplementary glycolytic flux as sufficient to protect against ischemic myopathy in instances where reduced blood flow–related mitochondrial function is compromised preclinically. Additionally, our data reveal reduced glycolytic flux as a common characteristic of the failing CLI patient limb skeletal muscle

Alternative splicing of barley clock genes in response to low temperature:evidence for alternative splicing conservation

Alternative splicing (AS) is a regulated mechanism that generates multiple transcripts from individual genes. It is widespread in eukaryotic genomes and provides an effective way to control gene expression. At low temperatures, AS regulates Arabidopsis clock genes through dynamic changes in the levels of productive mRNAs. We examined AS in barley clock genes to assess whether temperature-dependent AS responses also occur in a monocotyledonous crop species. We identify changes in AS of various barley core clock genes including the barley orthologues of Arabidopsis AtLHY and AtPRR7 which showed the most pronounced AS changes in response to low temperature. The AS events modulate the levels of functional and translatable mRNAs, and potentially protein levels, upon transition to cold. There is some conservation of AS events and/or splicing behaviour of clock genes between Arabidopsis and barley. In addition, novel temperature-dependent AS of the core clock gene HvPPD-H1 (a major determinant of photoperiod response and AtPRR7 orthologue) is conserved in monocots. HvPPD-H1 showed a rapid, temperature-sensitive isoform switch which resulted in changes in abundance of AS variants encoding different protein isoforms. This novel layer of low temperature control of clock gene expression, observed in two very different species, will help our understanding of plant adaptation to different environments and ultimately offer a new range of targets for plant improvement

Probabilistic Integrity and Risk Assessment of Turbine Engines, Phase II

15-G-016This grant supported the efforts of the Federal Aviation Administration (FAA) to develop an enhanced life management process, based on probabilistic damage tolerance principles, to address the threat of material or manufacturing anomalies in high-energy rotating components of aircraft engines. Major research products included formal verification and validation of Design Assessment of Reliability With INspection (DARWIN\uae) stress-intensity factor solutions; enhanced DARWIN capabilities for manual and automatic fracture mechanics modeling, probabilistic methods, and fleet risk methods. Substantial improvements in the speed and robustness of DARWIN for large finite element (FE) models; streamlined methods for deterministic life calculations; a DARWIN Python module to facilitate scripting of multiple DARWIN runs; options to specify or limit optional features or default values available in DARWIN; new advanced visualization capabilities enabling users to define and manipulate regions within three-dimensional FE models; multiple new versions of the DARWIN computer code for technology transfer to industry and the FAA, and a large DARWIN training workshop are also included. The efforts facilitate implementation of official advisory material for axial blade slots, titanium hard alpha anomalies, and circular holes, while also developing improved analysis methods for other applications of deterministic and probabilistic damage tolerance to engine safety

The Regulation of Skeletal Muscle Protein Turnover during the Progression of Cancer Cachexia in the ApcMin/+ Mouse

Muscle wasting that occurs with cancer cachexia is caused by an imbalance in the rates of muscle protein synthesis and degradation. The ApcMin/+ mouse is a model of colorectal cancer that develops cachexia that is dependent on circulating IL-6. However, the IL-6 regulation of muscle protein turnover during the initiation and progression of cachexia in the ApcMin/+ mouse is not known. Cachexia progression was studied in ApcMin/+ mice that were either weight stable (WS) or had initial (≤5%), intermediate (6–19%), or extreme (≥20%) body weight loss. The initiation of cachexia reduced %MPS 19% and a further ∼50% with additional weight loss. Muscle IGF-1 mRNA expression and mTOR targets were suppressed with the progression of body weight loss, while muscle AMPK phosphorylation (Thr 172), AMPK activity, and raptor phosphorylation (Ser 792) were not increased with the initiation of weight loss, but were induced as cachexia progressed. ATP dependent protein degradation increased during the initiation and progression of cachexia. However, ATP independent protein degradation was not increased until cachexia had progressed beyond the initial phase. IL-6 receptor antibody administration prevented body weight loss and suppressed muscle protein degradation, without any effect on muscle %MPS or IGF-1 associated signaling. In summary, the %MPS reduction during the initiation of cachexia is associated with IGF-1/mTOR signaling repression, while muscle AMPK activation and activation of ATP independent protein degradation occur later in the progression of cachexia. IL-6 receptor antibody treatment blocked cachexia progression through the suppression of muscle protein degradation, while not rescuing the suppression of muscle protein synthesis. Attenuation of IL-6 signaling was effective in blocking the progression of cachexia, but not sufficient to reverse the process