Heat shock affects mitotic segregation of human chromosomes bound to stress-induced satellite III RNAs

Heat shock activates the transcription of arrays of Satellite III (SatIII) DNA repeats in the pericentromeric heterochromatic domains of specific human chromosomes, the longest of which is on chromosome 9. Long non-coding SatIII RNAs remain associated with transcription sites where they form nuclear stress bodies or nSBs. The biology of SatIII RNAs is still poorly understood. Here, we show that SatIII RNAs and nSBs are detectable up to four days after thermal stress and are linked to defects in chromosome behavior during mitosis. Heat shock perturbs the execution of mitosis. Cells reaching mitosis during the first 3 h of recovery accumulate in pro-metaphase. During the ensuing 48 h, this block is no longer detectable; however, a significant fraction of mitoses shows chromosome segregation defects. Notably, most of lagging chromosomes and chromosomal bridges are bound to nSBs and contain arrays of SatIII DNA. Disappearance of mitotic defects at the end of day 2 coincides with the processing of long non-coding SatIII RNAs into a ladder of small RNAs associated with chromatin and ranging in size from 25 to 75 nt. The production of these molecules does not rely on DICER and Argonaute 2 components of the RNA interference apparatus. Thus, massive transcription of SatIII DNA may contribute to chromosomal instability

TRANSCRIPTION OF THE MITOCHONDRIAL CITRATE CARRIER GENE: ROLE OF SREBP-1, UPREGULATION BY INSULIN AND DOWNREGULATION BY PUFA

In this study we investigated the transcriptional role of the sterol regulatory element (SRE) present in the promoter of the mitochon- drial citrate carrier (CIC). We show that wild-type (but not mutated) CIC SRE cloned in front of the luciferase promoter confers tran- scriptional activation of the gene reporter. We also demonstrate that insulin activates, and polyunsaturated fatty acids (PUFA) inhibit, the gene reporter activity driven by the CIC promoter containing wild-type (but not mutated) SRE. Finally, both insulin treatment and overexpression of SRE binding protein (SREBP-1) increase the CIC transcript and protein levels, whereas PUFA have an opposite effect. These results show that SRE/SREBP-1 play a role in the transcriptional regulation of CIC by insulin and PUFA

Monte-Carlo simulation with FLUKA for liquid and solid targets

Introduction Monte-Carlo simulations can be used to assess isotope production on small medical cyclotrons. These simulations calculate the particle interactions with electric and magnetic fields, as well as the nuclear reactions. The results can be used to predict both yields and isotopic contaminations and can aid in the optimum design of target material and target geometry [1,2]. FLUKA is a general-purpose tool widely used in many applications from accelerator shielding to target design, calorimetry, activation, dosimetry, detector design, neutrino physics, or radiotherapy [3,4]. In this work, we applied the Monte-Carlo code FLUKA to determine the accuracy of predicting yields of various isotopes as compared to experimental yields. Material and Methods The proton beam collimation system, as well as the liquid and solid target of the TR13 cyclotron at TRIUMF, has been modeled in FLUKA. The proton beam parameters were initially taken from the cyclotron design specifications and were optimized against experimental measurements from the TR13. Data from irradiations of different targets and with different beam currents were collected in order to account for average behavior, see FIG. 1. Yields for a pencil proton beam as well as a beam spread out in direction and energy have been calculated and have been compared to experimental results obtained with the TR13. Results and Conclusion The reactions listed in TABLE 1 were assessed. For most reactions a good agreement was found in the comparison between experimental and simulated saturation yield. TABLE 1 only shows the yields simulated with a proton beam with a spread in both direction and energy. In most cases, the simulated yield is slightly larger or comparable. Only the calculated yield for 55Co was significantly lower by a factor of 4.2. This is still a good agreement considering that FLUKA was originally a high-energy physics code. It may indicate that the FLUKA internal cross-section calculation for this isotope production needs some optimization. In summary, we conclude that FLUKA can be used as a tool for the prediction of isotope production as well as for target design

A key role of the mitochondrial citrate carrier (SLC25A1) in TNFα- and IFNγ-triggered inflammation

The chronic induction of inflammation underlies multiple pathological conditions, including metabolic, autoimmune disorders and cancer. The mitochondrial citrate carrier (CIC), encoded by the SLC25A1 gene, promotes the export of citrate from the mitochondria to the cytoplasm, a process that profoundly influences energy balance in the cells. We have previously shown that SLC25A1 is a target gene for lipopolysaccharide signaling and promotes the production of inflammatory mediators. We now demonstrate that SLC25A1 is induced at the transcriptional level by two key pro-inflammatory cytokines, tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ), and such induction involves the activity of the nuclear factor kappa B and STAT1 transcription factors. By studying the down-stream events following SLC25A1 activation during signals that mimic inflammation, we demonstrate that CIC is required for regulating the levels of nitric oxide and of prostaglandins by TNFα or IFNγ. Importantly, we show that the citrate exported from mitochondria via CIC and its downstream metabolic intermediate, acetyl-coenzyme A, are necessary for TNFα or IFNγ to induce nitric oxide and prostaglandin production. These findings provide the first line of evidence that the citrate export pathway, via CIC, is central for cytokine-induced inflammatory signals and shed new light on the relationship between energy metabolism and inflammation

Is vitamin D-fortified yogurt a value-added strategy for improving human health? A systematic review and meta-analysis of randomized trials

Yogurt is a good source of probiotics, calcium, and proteins, but its content of vitamin D is low. Therefore, yogurt could be a good choice for vitamin D fortification to improve the positive health outcomes associated with its consumption. The primary aim of this systematic review and meta-analysis was to investigate the effect of vitamin D-fortified yogurt compared with plain yogurt on levels of serum 25-hydroxy vitamin D (25OHD). The secondary aim was to evaluate the effect of fortified yogurt on parathyroid hormone, anthropometric parameters, blood pressure, glucose metabolism, and lipid profile. We searched PubMed, Scopus, and Google Scholar for eligible studies; that is, randomized controlled trials (RCT) that compared vitamin D-fortified yogurt with control treatment without any additional supplement. Random-effects models were used to estimate pooled effect sizes and 95% confidence intervals. Findings from 9 RCT (n = 665 participants) that lasted from 8 to 16 wk are summarized in this review. The meta-analyzed mean differences for random effects showed that vitamin D-fortified yogurt (from 400 to 2,000 IU) increased serum 25OHD by 31.00 nmol/L. In addition, vitamin D-fortified yogurt decreased parathyroid hormone by 15.47 ng/L, body weight by 0.92 kg, waist circumference by 2.01 cm, HOMA-IR by 2.18 mass units, fasting serum glucose by 22.54 mg/dL, total cholesterol by 13.38 mg/dL, and triglycerides by 30.12 mg/dL compared with the controlled treatments. No publication bias was identified. Considerable between-study heterogeneity was observed for most outcomes. Vitamin D-fortified yogurt may be beneficial in improving serum 25OHD, lipid profile, glucose metabolism, and anthropometric parameters and decreasing parathyroid hormone level in pregnant women and adult and elderly subjects with or without diabetes, prediabetes, or metabolic syndrome

Is a combination of melatonin and amino acids useful to sarcopenic elderly patients? A randomized trial

This study evaluated the effectiveness of a 4-week intervention of melatonin and essential aminoacid supplementation on body composition, protein metabolism, strength and inflammation in 159 elderly sarcopenic patients (42/117, men/women), assigned to four groups: isocaloric placebo (P, n = 44), melatonin (M, 1 mg/daily, n = 42), essential amino acids (eAA 4 g/daily, n = 40) or eAA plus melatonin (eAAM, 4 g eAA and 1 mg melatonin/daily, n = 30). Data from body composition (dual X-ray absortiometry (DXA)), strength (handgrip test) and biochemical parameters for the assessment of protein metabolism (albumin) and inflammation (CRP) were collected at baseline and after the 4-week intervention. Compared with P and M, supplementation with eAA plus M increased total fat-free mass (vs. P: +2190 g; p < 0.01; vs. M: +2107 g; p < 0.05). M alone lowered albumin levels (vs. P: -0.39 g; p < 0.01; vs. eAA: -0.47 g; p < 0.01). This data on albumin was confirmed by within-group analysis (M -0.44g; p < 0.001; eAAM: -0.34 p < 0.05). M and eAA seemed to lower the percentage of gynoid fat (p < 0.05) and android fat (p < 0.01). No significant changes in inflammation or strength were reported. A 4-week intervention with eAA plus M together may be effective in enhancing fat-free-mass compared to M and P but not versus eAA. M alone demonstrates a negative effect on albumin level

Current opinion on dietary advice in order to preserve fat-free mass during a low-calorie diet

Objectives: The loss of fat-free mass (FFM) that occurs during weight loss secondary to low-calorie diet can lead to numerous and deleterious consequences. We performed a review to evaluate the state of the art on metabolic and nutritional correlates of loss of fat free mass during low calorie diet and treatment for maintaining fat free mass. Methods: This review included 44 eligible studies. There are various diet strategies to maintain FFM during a low-calorie diet, including adoption of a very low carbohydrate ketogenic diet (VLCKD) and taking an adequate amount of specific nutrients (vitamin D, leucine, whey protein). Results: Regarding the numerous and various low-calorie diet proposals for achieving weight loss, the comparison of VLCKD with prudent low-calorie diet found that FFM was practically unaffected by VLCKD. There are numerous possible mechanisms for this, involving insulin and the insulin-like growth factor-1–growth hormone axis, which acts by stimulating protein synthesis. Conclusions: Considering protein and amino acids intake, an adequate daily intake of leucine (4 g/d) and whey protein (20 g/d) is recommended. Regarding vitamin D, if the blood vitamin D has low values (<30 ng/mL), it is mandatory that adequate supplementation is provided, specifically calcifediol, because in the obese patient this form is recommended to avoid seizure in the adipose tissue; 3 to 4 drops/d or 20 to 30 drops/wk of calcifediol are generally adequate to restore normal 25(OH)D plasma levels in obese patients

Rice germ macro- and micronutrients: a new opportunity for the nutraceutics

The aim of this study is to characterise the rice germ from the nutritional point of view. The latest laboratory methods for evaluation of macronutrients and micronutrients have been used. Rice germ has a high protein content (18 g per 100 g of edible product) with considerable amounts of essential amino acids (mainly lysine, histidine and valine), fatty acids (mainly monounsaturated and polyunsaturated fatty acids), and fibre (7 g per 100 g). Regarding water-soluble vitamins, rice germ has high amounts of thiamine (B1) and vitamin B6, while vitamin E is the main fat-soluble vitamin present. Iron (77% of RDA) and magnesium (108% of RDA) are the two main minerals found in rice germ. Given its great nutritional value, it will be of interest in future studies to explore ways for rice germ to be incorporated into dietary supplements aimed at increasing nutrition intake for a specific population

Polycystic ovary syndrome management: a review of the possible amazing role of berberine

Purpose: The therapy of polycystic ovary syndrome (PCOS) is based on synthetic hormones associated with lifestyle changes, but these therapies cannot be taken continuously, especially by women who would like to become pregnant. Thus, nutraceutical compounds were investigated as possible agents for treatment of PCOS. Berberine is shown to be effective against insulin resistance and obesity, particularly against visceral adipose tissue (VAT). Because of these properties, researchers theorized that berberine could be effective in PCOS treatment. Methods: The aim of this narrative review was to assess the state of the art about the use of berberine in PCOS management. Results: This review included 5 eligible studies. Despite the number of studies considered being low, the number of women studied is high (1078) and the results are interesting. Two authors find out that berberine induced a redistribution of adipose tissue, reducing VAT in the absence of weight loss and improved insulin sensitivity, quite like metformin. One author demonstrated that berberine improved the lipid pattern. Moreover, three authors demonstrated that berberine improved insulin resistance in theca cells with an improvement of the ovulation rate per cycle, so berberine is also effective on fertility and live birth rates. Conclusions: Finally, berberine is safe to use in premenopausal women who want to get pregnant and showed few side effects in all the cited studies. In conclusion, the use of berberine for PCOS is safe and promising, even if more studies are needed to create a consensus about the dosage of berberine useful for long-term therapy