Regulation of proximal tubular cell differentiation and proliferation in primary culture by matrix stiffness and ECM components.

PubMed

Chen, Wan-Chun; Lin, Hsi-Hui; Tang, Ming-Jer

2014-09-15

To explore whether matrix stiffness affects cell differentiation, proliferation, and transforming growth factor (TGF)-β1-induced epithelial-mesenchymal transition (EMT) in primary cultures of mouse proximal tubular epithelial cells (mPTECs), we used a soft matrix made from monomeric collagen type I-coated polyacrylamide gel or matrigel (MG). Both kinds of soft matrix benefited primary mPTECs to retain tubular-like morphology with differentiation and growth arrest and to evade TGF-β1-induced EMT. However, the potent effect of MG on mPTEC differentiation was suppressed by glutaraldehyde-induced cross-linking and subsequently stiffening MG or by an increasing ratio of collagen in the soft mixed gel. Culture media supplemented with MG also helped mPTECs to retain tubular-like morphology and a differentiated phenotype on stiff culture dishes as soft MG did. We further found that the protein level and activity of ERK were scaled with the matrix stiffness. U-0126, a MEK inhibitor, abolished the stiff matrix-induced dedifferentiation and proliferation. These data suggest that the ERK signaling pathway plays a vital role in matrix stiffness-regulated cell growth and differentiation. Taken together, both compliant property and specific MG signals from the matrix are required for the regulation of epithelial differentiation and proliferation. This study provides a basic understanding of how physical and chemical cues derived from the extracellular matrix regulate the physiological function of proximal tubules and the pathological development of renal fibrosis. Copyright © 2014 the American Physiological Society.

Effects of Taurine Supplementation on Neuronal Excitability and Glucose Homeostasis.

PubMed

El Idrissi, Abdeslem; El Hilali, Fatiha; Rotondo, Salvatore; Sidime, Francoise

2017-01-01

In this study we examined the role of chronic taurine supplementation on plasma glucose homeostasis and brain excitability through activation of the insulin receptor. FVB/NJ male mice were supplemented with taurine in drinking water (0.05% w/v) for 4 weeks and subjected to a glucose tolerance test (7.5 mg/kg BW) after 12 h fasting. We found that taurine-fed mice were slightly hypoglycemic prior to glucose injection and showed significantly reduced plasma glucose at 30 and 60 min post-glucose injection when compared to control mice. Previously, we reported that taurine supplementation induces biochemical changes that target the GABAergic system. Those studies show that taurine-fed mice are hyperexcitable, have reduced GABA A receptors expression and increased GAD and somatostatin expression in the brain. In this study, we found that taurine-fed mice had a significant increase in insulin receptor (IR) immuno-reactivity in the pancreas and all brain regions examined. At the mRNA level, we found that the IR showed differential regional expression. Surprisingly, we found that neurons express the gene for insulin and that taurine had a significant role in regulating insulin gene expression. We propose that increased insulin production and secretion in taurine-fed mice cause an increase activation of the central IR and may be partially responsible for the increased neuronal excitability observed in taurine supplemented mice. Furthermore, the high levels of neuronal insulin expression and its regulation by taurine implicates taurine in the regulation of metabolic homeostasis.

Osteogenic differentiation of immature osteoblasts: Interplay of cell culture media and supplements.

PubMed

Brauer, A; Pohlemann, T; Metzger, W

2016-01-01

Differentiation of immature osteoblasts to mature osteoblasts in vitro initially was induced by supplementing the medium with β-gylcerophosphate and dexamethasone. Later, ascorbic acid, vitamin D3, vitamin K3 and TGFβ1 were used in varying concentrations as supplements to generate a mature osteoblast phenotype. We tested the effects of several combinations of cell culture media, seeding protocols and osteogenic supplements on osteogenic differentiation of human primary osteoblasts. Osteogenic differentiation was analyzed by staining alkaline phosphatase (ALP) with 5-bromo-4-chloro-3-indolyl-phosphate/nitro blue tetrazolium (BCIP/NBT) and by von Kossa staining of deposited calcium phosphate. The combinations of culture media and supplements significantly influenced osteogenic differentiation, but the seeding protocol did not. Staining of ALP and calcium phosphate could be achieved only if our own mix of osteogenic supplements was used in combination with Dulbecco's modified Eagle medium or if a commercial mix of osteogenic supplements was used in combination with osteoblast growth medium. Especially for von Kossa, we observed great variations in the staining intensity. Because osteogenic differentiation is a complex process, the origin of the osteoblasts, cell culture media and osteogenic supplements should be established by preliminary experiments to achieve optimal differentiation. Staining of ALP or deposited calcium phosphate should be supplemented with qRT-PCR studies to learn more about the influence of specific supplements on osteogenic markers.

Oral Supplementation with Cocoa Extract Reduces UVB-Induced Wrinkles in Hairless Mouse Skin.

PubMed

Kim, Jong-Eun; Song, Dasom; Kim, Junil; Choi, Jina; Kim, Jong Rhan; Yoon, Hyun-Sun; Bae, Jung-Soo; Han, Mira; Lee, Sein; Hong, Ji Sun; Song, Dayoung; Kim, Seong-Jin; Son, Myoung-Jin; Choi, Sang-Woon; Chung, Jin Ho; Kim, Tae-Aug; Lee, Ki Won

2016-05-01

Cacao beans contain various bioactive phytochemicals that could modify the pathogeneses of certain diseases. Here, we report that oral administration of cacao powder (CP) attenuates UVB-induced skin wrinkling by the regulation of genes involved in dermal matrix production and maintenance. Transcriptome analysis revealed that 788 genes are down- or upregulated in the CP supplemented group, compared with the UVB-irradiated mouse skin controls. Among the differentially expressed genes, cathepsin G and serpin B6c play important roles in UVB-induced skin wrinkle formation. Gene regulatory network analysis also identified several candidate regulators responsible for the protective effects of CP supplementation against UVB-induced skin damage. CP also elicited antiwrinkle effects via inhibition of UVB-induced matrix metalloproteinases-1 expression in both the human skin equivalent model and human dermal fibroblasts. Inhibition of UVB-induced activator protein-1 via CP supplementation is likely to affect the expression of matrix metalloproteinases-1. CP supplementation also downregulates the expression of cathepsin G in human dermal fibroblasts. 5-(3',4'-Dihydroxyphenyl)-γ-valerolactone, a major in vivo metabolite of CP, showed effects similar to CP supplementation. These results suggest that cacao extract may offer a protective effect against photoaging by inhibiting the breakdown of dermal matrix, which leads to an overall reduction in wrinkle formation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Fetal bovine serum enables cardiac differentiation of human embryonic stem cells.

PubMed

Bettiol, Esther; Sartiani, Laura; Chicha, Laurie; Krause, Karl Heinz; Cerbai, Elisabetta; Jaconi, Marisa E

2007-10-01

During development, cardiac commitment within the mesoderm requires endoderm-secreted factors. Differentiation of embryonic stem cells into the three germ layers in vitro recapitulates developmental processes and can be influenced by supplements added to culture medium. Hence, we investigated the effect of fetal bovine serum (FBS) and KnockOut serum replacement (SR) on germ layers specification and cardiac differentiation of H1 human embryonic stem cells (hESC) within embryoid bodies (EB). At the time of EB formation, FBS triggered an increased apoptosis. As assessed by quantitative PCR on 4-, 10-, and 20-day-old EB, FBS promoted a faster down-regulation of pluripotency marker Oct4 and an increased expression of endodermal (Sox17, alpha-fetoprotein, AFP) and mesodermal genes (Brachyury, CSX). While neuronal and hematopoietic differentiation occurred in both supplements, spontaneously beating cardiomyocytes were only observed in FBS. Action potential (AP) morphology of hESC-derived cardiomyocytes indicated that ventricular cells were present only after 2 months of culture. However, quantification of myosin light chain 2 ventricular (mlc2v)-positive areas revealed that mlc2v-expressing cardiomyocytes could be detected already after 2 weeks of differentiation, but not in all beating clusters. In conclusion, FBS enabled cardiac differentiation of hESC, likely in an endodermal-dependent pathway. Among cardiac cells, ventricular cardiomyocytes differentiated over time, but not as the predominant cardiac cell subtype.

Phenolic acid intake, delivered via moderate champagne wine consumption, improves spatial working memory via the modulation of hippocampal and cortical protein expression/activation.

PubMed

Corona, Giulia; Vauzour, David; Hercelin, Justine; Williams, Claire M; Spencer, Jeremy P E

2013-11-10

While much data exist for the effects of flavonoid-rich foods on spatial memory in rodents, there are no such data for foods/beverages predominantly containing hydroxycinnamates and phenolic acids. To address this, we investigated the effects of moderate Champagne wine intake, which is rich in these components, on spatial memory and related mechanisms relative to the alcohol- and energy-matched controls. In contrast to the isocaloric and alcohol-matched controls, supplementation with Champagne wine (1.78 ml/kg BW, alcohol 12.5% vol.) for 6 weeks led to an improvement in spatial working memory in aged rodents. Targeted protein arrays indicated that these behavioral effects were paralleled by the differential expression of a number of hippocampal and cortical proteins (relative to the isocaloric control group), including those involved in signal transduction, neuroplasticity, apoptosis, and cell cycle regulation. Western immunoblotting confirmed the differential modulation of brain-derived neurotrophic factor, cAMP response-element-binding protein (CREB), p38, dystrophin, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, mammalian target of rapamycin (mTOR), and Bcl-xL in response to Champagne supplementation compared to the control drink, and the modulation of mTOR, Bcl-xL, and CREB in response to alcohol supplementation. Our data suggest that smaller phenolics such as gallic acid, protocatechuic acid, tyrosol, caftaric acid, and caffeic acid, in addition to flavonoids, are capable of exerting improvements in spatial memory via the modulation in hippocampal signaling and protein expression. Changes in spatial working memory induced by the Champagne supplementation are linked to the effects of absorbed phenolics on cytoskeletal proteins, neurotrophin expression, and the effects of alcohol on the regulation of apoptotic events in the hippocampus and cortex.

DREAM Mediated Regulation of GCM1 in the Human Placental Trophoblast

PubMed Central

Baczyk, Dora; Kibschull, Mark; Mellstrom, Britt; Levytska, Khrystyna; Rivas, Marcos; Drewlo, Sascha; Lye, Stephen J.; Naranjo, Jose R.; Kingdom, John C. P.

2013-01-01

The trophoblast transcription factor glial cell missing-1 (GCM1) regulates differentiation of placental cytotrophoblasts into the syncytiotrophoblast layer in contact with maternal blood. Reduced placental expression of GCM1 and abnormal syncytiotrophoblast structure are features of hypertensive disorder of pregnancy – preeclampsia. In-silico techniques identified the calcium-regulated transcriptional repressor – DREAM (Downstream Regulatory Element Antagonist Modulator) - as a candidate for GCM1 gene expression. Our objective was to determine if DREAM represses GCM1 regulated syncytiotrophoblast formation. EMSA and ChIP assays revealed a direct interaction between DREAM and the GCM1 promoter. siRNA-mediated DREAM silencing in cell culture and placental explant models significantly up-regulated GCM1 expression and reduced cytotrophoblast proliferation. DREAM calcium dependency was verified using ionomycin. Furthermore, the increased DREAM protein expression in preeclamptic placental villi was predominantly nuclear, coinciding with an overall increase in sumolylated DREAM and correlating inversely with GCM1 levels. In conclusion, our data reveal a calcium-regulated pathway whereby GCM1-directed villous trophoblast differentiation is repressed by DREAM. This pathway may be relevant to disease prevention via calcium-supplementation. PMID:23300953

ω-3 polyunsaturated fatty acids direct differentiation of the membrane phenotype in mesenchymal stem cells to potentiate osteogenesis

PubMed Central

Levental, Kandice R.; Surma, Michal A.; Skinkle, Allison D.; Lorent, Joseph H.; Zhou, Yong; Klose, Christian; Chang, Jeffrey T.; Hancock, John F.; Levental, Ilya

2017-01-01

Mammalian cells produce hundreds of dynamically regulated lipid species that are actively turned over and trafficked to produce functional membranes. These lipid repertoires are susceptible to perturbations from dietary sources, with potentially profound physiological consequences. However, neither the lipid repertoires of various cellular membranes, their modulation by dietary fats, nor their effects on cellular phenotypes have been widely explored. We report that differentiation of human mesenchymal stem cells (MSCs) into osteoblasts or adipocytes results in extensive remodeling of the plasma membrane (PM), producing cell-specific membrane compositions and biophysical properties. The distinct features of osteoblast PMs enabled rational engineering of membrane phenotypes to modulate differentiation in MSCs. Specifically, supplementation with docosahexaenoic acid (DHA), a lipid component characteristic of osteoblast membranes, induced broad lipidomic remodeling in MSCs that reproduced compositional and structural aspects of the osteoblastic PM phenotype. The PM changes induced by DHA supplementation potentiated osteogenic differentiation of MSCs concurrent with enhanced Akt activation at the PM. These observations prompt a model wherein the DHA-induced lipidome leads to more stable membrane microdomains, which serve to increase Akt activity and thereby enhance osteogenic differentiation. More broadly, our investigations suggest a general mechanism by which dietary fats affect cellular physiology through remodeling of membrane lipidomes, biophysical properties, and signaling. PMID:29134198

Alterations in expression of imprinted genes from the H19/IGF2 loci in a multigenerational model of intrauterine growth restriction (IUGR).

PubMed

Gonzalez-Rodriguez, Pablo; Cantu, Jessica; O'Neil, Derek; Seferovic, Maxim D; Goodspeed, Danielle M; Suter, Melissa A; Aagaard, Kjersti M

2016-05-01

The H19/IGF2 imprinted loci have attracted recent attention because of their role in cellular differentiation and proliferation, heritable gene regulation, and in utero or early postnatal growth and development. Expression from the imprinted H19/IGF2 locus involves a complex interplay of 3 means of epigenetic regulation: proper establishment of DNA methylation, promoter occupancy of CTCF, and expression of microRNA-675. We have demonstrated previously in a multigenerational rat model of intrauterine growth restriction the epigenetic heritability of adult metabolic syndrome in a F2 generation. We have further demonstrated abrogation of the F2 adult metabolic syndrome phenotype with essential nutrient supplementation of intermediates along the 1-carbon pathway and shown that alterations in the metabolome precede the adult onset of metabolic syndrome. The upstream molecular and epigenomic mediators underlying these observations, however, have yet to be elucidated fully. In the current study, we sought to characterize the impact of the intrauterine growth-restricted lineage and essential nutrient supplementation on both levels and molecular mediators of H19 and IGF2 gene expression in the F2 generation. F2 intrauterine growth-restricted and sham lineages were obtained by exposing P1 (grandmaternal) pregnant dams to bilateral uterine artery ligation or sham surgery at gestational day 19.5. F1 pups were allocated to the essential nutrient supplemented or control diet at postnatal day 21, and bred at 6-7 weeks of age. Hepatic tissues from the resultant F2 offspring at birth and at weaning (day 21) were obtained. Bisulfite modification and sequencing was employed for methylation analysis. H19 and IGF2 expression was measured by quantitative polymerase chain reaction. Promoter occupancy was quantified by the use of chromatin immunoprecipitation, or ChIP, against CTCF insulator proteins. Growth-restricted F2 on control diet demonstrated significant down-regulation in H19 expression compared with sham lineage (0.7831 vs 1.287; P < .05); however, essential nutrient supplementation diet abrogates this difference (4.995 vs 5.100; P > .05). Conversely, Igf2 was up-regulated by essential nutrient supplemented diet on the sham lineage (2.0 fold, P = .01), an effect that was not observed in the growth restricted offspring. A significant differential methylation was observed in the promoter region of region H19 among the intrauterine growth-restricted lineage (18% vs 25%; P < .05) on a control diet, whereas the essential nutrient supplemented diet was alternately associated with hypermethylation in both lineages (sham: 50%; intrauterine growth restriction: 84%, P < .05). Consistent with essential nutrient supplementation impacting the epigenome, a decrease of CTCF promoter occupancy was observed in CTCF4 of the growth restricted lineage (2.45% vs 0.56%; P < .05) on the control diet, an effect that was repressed with essential nutrient supplementation. Heritable growth restriction is associated with changes in H19 gene expression; these changes are reversible with diet supplementation to favorably impact adult metabolic syndrome. Copyright © 2016. Published by Elsevier Inc.

Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites.

PubMed

Kim, Duk Kyung; Lillehoj, Hyun S; Lee, Sung Hyen; Lillehoj, Erik P; Bravo, David

2013-01-14

The effects of a compound including the secondary metabolites of garlic, propyl thiosulphinate (PTS) and propyl thiosulphinate oxide (PTSO), on the in vitro and in vivo parameters of chicken gut immunity during experimental Eimeria acervulina infection were evaluated. In in vitro assays, the compound comprised of PTSO (67 %) and PTS (33 %) dose-dependently killed invasive E. acervulina sporozoites and stimulated higher spleen cell proliferation. Broiler chickens continuously fed from hatch with PTSO/PTS compound-supplemented diet and orally challenged with live E. acervulina oocysts had increased body weight gain, decreased faecal oocyst excretion and greater E. acervulina profilin antibody responses, compared with chickens fed a non-supplemented diet. Differential gene expression by microarray hybridisation identified 1227 transcripts whose levels were significantly altered in the intestinal lymphocytes of PTSO/PTS-fed birds compared with non-supplemented controls (552 up-regulated, 675 down-regulated). Biological pathway analysis identified the altered transcripts as belonging to the categories 'Disease and Disorder' and 'Physiological System Development and Function'. In the former category, the most significant function identified was 'Inflammatory Response', while the most significant function in the latter category was 'Cardiovascular System Development and Function'. This new information documents the immunologic and genomic changes that occur in chickens following PTSO/PTS dietary supplementation, which are relevant to protective immunity during avian coccidiosis.

Electrospun biomimetic scaffold of hydroxyapatite/chitosan supports enhanced osteogenic differentiation of mMSCs

NASA Astrophysics Data System (ADS)

Peng, Hongju; Yin, Zi; Liu, Huanhuan; Chen, Xiao; Feng, Bei; Yuan, Huihua; Su, Bo; Ouyang, Hongwei; Zhang, Yanzhong

2012-12-01

Engaging functional biomaterial scaffolds to regulate stem cell differentiation has drawn a great deal of attention in the tissue engineering and regenerative medicine community. In this study, biomimetic composite nanofibrous scaffolds of hydroxyapatite/chitosan (HAp/CTS) were prepared to investigate their capacity for inducing murine mesenchymal stem cells (mMSCs) to differentiate into the osteogenic lineage, in the absence and presence of an osteogenic supplementation (i.e., ascorbic acid, β-glycerol phosphate, and dexamethasone), respectively. Using electrospun chitosan (CTS) nanofibrous scaffolds as the control, cell morphology, growth, specific osteogenic genes expression, and quantified proteins secretion on the HAp/CTS scaffolds were sequentially examined and assessed. It appeared that the HAp/CTS scaffolds supported better attachment and proliferation of the mMSCs. Most noteworthy was that in the absence of the osteogenic supplementation, expression of osteogenic genes including collagen I (Col I), runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and osteocalcin (OCN) were significantly upregulated in mMSCs cultured on the HAp/CTS nanofibrous scaffolds. Also increased secretion of the osteogenesis protein markers of alkaline phosphatase and collagen confirmed that the HAp/CTS nanofibrous scaffold markedly promoted the osteogenic commitment in the mMSCs. Moreover, the presence of osteogenic supplementation proved an enhanced efficacy of mMSC osteogenesis on the HAp/CTS nanofibrous scaffolds. Collectively, this study demonstrated that the biomimetic nanofibrous HAp/CTS scaffolds could support and enhance the adhesion, proliferation, and particularly osteogenic differentiation of the mMSCs. It also substantiated the potential of using biomimetic nanofibrous scaffolds of HAp/CTS for functional bone repair and regeneration applications.

Comparison of human dermal fibroblasts (HDFs) growth rate in culture media supplemented with or without basic fibroblast growth factor (bFGF).

PubMed

Abdian, Narges; Ghasemi-Dehkordi, Payam; Hashemzadeh-Chaleshtori, Morteza; Ganji-Arjenaki, Mahbobe; Doosti, Abbas; Amiri, Beheshteh

2015-12-01

Basic fibroblast growth factor (bFGF or FGF-2) is a member of the FGF family secreted by different kinds of cells like HDFs and it is an important nutritional factor for cell growth and differentiation. The HDFs release bFGF in culture media at very low. The present study aims to investigate the HDFs growth rate in culture media supplemented either with or without bFGF. In brief, HDFs were isolated from human foreskin sample and were cultured in vitro in media containing bFGF and lack of this factor. The cells growth rate was calculated by trypan blue. The karyotyping was performed using G-banding to investigate the chromosomal abnormality of HDFs in both groups. Total RNA of each groups were extracted and cDNA samples were synthesized then, real-time Q-PCR was used to measure the expression level of p27kip1 and cyclin D1 genes normalized to internal control gene (GAPDH). The karyotype analysis showed that HDFs cultured in media or without bFGF had normal karyotype (46 chromosomes, XY) and chromosomal abnormalities were not observed. The cell growth rates in both groups were normal with proliferated exponentially but the slope of growth curve in HDFs cultured in media containing bFGF was increased. Karyotyp test showed that bFGF does not affect on cytogenetic stability of cells. The survey of p27kip1 and cyclin D1 genes by real-time Q-PCR showed that the expression level of these genes were up-regulated when adding bFGF in culture media (p < 0.05). The findings of the present study demonstrate that appropriate supplementation of culture media with growth factor like bFGF could enhance the proliferation and differentiation capacity of cells and improve cells growth rate. Similarly, fibroblast growth factors did not induce any chromosomal abnormality in cells. Furthermore, in HDFs cultured in bFGF supplemented media, the p27kip1 and cyclin D1 genes were up-regulated and suggesting an important role for bFGF in cell-cycle regulation and progression and fibroblast division stimulation. It also suggests that the effects of bFGF on different cell types with/or without production of bFGF or other regulation factors be investigated in future.

Effects of vitamin D supplementation on alveolar macrophage gene expression: preliminary results of a randomized, controlled trial.

PubMed

Gerke, Alicia K; Pezzulo, Alejandro A; Tang, Fan; Cavanaugh, Joseph E; Bair, Thomas B; Phillips, Emily; Powers, Linda S; Monick, Martha M

2014-03-26

Vitamin D deficiency has been implicated as a factor in a number of infectious and inflammatory lung diseases. In the lung, alveolar macrophages play a key role in inflammation and defense of infection, but there are little data exploring the immunomodulatory effects of vitamin D on innate lung immunity in humans. The objective of this study was to determine the effects of vitamin D supplementation on gene expression of alveolar macrophages. We performed a parallel, double-blind, placebo-controlled, randomized trial to determine the effects of vitamin D on alveolar macrophage gene expression. Vitamin D3 (1000 international units/day) or placebo was administered to adults for three months. Bronchoscopy was performed pre- and post-intervention to obtain alveolar macrophages. Messenger RNA was isolated from the macrophages and subjected to whole genome exon array analysis. The primary outcome was differential gene expression of the alveolar macrophage in response to vitamin D supplementation. Specific genes underwent validation by polymerase chain reaction methods. Fifty-eight subjects were randomized to vitamin D (n = 28) or placebo (n = 30). There was a marginal overall difference between treatment group and placebo group in the change of 25-hydroxyvitaminD levels (4.43 ng/ml vs. 0.2 ng/ml, p = 0.10). Whole genome exon array analysis revealed differential gene expression associated with change in serum vitamin D levels in the treated group. CCL8/MCP-2 was the top-regulated cytokine gene and was further validated. Although only a non-significant increased trend was seen in serum vitamin D levels, subjects treated with vitamin D supplementation had immune-related differential gene expression in alveolar macrophages. ClinicalTrials.org: NCT01967628.

New potential markers of in vitro tomato morphogenesis identified by mRNA differential display.

PubMed

Torelli, A; Soragni, E; Bolchi, A; Petrucco, S; Ottonello, S; Branca, C

1996-12-01

The identification of plant genes involved in early phases of in vitro morphogenesis can not only contribute to our understanding of the processes underlying growth regulator-controlled determination, but also provide novel markers for evaluating the outcome of in vitro regeneration experiments. To search for such genes and to monitor changes in gene expression accompanying in vitro regeneration, we have adapted the mRNA differential display technique to the comparative analysis of a model system of tomato cotyledons that can be driven selectively toward either shoot or callus formation by means of previously determined growth regulator supplementations. Hormone-independent transcriptional modulation (mainly down-regulation) has been found to be the most common event, indicating that a non-specific reprogramming of gene expression quantitatively predominates during the early phases of in vitro culture. However, cDNA fragments representative of genes that are either down-regulated or induced in a programme-specific manner could also be identified, and two of them (G35, G36) were further characterized. One of these cDNA fragments, G35, corresponds to an mRNA that is down-regulated much earlier in callus- (day 2) than in shoot-determined explants (day 6). The other, G36, identifies an mRNA that is transiently expressed in shoot-determined explants only, well before any macroscopic signs of differentiation become apparent, and thus exhibits typical features of a morphogenetic marker.

28 CFR 14.11 - Supplementing regulations.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Supplementing regulations. 14.11 Section... ACT § 14.11 Supplementing regulations. Each agency is authorized to issue regulations and establish procedures consistent with the regulations in this part. ...

28 CFR 14.11 - Supplementing regulations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Supplementing regulations. 14.11 Section... ACT § 14.11 Supplementing regulations. Each agency is authorized to issue regulations and establish procedures consistent with the regulations in this part. ...

75 FR 78619 - Defense Federal Acquisition Regulation Supplement; Technical Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-16

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76 FR 27274 - Defense Federal Acquisition Regulation Supplement; Technical Amendments

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-11

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Differentiation of Crataegus spp. guided by nuclear magnetic resonance spectrometry with chemometric analyses.

PubMed

Lund, Jensen A; Brown, Paula N; Shipley, Paul R

2017-09-01

For compliance with US Current Good Manufacturing Practice regulations for dietary supplements, manufacturers must provide identity of source plant material. Despite the popularity of hawthorn as a dietary supplement, relatively little is known about the comparative phytochemistry of different hawthorn species, and in particular North American hawthorns. The combination of NMR spectrometry with chemometric analyses offers an innovative approach to differentiating hawthorn species and exploring the phytochemistry. Two European and two North American species, harvested from a farm trial in late summer 2008, were analyzed by standard 1D 1 H and J-resolved (JRES) experiments. The data were preprocessed and modelled by principal component analysis (PCA). A supervised model was then generated by partial least squares-discriminant analysis (PLS-DA) for classification and evaluated by cross validation. Supervised random forests models were constructed from the dataset to explore the potential of machine learning for identification of unique patterns across species. 1D 1 H NMR data yielded increased differentiation over the JRES data. The random forests results correlated with PLS-DA results and outperformed PLS-DA in classification accuracy. In all of these analyses differentiation of the Crataegus spp. was best achieved by focusing on the NMR spectral region that contains signals unique to plant phenolic compounds. Identification of potentially significant metabolites for differentiation between species was approached using univariate techniques including significance analysis of microarrays and Kruskall-Wallis tests. Copyright © 2017 Elsevier Ltd. All rights reserved.

5 CFR 2634.103 - Executive agency supplemental regulations.

Code of Federal Regulations, 2010 CFR

2010-01-01

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5 CFR 610.306 - Supplemental regulations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Supplemental regulations. 610.306 Section 610.306 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS HOURS OF... regulations. Each agency is authorized to issue supplemental regulations not inconsistent with this subpart...

5 CFR 610.306 - Supplemental regulations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Supplemental regulations. 610.306 Section 610.306 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS HOURS OF... regulations. Each agency is authorized to issue supplemental regulations not inconsistent with this subpart...

Oral iron supplementation: Potential implications for the gut microbiome and metabolome in patients with CKD.

PubMed

Kortman, Guus A M; Reijnders, Dorien; Swinkels, Dorine W

2017-06-01

Patients with chronic kidney disease (CKD) and loss of kidney function are at increased risk for morbidity and mortality. The risks of CKD are attributed to "uremia," an increased concentration of uremic retention solutes (toxins) in the plasma. Recently, a colo-renal axis became clearly apparent and uremia has been associated with an altered gut microbiome composition and metabolism. There is a high prevalence of anemia in patients with CKD, for which patients are often treated with oral or intravenous iron. Recent in vivo and in vitro studies have reported adverse effects of oral iron supplementation on the gut microbiota composition, gut metabolome, and intestinal health, which in turn may result in an increased production of uremic toxins. It may also affect circulating levels of other microbe-derived molecules, that can act as mediators of immune regulation. Changes in body iron levels have also been reported to exert subtle effects on host immune function by modulating immune cell proliferation and differentiation, and by directly regulating cytokine formation and antimicrobial immune effector mechanisms. Based on the foregoing it is conceivable that oral iron supplementation in iron deficient predialysis CKD patients adversely changes gut microbiota composition, the gut and systemic metabolome, and host immunity and infection. Future studies are needed to confirm these hypotheses and to assess whether, compared to IV iron supplementation, oral iron supplementation negatively impacts on morbidity of CKD, and whether these adverse effects depend on the iron bioavailability of the iron formulation to the microbiota. © 2017 International Society for Hemodialysis.

Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement

PubMed Central

Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A.

2014-01-01

Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2–24 hours post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16–24 hpf) produced retinal defects like those seen with ethanol exposure between 2–24 hpf. Significantly, during an ethanol-sensitive time window (16–24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects. PMID:25541501

Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement.

PubMed

Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A

2015-03-01

Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2-24 h post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16-24 hpf) produced retinal defects like those seen with ethanol exposure between 2 and 24 hpf. Significantly, during an ethanol-sensitive time window (16-24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects. Copyright © 2015 Elsevier Inc. All rights reserved.

In vitro differentiation of embryonic stem cells into hepatocytes induced by fibroblast growth factors and bone morphological protein-4.

PubMed

Zhou, Qing-Jun; Huang, Yan-Dan; Xiang, Li-Xin; Shao, Jian-Zhong; Zhou, Guo-Shun; Yao, Hang; Dai, Li-Cheng; Lu, Yong-Liang

2007-01-01

The feasibility of transforming embryonic endoderm into different cell types is tightly controlled by mesodermal and septum transversumal signalings during early embryonic development. Here, an induction protocol tracing embryonic liver development was designed, in which, three growth factors, acid fibroblast growth factor, basic fibroblast growth factor and bone morphological protein-4 that secreted from pre-cardiac mesoderm and septum transversum mesenchyme, respectively, were employed to investigate their specific potency of modulating the mature hepatocyte proportion during the differentiation process. Results showed that hepatic differentiation took place spontaneously at a low level, however, supplements of the three growth factors gave rise to a significant up-regulation of mature hepatocytes. Bone morphological protein-4 highlighted the differentiation ratio to 40-55%, showing the most effective promotion, and also exhibited a synergistic effect with the other two fibroblast factors, whereas no similar phenomenon was observed between the other two factors, which was reported for the first time. Our study not only provides a high-performance system of embryonic stem cells differentiating into hepatocytes, which would supply a sufficient hepatic population for related studies, but also make it clear of the inductive effects of three important growth factors, which could support for further investigation on the mechanisms of mesodermal and septumal derived signalings that regulate hepatic differentiation.

Antioxidant nutrient intake and supplements as potential moderators of cognitive decline and cardiovascular disease in obstructive sleep apnea.

PubMed

Baldwin, Carol M; Bootzin, Richard R; Schwenke, Dawn C; Quan, Stuart F

2005-12-01

Cognitive deficits and cardiovascular disease (CVD) are comorbid conditions frequently associated with obstructive sleep apnea (OSA). Oxygen free radical release and its differential regulation of cytokine synthesis and immune modulation resulting from OSA-related hypoxic events have been hypothesized as the underlying mechanism(s) for the cognitive deficits and CVD in OSA. A number of studies have suggested that increased levels of oxidative stress and/or antioxidant deficiencies may also be risk factors in cognitive decline and CVD. The influence of antioxidant nutrients and supplements, such as Vitamins B6, B12, C, E, folic acid, alpha-lipoic acid and Coenzyme Q(10) on cognitive decline and CVD have been investigated. The influence of antioxidant nutrients or supplements on OSA remains to be investigated. Even if dietary or supplemental antioxidants do not prove to be effective therapies for OSA, dietary assessment and prescription to increase dietary intake of neuro- and cardio-protective nutrients may make it possible to reduce some of the cognitive and cardiovascular sequelae associated with OSA.

MicroRNA-Mediated Down-Regulation of M-CSF Receptor Contributes to Maturation of Mouse Monocyte-Derived Dendritic Cells

PubMed Central

Riepsaame, Joey; van Oudenaren, Adri; den Broeder, Berlinda J. H.; van IJcken, Wilfred F. J.; Pothof, Joris; Leenen, Pieter J. M.

2013-01-01

Dendritic cell (DC) maturation is a tightly regulated process that requires coordinated and timed developmental cues. Here we investigate whether microRNAs are involved in this process. We identify microRNAs in mouse GM-CSF-generated, monocyte-related DC (GM-DC) that are differentially expressed during both spontaneous and LPS-induced maturation and characterize M-CSF receptor (M-CSFR), encoded by the Csf1r gene, as a key target for microRNA-mediated regulation in the final step toward mature DC. MicroRNA-22, -34a, and -155 are up-regulated in mature MHCIIhi CD86hi DC and mediate Csf1r mRNA and protein down-regulation. Experimental inhibition of Csf1r-targeting microRNAs in vitro results not only in sustained high level M-CSFR protein expression but also in impaired DC maturation upon stimulation by LPS. Accordingly, over-expression of Csf1r in GM-DC inhibits terminal differentiation. Taken together, these results show that developmentally regulated microRNAs control Csf1r expression, supplementing previously identified mechanisms that regulate its transcription and protein surface expression. Furthermore, our data indicate a novel function for Csf1r in mouse monocyte-derived DC, showing that down-regulation of M-CSFR expression is essential for final DC maturation. PMID:24198819

48 CFR 1801.105-2 - Arrangement of regulations. (NASA supplements paragraph (b))

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Arrangement of regulations. (NASA supplements paragraph (b)) 1801.105-2 Section 1801.105-2 Federal Acquisition Regulations System..., Authority, Issuance 1801.105-2 Arrangement of regulations. (NASA supplements paragraph (b)) (b)(1)(A...

48 CFR 1801.105-2 - Arrangement of regulations. (NASA supplements paragraph (b))

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Arrangement of regulations. (NASA supplements paragraph (b)) 1801.105-2 Section 1801.105-2 Federal Acquisition Regulations System..., Authority, Issuance 1801.105-2 Arrangement of regulations. (NASA supplements paragraph (b)) (b)(1)(A...

48 CFR 1801.105-2 - Arrangement of regulations. (NASA supplements paragraph (b))

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Arrangement of regulations. (NASA supplements paragraph (b)) 1801.105-2 Section 1801.105-2 Federal Acquisition Regulations System..., Authority, Issuance 1801.105-2 Arrangement of regulations. (NASA supplements paragraph (b)) (b)(1)(A...

48 CFR 1801.105-2 - Arrangement of regulations. (NASA supplements paragraph (b))

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Arrangement of regulations. (NASA supplements paragraph (b)) 1801.105-2 Section 1801.105-2 Federal Acquisition Regulations System..., Authority, Issuance 1801.105-2 Arrangement of regulations. (NASA supplements paragraph (b)) (b)(1)(A...

48 CFR 1801.105-2 - Arrangement of regulations. (NASA supplements paragraph (b))

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Arrangement of regulations. (NASA supplements paragraph (b)) 1801.105-2 Section 1801.105-2 Federal Acquisition Regulations System..., Authority, Issuance 1801.105-2 Arrangement of regulations. (NASA supplements paragraph (b)) (b)(1)(A...

Human umbilical cord blood serum promotes growth, proliferation, as well as differentiation of human bone marrow-derived progenitor cells.

PubMed

Phadnis, Smruti M; Joglekar, Mugdha V; Venkateshan, Vijayalakshmi; Ghaskadbi, Surendra M; Hardikar, Anandwardhan A; Bhonde, Ramesh R

2006-01-01

Fetal calf serum (FCS) is conventionally used for animal cell cultures due to its inherent growth-promoting activities. However animal welfare issues and stringent requirements for human transplantation studies demand a suitable alternative for FCS. With this view, we studied the effect of FCS, human AB serum (ABS), and human umbilical cord blood serum (UCBS) on murine islets of Langerhans and human bone marrow-derived mesenchymal-like cells (hBMCs). We found that there was no difference in morphology and functionality of mouse islets cultured in any of these three different serum supplements as indicated by insulin immunostaining. A comparative analysis of hBMCs maintained in each of these three different serum supplements demonstrated that UCBS supplemented media better supported proliferation of hBMCs. Moreover, a modification of adipogenic differentiation protocol using UCBS indicates that it can be used as a supplement to support differentiation of hBMCs into adipocytes. Our results demonstrate that UCBS not only is suitable for maintenance of murine pancreatic islets, but also supports attachment, propagation, and differentiation of hBMCs in vitro. We conclude that UCBS can serve as a better serum supplement for growth, maintenance, and differentiation of hBMCs, making it a more suitable supplement in cell systems that have therapeutic potential in human transplantation programs.

76 FR 53886 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Special...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-30

...; Defense Federal Acquisition Regulation Supplement; Special Contracting Methods AGENCY: Defense Acquisition...-0214, using any of the following methods: [cir] Regulations.gov : http://www.regulations.gov . Follow... Supplement (DFARS) Part 217, Special Contracting Methods, and related provisions and clauses at DFARS 252.217...

Dietary supplementation with vitamin k affects transcriptome and proteome of Senegalese sole, improving larval performance and quality.

PubMed

Richard, Nadège; Fernández, Ignacio; Wulff, Tune; Hamre, Kristin; Cancela, Leonor; Conceição, Luis E C; Gavaia, Paulo J

2014-10-01

Nutritional factors strongly influence fish larval development and skeletogenesis, and may induce skeletal deformities. Vitamin K (VK) has been largely disregarded in aquaculture nutrition, despite its important roles in bone metabolism, in γ-carboxylation of Gla proteins, and in regulating gene expression through the pregnane X receptor (Pxr). Since the mechanisms mediating VK effects over skeletal development are poorly known, we investigated the effects of VK-supplementation on skeletal development in Senegalese sole larvae, aiming to identify molecular pathways involved. Larvae were fed live preys enriched with graded levels of phylloquinone (PK) (0, 50, and 250 mg kg(-1)) and survival rate, growth, VK contents, calcium content and incidence of skeletal deformities were determined, revealing an improvement of larval performance and decreasing the incidence of deformities in VK-supplemented groups. Comparative proteome analysis revealed a number of differentially expressed proteins between Control and Diet 250 associated with key biological processes including skin, muscle, and bone development. Expression analysis showed that genes encoding proteins related to the VK cycle (ggcx, vkor), VK nuclear receptor (pxr), and VK-dependent proteins (VKDPs; oc1 and grp), were differentially expressed. This study highlights the potential benefits of increasing dietary VK levels in larval diets, and brings new insights on the mechanisms mediating the positive effects observed on larval performance and skeletal development.

77 FR 2680 - Defense Federal Acquisition Regulation Supplement; Definition of Cost or Pricing Data

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-19

... Regulation Supplement; Definition of Cost or Pricing Data AGENCY: Defense Acquisition Regulations System... Acquisition Regulation Supplement (DFARS) to update text addressing the definition of cost or pricing data... update the DFARS for consistency with FAR changes addressing the definition of cost or pricing data...

76 FR 71468 - Defense Federal Acquisition Regulation Supplement: Accelerate Small Business Payments (DFARS Case...

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2011-11-18

... all small business concerns. In combination with the change to the regulations, DoD immediately began... Federal Acquisition Regulation Supplement: Accelerate Small Business Payments (DFARS Case 2011-D008... Regulation Supplement to accelerate payments to all small business concerns. DATES: Effective Date: November...

75 FR 6819 - Defense Federal Acquisition Regulation Supplement; Limitation on Procurements on Behalf of DoD

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-11

... follows: 1. Compliance With Financial Management Regulations Comment: Public Law 110-181 states that the...] RIN 0750-AG24 Defense Federal Acquisition Regulation Supplement; Limitation on Procurements on Behalf... Acquisition Regulation Supplement (DFARS) to address statutory provisions relating to interagency procurements...

Postnatal expression and androgen regulation of HOXBES2 homeoprotein in rat epididymis.

PubMed

Prabagaran, Esakki; Hegde, Uma C; Moodbidri, Sudhir B; Bandivdekar, Atmaram H; Raghavan, Vijaya P

2007-01-01

The multifunctional and androgen-regulated epididymis is known to provide a conducive microenvironment for the maturation and storage of mature spermatozoa. HOXB2 homeodomain-containing epididymis-specific sperm protein (HOXBES2), a molecule first reported by our group, exhibits cell- and region-specific expression. It was found in the cytoplasm of the principal epithelial cells with maximum in the distal segments of the rat epididymis. The present study was undertaken to determine whether HOXBES2 expression is regulated by androgens and postnatal epididymal development. Toward this, the epididymis was disallowed access to circulating androgens either by chemical or biologic castration. In bilaterally orchidectomized animals, the levels of immunoreactive HOXBES2 declined to <5 % of those seen in sham-operated animals. Exogenous dihydrotestosterone (DHT) supplementation (250 microg/kg body weight) for 7 days restored the expression levels to >or= 90 % of that observed in intact animals. Ethylene dimethane sulfonate (EDS) administration completely abolished HOXBES2 expression in the epididymis, and supplementation with DHT or DHT + estradiol for 10 days re-established HOXBES2 expression to near normalcy. However, in the estradiol alone-supplemented EDS-treated group, HOXBES2 remained undetected. The unaltered HOXBES2 expression following efferent duct ligation suggested that HOXBES2 is not critically dependent on testicular factors. During postnatal development, protein expression in the epididymis begins to appear from day 40 and 50 and increased from day 60 onward, coinciding with the mature levels of circulating androgens and the well-differentiated epididymis. Thus, the data obtained from this study suggests that HOXBES2 expression could be regulated by androgens, and its expression level is closely associated with the postnatal development of the epididymis.

Trivalent Chromium Supplementation Ameliorates Oleic Acid-Induced Hepatic Steatosis in Mice.

PubMed

Wang, Song; Wang, Jian; Liu, Yajing; Li, Hui; Wang, Qiao; Huang, Zhiwei; Liu, Wenbin; Shi, Ping

2018-05-24

Trivalent chromium [Cr(III)] is recognized as an essential trace element for human health, whereas its effect on hepatic lipid metabolism has not yet been fully understood. This study aimed to investigate the beneficial effects and potential mechanisms of Cr(III) on hepatic steatosis in an oleic acid (OA) induced mice model. Mice were fed with high OA for 12 weeks to induce lipid accumulation, and co-administrated with Cr(III) supplementation. Indexes of liver lipid accumulation, associated lipid genes expression, fatty acids (FAs) profile and inflammatory cytokines were analyzed. The data showed that Cr(III) supplementation could attenuate disease progress of hepatic steatosis and protect liver from high OA. After Cr(III) supplementation, elevated body weight and liver injury in steatosis mice were reversed, excessive lipid accumulation and FAs were also reduced. The up-regulation of cluster of differentiation 36 (CD36) and diacylglycerol acyltransferase 2 (DGAT2) following steatosis induction were inhibited by Cr(III). Cr(III) reduced the content of pro-inflammatory cytokines (IL-1β and TNF-α, IL-12) and restored the level of anti-inflammatory cytokine (IL-10) to the control values. Our results suggest that Cr(III) supplementation is a novel strategy for alleviating OA-induced hepatic steatosis.

Characterization of keratinocyte differentiation induced by ascorbic acid: protein kinase C involvement and vitamin C homeostasis.

PubMed

Savini, Isabella; Catani, Maria Valeria; Rossi, Antonello; Duranti, Guglielmo; Melino, Gerry; Avigliano, Luciana

2002-02-01

Epidermal keratinocytes undergo differentiation in response to several stimuli to form the cornified envelope, a structure that contributes to the barrier function of skin. Although differentiation has been extensively analyzed, the precise role of vitamin C during this process is still not defined. Ascorbic acid, besides acting as a radical scavenger, has been shown to promote mesenchymal differentiation. In this study, we found that keratinocytes grown in ascorbate-supplemented medium developed a differentiated phenotype, as demonstrated by enhanced expression of marker genes and increase in cornified envelope content. The pro-differentiating effects of ascorbate were mediated by the protein-kinase-C-dependent induction of activating protein 1 DNA binding activity; indeed, down-modulation of protein kinase C activity abolished differentiation triggered by ascorbic acid. Although vitamin C appeared to regulate the same signaling pathway modulated by calcium, a classical in vitro inducer of epidermal differentiation, nonetheless terminally differentiated keratinocytes exhibited different ascorbate homeostasis and cellular antioxidant status. Indeed, we found that, unlike calcium, differentiation promoted by ascorbate was accompanied by (i) an enhanced ascorbate transport, due to overexpression of specific transporters, (ii) a great efficiency of dehydroascorbate uptake, and (iii) an increase in glutathione content with respect to proliferating cells. Ascorbic acid may be useful to promote epidermal differentiation, avoiding depletion of hydrophilic antioxidant stores.

75 FR 45104 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-02

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System [OMB Control Number 0704-0225] Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Administrative Matters... Supplement (DFARS) Part 204, Administrative Matters, and related clauses at DFARS 252.204; DD Form 2051...

Mechanisms Behind Pyrroloquinoline Quinone Supplementation on Skeletal Muscle Mitochondrial Biogenesis: Possible Synergistic Effects with Exercise.

PubMed

Hwang, Paul; Willoughby, Darryn S

2018-05-01

There is clear evidence that endurance exercise training elicits intramuscular adaptations that can lead to elevations in mitochondrial biogenesis, oxidative capacity, mitochondrial density, and mitochondrial function. Mitochondrial biogenesis is regulated by the activation of the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha. This master regulator of mitochondrial biogenesis activates nuclear respiratory factors (NRF-1, NRF-2) and mitochondrial transcription factor A, which enables the expansion of mitochondrial size and transcription of mitochondrial DNA. Pyrroloquinoline quinone (PQQ) has been identified as a novel supplement that is involved in various physiological processes such as redox modulation, cellular energy metabolism, and mitochondrial biogenesis and is a potent antioxidant. Since both exercise and supplemental PQQ have mechanisms associated with mitochondrial biogenesis, it is plausible that a differential additive ergogenic benefit with PQQ can ensue. However, there is a major paucity of research exploring the role of PQQ in conjunction with exercise. In this respect, the purpose of the critical literature review will be to present a comprehensive overview of PQQ and the proposed mechanisms underlying mitochondrial biogenesis. Because exercise can instigate the molecular responses indicative of mitochondrial biogenesis, it is plausible that PQQ and exercise may instigate a synergistic response. Key teaching points • Endurance exercise training enables skeletal muscle adaptations that can induce increases in mitochondrial biogenesis, improve oxidative capacity, mitochondrial density, and mitochondrial function. • Pyrroloquinoline quinone (PQQ) has been identified as a novel supplement that is involved in physiological processes including redox modulation, cellular energy metabolism, mitochondrial biogenesis, and antioxidant potential. • There is emerging evidence to support that PQQ supplementation can upregulate the molecular signaling responses indicative of mitochondrial biogenesis within skeletal muscle. • If both endurance exercise and PQQ supplementation can elicit increases in the molecular responses indicative of mitochondrial biogenesis, it is possible that both PQQ and exercise may instigate a synergistic ergogenic response. • There is a scarcity of research exploring the possible role of PQQ supplementation with concomitant endurance exercise. Therefore, future research is necessary to investigate the ergogenic potential behind PQQ supplementation in conjunction with endurance exercise.

Effect of three lactobacilli with strain-specific activities on the growth performance, faecal microbiota and ileum mucosa proteomics of piglets.

PubMed

Su, Yating; Chen, Xingjie; Liu, Ming; Guo, Xiaohua

2017-01-01

The beneficial effects of Lactobacillus probiotics in animal production are often strain-related. Different strains from the same species may exert different weight-gain effect on hosts in vivo. Most lactobacilli are selected based on their in vitro activities, and their metabolism and regulation on the intestine based on strain-related characters are largely unexplored. The objective of the present study was to study the in vivo effects of the three lactobacilli on growth performance and to compare the differential effects of the strains on the faecal microbiota and ileum mucosa proteomics of piglets. Three hundred and sixty piglets were assigned to one of four treatments, which included an antibiotics-treated control and three experimental groups supplemented with the three lactobacilli, L. salivarius G1-1, L. reuteri G8-5 and L. reuteri G22-2, respectively. Piglets were weighed and the feed intake was recorded to compare the growth performance. The faecal lactobacilli and coliform was quantified using quantitative PCR and the faecal microbiota was profiled by denaturing gradient gel electrophoresis (DGGE). The proteomic approach was applied to compare the differential expression of proteins in the ileum mucosa. No statistical difference was found among the three Lactobacillus -treated groups in animal growth performance compared with the antibiotics-treated group ( P  > 0.05). Supplementation of lactobacilli in diets significantly increased the relative 16S rRNA gene copies of Lactobacillus genus on both d 14 and d 28 ( P  < 0.05)., and the bacterial community profiles based on DGGE from the lactobacilli-treated groups were distinctly different from the antibiotics-treated group ( P  < 0.05). The ileum mucosa of piglets responded to all Lactobacillus supplementation by producing more newly expressed proteins and the identified proteins were all associated with the functions beneficial for stabilization of cell structure. Besides, some other up-regulated and down-regulated proteins in different Lactobacillus -treated groups showed the expression of proteins were partly strain-related. All the three lactobacilli in this study show comparable effects to antibiotics on piglets growth performance. The three lactobacilli were found able to modify intestinal microbiota and mucosa proteomics. The regulation of protein expression in the intestinal mucosa are partly associated with the strains administrated in feed.

Acetate supplementation induces growth arrest of NG2/PDGFRα-positive oligodendroglioma-derived tumor-initiating cells.

PubMed

Long, Patrick M; Tighe, Scott W; Driscoll, Heather E; Moffett, John R; Namboodiri, Aryan M A; Viapiano, Mariano S; Lawler, Sean E; Jaworski, Diane M

2013-01-01

Cancer is associated with globally hypoacetylated chromatin and considerable attention has recently been focused on epigenetic therapies. N-acetyl-L-aspartate (NAA), the primary storage form of acetate in the brain, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis to generate acetate and ultimately acetyl-Coenzyme A for histone acetylation, are reduced in oligodendroglioma. The short chain triglyceride glyceryl triacetate (GTA), which increases histone acetylation and inhibits histone deacetylase expression, has been safely used for acetate supplementation in Canavan disease, a leukodystrophy due to ASPA mutation. We demonstrate that GTA induces cytostatic G0 growth arrest of oligodendroglioma-derived cells in vitro, without affecting normal cells. Sodium acetate, at doses comparable to that generated by complete GTA catalysis, but not glycerol also promoted growth arrest, whereas long chain triglycerides promoted cell growth. To begin to elucidate its mechanism of action, the effects of GTA on ASPA and acetyl-CoA synthetase protein levels and differentiation of established human oligodendroglioma cells (HOG and Hs683) and primary tumor-derived oligodendroglioma cells that exhibit some features of cancer stem cells (grade II OG33 and grade III OG35) relative to an oligodendrocyte progenitor line (Oli-Neu) were examined. The nuclear localization of ASPA and acetyl-CoA synthetase-1 in untreated cells was regulated during the cell cycle. GTA-mediated growth arrest was not associated with apoptosis or differentiation, but increased expression of acetylated proteins. Thus, GTA-mediated acetate supplementation may provide a safe, novel epigenetic therapy to reduce the growth of oligodendroglioma cells without affecting normal neural stem or oligodendrocyte progenitor cell proliferation or differentiation.

Acetate Supplementation Induces Growth Arrest of NG2/PDGFRα-Positive Oligodendroglioma-Derived Tumor-Initiating Cells

PubMed Central

Long, Patrick M.; Tighe, Scott W.; Driscoll, Heather E.; Moffett, John R.; Namboodiri, Aryan M. A.; Viapiano, Mariano S.; Lawler, Sean E.; Jaworski, Diane M.

2013-01-01

Cancer is associated with globally hypoacetylated chromatin and considerable attention has recently been focused on epigenetic therapies. N-acetyl-L-aspartate (NAA), the primary storage form of acetate in the brain, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis to generate acetate and ultimately acetyl-Coenzyme A for histone acetylation, are reduced in oligodendroglioma. The short chain triglyceride glyceryl triacetate (GTA), which increases histone acetylation and inhibits histone deacetylase expression, has been safely used for acetate supplementation in Canavan disease, a leukodystrophy due to ASPA mutation. We demonstrate that GTA induces cytostatic G0 growth arrest of oligodendroglioma-derived cells in vitro, without affecting normal cells. Sodium acetate, at doses comparable to that generated by complete GTA catalysis, but not glycerol also promoted growth arrest, whereas long chain triglycerides promoted cell growth. To begin to elucidate its mechanism of action, the effects of GTA on ASPA and acetyl-CoA synthetase protein levels and differentiation of established human oligodendroglioma cells (HOG and Hs683) and primary tumor-derived oligodendroglioma cells that exhibit some features of cancer stem cells (grade II OG33 and grade III OG35) relative to an oligodendrocyte progenitor line (Oli-Neu) were examined. The nuclear localization of ASPA and acetyl-CoA synthetase-1 in untreated cells was regulated during the cell cycle. GTA-mediated growth arrest was not associated with apoptosis or differentiation, but increased expression of acetylated proteins. Thus, GTA-mediated acetate supplementation may provide a safe, novel epigenetic therapy to reduce the growth of oligodendroglioma cells without affecting normal neural stem or oligodendrocyte progenitor cell proliferation or differentiation. PMID:24278309

Zinc Up-Regulates Insulin Secretion from β Cell-Like Cells Derived from Stem Cells from Human Exfoliated Deciduous Tooth (SHED).

PubMed

Kim, Gyuyoup; Shin, Ki-Hyuk; Pae, Eung-Kwon

2016-12-13

Stem cells from human exfoliated deciduous tooth (SHED) offer several advantages over other stem cell sources. Using SHED, we examined the roles of zinc and the zinc uptake transporter ZIP8 (Zrt- and irt-like protein 8) while inducing SHED into insulin secreting β cell-like stem cells (i.e., SHED-β cells). We observed that ZIP8 expression increased as SHED differentiated into SHED-β cells, and that zinc supplementation at day 10 increased the levels of most pancreatic β cell markers-particularly Insulin and glucose transporter 2 (GLUT2). We confirmed that SHED-β cells produce insulin successfully. In addition, we note that zinc supplementation significantly increases insulin secretion with a significant elevation of ZIP8 transporters in SHED-β cells. We conclude that SHED can be converted into insulin-secreting β cell-like cells as zinc concentration in the cytosol is elevated. Insulin production by SHED-β cells can be regulated via modulation of zinc concentration in the media as ZIP8 expression in the SHED-β cells increases.

Protein arginine methyltransferase 1 modulates innate immune responses through regulation of peroxisome proliferator-activated receptor γ-dependent macrophage differentiation.

PubMed

Tikhanovich, Irina; Zhao, Jie; Olson, Jody; Adams, Abby; Taylor, Ryan; Bridges, Brian; Marshall, Laurie; Roberts, Benjamin; Weinman, Steven A

2017-04-28

Arginine methylation is a common posttranslational modification that has been shown to regulate both gene expression and extranuclear signaling events. We recently reported defects in protein arginine methyltransferase 1 (PRMT1) activity and arginine methylation in the livers of cirrhosis patients with a history of recurrent infections. To examine the role of PRMT1 in innate immune responses in vivo , we created a cell type-specific knock-out mouse model. We showed that myeloid-specific PRMT1 knock-out mice demonstrate higher proinflammatory cytokine production and a lower survival rate after cecal ligation and puncture. We found that this defect is because of defective peroxisome proliferator-activated receptor γ (PPARγ)-dependent M2 macrophage differentiation. PPARγ is one of the key transcription factors regulating macrophage polarization toward a more anti-inflammatory and pro-resolving phenotype. We found that PRMT1 knock-out macrophages failed to up-regulate PPARγ expression in response to IL4 treatment resulting in 4-fold lower PPARγ expression in knock-out cells than in wild-type cells. Detailed study of the mechanism revealed that PRMT1 regulates PPARγ gene expression through histone H4R3me2a methylation at the PPARγ promoter. Supplementing with PPARγ agonists rosiglitazone and GW1929 was sufficient to restore M2 differentiation in vivo and in vitro and abrogated the difference in survival between wild-type and PRMT1 knock-out mice. Taken together these data suggest that PRMT1-dependent regulation of macrophage PPARγ expression contributes to the infection susceptibility in PRMT1 knock-out mice. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Effects of creatine and its analog, β-guanidinopropionic acid, on the differentiation of and nucleoli in myoblasts.

PubMed

Ohira, Yoshinobu; Matsuoka, Yoshikazu; Kawano, Fuminori; Ogura, Akihiko; Higo, Yoko; Ohira, Takashi; Terada, Masahiro; Oke, Yoshihiko; Nakai, Naoya

2011-01-01

The effects of supplementation with creatine (Cr) and its analog, β-guanidinopropionic acid (β-GPA), on the differentiation of myoblasts and the numbers of nucleoli were studied in C2C12 cells. The cells were cultured in differentiation medium for 4 d. Then Cr (1 mM) or β-GPA (1 mM) was added to the cells, and the mixture was cultured for an additional 2 d. Although the number of myotubes was not different among the groups, myotube diameters and nuclear numbers in myotubes were increased by Cr and β-GPA treatment respectively. The expression of differentiation marker proteins, myogenin, and the myosine heavy chain, was increased in the β-GPA group. Supplementation with β-GPA also increased the percentage of p21 (inhibitor for cell cycle progression)-positive myoblasts. Supplementation with Cr inhibited the decrease in nucleoli numbers, whereas β-GPA increased nucleolar sizes in the myotubes. These results suggest that β-GPA supplementation stimulated the differentiation of myoblasts into multi-nucleated myotubes through induction of p21 expression.

Paracrine control of vascularization and neurogenesis by neurotrophins.

PubMed

Emanueli, Costanza; Schratzberger, Peter; Kirchmair, Rudolf; Madeddu, Paolo

2003-10-01

The neuronal system plays a fundamental role in the maturation of primitive embryonic vascular network by providing a paracrine template for blood vessel branching and arterial differentiation. Furthermore, postnatal vascular and neural regeneration cooperate in the healing of damaged tissue. Neurogenesis continues in adulthood although confined to specific brain regions. Following ischaemic insult, neural staminal cells contribute towards the healing process through the stimulation of neurogenesis and vasculogenesis. Evidence indicates that nerves and blood vessels exert a reciprocal control of their own growth by paracrine mechanisms. For instance, guidance factors, including vascular endothelial growth factor A (VEGF-A) and semaphorins, which share the ability of binding neuropilin receptors, play a pivotal role in the tridimensional growth pattern of arterial vessels and nerves. Animal models and clinical studies have demonstrated a role of VEGF-A in the pathogenesis of ischaemic and diabetic neuropathies. Further, supplementation with VEGF-A ameliorates neuronal recovery by exerting protective effects on nerves and stimulating reparative neovascularization. Human tissue kallikrein, a recently discovered angiogenic and arteriogenic factor, accelerates neuronal recovery by stimulating the growth of vasa nervorum. Conversely, the neurotrophin nerve growth factor, known to regulate neuronal survival and differentiation, is now regarded as a stimulator of angiogenesis and arteriogenesis. These results indicate that angiogenesis and neurogenesis are paracrinally regulated by growth factors released by endothelial cells and neurons. Supplementation of these growth factors, alone or in combination, could benefit the treatment of ischaemic diseases and neuropathies.

75 FR 41161 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Part 251...

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Synthesis, characterization, and in-vitro cytocompatibility of amorphous β-tri-calcium magnesium phosphate ceramics.

PubMed

Singh, Satish S; Roy, Abhijit; Lee, Boeun; Banerjee, Ipsita; Kumta, Prashant N

2016-10-01

Biphasic mixtures of crystalline β-tricalcium magnesium phosphate (β-TCMP) and an amorphous calcium magnesium phosphate have been synthesized and reported to support enhanced hMSC differentiation in comparison to β-tricalcium phosphate (β-TCP) due to the release of increased amounts of bioactive ions. In the current study, completely amorphous β-TCMP has been synthesized which is capable of releasing increased amounts of Mg(2+) and PO4(3-) ions, rather than a biphasic mixture as earlier reported. The amorphous phase formed was observed to crystallize between temperatures of 400-600°C. The scaffolds prepared with amorphous β-TCMP were capable of supporting enhanced hMSC proliferation and differentiation in comparison to commercially available β-TCP. However, a similar gene expression of mature osteoblast markers, OCN and COL-1, in comparison to biphasic β-TCMP was observed. To further study the role of Mg(2+) and PO4(3-) ions in regulating hMSC osteogenic differentiation, the capability of hMSCs to mineralize in growth media supplemented with Mg(2+) and PO4(3-) ions was studied. Interestingly, 5mM PO4(3-) supported mineralization while the addition of 5mM Mg(2+) to 5mM PO4(3-) inhibited mineralization. It was therefore concluded that the release of Ca(2+) ions from β-TCMP scaffolds also plays a role in regulating osteogenic differentiation on these scaffolds and it is noted that further work is required to more accurately determine the exact role of Mg(2+) in regulating hMSC osteogenic differentiation. Copyright © 2016 Elsevier B.V. All rights reserved.

Platelet lysate induces chondrogenic differentiation of umbilical cord-derived mesenchymal stem cells.

PubMed

Hassan, Ghmkin; Bahjat, Mohammad; Kasem, Issam; Soukkarieh, Chadi; Aljamali, Majd

2018-01-01

Articular cartilage has a poor capacity for self-repair, and thus still presents a major challenge in orthopedics. Mesenchymal stem cells (MSCs) are multipotent stem cells with the potential to differentiate into chondrocytes in the presence of transforming growth factor beta (TGF-β). Platelet lysate (PL) contains a relatively large number of growth factors, including TGF-β, and has been shown to ameliorate cartilage repair. Here, we investigated the ability of PL to direct chondrogenic differentiation of MSCs along with other standard differentiation components in a pellet culture system. We isolated and expanded MSCs from human umbilical cords using a PL-supplemented medium and characterized the cells based on immunophenotype and potential for differentiation to adipocytes and osteocytes. We further cultured MSCs as pellets in a chondrogenic-differentiation medium supplemented with PL. After 21 days, the pellets were processed for histological analysis and stained with alician blue and acridine orange. The expression of SOX9 was investigated using RT-PCR. MSCs maintained their stemness characteristics in the PL-supplemented medium. However, the distribution of cells in the pellets cultured in the PL-supplemented chondrogenic differentiation medium had a greater similarity to cartilage tissue-derived chondrocytes than to the negative control. The intense alician blue staining indicated an increased production of mucopolysaccharides in the differentiated pellets, which also showed elevated expression of SOX9 . Our data suggest that MSCs could be differentiated to chondrocytes in the presence of PL and absence of exogenous TGF-β. Further research needs to be conducted to understand the exact role and potential of PL in chondrogenic differentiation and chondrocyte regeneration.

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Human pancreatic islet-derived extracellular vesicles modulate insulin expression in 3D-differentiating iPSC clusters

PubMed Central

Andersson, Eva-Marie; Heath, Nikki; Persson-kry, Anette; Collins, Richard; Hicks, Ryan; Dekker, Niek; Forslöw, Anna

2017-01-01

It has been suggested that extracellular vesicles (EVs) can mediate crosstalk between hormones and metabolites within pancreatic tissue. However, the possible effect of pancreatic EVs on stem cell differentiation into pancreatic lineages remains unknown. Herein, human islet-derived EVs (h-Islet-EVs) were isolated, characterized and subsequently added to human induced pluripotent stem cell (iPSC) clusters during pancreatic differentiation. The h-islet-EVs had a mean size of 117±7 nm and showed positive expression of CD63 and CD81 EV markers as measured by ELISA. The presence of key pancreatic transcription factor mRNA, such as NGN3, MAFA and PDX1, and pancreatic hormone proteins such as C-peptide and glucagon, were confirmed in h-Islet-EVs. iPSC clusters were differentiated in suspension and at the end stages of the differentiation protocol, the mRNA expression of the main pancreatic transcription factors and pancreatic hormones was increased. H-Islet-EVs were supplemented to the iPSC clusters in the later stages of differentiation. It was observed that h-Islet-EVs were able to up-regulate the intracellular levels of C-peptide in iPSC clusters in a concentration-dependent manner. The effect of h-Islet-EVs on the differentiation of iPSC clusters cultured in 3D-collagen hydrogels was also assessed. Although increased mRNA expression for pancreatic markers was observed when culturing the iPSC clusters in 3D-collagen hydrogels, delivery of EVs did not affect the insulin or C-peptide intracellular content. Our results provide new information on the role of h-Islet-EVs in the regulation of insulin expression in differentiating iPSC clusters, and are highly relevant for pancreatic tissue engineering applications. PMID:29117231

Role of geometrical cues in bone marrow-derived mesenchymal stem cell survival, growth and osteogenic differentiation.

PubMed

Gupta, Dhanak; Grant, David M; Zakir Hossain, Kazi M; Ahmed, Ifty; Sottile, Virginie

2018-02-01

Mesenchymal stem cells play a vital role in bone formation process by differentiating into osteoblasts, in a tissue that offers not a flat but a discontinuous three-dimensional (3D) topography in vivo. In order to understand how geometry may be affecting mesenchymal stem cells, this study explored the influence of 3D geometry on mesenchymal stem cell-fate by comparing cell growth, viability and osteogenic potential using monolayer (two-dimensional, 2D) with microsphere (3D) culture systems normalised to surface area. The results suggested lower cell viability and reduced cell growth in 3D. Alkaline phosphatase activity was higher in 3D; however, both collagen and mineral deposition appeared significantly lower in 3D, even after osteogenic supplementation. Also, there were signs of patchy mineralisation in 3D with or without osteogenic supplementation as early as day 7. These results suggest that the convex surfaces on microspheres and inter-particulate porosity may have led to variable cell morphology and fate within the 3D culture. This study provides deeper insights into geometrical regulation of mesenchymal stem cell responses applicable for bone tissue engineering.

Phenotypical and functional characteristics of mesenchymal stem cells from bone marrow: comparison of culture using different media supplemented with human platelet lysate or fetal bovine serum

PubMed Central

2012-01-01

Introduction Mesenchymal stem cells (MSCs) are multipotent cells able to differentiate into several mesenchymal lineages, classically derived from bone marrow (BM) but potentially from umbilical cord blood (UCB). Although they are becoming a good tool for regenerative medicine, they usually need to be expanded in fetal bovine serum (FBS)-supplemented media. Human platelet lysate (HPL) has recently been proposed as substitute for safety reasons, but it is not yet clear how this supplement influences the properties of expanded MSCs. Methods In the present study, we compared the effect of various media combining autologous HPL with or without FBS on phenotypic, proliferative and functional (differentiation, cytokine secretion profile) characteristics of human BM-derived MSCs. Results Despite less expression of adipogenic and osteogenic markers, MSCs cultured in HPL-supplemented media fully differentiated along osteoblastic, adipogenic, chondrogenic and vascular smooth muscle lineages. The analyses of particular specific proteins expressed during osteogenic differentiation (calcium-sensing receptor (CaSR) and parathormone receptor (PTHR)) showed their decrease at D0 before any induction for MSC cultured with HPL mostly at high percentage (10%HPL). The cytokine dosage showed a clear increase of proliferation capacity and interleukin (IL)-6 and IL-8 secretion. Conclusions This study shows that MSCs can be expanded in media supplemented with HPL that can totally replace FBS. HPL-supplemented media not only preserves their phenotype as well as their differentiation capacity, but also shortens culture time by increasing their growth rate. PMID:22333342

Altered gene expression of epigenetic modifying enzymes in response to dietary supplementation with linseed oil.

PubMed

Li, Ran; Ibeagha-Awemu, Eveline M

2017-05-01

Recently we showed that 5% linseed oil (LSO) and 5% safflower oil (SFO) supplementation of cow's diets reduced milk fat yield by 30·38 and 32·42% respectively, accompanied by differential expression of genes and regulation by microRNAs (miRNA). This research communication addresses the hypothesis that epigenetic regulation could be involved in the observed milk fat reduction. Thus, this study investigated the gene expression pattern of major epigenetic modifying enzymes in response to dietary supplementation with LSO or SFO. Twenty-six Canadian Holstein cows in mid lactation were randomly assigned to two groups (13/group) and fed a control diet for 28 d (day -28 to -1) (control period- CP) followed by a treatment period (TP) (control diet supplemented with 5% LSO (LSO treatment) or 5% SFO (SFO treatment) of 28 d (day +1 to +28). After treatment, cows in the two groups were returned to the control diet for another 28 d (day +29 to +56) (post treatment period-PTP). Milk samples were collected on day -1 (CP), +7, +28 (TP) and +56 (PTP) for RNA isolation and measurement of the expression of thirteen epigenetic modifying genes including two DNA methytrasferases (DNMT1, DNMT3A), four histone acetylases (HAT1, KAT2A, KAT5 and CREBBP), five histone deacetylases (HDAC1, HDAC2, HDAC3, SIRT1 and SIRT2) and two histone methytransferases (EHMT2 and PRMT1) by qPCR. Linseed oil supplementation significantly repressed the expression of EHMT2, HDAC2 and HDAC3 on day +7 (P < 0·05) and KAT2A and SIRT2 on day +28 (P < 0·05) as compared with the control period (day -1) while SFO had no effect. When LSO was withdrawn, the expression of some of the genes increased slightly but did not reach control (day -1) levels at the end of the PTP. Our study demonstrated a significant role of LSO in the epigenetic regulation of fatty acid synthesis as compared to SFO. The effect of LSO may be related to its higher degree of unsaturation and might represent a different regulatory mechanism which needs further investigation.

76 FR 36905 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Taxes

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Flavonoid supplementation affects the expression of genes involved in cell wall formation and lignification metabolism and increases sugar content and saccharification in the fast-growing eucalyptus hybrid E. urophylla x E. grandis.

PubMed

Lepikson-Neto, Jorge; Nascimento, Leandro C; Salazar, Marcela M; Camargo, Eduardo L O; Cairo, João P F; Teixeira, Paulo J; Marques, Wesley L; Squina, Fabio M; Mieczkowski, Piotr; Deckmann, Ana C; Pereira, Gonçalo A G

2014-11-19

Eucalyptus species are the most widely planted hardwood species in the world and are renowned for their rapid growth and adaptability. In Brazil, one of the most widely grown Eucalyptus cultivars is the fast-growing Eucalyptus urophylla x Eucalyptus grandis hybrid. In a previous study, we described a chemical characterization of these hybrids when subjected to flavonoid supplementation on 2 distinct timetables, and our results revealed marked differences between the wood composition of the treated and untreated trees. In this work, we report the transcriptional responses occurring in these trees that may be related to the observed chemical differences. Gene expression was analysed through mRNA-sequencing, and notably, compared to control trees, the treated trees display differential down-regulation of cell wall formation pathways such as phenylpropanoid metabolism as well as differential expression of genes involved in sucrose, starch and minor CHO metabolism and genes that play a role in several stress and environmental responses. We also performed enzymatic hydrolysis of wood samples from the different treatments, and the results indicated higher sugar contents and glucose yields in the flavonoid-treated plants. Our results further illustrate the potential use of flavonoids as a nutritional complement for modifying Eucalyptus wood, since, supplementation with flavonoids alters its chemical composition, gene expression and increases saccharification probably as part of a stress response.

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Stimulation of GABA-Induced Ca2+ Influx Enhances Maturation of Human Induced Pluripotent Stem Cell-Derived Neurons

PubMed Central

Rushton, David J.; Mattis, Virginia B.; Svendsen, Clive N.; Allen, Nicholas D.; Kemp, Paul J.

2013-01-01

Optimal use of patient-derived, induced pluripotent stem cells for modeling neuronal diseases is crucially dependent upon the proper physiological maturation of derived neurons. As a strategy to develop defined differentiation protocols that optimize electrophysiological function, we investigated the role of Ca2+ channel regulation by astrocyte conditioned medium in neuronal maturation, using whole-cell patch clamp and Ca2+ imaging. Standard control medium supported basic differentiation of induced pluripotent stem cell-derived neurons, as assayed by the ability to fire simple, single, induced action potentials. In contrast, treatment with astrocyte conditioned medium elicited complex and spontaneous neuronal activity, often with rhythmic and biphasic characteristics. Such augmented spontaneous activity correlated with astrocyte conditioned medium-evoked hyperpolarization and was dependent upon regulated function of L-, N- and R-type Ca2+ channels. The requirement for astrocyte conditioned medium could be substituted by simply supplementing control differentiation medium with high Ca2+ or γ-amino butyric acid (GABA). Importantly, even in the absence of GABA signalling, opening Ca2+ channels directly using Bay K8644 was able to hyperpolarise neurons and enhance excitability, producing fully functional neurons. These data provide mechanistic insight into how secreted astrocyte factors control differentiation and, importantly, suggest that pharmacological modulation of Ca2+ channel function leads to the development of a defined protocol for improved maturation of induced pluripotent stem cell-derived neurons. PMID:24278369

IFN-γ regulates human dental pulp stem cells behavior via NF-κB and MAPK signaling

PubMed Central

He, Xinyao; Jiang, Wenkai; Luo, Zhirong; Qu, Tiejun; Wang, Zhihua; Liu, Ningning; Zhang, Yaqing; Cooper, Paul R.; He, Wenxi

2017-01-01

During caries, dental pulp expresses a range of pro-inflammatory cytokines in response to the infectious challenge. Interferon gamma (IFN-γ) is a dimerized soluble cytokine, which is critical for immune responses. Previous study has demonstrated that IFN-γ at relative high concentration (100 ng/mL) treatment improved the impaired dentinogenic and immunosuppressive regulatory functions of disease-derived dental pulp stem cells (DPSCs). However, little is known about the regulatory effects of IFN-γ at relative low concentration on healthy DPSC behavior (including proliferation, migration, and multiple-potential differentiation). Here we demonstrate that IFN-γ at relatively low concentrations (0.5 ng/mL) promoted the proliferation and migration of DPSCs, but abrogated odonto/osteogenic differentiation. Additionally, we identified that NF-κB and MAPK signaling pathways are both involved in the process of IFN-γ-regulated odonto/osteogenic differentiation of DPSCs. DPSCs treated with IFN-γ and supplemented with pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor) or SB203580 (a MAPK inhibitor) showed significantly improved potential for odonto/osteogenic differentiation of DPSCs both in vivo and in vitro. These data provide important insight into the regulatory effects of IFN-γ on the biological behavior of DPSCs and indicate a promising therapeutic strategy for dentin/pulp tissue engineering in future endodontic treatment. PMID:28098169

Indole-3-Carbinol Promotes Goblet-Cell Differentiation Regulating Wnt and Notch Signaling Pathways AhR-Dependently.

PubMed

Park, Joo-Hung; Lee, Jeong-Min; Lee, Eun-Jin; Hwang, Won-Bhin; Kim, Da-Jeong

2018-04-30

Using an in vitro model of intestinal organoids derived from intestinal crypts, we examined effects of indole-3-carbinol (I3C), a phytochemical that has anticancer and aryl hydrocarbon receptor (AhR)-activating abilities and thus is sold as a dietary supplement, on the development of intestinal organoids and investigated the underlying mechanisms. I3C inhibited the in vitro development of mouse intestinal organoids. Addition of α-naphthoflavone, an AhR antagonist or AhR siRNA transfection, suppressed I3C function, suggesting that I3C-mediated interference with organoid development is AhR-dependent. I3C increased the expression of Muc2 and lysozyme, lineage-specific genes for goblet cells and Paneth cells, respectively, but inhibits the expression of IAP, a marker gene for enterocytes. In the intestines of mice treated with I3C, the number of goblet cells was reduced, but the number of Paneth cells and the depth and length of crypts and villi were not changed. I3C increased the level of active nonphosphorylated β-catenin, but suppressed the Notch signal. As a result, expression of Hes1, a Notch target gene and a transcriptional repressor that plays a key role in enterocyte differentiation, was reduced, whereas expression of Math1, involved in the differentiation of secretory lineages, was increased. These results provide direct evidence for the role of AhR in the regulation of the development of intestinal stem cells and indicate that such regulation is likely mediated by regulation of Wnt and Notch signals.

Influence of betaine and arginine supplementation of reduced protein diets on fatty acid composition and gene expression in the muscle and subcutaneous adipose tissue of cross-bred pigs.

PubMed

Madeira, Marta S; Rolo, Eva S; Alfaia, Cristina M; Pires, Virgínia R; Luxton, Richard; Doran, Olena; Bessa, Rui J B; Prates, José A M

2016-03-28

The isolated or combined effects of betaine and arginine supplementation of reduced protein diets (RPD) on fat content, fatty acid composition and mRNA levels of genes controlling lipid metabolism in pig m. longissimus lumborum and subcutaneous adipose tissue (SAT) were assessed. The experiment was performed on forty intact male pigs (Duroc×Large White×Landrace cross-breed) with initial and final live weights of 60 and 93 kg, respectively. Pigs were randomly assigned to one of the following five diets (n 8): 16·0 % of crude protein (control), 13·0 % of crude protein (RPD), RPD supplemented with 0·33 % of betaine, RPD supplemented with 1·5 % of arginine and RPD supplemented with 0·33 % of betaine and 1·5 % of arginine. Data confirmed that RPD increase intramuscular fat (IMF) content and total fat content in SAT. The increased total fat content in SAT was accompanied by higher GLUT type 4, lipoprotein lipase and stearoyl-CoA desaturase mRNA expression levels. In addition, the supplementation of RPD with betaine and/or arginine did not affect either IMF or total fat in SAT. However, dietary betaine supplementation slightly affected fatty acid composition in both muscle and SAT. This effect was associated with an increase of carnitine O-acetyltransferase mRNA levels in SAT but not in muscle, which suggests that betaine might be involved in the differential regulation of some key genes of lipid metabolism in pig muscle and SAT. Although the arginine-supplemented diet decreased the mRNA expression level of PPARG in muscle and SAT, it did not influence fat content or fatty acid composition in any of these pig tissues.

Supplemental and highly-elevated tocopherol doses differentially regulate allergic inflammation: reversibility of α-tocopherol and γ-tocopherol's effects

PubMed Central

McCary, Christine A.; Abdala-Valencia, Hiam; Berdnikovs, Sergejs; Cook-Mills, Joan M.

2011-01-01

We have reported that supplemental doses of the α- and γ-tocopherol isoforms of vitamin E decrease and increase, respectively, allergic lung inflammation. We have now assessed whether these effects of tocopherols are reversible. For these studies, mice were treated with antigen and supplemental tocopherols in a first phase of treatment followed by a 4 week clearance phase and then the mice received a second phase of antigen and tocopherol treatments. The pro-inflammatory effects of supplemental levels of γ-tocopherol in phase 1 were only partially reversed by supplemental α-tocopherol in phase 2 but were completely reversed by raising α-tocopherol levels 10-fold in phase 2. When γ-tocopherol levels were increased 10-fold (highly-elevated tocopherol) so that the lung tissue γ-tocopherol levels were equal to the lung tissue levels of supplemental α-tocopherol, γ-tocopherol reduced leukocyte numbers in the lung lavage fluid. In contrast to the lung lavage fluid, highly-elevated levels of γ-tocopherol increased inflammation in the lung tissue. These regulatory effects of highly-elevated tocopherols on tissue inflammation and lung lavage fluid were reversible in a second phase of antigen challenge without tocopherols. In summary, the pro-inflammatory effects of supplemental γ-tocopherol on lung inflammation were partially reversed by supplemental levels of α-tocopherol but were completely reversed by highly-elevated-levels of α-tocopherol. Also, highly-elevated levels of γ-tocopherol were inhibitory and reversible in lung lavage but, importantly, were pro-inflammatory in lung tissue sections. These results have implications for future studies with tocopherols and provide a new context in which to review vitamin E studies in the literature. PMID:21317387

Nutritional supplements and the EU: is anyone happy?

PubMed

Eberhardie, Christine

2007-11-01

In 2000 an estimated pound sterling 335 x 106 was spent on food supplements and herbal remedies in the UK. Until recently, The Trades Description Act 1968, the Food Safety Act 1990 and The Food Labelling Regulations 1996 (amended 2004) were the only form of regulation available to protect the public. The medical community has been concerned about the risk to patients of inaccurate dosages and poor-quality products as well as drug-nutrient and nutrient-nutrient interactions. Following growing concern about the type and quality of food supplements and herbal remedies available in the EU, the European Commission has published directives regulating food supplements (2002/46/EC) and herbal remedies (2004/24/EC and 2004/27/EC) available within the EU. The directives came into force in 2005 and limit the number and quality of permitted food supplements through the creation of a 'positive list' of approved supplements. In the present paper the new regulatory frameworks and the implications for the food supplement manufacturers, traditional and complementary therapists, the healthcare professions and patients will be examined. It would appear that there is considerable dissatisfaction with the regulations in their present form. Several questions remain: is regulation the answer; who decides which nutrients go on the positive list; what effect has the regulation had on patient safety and patient choice?

Twenty Years of the Dietary Supplement Health and Education Act--How Should Dietary Supplements Be Regulated?

PubMed

Wallace, Taylor C

2015-08-01

The Dietary Supplement Health and Education Act (DSHEA) of 1994 defines the FDA's statutory authority to regulate dietary supplement products in the United States. The dietary supplement industry has rapidly expanded since 1994, presenting an obvious need for "DSHEA 2.0." Current regulations surrounding dietary supplements have been increasingly and reasonably scrutinized, given their widespread use by over one-half of the US population as well as highly publicized safety concerns over the past 20 y. As the market continues to expand and evolve, so too must the laws that protect consumers from potential harm and misleading communication. This article is meant to begin a scientific dialogue on how regulations may be improved to provide both ease of access and safer products to the consumer by focusing on 4 topics: premarket approval, label claims, current Good Manufacturing Practices, and adverse event reporting. © 2015 American Society for Nutrition.

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Differential regulation of glutathione peroxidase by selenomethionine and hyperoxia in endothelial cells.

PubMed Central

Jornot, L; Junod, A F

1995-01-01

We have studied the effect of selenomethionine (SeMet) and hyperoxia on the expression of glutathione peroxidase (GP) in human umbilical vein endothelial cells. Incubation of HUVEC with 1 x 10(-6) M SeMet for 24 h and 48 h caused a 65% and 86% increase in GP activity respectively. The same treatment did not result in significant changes in GP gene transcription and mRNA levels. Pactamycin, a specific inhibitor of the initiation step of translation, prevented the rise in GP activity induced by SeMet and caused an increase in GP mRNA in both cells grown in normal and SeMet-supplemented medium. Interestingly, SeMet supplementation stimulated the recruitment of GP mRNA from an untranslatable pool on to polyribosomes, so that the concentration of GP mRNA in polyribosomal translatable pools was 50% higher in cells grown in SeMet-supplemented medium than in cells grown in normal medium. On the other hand, cells exposed to 95% O2 for 3 days in normal medium showed a 60%, 394% and 81% increase in GP gene transcription rate, mRNA levels and activity respectively. Hyperoxia also stabilized GP mRNA. Hyperoxic cells grown in SeMet-supplemented medium did not show any change in GP gene transcription and mRNA levels, but expressed an 81% and 100% increase in GP activity and amount of GP mRNA associated with polyribosomes respectively, when compared with hyperoxic cells maintained in normal medium. Thus, GP appeared to be regulated post-transcriptionally, most probably co-translationally, in response to selenium availability, and transcriptionally and post-transcriptionally in response to oxygen. Images Figure 1 Figure 2 Figure 4 Figure 7 Figure 8 PMID:7887914

The expression and activity of thioredoxin reductase 1 splice variants v1 and v2 regulate the expression of genes associated with differentiation and adhesion

PubMed Central

Nalvarte, Ivan; Damdimopoulos, Anastasios E.; Rüegg, Joëlle; Spyrou, Giannis

2015-01-01

The mammalian redox-active selenoprotein thioredoxin reductase (TrxR1) is a main player in redox homoeostasis. It transfers electrons from NADPH to a large variety of substrates, particularly to those containing redox-active cysteines. Previously, we reported that the classical form of cytosolic TrxR1 (TXNRD1_v1), when overexpressed in human embryonic kidney cells (HEK-293), prompted the cells to undergo differentiation [Nalvarte et al. (2004) J. Biol. Chem. 279, 54510–54517]. In the present study, we show that several genes associated with differentiation and adhesion are differentially expressed in HEK-293 cells stably overexpressing TXNRD1_v1 compared with cells expressing its splice variant TXNRD1_v2. Overexpression of these two splice forms resulted in distinctive effects on various aspects of cellular functions including gene regulation patterns, alteration of growth rate, migration and morphology and susceptibility to selenium-induced toxicity. Furthermore, differentiation of the neuroblastoma cell line SH-SY5Y induced by all-trans retinoic acid (ATRA) increased both TXNRD1_v1 and TXNRD1_v2 expressions along with several of the identified genes associated with differentiation and adhesion. Selenium supplementation in the SH-SY5Y cells also induced a differentiated morphology and changed expression of the adhesion protein fibronectin 1 and the differentiation marker cadherin 11, as well as different temporal expression of the studied TXNRD1 variants. These data suggest that both TXNRD1_v1 and TXNRD1_v2 have distinct roles in differentiation, possibly by altering the expression of the genes associated with differentiation, and further emphasize the importance in distinguishing each unique action of different TrxR1 splice forms, especially when studying the gene silencing or knockout of TrxR1. PMID:26464515

78 FR 67132 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Contract...

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7 CFR 2201.29 - Supplemental guarantees.

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48 CFR 1801.103 - Authority. (NASA supplements paragraph (a))

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2014-10-01

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48 CFR 1801.103 - Authority. (NASA supplements paragraph (a))

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... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Authority. (NASA supplements paragraph (a)) 1801.103 Section 1801.103 Federal Acquisition Regulations System NATIONAL..., Issuance 1801.103 Authority. (NASA supplements paragraph (a)) (a) Under the following authorities, the...

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7 CFR 1955.82 - State supplements.

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2010-01-01

... 7 Agriculture 14 2010-01-01 2009-01-01 true State supplements. 1955.82 Section 1955.82 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... REGULATIONS (CONTINUED) PROPERTY MANAGEMENT Management of Property § 1955.82 State supplements. State...

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2010-10-01

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48 CFR 1814.302 - Bid submission. (NASA supplements paragraph (b))

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2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Bid submission. (NASA supplements paragraph (b)) 1814.302 Section 1814.302 Federal Acquisition Regulations System NATIONAL... 1814.302 Bid submission. (NASA supplements paragraph (b)) (b) NASA contracting officers shall not...

Should states and local governments regulate dietary supplements?

PubMed

Starr, Ranjani

2016-01-01

Federal regulation of dietary supplements in the United States is governed by the Dietary Supplement Health and Education Act of 1994. The law has been criticized as weak and ineffective. Alarming research has emerged demonstrating that supplements may be mislabelled, contaminated, adulterated with dangerous or unknown compounds, or sold at toxic doses. As a result, the health community has raised concerns about the safety and quality of dietary supplements. Increased federal oversight is an important avenue for improving supplement safety; however, states and local governments may also pursue strategies to strengthen the overall regulatory control of dietary supplements. States and local governments have substantial experience in regulating other products that pose a risk to public health, such as tobacco. Additionally, much has been learned about the tactics the tobacco industry has employed to protect its interests. Lessons learned may be applied to new regulatory efforts aimed at improving the safety of dietary supplements at the state and local levels. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Long term betaine supplementation regulates genes involved in lipid and cholesterol metabolism of two muscles from an obese pig breed.

PubMed

Albuquerque, A; Neves, José A; Redondeiro, M; Laranjo, M; Félix, M R; Freitas, Amadeu; Tirapicos, José L; Martins, José M

2017-02-01

This study evaluates the effects of betaine supplementation (1gkg -1 for 20weeks) on the regulation of genes involved in lipid and cholesterol metabolism of Longissimus lumborum and Biceps femoris from obese Alentejano pigs. Betaine supplementation led to an increase in total cholesterol in both muscles, complementing results previously published indicating a significant increase on the intramuscular lipid content. The expression of twelve genes involved in lipogenesis, lipolysis/FA oxidation, FA transport, and cholesterol metabolism, as well as two transcription factors were also evaluated. Genes related to lipid and cholesterol synthesis plus FA transport were consistently up-regulated in both muscles of betaine fed pigs. On the other hand, genes related to lipolysis/FA oxidation were not affected or down-regulated by betaine supplementation. Our data suggest that the underlying mechanism regulating IMF and cholesterol accumulation in Alentejano pigs supplemented with betaine is associated with the up-regulation of genes involved in lipid synthesis, FA transport, and cholesterol synthesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effect of noncoherent red light irradiation on proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells.

PubMed

Peng, Fei; Wu, Hua; Zheng, Yadong; Xu, Xiqiang; Yu, Jizhe

2012-05-01

Mesenchymal stem cells (MSCs) are promising for use in regenerative medicine. Low-level light irradiation (LLLI) has been shown to modulate various processes in different biological systems. The aim of our study was to investigate the effect of red light emitted from a light-emitting diode (LED) on bone marrow MSCs with or without osteogenic supplements. MSCs both with and without osteogenic supplements were divided into four groups, and each group was irradiated at doses of 0, 1, 2 and 4 J/cm(2). Cellular proliferation was evaluated using WST-8 and 5-ethynyl-2'-deoxyuridine (EdU) fluorescence staining. The alkaline phosphatase activity, mineralization, and expression of osteoblast master genes (Col1α1, Alpl, Bglap and Runx2) were monitored as indicators of MSC differentiation towards osteoblasts. In groups without osteogenic supplements, red light at all doses significantly stimulated cellular proliferation, whereas the osteogenic phenotype of the MSCs was not enhanced. In groups with osteogenic supplements, red light increased alkaline phosphatase activity and mineralized nodule formation, and stimulated the expression of Bglap and Runx2, but decreased cellular proliferation. In conclusion, nonconherent red light can promote proliferation but cannot induce osteogenic differentiation of MSCs in normal media, while it enhances osteogenic differentiation and decreases proliferation of MSCs in media with osteogenic supplements.

75 FR 48278 - Defense Federal Acquisition Regulation Supplement; Excessive Pass-Through Charges

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... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 215, 231, and 252 [DFARS Case 2006-D057] Defense Federal Acquisition Regulation Supplement; Excessive Pass-Through Charges AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Final rule. SUMMARY...

77 FR 2653 - Defense Federal Acquisition Regulation Supplement; Pilot Program for Acquisition of Military...

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2012-01-19

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48 CFR 1480.102 - Buy Indian Act acquisition regulations.

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2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Buy Indian Act acquisition... INDIAN AFFAIRS SUPPLEMENT ACQUISITIONS UNDER THE BUY INDIAN ACT Subpart 1480.1 General 1480.102 Buy Indian Act acquisition regulations. (a) This part supplements Federal Acquisition Regulation (FAR) and...

48 CFR 1850.403-1 - Indemnification requests. (NASA supplements paragraph (a))

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2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Indemnification requests. (NASA supplements paragraph (a)) 1850.403-1 Section 1850.403-1 Federal Acquisition Regulations System... Residual Powers 1850.403-1 Indemnification requests. (NASA supplements paragraph (a)) (a) Contractor...

48 CFR 1819.708 - Contract clauses. (NASA supplements paragraph (b))

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2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Contract clauses. (NASA supplements paragraph (b)) 1819.708 Section 1819.708 Federal Acquisition Regulations System NATIONAL... Subcontracting Program 1819.708 Contract clauses. (NASA supplements paragraph (b)) (b)(1) The contracting officer...

48 CFR 1827.304-4 - Subcontracts. (NASA supplements paragraph (a))

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2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Subcontracts. (NASA supplements paragraph (a)) 1827.304-4 Section 1827.304-4 Federal Acquisition Regulations System NATIONAL... Rights Under Government Contracts 1827.304-4 Subcontracts. (NASA supplements paragraph (a)) (a)(i) Unless...

48 CFR 1827.304-4 - Subcontracts. (NASA supplements paragraph (a))

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2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Subcontracts. (NASA supplements paragraph (a)) 1827.304-4 Section 1827.304-4 Federal Acquisition Regulations System NATIONAL... Rights Under Government Contracts 1827.304-4 Subcontracts. (NASA supplements paragraph (a)) (a)(i) Unless...

48 CFR 1819.708 - Contract clauses. (NASA supplements paragraph (b))

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2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Contract clauses. (NASA supplements paragraph (b)) 1819.708 Section 1819.708 Federal Acquisition Regulations System NATIONAL... Subcontracting Program 1819.708 Contract clauses. (NASA supplements paragraph (b)) (b)(1) The contracting officer...

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48 CFR 1819.708 - Contract clauses. (NASA supplements paragraph (b))

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2014-10-01

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48 CFR 1832.1005 - Contract clauses. (NASA supplements paragraph (a))

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2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Contract clauses. (NASA supplements paragraph (a)) 1832.1005 Section 1832.1005 Federal Acquisition Regulations System NATIONAL... Payments 1832.1005 Contract clauses. (NASA supplements paragraph (a)) (a) If the contract is for launch...

48 CFR 1832.1005 - Contract clauses. (NASA supplements paragraph (a))

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2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Contract clauses. (NASA supplements paragraph (a)) 1832.1005 Section 1832.1005 Federal Acquisition Regulations System NATIONAL... Payments 1832.1005 Contract clauses. (NASA supplements paragraph (a)) (a) If the contract is for launch...

48 CFR 1832.1005 - Contract clauses. (NASA supplements paragraph (a))

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2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Contract clauses. (NASA supplements paragraph (a)) 1832.1005 Section 1832.1005 Federal Acquisition Regulations System NATIONAL... Payments 1832.1005 Contract clauses. (NASA supplements paragraph (a)) (a) If the contract is for launch...

48 CFR 1819.708 - Contract clauses. (NASA supplements paragraph (b))

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2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Contract clauses. (NASA supplements paragraph (b)) 1819.708 Section 1819.708 Federal Acquisition Regulations System NATIONAL... Subcontracting Program 1819.708 Contract clauses. (NASA supplements paragraph (b)) (b)(1) The contracting officer...

48 CFR 1827.304-4 - Subcontracts. (NASA supplements paragraph (a))

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2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Subcontracts. (NASA supplements paragraph (a)) 1827.304-4 Section 1827.304-4 Federal Acquisition Regulations System NATIONAL... Rights Under Government Contracts 1827.304-4 Subcontracts. (NASA supplements paragraph (a)) (a)(i) Unless...

48 CFR 1827.304-4 - Subcontracts. (NASA supplements paragraph (a))

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2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Subcontracts. (NASA supplements paragraph (a)) 1827.304-4 Section 1827.304-4 Federal Acquisition Regulations System NATIONAL... Rights Under Government Contracts 1827.304-4 Subcontracts. (NASA supplements paragraph (a)) (a)(i) Unless...

48 CFR 1832.1005 - Contract clauses. (NASA supplements paragraph (a))

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Contract clauses. (NASA supplements paragraph (a)) 1832.1005 Section 1832.1005 Federal Acquisition Regulations System NATIONAL... Payments 1832.1005 Contract clauses. (NASA supplements paragraph (a)) (a) If the contract is for launch...

48 CFR 1850.403-1 - Indemnification requests. (NASA supplements paragraph (a))

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Indemnification requests. (NASA supplements paragraph (a)) 1850.403-1 Section 1850.403-1 Federal Acquisition Regulations System... Residual Powers 1850.403-1 Indemnification requests. (NASA supplements paragraph (a)) (a) Contractor...

48 CFR 1832.1005 - Contract clauses. (NASA supplements paragraph (a))

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Contract clauses. (NASA supplements paragraph (a)) 1832.1005 Section 1832.1005 Federal Acquisition Regulations System NATIONAL... Payments 1832.1005 Contract clauses. (NASA supplements paragraph (a)) (a) If the contract is for launch...

48 CFR 1827.304-4 - Subcontracts. (NASA supplements paragraph (a))

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Subcontracts. (NASA supplements paragraph (a)) 1827.304-4 Section 1827.304-4 Federal Acquisition Regulations System NATIONAL... Rights Under Government Contracts 1827.304-4 Subcontracts. (NASA supplements paragraph (a)) (a)(i) Unless...

Differentiation and sarcomere formation in skeletal myocytes directly prepared from human induced pluripotent stem cells using a sphere-based culture.

PubMed

Jiwlawat, Saowanee; Lynch, Eileen; Glaser, Jennifer; Smit-Oistad, Ivy; Jeffrey, Jeremy; Van Dyke, Jonathan M; Suzuki, Masatoshi

Human induced-pluripotent stem cells (iPSCs) are a promising resource for propagation of myogenic progenitors. Our group recently reported a unique protocol for the derivation of myogenic progenitors directly (without genetic modification) from human pluripotent cells using free-floating spherical culture. Here we expand our previous efforts and attempt to determine how differentiation duration, culture surface coatings, and nutrient supplements in the medium influence progenitor differentiation and formation of skeletal myotubes containing sarcomeric structures. A long differentiation period (over 6 weeks) promoted the differentiation of iPSC-derived myogenic progenitors and subsequent myotube formation. These iPSC-derived myotubes contained representative sarcomeric structures, consisting of organized myosin and actin filaments, and could spontaneously contract. We also found that a bioengineering approach using three-dimensional (3D) artificial muscle constructs could facilitate the formation of elongated myotubes. Lastly, we determined how culture surface coating matrices and different supplements would influence terminal differentiation. While both Matrigel and laminin coatings showed comparable effects on muscle differentiation, B27 serum-free supplement in the differentiation medium significantly enhanced myogenesis compared to horse serum. Our findings support the possibility to create an in vitro model of contractile sarcomeric myofibrils for disease modeling and drug screening to study neuromuscular diseases. Copyright © 2017 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Efficient stage-specific differentiation of human pluripotent stem cells toward retinal photoreceptor cells.

PubMed

Mellough, Carla B; Sernagor, Evelyne; Moreno-Gimeno, Inmaculada; Steel, David H W; Lako, Majlinda

2012-04-01

Recent successes in the stem cell field have identified some of the key chemical and biological cues which drive photoreceptor derivation from human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC); however, the efficiency of this process is variable. We have designed a three-step photoreceptor differentiation protocol combining previously published methods that direct the differentiation of hESC and hiPSC toward a retinal lineage, which we further modified with additional supplements selected on the basis of reports from the eye field and retinal development. We report that hESC and hiPSC differentiating under our regimen over a 60 day period sequentially acquire markers associated with neural, retinal field, retinal pigmented epithelium and photoreceptor cells, including mature photoreceptor markers OPN1SW and RHODOPSIN with a higher efficiency than previously reported. In addition, we report the ability of hESC and hiPSC cultures to generate neural and retinal phenotypes under minimal culture conditions, which may be linked to their ability to endogenously upregulate the expression of a range of factors important for retinal cell type specification. However, cultures that were differentiated with full supplementation under our photoreceptor-induction regimen achieve this within a significantly shorter time frame and show a substantial increase in the expression of photoreceptor-specific markers in comparison to cultures differentiated under minimal conditions. Interestingly, cultures supplemented only with B27 and/or N2 displayed comparable differentiation efficiency to those under full supplementation, indicating a key role for B27 and N2 during the differentiation process. Furthermore, our data highlight an important role for Dkk1 and Noggin in enhancing the differentiation of hESC and hiPSC toward retinal progenitor cells and photoreceptor precursors during the early stages of differentiation, while suggesting that further maturation of these cells into photoreceptors may not require additional factors and can ensue under minimal culture conditions. Copyright © 2012 AlphaMed Press.

78 FR 33993 - Defense Federal Acquisition Regulation Supplement; Clarification of “F” Orders in the Procurement...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 204 RIN 0750-AH80 Defense Federal Acquisition Regulation Supplement; Clarification of ``F'' Orders in the Procurement Instrument Identification Number Structure (DFARS Case 2012-D040); Correction AGENCY: Defense Acquisition Regulations System...

77 FR 14480 - Defense Federal Acquisition Regulation Supplement: Commercial Determination Approval (DFARS Case...

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2012-03-12

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77 FR 35921 - Defense Federal Acquisition Regulation Supplement: Item Unique Identifier Update (DFARS Case 2011...

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... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 213 RIN 0750-AH07 Defense Federal Acquisition Regulation Supplement; Ships Bunkers Easy Acquisition (SEA) Card[supreg] and Aircraft Ground Services (DFARS Case 2009-D019) AGENCY: Defense Acquisition Regulations System, Department of...

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Herbs and dietary supplements in the European Union: a review of the regulations with special focus on Germany and Poland.

PubMed

Konik, Ewa A; Jungling, Roman C; Bauer, Brent A

2011-03-01

In the European Union, the manufacturing of and the trade in herbs and dietary supplements are regulated by pharmaceutical and food laws. While dietary supplements are subject to food laws, provisions dealing with herbs are primarily to be found in pharmaceutical regulations. Having a basic understanding of the complexities of this regulatory environment can help clinicians and their patients understand the unique challenges and opportunities presented by EU herbs and supplements and may help inform regulatory practices in other countries struggling to ensure quality and safety of such products.

Tenascin-C mimetic Peptide nanofibers direct stem cell differentiation to osteogenic lineage.

PubMed

Sever, Melike; Mammadov, Busra; Guler, Mustafa O; Tekinay, Ayse B

2014-12-08

Extracellular matrix contains various signals for cell surface receptors that regulate cell fate through modulation of cellular activities such as proliferation and differentiation. Cues from extracellular matrix components can be used for development of new materials to control the stem cell fate. In this study, we achieved control of stem cell fate toward osteogenic commitment by using a single extracellular matrix element despite the contradictory effect of mechanical stiffness. For this purpose, we mimicked bone extracellular matrix by incorporating functional sequence of fibronectin type III domain from native tenascin-C on self-assembled peptide nanofibers. When rat mesenchymal stem cells (rMSCs) were cultured on these peptide nanofibers, alkaline phosphatase (ALP) activity and alizarin red staining indicated osteogenic differentiation even in the absence of osteogenic supplements. Moreover, expression levels of osteogenic marker genes were significantly enhanced revealed by quantitative real-time polymerase chain reaction (qRT-PCR), which showed the remarkable bioactive role of this nanofiber system on osteogenic differentiation. Overall, these results showed that tenascin-C mimetic peptides significantly enhanced the attachment, proliferation, and osteogenic differentiation of rMSCs even in the absence of any external bioactive factors and regardless of the suitable stiff mechanical properties normally required for osteogenic differentiation. Thus, these peptide nanofibers provide a promising new platform for bone regeneration.

75 FR 66679 - Defense Federal Acquisition Regulation Supplement; Continuation of Current Contracts-Deletion of...

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2010-10-29

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76 FR 61282 - Defense Federal Acquisition Regulation Supplement; Definition of “Qualifying Country End Product...

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2011-10-04

... Federal Acquisition Regulation Supplement; Definition of ``Qualifying Country End Product'' (DFARS Case... Supplement (DFARS) to revise the definition of ``qualifying country end product.'' This final rule eliminates the component test for qualifying country end products that are commercially available off-the-shelf...

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... Service 50 CFR Part 20 Migratory Bird Hunting; Supplemental Proposals for Migratory Game Bird Hunting...] RIN 1018-AX97 Migratory Bird Hunting; Supplemental Proposals for Migratory Game Bird Hunting... in an earlier document to establish annual hunting regulations for certain migratory game birds for...

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... 0750-AH42 Defense Federal Acquisition Regulation Supplement: Contracting With the Canadian Commercial... Supplement (DFARS) to clarify the requirements for the Canadian Commercial Corporation to submit data other... 225.870-1(c), the Canadian Commercial Corporation awards and administers DoD contracts with...

48 CFR 1816.307 - Contract clauses. (NASA supplements paragraphs (a), (b), (d), and (g)).

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2013-10-01

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48 CFR 1832.202-1 - Policy. (NASA supplements paragraph (b))

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... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Policy. (NASA supplements paragraph (b)) 1832.202-1 Section 1832.202-1 Federal Acquisition Regulations System NATIONAL AERONAUTICS AND... Financing 1832.202-1 Policy. (NASA supplements paragraph (b)) (b)(6) Advance payment limitations do not...

48 CFR 1832.202-1 - Policy. (NASA supplements paragraph (b))

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2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Policy. (NASA supplements paragraph (b)) 1832.202-1 Section 1832.202-1 Federal Acquisition Regulations System NATIONAL AERONAUTICS AND... Financing 1832.202-1 Policy. (NASA supplements paragraph (b)) (b)(6) Advance payment limitations do not...

48 CFR 1845.607-2 - Recovering precious metals. (NASA supplements paragraph (b)).

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2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Recovering precious metals. (NASA supplements paragraph (b)). 1845.607-2 Section 1845.607-2 Federal Acquisition Regulations System..., Redistribution, and Disposal of Contractor Inventory 1845.607-2 Recovering precious metals. (NASA supplements...

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Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Policy. (NASA supplements paragraph (b)) 1832.202-1 Section 1832.202-1 Federal Acquisition Regulations System NATIONAL AERONAUTICS AND... Financing 1832.202-1 Policy. (NASA supplements paragraph (b)) (b)(6) Advance payment limitations do not...

48 CFR 1845.607-2 - Recovering precious metals. (NASA supplements paragraph (b)).

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2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Recovering precious metals. (NASA supplements paragraph (b)). 1845.607-2 Section 1845.607-2 Federal Acquisition Regulations System..., Redistribution, and Disposal of Contractor Inventory 1845.607-2 Recovering precious metals. (NASA supplements...

48 CFR 1832.202-1 - Policy. (NASA supplements paragraph (b))

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2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Policy. (NASA supplements paragraph (b)) 1832.202-1 Section 1832.202-1 Federal Acquisition Regulations System NATIONAL AERONAUTICS AND... Financing 1832.202-1 Policy. (NASA supplements paragraph (b)) (b)(6) Advance payment limitations do not...

48 CFR 1845.607-2 - Recovering precious metals. (NASA supplements paragraph (b)).

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Recovering precious metals. (NASA supplements paragraph (b)). 1845.607-2 Section 1845.607-2 Federal Acquisition Regulations System..., Redistribution, and Disposal of Contractor Inventory 1845.607-2 Recovering precious metals. (NASA supplements...

48 CFR 1832.202-1 - Policy. (NASA supplements paragraph (b))

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Policy. (NASA supplements paragraph (b)) 1832.202-1 Section 1832.202-1 Federal Acquisition Regulations System NATIONAL AERONAUTICS AND... Financing 1832.202-1 Policy. (NASA supplements paragraph (b)) (b)(6) Advance payment limitations do not...

48 CFR 1816.307 - Contract clauses. (NASA supplements paragraphs (a), (b), (d), and (g)).

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Contract clauses. (NASA supplements paragraphs (a), (b), (d), and (g)). 1816.307 Section 1816.307 Federal Acquisition Regulations... CONTRACTS Cost-Reimbursement Contracts 1816.307 Contract clauses. (NASA supplements paragraphs (a), (b), (d...

48 CFR 1815.606 - Agency procedures. (NASA supplements paragraphs (a) and (b))

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2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Agency procedures. (NASA supplements paragraphs (a) and (b)) 1815.606 Section 1815.606 Federal Acquisition Regulations System NATIONAL... Unsolicited Proposals 1815.606 Agency procedures. (NASA supplements paragraphs (a) and (b)) (a) NASA will not...

48 CFR 1845.607-2 - Recovering precious metals. (NASA supplements paragraph (b)).

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Recovering precious metals. (NASA supplements paragraph (b)). 1845.607-2 Section 1845.607-2 Federal Acquisition Regulations System..., Redistribution, and Disposal of Contractor Inventory 1845.607-2 Recovering precious metals. (NASA supplements...

48 CFR 1845.607-2 - Recovering precious metals. (NASA supplements paragraph (b)).

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Recovering precious metals. (NASA supplements paragraph (b)). 1845.607-2 Section 1845.607-2 Federal Acquisition Regulations System..., Redistribution, and Disposal of Contractor Inventory 1845.607-2 Recovering precious metals. (NASA supplements...

48 CFR 1815.606 - Agency procedures. (NASA supplements paragraphs (a) and (b))

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Agency procedures. (NASA supplements paragraphs (a) and (b)) 1815.606 Section 1815.606 Federal Acquisition Regulations System NATIONAL... Unsolicited Proposals 1815.606 Agency procedures. (NASA supplements paragraphs (a) and (b)) (a) NASA will not...

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Patient use of dietary supplements: a clinician's perspective.

PubMed

Sadovsky, Richard; Collins, Nancy; Tighe, Ann P; Brunton, Stephen A; Safeer, Richard

2008-04-01

The estimated prevalence of dietary-supplement use among US adults was 73% in 2002. Appropriate use of dietary supplements within the paradigm of evidence-based medicine may be a challenge for medical doctors and non-physician clinicians. Randomized, controlled, clinical trial data, which are considered the gold standard for evidence-based decision making, are lacking. Standardized guidelines for the use of dietary supplements are lacking, and dietary supplements can bear unsupported claims. This article is intended to review clinically-relevant issues related to the widespread use of dietary supplements, with emphasis on regulatory oversight and safety. Review articles and clinical trial articles published up until December 2007 were selected based on a search of the MEDLINE electronic database using PubMed. The Food and Drug Administration (FDA) Website was also used as a resource. We used the search terms dietary supplement(s), vitamin supplements, mineral supplements, and Dietary Supplement and Health Education Act. Articles discussing dietary supplements and their regulation, prevalence of use, prescription and nonprescription formulations, and/or adverse events were selected for review. Articles discussing one or more of these topics in adults were selected for inclusion. New FDA regulations require dietary-supplement manufacturers to evaluate the identity, purity, strength, and composition of their products. However, these regulations are not designed to demonstrate product efficacy and safety, and dietary-supplement manufacturers are not required to submit efficacy and safety data to the FDA prior to marketing. Product contamination and/or mislabeling may undermine the integrity of dietary-supplement formulations. The use of dietary supplements may be associated with adverse events. Although there are new regulatory requirements for dietary supplements, these products will not require FDA approval or submission of efficacy and safety data prior to marketing under the new regulation. A limitation to the literature used for this review is the lack of prospective, randomized clinical trials on the safety and efficacy of dietary supplements. Clinicians should be aware of all the dietary supplements that their patients consume, and help their patients make informed decisions appropriate to their medical care.

Dietary Supplements and Cancer Prevention: Balancing Potential Benefits Against Proven Harms

PubMed Central

Jacobs, Elizabeth T.; Baron, John A.; Marshall, James R.; Byers, Tim

2012-01-01

Nutritional supplementation is now a multibillion-dollar industry, and about half of all US adults take supplements. Supplement use is fueled in part by the belief that nutritional supplements can ward off chronic disease, including cancer, although several expert committees and organizations have concluded that there is little to no scientific evidence that supplements reduce cancer risk. To the contrary, there is now evidence that high doses of some supplements increase cancer risk. Despite this evidence, marketing claims by the supplement industry continue to imply anticancer benefits. Insufficient government regulation of the marketing of dietary supplement products may continue to result in unsound advice to consumers. Both the scientific community and government regulators need to provide clear guidance to the public about the use of dietary supplements to lower cancer risk. PMID:22534785

76 FR 35424 - Information Collection Requirements; Defense Federal Acquisition Regulation Supplement...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-17

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System Information Collection Requirements; Defense Federal Acquisition Regulation Supplement; Construction and Architect-Engineer Contracts AGENCY..., Construction and Architect-Engineer Contracts, and Related Clauses at DFARS 252.236; OMB Control Number 0704...

D-Xylose as a sugar complement regulates blood glucose levels by suppressing phosphoenolpyruvate carboxylase (PEPCK) in streptozotocin-nicotinamide-induced diabetic rats and by enhancing glucose uptake in vitro

PubMed Central

Kim, Eunju; Kim, Yoo-Sun; Kim, Kyung-Mi; Jung, Sangwon; Yoo, Sang-Ho

2016-01-01

BACKGROUND/OBJECTIVES Type 2 diabetes (T2D) is more frequently diagnosed and is characterized by hyperglycemia and insulin resistance. D-Xylose, a sucrase inhibitor, may be useful as a functional sugar complement to inhibit increases in blood glucose levels. The objective of this study was to investigate the anti-diabetic effects of D-xylose both in vitro and stretpozotocin (STZ)-nicotinamide (NA)-induced models in vivo. MATERIALS/METHODS Wistar rats were divided into the following groups: (i) normal control; (ii) diabetic control; (iii) diabetic rats supplemented with a diet where 5% of the total sucrose content in the diet was replaced with D-xylose; and (iv) diabetic rats supplemented with a diet where 10% of the total sucrose content in the diet was replaced with D-xylose. These groups were maintained for two weeks. The effects of D-xylose on blood glucose levels were examined using oral glucose tolerance test, insulin secretion assays, histology of liver and pancreas tissues, and analysis of phosphoenolpyruvate carboxylase (PEPCK) expression in liver tissues of a STZ-NA-induced experimental rat model. Levels of glucose uptake and insulin secretion by differentiated C2C12 muscle cells and INS-1 pancreatic β-cells were analyzed. RESULTS In vivo, D-xylose supplementation significantly reduced fasting serum glucose levels (P < 0.05), it slightly reduced the area under the glucose curve, and increased insulin levels compared to the diabetic controls. D-Xylose supplementation enhanced the regeneration of pancreas tissue and improved the arrangement of hepatocytes compared to the diabetic controls. Lower levels of PEPCK were detected in the liver tissues of D-xylose-supplemented rats (P < 0.05). In vitro, both 2-NBDG uptake by C2C12 cells and insulin secretion by INS-1 cells were increased with D-xylose supplementation in a dose-dependent manner compared to treatment with glucose alone. CONCLUSIONS In this study, D-xylose exerted anti-diabetic effects in vivo by regulating blood glucose levels via regeneration of damaged pancreas and liver tissues and regulation of PEPCK, a key rate-limiting enzyme in the process of gluconeogenesis. In vitro, D-xylose induced the uptake of glucose by muscle cells and the secretion of insulin cells by β-cells. These mechanistic insights will facilitate the development of highly effective strategy for T2D. PMID:26865911

Oxygen Tension Modulates Differentiation and Primary Macrophage Functions in the Human Monocytic THP-1 Cell Line

PubMed Central

Grodzki, Ana Cristina G.; Giulivi, Cecilia; Lein, Pamela J.

2013-01-01

The human THP-1 cell line is widely used as an in vitro model system for studying macrophage differentiation and function. Conventional culture conditions for these cells consist of ambient oxygen pressure (∼20% v/v) and medium supplemented with the thiol 2-mercaptoethanol (2-ME) and serum. In consideration of the redox activities of O2 and 2-ME, and the extensive experimental evidence supporting a role for reactive oxygen species (ROS) in the differentiation and function of macrophages, we addressed the question of whether culturing THP-1 cells under a more physiologically relevant oxygen tension (5% O2) in the absence of 2-ME and serum would alter THP-1 cell physiology. Comparisons of cultures maintained in 18% O2 versus 5% O2 indicated that reducing oxygen tension had no effect on the proliferation of undifferentiated THP-1 cells. However, decreasing the oxygen tension to 5% O2 significantly increased the rate of phorbol ester-induced differentiation of THP-1 cells into macrophage-like cells as well as the metabolic activity of both undifferentiated and PMA-differentiated THP-1 cells. Removal of both 2-ME and serum from the medium decreased the proliferation of undifferentiated THP-1 cells but increased metabolic activity and the rate of differentiation under either oxygen tension. In differentiated THP-1 cells, lowering the oxygen tension to 5% O2 decreased phagocytic activity, the constitutive release of β-hexosaminidase and LPS-induced NF-κB activation but enhanced LPS-stimulated release of cytokines. Collectively, these data demonstrate that oxygen tension influences THP-1 cell differentiation and primary macrophage functions, and suggest that culturing these cells under tightly regulated oxygen tension in the absence of exogenous reducing agent and serum is likely to provide a physiologically relevant baseline from which to study the role of the local redox environment in regulating THP-1 cell physiology. PMID:23355903

Selenium and its supplementation in cardiovascular disease--what do we know?

PubMed

Benstoem, Carina; Goetzenich, Andreas; Kraemer, Sandra; Borosch, Sebastian; Manzanares, William; Hardy, Gil; Stoppe, Christian

2015-04-27

The trace element selenium is of high importance for many of the body's regulatory and metabolic functions. Balanced selenium levels are essential, whereas dysregulation can cause harm. A rapidly increasing number of studies characterizes the wide range of selenium dependent functions in the human body and elucidates the complex and multiple physiological and pathophysiological interactions of selenium and selenoproteins. For the majority of selenium dependent enzymes, several biological functions have already been identified, like regulation of the inflammatory response, antioxidant properties and the proliferation/differentiation of immune cells. Although the potential role of selenium in the development and progression of cardiovascular disease has been investigated for decades, both observational and interventional studies of selenium supplementation remain inconclusive and are considered in this review. This review covers current knowledge of the role of selenium and selenoproteins in the human body and its functional role in the cardiovascular system. The relationships between selenium intake/status and various health outcomes, in particular cardiomyopathy, myocardial ischemia/infarction and reperfusion injury are reviewed. We describe, in depth, selenium as a biomarker in coronary heart disease and highlight the significance of selenium supplementation for patients undergoing cardiac surgery.

Selenium and Its Supplementation in Cardiovascular Disease—What do We Know?

PubMed Central

Benstoem, Carina; Goetzenich, Andreas; Kraemer, Sandra; Borosch, Sebastian; Manzanares, William; Hardy, Gil; Stoppe, Christian

2015-01-01

The trace element selenium is of high importance for many of the body’s regulatory and metabolic functions. Balanced selenium levels are essential, whereas dysregulation can cause harm. A rapidly increasing number of studies characterizes the wide range of selenium dependent functions in the human body and elucidates the complex and multiple physiological and pathophysiological interactions of selenium and selenoproteins. For the majority of selenium dependent enzymes, several biological functions have already been identified, like regulation of the inflammatory response, antioxidant properties and the proliferation/differentiation of immune cells. Although the potential role of selenium in the development and progression of cardiovascular disease has been investigated for decades, both observational and interventional studies of selenium supplementation remain inconclusive and are considered in this review. This review covers current knowledge of the role of selenium and selenoproteins in the human body and its functional role in the cardiovascular system. The relationships between selenium intake/status and various health outcomes, in particular cardiomyopathy, myocardial ischemia/infarction and reperfusion injury are reviewed. We describe, in depth, selenium as a biomarker in coronary heart disease and highlight the significance of selenium supplementation for patients undergoing cardiac surgery. PMID:25923656

Effects of Recombinant Human Lactoferrin on Osteoblast Growth and Bone Status in Piglets.

PubMed

Li, Qiuling; Zhao, Jie; Hu, Wenping; Wang, Jianwu; Yu, Tian; Dai, Yunping; Li, Ning

2018-04-03

Lactoferrin (LF), an ~80 kDa iron-binding glycoprotein, modulates many biological effects, including antimicrobial and immunomodulatory activities. Recently, it was shown that LF also regulates bone cell activity, suggesting its therapeutic effect on postmenopausal bone loss. However, a minimal amount is known regarding the effects of recombinant human LF (rhLF) supplementation on bone status in young healthy infants. We found osteoblast cell differentiation was significantly promoted in vitro. Furthermore, treatment of human osteoblast cells with rhLF rapidly induced phosphorylation of p44/p42 mitogen-activated protein kinase (p44/p42 MAPK, ERK1/2). In order to investigate the effects of rhLF on bone status in vivo, we used a piglet model, which is a useful model for human infants. Piglets were supplemented with rhLF milk for 30 days. Bone formation markers, Serum calcium concentration, bone mineral density (BMD), bone mineral content (BMC), tibia bone strength, and the overall metabolite profile analysis showed that rhLF was advantageous to the bone growth in piglets. These findings suggest that rhLF supplementation benefits neonate bone health by modulating bone formation.

Vitamin supplementation by gut symbionts ensures metabolic homeostasis in an insect host

PubMed Central

Salem, Hassan; Bauer, Eugen; Strauss, Anja S.; Vogel, Heiko; Marz, Manja; Kaltenpoth, Martin

2014-01-01

Despite the demonstrated functional importance of gut microbes, our understanding of how animals regulate their metabolism in response to nutritionally beneficial symbionts remains limited. Here, we elucidate the functional importance of the African cotton stainer's (Dysdercus fasciatus) association with two actinobacterial gut symbionts and subsequently examine the insect's transcriptional response following symbiont elimination. In line with bioassays demonstrating the symbionts' contribution towards host fitness through the supplementation of B vitamins, comparative transcriptomic analyses of genes involved in import and processing of B vitamins revealed an upregulation of gene expression in aposymbiotic (symbiont-free) compared with symbiotic individuals; an expression pattern that is indicative of B vitamin deficiency in animals. Normal expression levels of these genes, however, can be restored by either artificial supplementation of B vitamins into the insect's diet or reinfection with the actinobacterial symbionts. Furthermore, the functional characterization of the differentially expressed thiamine transporter 2 through heterologous expression in Xenopus laevis oocytes confirms its role in cellular uptake of vitamin B1. These findings demonstrate that despite an extracellular localization, beneficial gut microbes can be integral to the host's metabolic homeostasis, reminiscent of bacteriome-localized intracellular mutualists. PMID:25339726

Use of botanicals in food supplements. Regulatory scope, scientific risk assessment and claim substantiation. 2005.

PubMed

Coppens, P; Delmulle, L; Gulati, O; Richardson, D; Ruthsatz, M; Sievers, H; Sidani, S

2006-01-01

In the European Union, an elaborate legal framework regulates botanical products both under food and medicinal law. The decision as to which legal framework applies to an individual product may differ between the Member States. In the case of botanical food supplements, all food law provisions apply to their manufacturing, composition and marketing, including the new claims legislation. Elements from EU and national law, scientific and other publications are brought together to investigate how to clarify the differentiation between the use of botanicals for medicinal and health-promoting purposes on a scientific basis. Guidance on the safety assessment and quality evaluation of botanicals is proposed in light of the different approaches described in the scientific literature with particular attention to the concept of long-term use as an integral part of safety evaluation. Guidance on claims substantiation is also included, taking into consideration the proposed legislation, the concept of long-term experience and grading of evidence. A model for safety and efficacy assessment of botanical food supplements in the EU is proposed, and should be taken into consideration in the development of legislation and scientific research on botanicals. Copyright 2006 S. Karger AG, Basel.

78 FR 18877 - Defense Federal Acquisition Regulation Supplement; Specialty Metals-Definition of “Produce...

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2013-03-28

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 252 RIN 0750-AH78 Defense...-D041) AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Final rule. SUMMARY: DoD is issuing a final rule amending the Defense Federal Acquisition Regulation Supplement (DFARS...

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2013-10-24

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System [Docket Number DARS-2013-0035] Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Organizational Conflict..., Department of Defense (DoD). ACTION: Notice and request for comments regarding a proposed extension of an...

15 CFR Supplement No. 1 to Part 715 - Definition of an Unscheduled Discrete Organic Chemical

Code of Federal Regulations, 2012 CFR

2012-01-01

... Organic Chemical No. Supplement No. 1 to Part 715 Commerce and Foreign Trade Regulations Relating to... WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING UNSCHEDULED DISCRETE ORGANIC CHEMICALS (UDOCs) Pt. 715, Supp. 1 Supplement No. 1 to Part 715—Definition of an Unscheduled Discrete Organic Chemical Unscheduled...

15 CFR Supplement No. 1 to Part 715 - Definition of an Unscheduled Discrete Organic Chemical

Code of Federal Regulations, 2014 CFR

2014-01-01

... Organic Chemical No. Supplement No. 1 to Part 715 Commerce and Foreign Trade Regulations Relating to... WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING UNSCHEDULED DISCRETE ORGANIC CHEMICALS (UDOCs) Pt. 715, Supp. 1 Supplement No. 1 to Part 715—Definition of an Unscheduled Discrete Organic Chemical Unscheduled...

15 CFR Supplement No. 1 to Part 715 - Definition of an Unscheduled Discrete Organic Chemical

Code of Federal Regulations, 2011 CFR

2011-01-01

... Organic Chemical No. Supplement No. 1 to Part 715 Commerce and Foreign Trade Regulations Relating to... WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING UNSCHEDULED DISCRETE ORGANIC CHEMICALS (UDOCs) Pt. 715, Supp. 1 Supplement No. 1 to Part 715—Definition of an Unscheduled Discrete Organic Chemical Unscheduled...

15 CFR Supplement No. 1 to Part 715 - Definition of an Unscheduled Discrete Organic Chemical

Code of Federal Regulations, 2013 CFR

2013-01-01

... Organic Chemical No. Supplement No. 1 to Part 715 Commerce and Foreign Trade Regulations Relating to... WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING UNSCHEDULED DISCRETE ORGANIC CHEMICALS (UDOCs) Pt. 715, Supp. 1 Supplement No. 1 to Part 715—Definition of an Unscheduled Discrete Organic Chemical Unscheduled...

48 CFR 1809.206-1 - General. (NASA supplements paragraph (b) and (c))

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true General. (NASA supplements paragraph (b) and (c)) 1809.206-1 Section 1809.206-1 Federal Acquisition Regulations System NATIONAL... Qualification requirements 1809.206-1 General. (NASA supplements paragraph (b) and (c)) (c) If an offeror seeks...

48 CFR 1815.407-2 - Make-or-buy programs. (NASA supplements paragraph (e))

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Make-or-buy programs. (NASA supplements paragraph (e)) 1815.407-2 Section 1815.407-2 Federal Acquisition Regulations System... NEGOTIATION Contract Pricing 1815.407-2 Make-or-buy programs. (NASA supplements paragraph (e)) (e)(1) Make-or...

48 CFR 1809.206-1 - General. (NASA supplements paragraph (b) and (c))

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false General. (NASA supplements paragraph (b) and (c)) 1809.206-1 Section 1809.206-1 Federal Acquisition Regulations System NATIONAL... Qualification requirements 1809.206-1 General. (NASA supplements paragraph (b) and (c)) (c) If an offeror seeks...

48 CFR 1809.206-1 - General. (NASA supplements paragraph (b) and (c))

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false General. (NASA supplements paragraph (b) and (c)) 1809.206-1 Section 1809.206-1 Federal Acquisition Regulations System NATIONAL... Qualification requirements 1809.206-1 General. (NASA supplements paragraph (b) and (c)) (c) If an offeror seeks...

48 CFR 1809.206-1 - General. (NASA supplements paragraph (b) and (c))

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false General. (NASA supplements paragraph (b) and (c)) 1809.206-1 Section 1809.206-1 Federal Acquisition Regulations System NATIONAL... Qualification requirements 1809.206-1 General. (NASA supplements paragraph (b) and (c)) (c) If an offeror seeks...

48 CFR 1809.206-1 - General. (NASA supplements paragraph (b) and (c))

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false General. (NASA supplements paragraph (b) and (c)) 1809.206-1 Section 1809.206-1 Federal Acquisition Regulations System NATIONAL... Qualification requirements 1809.206-1 General. (NASA supplements paragraph (b) and (c)) (c) If an offeror seeks...

48 CFR 1815.407-2 - Make-or-buy programs. (NASA supplements paragraph (e))

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Make-or-buy programs. (NASA supplements paragraph (e)) 1815.407-2 Section 1815.407-2 Federal Acquisition Regulations System... NEGOTIATION Contract Pricing 1815.407-2 Make-or-buy programs. (NASA supplements paragraph (e)) (e)(1) Make-or...

The history of efforts to regulate dietary supplements in the USA.

PubMed

Swann, John P

2016-01-01

This review examines the emergence of dietary supplements and how the Food and Drug Administration (FDA) attempted to regulate these, beginning with the arrival of vitamins and how these were managed under the 1906 Food and Drugs Act, and ending with the seismic influence of the 1994 Dietary Supplement Health and Education Act (DSHEA). Included are the impact of major laws, key court decisions, and the construction of the FDA's supplement actions and rules from the 1920s to the 1990s for products that were neither drugs nor typical foods. Stiff resistance to the regulations by supplement manufacturers, trade associations, politicians, and especially the public at large is an important part of this story. The paper closes with the passage of DSHEA and how it literally changed the definition and parameters of control of dietary supplements. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

[Regulation of food supplements in the European Union and its member states. Part I].

PubMed

Petrenko, A S; Ponomareva, M N; Sukhanov, B P

2014-01-01

The article discusses aspects of the regional (the European Union) and national (European countries) regulation of food supplements. The definition of the supplement category is given. The contemporary issues of nutrition in developed countries are discussed, and the essential role of food supplements in the diet is emphasized. In particular, the use of vitamins, minerals, botanicals and their chemical constituents in food supplements as well as the issue of setting maximum daily limits are discussed. The positive lists of vitamins, minerals and their chemical modifications are presented. The paper also outlines aspects of supplement safety, requirements for their labelling and pre-market notification procedure.

Calcium transcriptionally regulates the biofilm machinery of Xylella fastidiosa to promote continued biofilm development in batch cultures.

PubMed

Parker, Jennifer K; Chen, Hongyu; McCarty, Sara E; Liu, Lawrence Y; De La Fuente, Leonardo

2016-05-01

The functions of calcium (Ca) in bacteria are less characterized than in eukaryotes, where its role has been studied extensively. The plant-pathogenic bacterium Xylella fastidiosa has several virulence features that are enhanced by increased Ca concentrations, including biofilm formation. However, the specific mechanisms driving modulation of this feature are unclear. Characterization of biofilm formation over time showed that 4 mM Ca supplementation produced denser biofilms that were still developing at 96 h, while biofilm in non-supplemented media had reached the dispersal stage by 72 h. To identify changes in global gene expression in X. fastidiosa grown in supplemental Ca, RNA-Seq of batch culture biofilm cells was conducted at three 24-h time intervals. Results indicate that a variety of genes are differentially expressed in response to Ca, including genes related to attachment, motility, exopolysaccharide synthesis, biofilm formation, peptidoglycan synthesis, regulatory functions, iron homeostasis, and phages. Collectively, results demonstrate that Ca supplementation induces a transcriptional response that promotes continued biofilm development, while biofilm cells in nonsupplemented media are driven towards dispersion of cells from the biofilm structure. These results have important implications for disease progression in planta, where xylem sap is the source of Ca and other nutrients for X. fastidiosa. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

The effect of concrete supplements on metacognitive regulation during learning and open-book test taking.

PubMed

Ackerman, Rakefet; Leiser, David

2014-06-01

Previous studies have suggested that when reading texts, lower achievers are more sensitive than their stronger counterparts to surface-level cues, such as graphic illustrations, and that even when uninformative, such concrete supplements tend to raise the text's subjective comprehensibility. We examined how being led astray by uninformative concrete supplements in expository texts affects achievement. We focused on the mediating role of metacognitive processes by partialling out the role of cognitive ability, as indicated by SAT scores, in accounting for the found differences between higher and lower achievers. Undergraduate students studied expository texts in their base versions or in concrete versions, including uninformative supplements, in a within-participant design. The procedure had three phases: Studying, open-book test taking, and reanswering questions of one's choice. Overall, judgements of comprehension (JCOMPs) were higher after participants studied the concrete than the base versions, and the participants benefited from the open-book test and the reanswering opportunity. An in-depth examination of time investment, JCOMP, confidence in test answers, choice of questions to reanswer, and test scores indicated that those whose metacognitive processes were more effective and goal driven achieved higher scores. The effectiveness of metacognitive processes during learning and test taking constitutes an important factor differentiating between higher and lower achievers when studying texts that include potentially misleading cues. © 2013 The British Psychological Society.

Characterisation of vitamin and mineral supplement users differentiated according to their motives for using supplements: results of the German National Nutrition Monitoring (NEMONIT).

PubMed

Frey, Anne; Hoffmann, Ingrid; Heuer, Thorsten

2017-08-01

To characterise German vitamin and mineral supplement users differentiated by their motives for supplement use. Data were obtained from the German National Nutrition Monitoring (2010/11) via two 24 h dietary recalls and a telephone interview. Motive-based subgroups of supplement users were identified by factor and cluster analysis. Sociodemographic, lifestyle, health and dietary characteristics and supplement use were examined. Differences were analysed using χ 2 tests, logistic and linear regression models. Germany, nationwide. Individuals (n 1589) aged 18-80 years. Three motive-based subgroups were identified: a 'Prevention' subgroup (n 324), characterised by the motive to prevent nutrient deficiencies; a 'Prevention and additional benefits' subgroup (n 166), characterised by motives to prevent health problems and improve well-being and performance; and a 'Treatment' subgroup (n 136), characterised by motives to treat nutrient deficiencies or diseases. Members of the two prevention subgroups had a higher Healthy Eating Index score and tended to be more physically active than non-users. Those in the 'Prevention and additional benefits' subgroup supplemented with a greater number of micronutrients. Members of the 'Treatment' subgroup tended to be older and have a lower self-reported health status than non-users, and supplemented with a smaller number of micronutrients. The majority of supplement users take supplements for preventive purposes and they are more health conscious than non-users of supplements due to their concerns about developing health problems. Those supplementing for treatment purposes may have underlying health indications and may be more likely to benefit from supplementation than those supplementing for preventive purposes.

77 FR 11367 - Defense Federal Acquisition Regulation Supplement; Extension of the Department of Defense Mentor...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-24

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 219 and Appendix I to Chapter 2 RIN 0750-AH59 Defense Federal Acquisition Regulation Supplement; Extension of the Department of... Regulations System, Department of Defense (DoD). ACTION: Final rule. SUMMARY: DoD is issuing this final rule...

A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk

DTIC Science & Technology

2016-10-01

patterns were observed for association with dietary factors or life style factors such as physical activity, occupational history, sexual behavior...The resultant differentiated cells are cultured in prostate epithelial cell growth medium (PrEGM) and stromal basal medium supplemented with R...Sponding1, Noggin, EGF, 1X B27 supplement , retinoic acid and dihydrotestosterone. BOTTOM: Preliminary iPSC differentiation into definitive endoderm over

Mice Fed a High-Cholesterol Diet Supplemented with Quercetin-3-Glucoside Show Attenuated Hyperlipidemia and Hyperinsulinemia Associated with Differential Regulation of PCSK9 and LDLR in their Liver and Pancreas.

PubMed

Mbikay, Majambu; Mayne, Janice; Sirois, Francine; Fedoryak, Olesya; Raymond, Angela; Noad, Jennifer; Chrétien, Michel

2018-05-01

Hepatic LDL receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) regulate the clearance of plasma LDL-cholesterol (LDL-C): LDLR promotes it, and PCSK9 opposes it. These proteins also express in pancreatic β cells. Using cultured hepatocytes, we previously showed that the plant flavonoid quercetin-3-glucoside (Q3G) inhibits PCSK9 secretion, stimulated LDLR expression, and enhanced LDL-C uptake. Here, we examine whether Q3G supplementation could reverse the hyperlipidemia and hyperinsulinemia of mice fed a high-cholesterol diet, and how it affects hepatic and pancreatic LDLR and PCSK9 expression. For 12 weeks, mice are fed a low- (0%) or high- (1%) cholesterol diet (LCD or HCD), supplemented or not with Q3G at 0.05 or 0.1% (w/w). Tissue LDLR and PCSK9 is analyzed by immunoblotting, plasma PCSK9 and insulin by ELISA, and plasma cholesterol and glucose by colorimetry. In LCD-fed mice, Q3G has no effect. In HCD-fed mice, it attenuates the increase in plasma cholesterol and insulin, accentuates the decrease in plasma PCSK9, and increases hepatic and pancreatic LDLR and PCSK9. In cultured pancreatic β cells, however, it stimulates PCSK9 secretion. In mice, dietary Q3G could counter HCD-induced hyperlipidemia and hyperinsulinemia, in part by oppositely modulating hepatic and pancreatic PCSK9 secretion. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterisation of equine satellite cell transcriptomic profile response to β-hydroxy-β-methylbutyrate (HMB).

PubMed

Szcześniak, Katarzyna A; Ciecierska, Anna; Ostaszewski, Piotr; Sadkowski, Tomasz

2016-10-01

β-Hydroxy-β-methylbutyrate (HMB) is a popular ergogenic aid used by human athletes and as a supplement to sport horses, because of its ability to aid muscle recovery, improve performance and body composition. Recent findings suggest that HMB may stimulate satellite cells and affect expressions of genes regulating skeletal muscle cell growth. Despite the scientific data showing benefits of HMB supplementation in horses, no previous study has explained the mechanism of action of HMB in this species. The aim of this study was to reveal the molecular background of HMB action on equine skeletal muscle by investigating the transcriptomic profile changes induced by HMB in equine satellite cells in vitro. Upon isolation from the semitendinosus muscle, equine satellite cells were cultured until the 2nd day of differentiation. Differentiating cells were incubated with HMB for 24 h. Total cellular RNA was isolated, amplified, labelled and hybridised to microarray slides. Microarray data validation was performed with real-time quantitative PCR. HMB induced differential expressions of 361 genes. Functional analysis revealed that the main biological processes influenced by HMB in equine satellite cells were related to muscle organ development, protein metabolism, energy homoeostasis and lipid metabolism. In conclusion, this study demonstrated for the first time that HMB has the potential to influence equine satellite cells by controlling global gene expression. Genes and biological processes targeted by HMB in equine satellite cells may support HMB utility in improving growth and regeneration of equine skeletal muscle; however, the overall role of HMB in horses remains equivocal and requires further proteomic, biochemical and pharmacokinetic studies.

Thyroid and Biochemical/Metabolic Effects of PFDA (Perfluoro-n-decanoic Acid).

DTIC Science & Technology

1988-01-04

could be explained by a chemically induced hypothyroidism. Experiments employing T4- supplementation suggests that the toxicity is more complex. Rats... supplementation was continued through the day prior to sacrifice. The liver enzymes c-glycerolphosphate dehydro- genase (GPD) and malic enzyme (ME) were...T4 supplementation had differential effects on anorexia, body wasting and hypothermia. Thyroxine supplementation completely prevented the PFDA-induced

76 FR 71465 - Defense Federal Acquisition Regulation Supplement: Management of Manufacturing Risk in Major...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-18

... Government procurement. Mary Overstreet, Editor, Defense Acquisition Regulations System. Interim Rule Adopted... Federal Acquisition Regulation Supplement: Management of Manufacturing Risk in Major Defense Acquisition...). ACTION: Final rule. SUMMARY: DoD is adopting as final, without change, an interim rule amending the...

Dietary Supplements: Foods, Medicines, or Both? A Controversial Designation with Unspecific Legislation.

PubMed

Pereira, Carla; Barros, Lillian; Ferreira, Isabel C F R

2017-01-01

Dietary supplements have been widely used among the United States of America (USA) and the European Union (EU) population not only as a form of nutrition but also for medicinal purposes. Still, the legislation regulating these supplements remains unclear due to the fact that they can be considered as foodstuffs and/or medicinal products depending on various factors. The present review article intends to provide information concerning the variations on the definition of dietary supplements, the allowable substances on it, as well as the marketing and labelling requirements among the USA and the EU legislation. In fact, several discrepancies can be found between regulations in the USA (mainly regulated by the Food and Drugs Administration) and in the EU (principally regulated by the Food Supplements Directive or by the Directive 2001/83/EC), and even between the different Member States of the EU, with the main differences observed in new products marketing requirements. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Galactoglucomannans increase cell population density and alter the protoxylem/metaxylem tracheary element ratio in xylogenic cultures of Zinnia.

PubMed

Benová-Kákosová, Anna; Digonnet, Catherine; Goubet, Florence; Ranocha, Philippe; Jauneau, Alain; Pesquet, Edouard; Barbier, Odile; Zhang, Zhinong; Capek, Peter; Dupree, Paul; Lisková, Desana; Goffner, Deborah

2006-10-01

Xylogenic cultures of zinnia (Zinnia elegans) provide a unique opportunity to study signaling pathways of tracheary element (TE) differentiation. In vitro TEs differentiate into either protoxylem (PX)-like TEs characterized by annular/helical secondary wall thickening or metaxylem (MX)-like TEs with reticulate/scalariform/pitted thickening. The factors that determine these different cell fates are largely unknown. We show here that supplementing zinnia cultures with exogenous galactoglucomannan oligosaccharides (GGMOs) derived from spruce (Picea abies) xylem had two major effects: an increase in cell population density and a decrease in the ratio of PX to MX TEs. In an attempt to link these two effects, the consequence of the plane of cell division on PX-MX differentiation was assessed. Although GGMOs did not affect the plane of cell division per se, they significantly increased the proportion of longitudinally divided cells differentiating into MX. To test the biological significance of these findings, we have determined the presence of mannan-containing oligosaccharides in zinnia cultures in vitro. Immunoblot assays indicated that beta-1,4-mannosyl epitopes accumulate specifically in TE-inductive media. These epitopes were homogeneously distributed within the thickened secondary walls of TEs when the primary cell wall was weakly labeled. Using polysaccharide analysis carbohydrate gel electrophoresis, glucomannans were specifically detected in cell walls of differentiating zinnia cultures. Finally, zinnia macroarrays probed with cDNAs from cells cultured in the presence or absence of GGMOs indicated that significantly more genes were down-regulated rather than up-regulated by GGMOs. This study constitutes a major step in the elucidation of signaling mechanisms of PX- and MX-specific genetic programs in zinnia.

Invited Review Vitamin D and skin cancer†

PubMed Central

Burns, Erin M.; Elmets, Craig A.; Yusuf, Nabiha

2014-01-01

Vitamin D signaling plays a key role in various important processes, including cellular proliferation, differentiation, and apoptosis, immune regulation, hormone secretion, and skeletal health. Further, vitamin D production and supplementation have been shown to exert protective effects via an unknown signaling mechanism involving the vitamin D receptor (VDR) in several diseases and cancer types, including skin cancer. With over 3.5 million new diagnoses in 2 million patients annually, skin cancer is the most common cancer type in the United States. While ultraviolet B (UVB) radiation is the main etiologic factor for non-melanoma skin cancer (NMSC), UVB also induces cutaneous vitamin D production. This paradox has been the subject of contradictory findings in the literature in regards to amount of sun exposure necessary for appropriate vitamin D production, as well as any beneficial or detrimental effects of vitamin D supplementation for disease prevention. Further clinical and epidemiological studies are necessary to elucidate the role of vitamin D in skin carcinogenesis. PMID:25378147

Weight Loss Supplements: Boon or Bane?

PubMed Central

Ansari, Reshma Mohamed; Omar, Norfaizatul Shalida

2017-01-01

Dietary health supplements for weight loss seem to be the future nowadays. However, this industry is plagued by lack of regulations and ignorance regarding the constituents of the supplements. Of all the supplements consumed, the ones for weight loss are most commonly found in the market. Reports of liver failure, kidney impairment and worsening of chronic ailments in patients who consume these supplements are surfacing recently which make us question the credibility of these products. The safety of these products lie in the clear stating of the ingredients by the manufacturer, well informed patient, knowledgeable physician and tight regulations from the regulatory board. PMID:28814927

Inhibition of adipogenic differentiation by myostatin is alleviated by arginine supplementation in porcine-muscle-derived mesenchymal stem cells.

PubMed

Lei, Hulong; Yu, Bing; Yang, Xuerong; Liu, Zehui; Huang, Zhiqing; Mao, Xiangbing; Tian, Gang; He, Jun; Han, Guoquan; Chen, Hong; Mao, Qian; Chen, Daiwen

2011-10-01

Porcine mesenchymal stem cells in postnatal muscle have been demonstrated to differentiate into adipocytes. This increases adipocyte number and lipid accumulation, and is thought to be the origin of intramuscular fat. In this study, the effects of myostatin and arginine on adipogenic differentiation in mesenchymal stem cells derived from porcine muscle (pMDSCs) were investigated in vitro. Intracellular triglyceride levels were reduced by exogenous myostatin and increased by arginine supplementation or myostatin antibody (P<0.01). The inhibition of lipid accumulation by myostatin in pMDSCs was alleviated by arginine supplementation (P<0.01). Expression patterns of adipogenic transcription factors showed that exogenous myostatin suppressed PPARγ2 and aP2 expression (P<0.01), while supplemental arginine or myostatin antibody promoted ADD1 expression (P<0.01). Furthermore, compared with the addition of either myostatin protein or antibody alone, ADD1 and PPARδ expression were promoted by the combination of arginine and myostatin (P<0.01), and arginine combined with myostatin antibody promoted the expression of ADD1, PPARδ, C/EBPα, PPARγ2 and LPL in pMDSCs (P<0.05). These results suggest that myostatin inhibits adipogenesis in pMDSCs, and that this can be alleviated by arginine supplementation, at least in part, through promoting ADD1 and PPARδ expression.

41 CFR 101-1.108 - Agency implementation and supplementation of FPMR.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Agency implementation and supplementation of FPMR. 101-1.108 Section 101-1.108 Public Contracts and Property Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS GENERAL 1-INTRODUCTION 1.1-Regulation...

75 FR 32639 - Defense Federal Acquisition Regulation Supplement; Limitations on Procurements With Non-Defense...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-08

... elements of the Department of Homeland Security concerned with the analysis of intelligence information... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 217 RIN 0750-AG67 Defense Federal Acquisition Regulation Supplement; Limitations on Procurements With Non-Defense Agencies (DFARS...

75 FR 3178 - Defense Federal Acquisition Regulation Supplement; Lead System Integrators

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-20

... Government procurement. Amy G. Williams, Editor, Defense Acquisition Regulations System. 0 Accordingly, the..., without change, an interim rule amending the Defense Federal Acquisition Regulation Supplement (DFARS) to... limitations on the award of new contracts for lead system integrator functions in the acquisition of major DoD...

75 FR 51416 - Defense Federal Acquisition Regulation Supplement; Acquisition of Commercial Items

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-20

... be used for the acquisition of commercial items, and revised the language to address the conditions... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 202, 212, and 234 [DFARS Case 2008-D011] Defense Federal Acquisition Regulation Supplement; Acquisition of Commercial Items...

75 FR 20954 - Defense Federal Acquisition Regulation Supplement; Organizational Conflicts of Interest in Major...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-22

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 202, 203, 212, and 252 RIN 0750-AG63 Defense Federal Acquisition Regulation Supplement; Organizational Conflicts of Interest... System, Department of Defense (DoD). ACTION: Proposed rule with request for comments. SUMMARY: DoD is...

76 FR 75875 - Defense Federal Acquisition Regulation Supplement; Open Source Software Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-05

... Regulation Supplement; Open Source Software Public Meeting AGENCY: Defense Acquisition Regulations System... initiate a dialogue with industry regarding the use of open source software in DoD contracts. DATES: Public... be held in the General Services Administration (GSA), Central Office Auditorium, 1800 F Street NW...

76 FR 44280 - Defense Federal Acquisition Regulation Supplement; Simplified Acquisition Threshold for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-25

...-AH29 Defense Federal Acquisition Regulation Supplement; Simplified Acquisition Threshold for.... 2302(7) to invoke a simplified acquisition threshold that is two times the amount specified at 41 U.S.C... acquisition threshold is $150,000 as specified in Federal Acquisition Regulation 2.101. DATES: Effective Date...

77 FR 52252 - Defense Federal Acquisition Regulation Supplement: Inflation Adjustment of Threshold for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-29

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 201 and 212 RIN 0750-AH65 Defense Federal Acquisition Regulation Supplement: Inflation Adjustment of Threshold for... respondent concurred with the inflation threshold increase listed at DFARS 212.271. There were no comments...

Too Little, Too Late: Ineffective Regulation of Dietary Supplements in the United States

PubMed Central

2015-01-01

Millions of people in the United States consume dietary supplements hoping to maintain or improve their health; however, extensive research has failed to demonstrate the efficacy of numerous supplements in disease prevention. In addition, concerns about the safety of routine and high-dose supplementation have been raised. The Food and Drug Administration regulates dietary supplement quality, safety, and labeling, and the Federal Trade Commission monitors advertisements and marketing; still, vast enforcement challenges remain, and optimal governmental oversight has not been achieved. If the composition and quality of ingredients cannot be reliably ensured, the validity of research on dietary supplements is questionable. Moreover, the health of the US public is put at risk. PMID:25602879

Effect of nano-sized, elemental selenium supplement on the proteome of chicken liver.

PubMed

Gulyas, G; Csosz, E; Prokisch, J; Javor, A; Mezes, M; Erdelyi, M; Balogh, K; Janaky, T; Szabo, Z; Simon, A; Czegledi, L

2017-06-01

The nano-sized (100-500 nm) selenium has higher bioavailability and relatively lower toxicity compared to other selenium forms. The objective of the present study was to compare liver proteome profiles of broiler chicken fed with control diet without Se supplementation and diet supplemented with nano-Se with 4.25 mg/kg DM. Differential proteome analyses were performed by two-dimensional gel electrophoresis (2D-PAGE) followed by tryptic digestion and protein identification by liquid chromatography-mass spectrometry (LC-MS). Seven hundred and eight spots were detected, and 18 protein spots showed significant difference in their intensity (p < 0.05) between the two groups. In response to nano-Se supplementation, the expression of 8 proteins was higher, and 5 proteins were lower in nano-Se supplemented group compared to control group. The functions of the differentially expressed proteins indicate that the high dose of selenium supplementation induced a dietary stress. Selenium supplementation may influence the metabolism of fatty acids and carbohydrates and antioxidant system, and increase the quantity of cytoskeletal actin and the expression of actin regulatory protein as well. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Reviewing the Effects of l-Leucine Supplementation in the Regulation of Food Intake, Energy Balance, and Glucose Homeostasis

PubMed Central

Pedroso, João A.B.; Zampieri, Thais T.; Donato, Jose

2015-01-01

Leucine is a well-known activator of the mammalian target of rapamycin (mTOR). Because mTOR signaling regulates several aspects of metabolism, the potential of leucine as a dietary supplement for treating obesity and diabetes mellitus has been investigated. The objective of the present review was to summarize and discuss the available evidence regarding the mechanisms and the effects of leucine supplementation on the regulation of food intake, energy balance, and glucose homeostasis. Based on the available evidence, we conclude that although central leucine injection decreases food intake, this effect is not well reproduced when leucine is provided as a dietary supplement. Consequently, no robust evidence indicates that oral leucine supplementation significantly affects food intake, although several studies have shown that leucine supplementation may help to decrease body adiposity in specific conditions. However, more studies are necessary to assess the effects of leucine supplementation in already-obese subjects. Finally, although several studies have found that leucine supplementation improves glucose homeostasis, the underlying mechanisms involved in these potential beneficial effects remain unknown and may be partially dependent on weight loss. PMID:26007339

Electron Transfer Dissociation with Supplemental Activation to Differentiate Aspartic and Isoaspartic Residues in Doubly Charged Peptide Cations

PubMed Central

Chan, Wai Yi Kelly; Chan, T. W. Dominic; O’Connor, Peter B.

2011-01-01

Electron-transfer dissociation (ETD) with supplemental activation of the doubly charged deamidated tryptic digested peptide ions allows differentiation of isoaspartic acid and aspartic acid residues using c + 57 or z• − 57 peaks. The diagnostic peak clearly localizes and characterizes the isoaspartic acid residue. Supplemental activation in ETD of the doubly charged peptide ions involves resonant excitation of the charge reduced precursor radical cations and leads to further dissociation, including extra backbone cleavages and secondary fragmentation. Supplemental activation is essential to obtain a high quality ETD spectrum (especially for doubly charged peptide ions) with sequence information. Unfortunately, the low-resolution of the ion trap mass spectrometer makes detection of the diagnostic peak for the aspartic acid residue difficult due to interference with side-chain loss from arginine and glutamic acid residues. PMID:20304674

76 FR 71464 - Defense Federal Acquisition Regulation Supplement; Transition to the System for Award Management...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-18

... Regulation Supplement for the transition of the Integrated Acquisition Environment systems to the new System... Acquisition Environment (IAE) is an electronic Government initiative that aggregates Federal acquisition...

Comparative epigenetic influence of autologous versus fetal bovine serum on mesenchymal stem cells through in vitro osteogenic and adipogenic differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fani, Nesa; Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran; Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran

Mesenchymal stem cells (MSCs) derived from bone marrow (BM) represents a useful source of adult stem cells for cell therapy and tissue engineering. MSCs are present at a low frequency in the BM; therefore expansion is necessary before performing clinical studies. Fetal bovine serum (FBS) as a nutritional supplement for in vitro culture of MSCs is a suitable additive for human cell culture, but not regarding subsequent use of these cells for clinical treatment of human patients due to the risk of viral and prion transmission as well as xenogeneic immune responses after transplantation. Recently, autologous serum (AS) has beenmore » as a supplement to replace FBS in culture medium. We compared the effect of FBS versus AS on the histone modification pattern of MSCs through in vitro osteogenesis and adipogenesis. Differentiation of stem cells under various serum conditions to a committed state involves global changes in epigenetic patterns that are critically determined by chromatin modifications. Chromatin immunoprecipitation (ChIP) coupled with real-time PCR showed significant changes in the acetylation and methylation patterns in lysine 9 (Lys9) of histone H3 on the regulatory regions of stemness (Nanog, Sox2, Rex1), osteogenic (Runx2, Oc, Sp7) and adipogenic (Ppar-γ, Lpl, adiponectin) marker genes in undifferentiated MSCs, FBS and AS. All epigenetic changes occurred in a serum dependent manner which resulted in higher expression level of stemness genes in undifferentiated MSCs compared to differentiated MSCs and increased expression levels of osteogenic genes in AS compared to FBS. Adipogenic genes showed greater expression in FBS compared to AS. These findings have demonstrated the epigenetic influence of serum culture conditions on differentiation potential of MSCs, which suggest that AS is possibly more efficient serum for osteogenic differentiation of MSCs in cell therapy purposes. - Highlights: • Bone marrow derived MSC could proliferate in AS as well as in FBS. • Different serum conditions influence epigentic patterns of genes. • Osteogenic genes specifically up-regulate in AS in response to differentiation signals.« less

Development of an in vitro culture method for stepwise differentiation of mouse embryonic stem cells and induced pluripotent stem cells into mature osteoclasts.

PubMed

Nishikawa, Keizo; Iwamoto, Yoriko; Ishii, Masaru

2014-05-01

The development of methods for differentiation of embryonic stem cells (ESCs) and induced pluripotent stem cell (iPSCs) into functional cells have helped to analyze the mechanism regulating cellular processes and to explore cell-based assays for drug discovery. Although several reports have demonstrated methods for differentiation of mouse ESCs into osteoclast-like cells, it remains unclear whether these methods are applicable for differentiation of iPSCs to osteoclasts. In this study, we developed a simple method for stepwise differentiation of mouse ESCs and iPSCs into bone-resorbing osteoclasts based upon a monoculture approach consisting of three steps. First, based on conventional hanging-drop methods, embryoid bodies (EBs) were produced from mouse ESCs or iPSCs. Second, EBs were cultured in medium supplemented with macrophage colony-stimulating factor (M-CSF), and differentiated to osteoclast precursors, which expressed CD11b. Finally, ESC- or iPSC-derived osteoclast precursors stimulated with receptor activator of nuclear factor-B ligand (RANKL) and M-CSF formed large multinucleated osteoclast-like cells that expressed tartrate-resistant acid phosphatase and were capable of bone resorption. Molecular analysis showed that the expression of osteoclast marker genes such as Nfatc1, Ctsk, and Acp5 are increased in a RANKL-dependent manner. Thus, our procedure is simple and easy and would be helpful for stem cell-based bone research.

75 FR 32872 - Migratory Bird Hunting; Supplemental Proposals for Migratory Game Bird Hunting Regulations for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-10

... Game Bird Hunting Regulations for the 2010-11 Hunting Season; Notice of Meetings AGENCY: Fish and... migratory game birds for the 2010-11 hunting season. This supplement to the proposed rule provides the... addressed the establishment of seasons, limits, and other regulations for hunting migratory game birds under...

76 FR 57671 - Defense Federal Acquisition Regulation Supplement; Display of DoD Inspector General Fraud Hotline...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-16

... General Fraud Hotline Posters AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD... Regulation Supplement (DFARS) to require contractors to display the DoD fraud hotline poster in common work....203-14, Display of Hotline Poster(s). Government Accountability Office (GAO) Report GAO-09-591...

5 CFR 842.504 - Amount of annuity supplement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Amount of annuity supplement. 842.504... REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-BASIC ANNUITY Annuity Supplement § 842.504 Amount of annuity supplement. (a) Subject to paragraph (b) of this section, an annuity supplement is an...

48 CFR 1631.205-10 - Cost of money.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Section 1631.205-10 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES..., the supplemental information supporting submitted costs (such as the Supplemental Schedule of...

48 CFR 1631.205-10 - Cost of money.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Section 1631.205-10 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES..., the supplemental information supporting submitted costs (such as the Supplemental Schedule of...

Lysine and Leucine Deficiencies Affect Myocytes Development and IGF Signaling in Gilthead Sea Bream (Sparus aurata)

PubMed Central

Azizi, Sheida; Nematollahi, Mohammad Ali; Mojazi Amiri, Bagher; Vélez, Emilio J.; Lutfi, Esmail; Navarro, Isabel; Capilla, Encarnación; Gutiérrez, Joaquim

2016-01-01

Optimizing aquaculture production requires better knowledge of growth regulation and improvement in diet formulation. A great effort has been made to replace fish meal for plant protein sources in aquafeeds, making necessary the supplementation of such diets with crystalline amino acids (AA) to cover the nutritional requirements of each species. Lysine and Leucine are limiting essential AA in fish, and it has been demonstrated that supplementation with them improves growth in different species. However, the specific effects of AA deficiencies in myogenesis are completely unknown and have only been studied at the level of hepatic metabolism. It is well-known that the TOR pathway integrates the nutritional and hormonal signals to regulate protein synthesis and cell proliferation, to finally control muscle growth, a process also coordinated by the expression of myogenic regulatory factors (MRFs). This study aimed to provide new information on the impact of Lysine and Leucine deficiencies in gilthead sea bream cultured myocytes examining their development and the response of insulin-like growth factors (IGFs), MRFs, as well as key molecules involved in muscle growth regulation like TOR. Leucine deficiency did not cause significant differences in most of the molecules analyzed, whereas Lysine deficiency appeared crucial in IGFs regulation, decreasing significantly IGF-I, IGF-II and IGF-IRb mRNA levels. This treatment also down-regulated the gene expression of different MRFs, including Myf5, Myogenin and MyoD2. These changes were also corroborated by a significant decrease in proliferation and differentiation markers in the Lysine-deficient treatment. Moreover, both Lysine and Leucine limitation induced a significant down-regulation in FOXO3 gene expression, which deserves further investigation. We believe that these results will be relevant for the production of a species as appreciated for human consumption as it is gilthead sea bream and demonstrates the importance of an adequate level of Lysine in fishmeal diet formulation for optimum growth. PMID:26808650

Simple low cost differentiation of Candida auris from Candida haemulonii complex using CHROMagar Candida medium supplemented with Pal's medium.

PubMed

Kumar, Anil; Sachu, Arun; Mohan, Karthika; Vinod, Vivek; Dinesh, Kavitha; Karim, Shamsul

Candida auris is unique due to its multidrug resistance and misidentification as Candida haemulonii by commercial systems. Its correct identification is important to avoid inappropriate treatments. To develop a cheap method for differentiating C. auris from isolates identified as C. haemulonii by VITEK2. Fifteen C. auris isolates, six isolates each of C. haemulonii and Candida duobushaemulonii, and one isolate of Candida haemulonii var. vulnera were tested using CHROMagar Candida medium supplemented with Pal's agar for better differentiation. On CHROMagar Candida medium supplemented with Pal's agar all C. auris strains showed confluent growth of white to cream colored smooth colonies at 37°C and 42°C after 24 and 48h incubation and did not produce pseudohyphae. The isolates of the C. haemulonii complex, on the contrary, showed poor growth of smooth, light-pink colonies at 24h while at 48h the growth was semiconfluent with the production of pseudohyphae. C. haemulonii complex failed to grow at 42°C. We report a rapid and cheap method using CHROMagar Candida medium supplemented with Pal's agar for differentiating C. auris from isolates identified as C. haemulonii by VITEK2. Copyright © 2017 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

Binding of Y-P30 to Syndecan 2/3 Regulates the Nuclear Localization of CASK

PubMed Central

Landgraf, Peter; Mikhaylova, Marina; Macharadze, Tamar; Borutzki, Corinna; Zenclussen, Ana-Claudia; Wahle, Petra; Kreutz, Michael R.

2014-01-01

The survival promoting peptide Y-P30 has documented neuroprotective effects as well as cell survival and neurite outgrowth promoting activity in vitro and in vivo. Previous work has shown that multimerization of the peptide with pleiotrophin (PTN) and subsequent binding to syndecan (SDC) -2 and -3 is involved in its neuritogenic effects. In this study we show that Y-P30 application regulates the nuclear localization of the SDC binding partner Calcium/calmodulin-dependent serine kinase (CASK) in neuronal primary cultures during development. In early development at day in vitro (DIV) 8 when mainly SDC-3 is expressed supplementation of the culture medium with Y-P30 reduces nuclear CASK levels whereas it has the opposite effect at DIV 18 when SDC-2 is the dominant isoform. In the nucleus CASK regulates gene expression via its association with the T-box transcription factor T-brain-1 (Tbr-1) and we indeed found that gene expression of downstream targets of this complex, like the GluN2B NMDA-receptor, exhibits a corresponding down- or up-regulation at the mRNA level. The differential effect of Y-P30 on the nuclear localization of CASK correlates with its ability to induce shedding of the ectodomain of SDC-2 but not -3. shRNA knockdown of SDC-2 at DIV 18 and SDC-3 at DIV 8 completely abolished the effect of Y-P30 supplementation on nuclear CASK levels. During early development a protein knockdown of SDC-3 also attenuated the effect of Y-P30 on axon outgrowth. Taken together these data suggest that Y-P30 can control the nuclear localization of CASK in a SDC-dependent manner. PMID:24498267

30 CFR 556.12 - Supplemental sales.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 2 2013-07-01 2013-07-01 false Supplemental sales. 556.12 Section 556.12... Management, General § 556.12 Supplemental sales. (a) The Secretary may conduct a supplemental sale in accordance with the provisions of this section. (b) Supplemental sales shall be governed by the regulations...

30 CFR 556.12 - Supplemental sales.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 2 2012-07-01 2012-07-01 false Supplemental sales. 556.12 Section 556.12... Management, General § 556.12 Supplemental sales. (a) The Secretary may conduct a supplemental sale in accordance with the provisions of this section. (b) Supplemental sales shall be governed by the regulations...

30 CFR 556.12 - Supplemental sales.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 2 2014-07-01 2014-07-01 false Supplemental sales. 556.12 Section 556.12... Management, General § 556.12 Supplemental sales. (a) The Secretary may conduct a supplemental sale in accordance with the provisions of this section. (b) Supplemental sales shall be governed by the regulations...

Influence of the dietary supplement health and education act on consumer beliefs about the safety and effectiveness of dietary supplements.

PubMed

Dodge, Tonya; Litt, Dana; Kaufman, Annette

2011-03-01

The authors conducted two studies to examine the influence of the U.S. Dietary Supplement Health and Education Act (DSHEA) on consumer beliefs about the safety and effectiveness of dietary supplements. Study 1 manipulated information about Food and Drug Administration (FDA) approval in the context of a dietary supplement designed to improve immune system functioning. Study 2 tested the effect of an educational intervention designed to improve knowledge about the DSHEA. Results of Study 1 highlighted deficits in consumer knowledge about FDA regulation of dietary supplements. Results also showed that information about FDA approval failed to have a statistically significant effect on beliefs about safety or effectiveness of the dietary supplement. Results of Study 2 showed that participants who were educated about the regulation of dietary supplements under the DSHEA rated dietary supplements as less safe and less effective than did participants in the control condition. The authors discuss the implications for consumers in the United States and for public policy.

77 FR 43477 - Defense Federal Acquisition Regulation Supplement: Ownership of Offeror (DFARS Case 2011-D044)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-24

... DEPARTMENT OF DEFENSE 48 CFR Parts 204, 212, and 252 RIN 0750-AH58 Defense Federal Acquisition Regulation Supplement: Ownership of Offeror (DFARS Case 2011-D044) AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Proposed rule. SUMMARY: DoD is proposing to amend the...

Tryptophan promotes morphological and physiological differentiation in Streptomyces coelicolor.

PubMed

Palazzotto, Emilia; Renzone, Giovanni; Fontana, Pietro; Botta, Luigi; Scaloni, Andrea; Puglia, Anna Maria; Gallo, Giuseppe

2015-12-01

The molecular mechanisms regulating tryptophan biosynthesis in actinomycetes are poorly understood; similarly, the possible roles of tryptophan in the differentiation program of microorganism life-cycle are still underexplored. To unveil the possible regulatory effect of this amino acid on gene expression, an integrated study based on quantitative teverse transcription-PCR (qRT-PCR) and proteomic approaches was performed on the actinomycete model Streptomyces coelicolor. Comparative analyses on the microorganism growth in a minimal medium with or without tryptophan supplementation showed that biosynthetic trp gene expression in S. coelicolor is not subjected to a negative regulation by the presence of the end product. Conversely, tryptophan specifically induces the transcription of trp genes present in the biosynthetic gene cluster of the calcium-dependent antibiotic (CDA), a lipopeptide containing D- and L-tryptophan residues. In addition, tryptophan stimulates the transcription of the CDA gene cluster regulator cdaR and, coherently, CDA production. Surprisingly, tryptophan also promotes the production of actinorhodin, another antibiotic that does not contain this amino acid in its structure. Combined 2D-DIGE and nano liquid chromatography electrospray linear ion trap tandem mass spectrometry (LC-ESI-LIT-MS/MS) analyses revealed that tryptophan exerts a growth-stage-dependent global effect on S. coelicolor proteome, stimulating anabolic pathways and promoting the accumulation of key factors associated with morphological and physiological differentiation at the late growth stages. Phenotypic observations by scanning electron microscopy and spore production assays demonstrated an increased sporulation in the presence of tryptophan. Transcriptional analysis of catabolic genes kynA and kynB suggested that the actinomycete also uses tryptophan as a carbon and nitrogen source. In conclusion, this study originally provides the molecular basis underlying the stimulatory effect of tryptophan on the production of antibiotics and morphological development program of this actinomycete.

T cell-intrinsic requirement for NF-kappa B induction in postdifferentiation IFN-gamma production and clonal expansion in a Th1 response.

PubMed

Corn, Radiah A; Aronica, Mark A; Zhang, Fuping; Tong, Yingkai; Stanley, Sarah A; Kim, Se Ryoung Agnes; Stephenson, Linda; Enerson, Ben; McCarthy, Susan; Mora, Ana; Boothby, Mark

2003-08-15

NF-kappaB/Rel transcription factors are linked to innate immune responses and APC activation. Whether and how the induction of NF-kappaB signaling in normal CD4(+) T cells regulates effector function are not well-understood. The liberation of NF-kappaB dimers from inhibitors of kappaB (IkappaBs) constitutes a central checkpoint for physiologic regulation of most forms of NF-kappaB. To investigate the role of NF-kappaB induction in effector T cell responses, we targeted inhibition of the NF-kappaB/Rel pathway specifically to T cells. The Th1 response in vivo is dramatically weakened when T cells defective in their NF-kappaB induction (referred to as IkappaBalpha(DeltaN) transgenic cells) are activated by a normal APC population. Analyses in vivo, and IL-12-supplemented T cell cultures in vitro, reveal that the mechanism underlying this T cell-intrinsic requirement for NF-kappaB involves activation of the IFN-gamma gene in addition to clonal expansion efficiency. The role of NF-kappaB in IFN-gamma gene expression includes a modest decrease in Stat4 activation, T box expressed in T cell levels, and differentiation efficiency along with a more prominent postdifferentiation step. Further, induced expression of Bcl-3, a trans-activating IkappaB-like protein, is decreased in T cells as a consequence of NF-kappaB inhibition. Together, these findings indicate that NF-kappaB induction in T cells regulates efficient clonal expansion, Th1 differentiation, and IFN-gamma production by Th1 lymphocytes at a control point downstream from differentiation.

Feeding Low or Pharmacological Concentrations of Zinc Oxide Changes the Hepatic Proteome Profiles in Weaned Piglets

PubMed Central

Bondzio, Angelika; Pieper, Robert; Gabler, Christoph; Weise, Christoph; Schulze, Petra; Zentek, Juergen; Einspanier, Ralf

2013-01-01

Pharmacological levels of zinc oxide can promote growth and health of weaning piglets, but the underlying molecular mechanisms are yet not fully understood. The aim of this study was to determine changes in the global hepatic protein expression in response to dietary zinc oxide in weaned piglets. Nine half-sib piglets were allocated to three dietary zinc treatment groups (50, 150, 2500 mg/kg dry matter). After 14 d, pigs were euthanized and liver samples taken. The increase in hepatic zinc concentration following dietary supplementation of zinc was accompanied by up-regulation of metallothionein mRNA and protein expression. Global hepatic protein profiles were obtained by two-dimensional difference gel electrophoresis following matrix-assisted laser desorption ionization/time-of-flight mass spectrometry. A total of 15 proteins were differentially (P<0.05) expressed between groups receiving control (150 mg/kg) or pharmacological levels of zinc (2500 mg/kg) with 7 down- (e.g. arginase1, thiosulfate sulfurtransferase, HSP70) and 8 up-regulated (e.g. apolipoprotein AI, transferrin, C1-tetrahydrofolate synthase) proteins. Additionally, three proteins were differentially expressed with low zinc supply (50 mg/kg Zn) in comparison to the control diet. The identified proteins were mainly associated with functions related to cellular stress, transport, metabolism, and signal transduction. The differential regulation was evaluated at the mRNA level and a subset of three proteins of different functional groups was selected for confirmation by western blotting. The results of this proteomic study suggest that zinc affects important liver functions such as blood protein secretion, protein metabolism, detoxification and redox homeostasis, thus supporting the hypothesis of intermediary effects of pharmacological levels of zinc oxide fed to pigs. PMID:24282572

How does the nucleolar number involve in muscle fiber atrophy? Response to Beta-guanidinopropionic acid supplementation

NASA Astrophysics Data System (ADS)

Matsuoka, Yoshikazu; Kawano, Fuminori; Oke, Yoshihiko; Higo, Yoko; Umemoto, Shiori; Kawabe, Naoko; Wang, Xiaodong; Terada, Masahiro; Shinoda, Yo; Lan, Yongbo; Ogura, Akihiko; Ohira, Yoshinobu

2005-08-01

To investigate the relationship between the myonuclear capability and the number of nucleolus during muscle remodeling, oral supplementation of β-guanidinopropionic acid (β-GPA) on the characteristics of plantaris muscle fibers was performed for 2 weeks in adult male Wistar rats. Effects of β-GPA supply in culture medium on mouse myoblast cell line C2C12 was also studied. The mean fiber cross-sectional area was less in β-GPA-fed than control rats (35%, p<0.05). And the myonuclear number per mm of fiber length was significantly greater (35%, p<0.05). Thus, the cytoplasmic volume per myonucleus was less (52%) in β-GPA-fed rats (p<0.05). The number of nucleolar organizer regions (NORs) per myonucleus was also less (17%) in β-GPA-fed group (p<0.05). The number of NORs was greater (14%) in the myoblasts cultured with creatine phosphate compared with non-supplemented control, but it was less (10%) in the myoblasts cultured with β-GPA (p<0.05). Further, the number of NORs was also greater (26%) in the differentiated myotubes cultured with creatine phosphate (p<0.05). The results suggested that the nucleoli may play some role(s) in the regulation of muscle fiber size and its number may be influenced by creatine content.

Small Molecule Supplements Improve Cultured Megakaryocyte Polyploidization by Modulating Multiple Cell Cycle Regulators.

PubMed

Zou, Xiaojing; Qu, Mingyi; Fang, Fang; Fan, Zeng; Chen, Lin; Yue, Wen; Xie, Xiaoyan; Pei, Xuetao

2017-01-01

Platelets (PLTs) are produced by megakaryocytes (MKs) that completed differentiation and endomitosis. Endomitosis is an important process in which the cell replicates its DNA without cytokinesis and develops highly polyploid MK. In this study, to gain a better PLTs production, four small molecules (Rho-Rock inhibitor (RRI), nicotinamide (NIC), Src inhibitor (SI), and Aurora B inhibitor (ABI)) and their combinations were surveyed as MK culture supplements for promoting polyploidization. Three leukemia cell lines as well as primary mononuclear cells were chosen in the function and mechanism studies of the small molecules. In an optimal culture method, cells were treated with different small molecules and their combinations. The impact of the small molecules on megakaryocytic surface marker expression, polyploidy, proliferation, and apoptosis was examined for the best MK polyploidization supplement. The elaborate analysis confirmed that the combination of SI and RRI together with our MK induction system might result in efficient ploidy promotion. Our experiments demonstrated that, besides direct downregulation on the expression of cytoskeleton protein actin, SI and RRI could significantly enhance the level of cyclins through the suppression of p53 and p21. The verified small molecule combination might be further used in the in vitro PLT manufacture and clinical applications.

Small Molecule Supplements Improve Cultured Megakaryocyte Polyploidization by Modulating Multiple Cell Cycle Regulators

PubMed Central

Fang, Fang; Chen, Lin; Yue, Wen

2017-01-01

Platelets (PLTs) are produced by megakaryocytes (MKs) that completed differentiation and endomitosis. Endomitosis is an important process in which the cell replicates its DNA without cytokinesis and develops highly polyploid MK. In this study, to gain a better PLTs production, four small molecules (Rho-Rock inhibitor (RRI), nicotinamide (NIC), Src inhibitor (SI), and Aurora B inhibitor (ABI)) and their combinations were surveyed as MK culture supplements for promoting polyploidization. Three leukemia cell lines as well as primary mononuclear cells were chosen in the function and mechanism studies of the small molecules. In an optimal culture method, cells were treated with different small molecules and their combinations. The impact of the small molecules on megakaryocytic surface marker expression, polyploidy, proliferation, and apoptosis was examined for the best MK polyploidization supplement. The elaborate analysis confirmed that the combination of SI and RRI together with our MK induction system might result in efficient ploidy promotion. Our experiments demonstrated that, besides direct downregulation on the expression of cytoskeleton protein actin, SI and RRI could significantly enhance the level of cyclins through the suppression of p53 and p21. The verified small molecule combination might be further used in the in vitro PLT manufacture and clinical applications. PMID:29201898

Freeze-dried strawberry and blueberry attenuates diet-induced obesity and insulin resistance in rats by inhibiting adipogenesis and lipogenesis.

PubMed

Aranaz, Paula; Romo-Hualde, Ana; Zabala, María; Navarro-Herrera, David; Ruiz de Galarreta, Marina; Gil, Ana Gloria; Martinez, J Alfredo; Milagro, Fermín I; González-Navarro, Carlos J

2017-11-15

Obesity and type 2-diabetes are becoming a worldwide health problem, reiterating the importance of alternative therapies to tackle their progression. Here, we hypothesized that supplementation of diet with 6% w/w of a freeze-dried strawberry-blueberry (5 : 1) powder (FDSB) could exert beneficial metabolic effects on Wistar rats. FDSB-supplemented animals experienced significantly reduced body weight gain, food efficiency and visceral adiposity accumulation in two independent experiments. FDSB supplementation also contributed to lower area under the curve after an intraperitoneal GTT and reduced serum insulin levels and an insulin resistance index (IR-HOMA) in HFS diet-fed animals, together with reduced plasma MCP-1 inflammation marker concentrations. Gene expression analysis in retroperitoneal adipocytes from experiment 1 and 3T3-L1 cells showed that FDSB inhibited adipogenesis and lipogenesis through down-regulation of Pparg, Cebpa, Lep, Fasn, Scd-1 and Lpl gene expression. Untargeted metabolomics identified the cis isomer of resveratrol-3-glucoside-sulphate as a metabolite differentially increased in FDSB-treated serum samples, which corresponds to a strawberry metabolite that could be considered a serum biomarker of FDSB-intake. Our results suggest that FDSB powder might be useful for treatment/prevention of obesity-related diseases.

[Fat and fatty acids chosen in chocolates content].

PubMed

Tarkowski, Andrzej; Kowalczyk, Magdalena

2007-01-01

The objective of present work was to comparison of fat and chosen fatty acid in chocolates with, approachable on national market. In the investigations on fat and fatty acids content in the milk chocolates, there were used 14 chocolates, divided into 3 groups either without, with supplements and stuffing. Crude fat content in the chocolates was determined on Soxhlet automatic apparatus. The saturated ad nsaturated acids content was determined using gas chromatographic method. Content of fat and fatty cids in chocolates were differentiation. The highest crude fat content was finding in chocolates with tuffing (31.8%) and without supplements (28.9%). The sum of saturated fatty acids content in fat above 62%) was highest and low differentiation in the chocolates without supplements. Among of saturated and unsaturated fatty acids depended from kind of chocolates dominated, palmitic, stearic, oleic and, linoleic acids. Supplements of nut in chocolates had on influence of high oleic and linoleic level

Differential effects of EPA, DPA and DHA on cardio-metabolic risk factors in high-fat diet fed mice.

PubMed

Guo, Xiao-Fei; Sinclair, Andrew J; Kaur, Gunveen; Li, Duo

2017-09-22

The aim of the present study was to assess and compare the effects of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) supplementation on lipid metabolism in 4 month-old male C57BL/6J mice fed a high-fat diet. The high-fat fed mice showed evidence of fatty liver, obesity and insulin resistance after being on the high-fat diet for 6 weeks compared with the control low-fat diet fed mice. Supplementation of the high-fat diet with either EPA, DPA or DHA prevented the fatty liver, prevented high serum cholesterol and serum glucose and prevented high liver cholesterol levels. DPA (but not EPA or DHA) was associated with a significantly improved homeostasis model assessment of insulin resistance (HOMA-IR) compared with the high-fat fed mice. Supplementation with DPA and DHA both prevented the decreased serum adiponectin levels, compared with EPA and the high-fat diet. In addition, supplementation with DPA and DHA both prevented the increased serum alanine aminotransferase (ALT) levels compared with EPA and the high-fat group, which can be attributed to down-regulation of TLR-4/NF-κB signaling pathway and decreasing lipogenesis in the liver. Therefore, DPA and DHA seem to exert similar effects in cardio-metabolic protection against the high-fat diet and these effects seem to be different to those of EPA. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Food supplements on the Hungarian market: regulations of marketing and of the composition of the products].

PubMed

Lugasi, Andrea; Horacsek, Márta; Martos, Eva

2010-09-26

According to recent legislation, food supplements are foodstuffs with the purpose of supplementing normal diet. Food supplements are concentrated sources of nutrients such as vitamins and minerals and other substances with a physiological or nutritional effect. In Hungary, marketing of food supplements has not been bound to pre-market authorization since joining to the European Union. The food business operator, who is responsible for production or distribution of the product, must notify it at National Institute for Food and Nutrition Science latest at the time when the product has been placed on the market and it can be distributed simultaneously. Distribution, ingredients, and all those information which appear on the label are determined by numerous regulations and prescriptions but at the same time the lack of harmonized legislation at certain places may cause a lot of problems on Community level. The first part of the study shows the laws and regulations influencing the distribution and ingredients of food supplements, while the main target of the second part is to introduce the evaluation process of components from nutritional and physiological point of view, and the role played by the food supplements in nutrition.

Culture of human mesenchymal stem cells using a candidate pharmaceutical grade xeno-free cell culture supplement derived from industrial human plasma pools.

PubMed

Díez, José M; Bauman, Ewa; Gajardo, Rodrigo; Jorquera, Juan I

2015-03-13

Fetal bovine serum (FBS) is an animal product used as a medium supplement. The animal origin of FBS is a concern if cultured stem cells are to be utilized for human cell therapy. Therefore, a substitute for FBS is desirable. In this study, an industrial, xeno-free, pharmaceutical-grade supplement for cell culture (SCC) under development at Grifols was tested for growth of human mesenchymal stem cells (hMSCs), cell characterization, and differentiation capacity. SCC is a freeze-dried product obtained through cold-ethanol fractionation of industrial human plasma pools from healthy donors. Bone marrow-derived hMSC cell lines were obtained from two commercial suppliers. Cell growth was evaluated by culturing hMSCs with commercial media or media supplemented with SCC or FBS. Cell viability and cell yield were assessed with an automated cell counter. Cell surface markers were studied by indirect immunofluorescence assay. Cells were cultured then differentiated into adipocytes, chondrocytes, osteoblasts, and neurons, as assessed by specific staining and microscopy observation. SCC supported the growth of commercial hMSCs. Starting from the same number of seeded cells in two consecutive passages of culture with medium supplemented with SCC, hMSC yield and cell population doubling time were equivalent to the values obtained with the commercial medium and was consistent among lots. The viability of hMSCs was higher than 90%, while maintaining the characteristic phenotype of undifferentiated hMSCs (positive for CD29, CD44, CD90, CD105, CD146, CD166 and Stro-1; negative for CD14 and CD19). Cultured hMSCs maintained the potential for differentiation into adipocytes, chondrocytes, osteoblasts, and neurons. The tested human plasma-derived SCC sustains the adequate growth of hMSCs, while preserving their differentiation capacity. SCC can be a potential candidate for cell culture supplement in advanced cell therapies.

Triennial Growth Symposium: important roles for L-glutamine in swine nutrition and production.

PubMed

Wu, G; Bazer, F W; Johnson, G A; Knabe, D A; Burghardt, R C; Spencer, T E; Li, X L; Wang, J J

2011-07-01

L-Glutamine (Gln) has traditionally not been considered a nutrient needed in diets for livestock species or even mentioned in classic animal nutrition textbooks. This is due to previous technical difficulties in Gln analysis and the unsubstantiated assumption that animals can synthesize sufficient amounts of Gln to meet their needs. Consequently, the current (1998) version of NRC does not recommend dietary Gln requirements for swine. This lack of knowledge about Gln nutrition has contributed to suboptimal efficiency of global pig production. Because of recent advances in research, Gln is now known to be an abundant AA in physiological fluids and proteins and a key regulator of gene expression. Additionally, Gln can regulate cell signaling via the mammalian target of rapamycin pathway, adenosine monophosphate-activated protein kinase, extracellular signal-related kinase, Jun kinase, mitogen-activated protein kinase, and nitric oxide. The exquisite integration of Gln-dependent regulatory networks has profound effects on cell proliferation, differentiation, migration, metabolism, homeostasis, survival, and function. As a result of translating basic research into practice, dietary supplementation with 1% Gln maintains gut health and prevents intestinal dysfunction in low-birth-weight or early-weaned piglets while increasing their growth performance and survival. In addition, supplementing 1% Gln to a corn- and soybean-meal-based diet between d 90 and 114 of gestation ameliorates fetal growth retardation in gilts and reduces preweaning mortality of piglets. Furthermore, dietary supplementation with 1% Gln enhances milk production by lactating sows. Thus, adequate amounts of dietary Gln, a major nutrient, are necessary to support the maximum growth, development, and production performance of swine. © 2011 American Society of Animal Science. All rights reserved.

Effect of alpha-lipoic acid on relieving ammonia stress and hepatic proteomic analyses of broilers.

PubMed

Lu, M; Bai, J; Xu, B; Sun, Q Y; Wei, F X; Tang, X F; Zhang, H F; Li, J; Wang, G L; Yin, Q Q; Li, S Y

2017-01-01

Ammonia in poultry houses not only affects worker health but also induces a variety of poultry diseases. Alpha-lipoic acid (LA) is an effective antioxidant that protects cells against oxidative injury during various toxic and pathological processes. This study was designed to evaluate the mitigating effects of LA supplementation on ammonia stress and hepatic proteome changes in broilers. Male broilers (22 d old) were allocated to 3 groups: (1) a control group without ammonia stress (CTRL); (2) exposure to 70 ppm ammonia (AM); and (3) exposure to 70 ppm ammonia and dietary administration of 300 mg/kg LA (AM+LA). Ammonia exposure significantly decreased broiler growth performance and plasma glutathione peroxidase activity (P < 0.05), and increased plasma malondialdehyde content and glutamic-pyruvic transaminase activity (P < 0.05). These negative effects were eliminated by LA supplementation. Comparative proteomic analyses revealed 291 differentially expressed proteins in the AM group compared to the CTRL and AM+LA groups. A total of 30 proteins were differentially expressed between the AM/CTRL and (AM+LA)/AM groups. The addition of LA restored 24 of these proteins to control levels; these proteins were mainly related to transcription regulation, detoxification, protein translation and degradation, and immune and stress responses. The differentially expressed proteins included the high mobility group box (HMGB) and glutathione S-transferase (GST), which is closely related to immune response and oxidative stress, and collagens, which are implicated in liver injury. The addition of LA to broiler diet may reduce ammonia toxicity by maintaining the antioxidant system, xenobiotic metabolism, and metabolic pathways. © 2016 Poultry Science Association Inc.

Can we induce spermatogenesis in the domestic cat using an in vitro tissue culture approach?

PubMed Central

Amaral, Sandra; Tavares, Renata S.; Schlatt, Stefan; Ramalho-Santos, João

2018-01-01

The reduced number of animals in most wild felid populations implies a loss of genetic diversity. The death of juveniles, prior to the production of mature sperm, represents a loss of potential genetic contribution to future populations. Since 2011 mouse testicular organ culture has introduced an alternative mechanism to produce sperm in vitro from immature tissue. However, extension of this technology to other species has remained limited. We have used the domestic cat (Felis catus) as a model for wild felids to investigate spermatogenesis initiation and regulation, with the mouse serving as a control species. Testicular tissue fragments were cultured in control medium or medium supplemented with knockout serum replacement (KSR), AlbuMax, beta-estradiol or AlbuMax plus beta-estradiol. Contrary to expectations, and unlike results obtained in mouse controls, no germ cell differentiation could be detected. The only germ cells observed after six weeks of culture were spermatogonia regardless of the initial stage of tubule development in the donor tissue. Moreover, the number of spermatogonia decreased with time in culture in all media tested, especially in the medium supplemented with KSR, while AlbuMax had a slight protective effect. The combination of AlbuMax and beta-estradiol led to an increase in the area occupied by seminiferous tubules, and thus to an increase in total number of spermatogonial cells. Considering all the media combinations tested the stimulus for felid germ cell differentiation in this type of system seems to be different from the mouse. Studies using other triggers of differentiation and tissue survival factors should be performed to pursue this technology for the genetic diversity preservation in wild felids. PMID:29414992

[Marrow stromal cells cultured in N2-supplemented medium: implications on the generation of neural cells].

PubMed

Castillo-Díaz, L; de la Cuétara-Bernal, K; García-Varona, A Y

Most of the culture system for in vitro maintenance and neural differentiation of marrow stromal cells (MSCs) use synthetic media supplemented with 10 or 20% fetal bovine serum (FBS). Serum, however, is comprised of unknown quantities of undefined substances which could interfere the effect of exogenous substances on neural differentiation of MSCs. AIM. Here we describe survival of MSCs cultured in culture conditions where serum was reduced at 0.5 and 1% using Bottenstein and Sato's N2 formula (1979) and poly-L-lysine (PLL)-coated substrate. Stromal cells isolated from rat femurs were cultivated in Dulbecco's modified Eagle medium at 10, 1, 0.5% FBS or in serum free medium containing N2 formula. In serum free medium or at low serum concentration culture surface was coated with PLL. Cell survival was determined by MTT method or by counting viable cells. Survival of MSCs cultured in N2 supplement was reduced at about 40% of that observed in 10% FBS containing medium. Under these conditions cell morphology was also affected. When N2 containing medium was supplemented with FBS at 0.5 or 1% a significant increase of survival with respect to that observed in N2-supplemented cultures was observed. Cells seeded on PLL-coated surface increased their survival by contrast with their homologous cultures seeded on uncoated surface. The culture system which combines N2 formula with FBS 1% and PLL-coated surface is useful for the maintenance of MSCs. These conditions offer advantages for the study of differentiation of these cells because they reduce the confounding influence of serum. The possible implication of this culture system for the study of neural differentiation by these cells is discussed.

Understanding supplement use: an application of temporal self-regulation theory.

PubMed

Allom, Vanessa; Mullan, Barbara; Clifford, Allison; Rebar, Amanda

2018-02-01

Vitamin and mineral supplement use is increasing worldwide. As evidence of the effects of these practices are equivocal at best, it is important to determine why individuals engage in vitamin and mineral supplement use through the application of a theoretical framework. The aim of this study was to employ temporal self-regulation theory (TST) to establish the determinants of supplement use. A cross-sectional design was used with a sample of 121 individuals who consume vitamins or minerals as dietary supplements. Hierarchical regression analyses were conducted to determine the influence of intention, habit, self-control, and the interaction between intention and habit and self-control on the frequency of supplement use. The model accounted for a significant proportion of variance in behaviour (R 2  = .44) with intention and habit significantly related to supplement use. Self-control moderated the relationship between intention and behaviour indicating that intention was not related to behaviour when self-control was low. The TST model offers a satisfactory account of supplement use and provides avenues for interventions aimed at increasing safe and beneficial supplement use and decreasing potentially harmful supplement use.

17 CFR 230.418 - Supplemental information.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false Supplemental information. 230... RULES AND REGULATIONS, SECURITIES ACT OF 1933 General Requirements § 230.418 Supplemental information. (a) The Commission or its staff may, where it is deemed appropriate, request supplemental information...

48 CFR 836.578 - Changes-supplement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Changes-supplement. 836... CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Contract Clauses 836.578 Changes—supplement. (a) The contracting officer shall insert the clause at 852.236-88, Contract changes—supplement...

Use of nutritional supplements in sports: risks, knowledge, and behavioural-related factors.

PubMed

Molinero, O; Márquez, S

2009-01-01

A large number of recreational and elite athletes use nutritional supplements in hopes of improving performance. These aids can be costly and potentially harmful, and the advertised ergogenic gains are often based on little or no scientific evidence. Due to the lack of regulation of the dietary supplement industry, an abundance of supplement products of dubious value, content, and quality are now available around the world. Many supplement products contain substances that are prohibited in sport or that have been associated with significant morbidity and mortality. For athletes, lack of knowledge or misinformation has been established despite numerous sources of information being available, and the reasons for, and implications of, unsupervised and unrestricted supplement use require further attention. In addition to the necessity of an appropriate regulation of dietary supplements, nutritional education and scientifically sound guidance for athletes is required. Intervention and prevention efforts should be particularly targeted to adolescents.

Interleukins-17 and 27 promote liver regeneration by sequentially inducing progenitor cell expansion and differentiation.

PubMed

Guillot, Adrien; Gasmi, Imène; Brouillet, Arthur; Ait-Ahmed, Yeni; Calderaro, Julien; Ruiz, Isaac; Gao, Bin; Lotersztajn, Sophie; Pawlotsky, Jean-Michel; Lafdil, Fouad

2018-03-01

Liver progenitor cells (LPCs)/ductular reactions (DRs) are associated with inflammation and implicated in the pathogenesis of chronic liver diseases. However, how inflammation regulates LPCs/DRs remains largely unknown. Identification of inflammatory processes that involve LPC activation and expansion represent a key step in understanding the pathogenesis of liver diseases. In the current study, we found that diverse types of chronic liver diseases are associated with elevation of infiltrated interleukin (IL)-17-positive (+) cells and cytokeratin 19 (CK19) + LPCs, and both cell types colocalized and their numbers positively correlated with each other. The role of IL-17 in the induction of LPCs was examined in a mouse model fed a choline-deficient and ethionine-supplemented (CDE) diet. Feeding of wild-type mice with the CDE diet markedly elevated CK19 + Ki67 + proliferating LPCs and hepatic inflammation. Disruption of the IL-17 gene or IL-27 receptor, alpha subunit (WSX-1) gene abolished CDE diet-induced LPC expansion and inflammation. In vitro treatment with IL-17 promoted proliferation of bipotential murine oval liver cells (a liver progenitor cell line) and markedly up-regulated IL-27 expression in macrophages. Treatment with IL-27 favored the differentiation of bipotential murine oval liver cells and freshly isolated LPCs into hepatocytes. Conclusion : The current data provide evidence for a collaborative role between IL-17 and IL-27 in promoting LPC expansion and differentiation, respectively, thereby contributing to liver regeneration. ( Hepatology Communications 2018;2:329-343).

Application of HC-AFW1 Hepatocarcinoma Cells for Mechanistic Studies: Regulation of Cytochrome P450 2B6 Expression by Dimethyl Sulfoxide and Early Growth Response 1.

PubMed

Petzuch, Barbara; Groll, Nicola; Schwarz, Michael; Braeuning, Albert

2015-11-01

Various exogenous compounds, for example, the drugs bupropione and propofol, but also various cytostatics, are metabolized in the liver by the enzyme cytochrome P450 (P450) CYP2B6. Transcription from the CYP2B6 gene is regulated mainly via the transcription factors constitutive androstane receptor (CAR) and pregnane-X-receptor (PXR). Most hepatic cell lines express no or only low levels of CYP2B6 because of loss of these two regulators. Dimethyl sulfoxide (DMSO) is frequently used in liver cell cultivation and is thought to affect the expression of various P450 isoforms by inducing or preserving cellular differentiation. We studied the effects of up to 1.5% of DMSO as cell culture medium supplement on P450 expression in hepatocarcinoma cells from line HC-AFW1. DMSO did not induce differentiation of the HC-AFW1 cell line, as demonstrated by unaltered levels of selected mRNA markers important for hepatocyte differentiation, and also by the lack of a DMSO effect on a broader spectrum of P450s. By contrast, CYP2B6 mRNA was strongly induced by DMSO. This process was independent of CAR or PXR activation. Interestingly, elevated transcription of CYP2B6 was accompanied by a simultaneous induction of early growth response 1 (EGR1), a transcription factor known to influence the expression of CYP2B6. Expression of wild-type EGR1 or of a truncated, dominant-negative EGR1 mutant was able to mimic or attenuate the DMSO effect, respectively. These findings demonstrate that EGR1 is involved in the regulation of CYP2B6 by DMSO in HC-AFW1 cells. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

76 FR 13327 - Defense Federal Acquisition Regulation Supplement; Display of DoD Inspector General Fraud Hotline...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-11

... Posters (DFARS Case 2010-D026) AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD... Regulation Supplement (DFARS) to require contractors to display the DoD fraud hotline poster in common work... providing a DFARS clause to use in lieu of the FAR clause 52.203-14, Display of Hotline Poster(s). GAO...

76 FR 58122 - Defense Federal Acquisition Regulation Supplement; Material Inspection and Receiving Report...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-20

...DoD is issuing a final rule amending the Defense Federal Acquisition Regulation Supplement (DFARS), Appendix F, Material Inspection and Receiving Report, to incorporate new procedures for using the electronic Wide Area WorkFlow (WAWF) Receiving Report.

7 CFR 1924.49 - State supplements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false State supplements. 1924.49 Section 1924.49 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS... REGULATIONS CONSTRUCTION AND REPAIR Planning and Performing Construction and Other Development § 1924.49 State...

[Marketability of food supplements - criteria for the legal assessment].

PubMed

Breitweg-Lehmann, Evelyn

2017-03-01

To be placed on the market legally, food supplements have to meet national and European food law regulations. This is true for all substances used as well as for the labeling on the packaging of and the advertising for food supplements. The food business operator is responsible for its compliance with all regulations. Therefore, in this article, a concise step-by-step assessment is presented, covering all necessary legal requirements to market food supplements. Additionally, all steps are visualized in a flow chart. All vitamins, minerals and other substances used have to meet the legal conditions. Food business operators have to make sure that their products do not contain medicinal ingredients based on their pharmacologic effect. It is prohibited to place medicinal products as food supplements on the market. Furthermore, food business operators have to make sure that their products are not non-authorized novel foods according to the novel food regulation (EC) no. 258/97. Also, food supplements have to meet the requirements of article 14 of Regulation (EC) No. 178/2002 concerning the safety of foodstuff. Food shall not be placed on the market if it is unsafe. For food supplements that fail the German food-related legal standards but are legally manufactured in another EU member state or are legally put into circulation, the importer requires the so-called general disposition, which must be applied for at the BVL according to § 54 of the German Food and Feed Act. Another possibility for food which fails to meet German food law is to apply for a certificate of exemption according to § 68 of the Food and Feed Act. The food business operator has to meet the harmonized regulations concerning maximum and minimum levels of additives, flavors and enzymes. The packaging has to meet the compulsory labeling as well the voluntary labeling, like health claims. The BVL is also the relevant authority for other tasks concerning food supplements. A figure shows all notifications since 2005 of food supplements in Germany at the BVL. Additionally, an overview for notifications in the rapid alert system for food and feed concerning food supplements is given as well as a brief introduction into the survey of food supplements marketed on the internet.

49 CFR 388.8 - Supplemental agreements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 5 2011-10-01 2011-10-01 false Supplemental agreements. 388.8 Section 388.8... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY REGULATIONS COOPERATIVE AGREEMENTS WITH STATES § 388.8 Supplemental agreements. The terms specified in this part may be supplemented from time to...

49 CFR 388.8 - Supplemental agreements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false Supplemental agreements. 388.8 Section 388.8... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY REGULATIONS COOPERATIVE AGREEMENTS WITH STATES § 388.8 Supplemental agreements. The terms specified in this part may be supplemented from time to...

49 CFR 388.8 - Supplemental agreements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 5 2013-10-01 2013-10-01 false Supplemental agreements. 388.8 Section 388.8... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY REGULATIONS COOPERATIVE AGREEMENTS WITH STATES § 388.8 Supplemental agreements. The terms specified in this part may be supplemented from time to...

Combined effects of dietary arginine, leucine and protein levels on fatty acid composition and gene expression in the muscle and subcutaneous adipose tissue of crossbred pigs.

PubMed

Madeira, Marta S; Pires, Virgínia M R; Alfaia, Cristina M; Luxton, Richard; Doran, Olena; Bessa, Rui J B; Prates, José A M

2014-05-01

The cumulative effects of dietary arginine, leucine and protein levels on fat content, fatty acid composition and mRNA levels of genes controlling lipid metabolism in pig longissimus lumborum muscle and subcutaneous adipose tissue (SAT) were investigated. The experiment was performed on fifty-four intact male pigs (Duroc × Pietrain × Large White × Landrace crossbred), with a live weight ranging from 59 to 92 kg. The pigs were randomly assigned to one of six experimental treatments (n 9). The treatments followed a 2 × 3 factorial arrangement, with two levels of arginine supplementation (0 v. 1 %) and three levels of a basal diet (normal protein diet, NPD; reduced protein diet, RPD; reduced protein diet to achieve 2 % of leucine, RPDL). The results showed that dietary arginine supplementation did not affect the intramuscular fat (IMF) content and back fat thickness, but increased the total fat in SAT. This effect was associated with an increase in fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD) mRNA levels in SAT, which suggests that arginine might be involved in the differential regulation of some key lipogenic genes in pig muscle and SAT. The increase in IMF content under the RPD, with or without leucine supplementation, was accompanied by increased FASN and SCD mRNA levels. Arginine supplementation did not influence the percentage of main fatty acids, while the RPD had a significant effect on fatty acid composition in both tissues. Leucine supplementation of RPD did not change IMF, total fat of SAT and back fat thickness, but increased 16 : 0 and 18 : 1cis-9 and decreased 18 : 2n-6 in muscle.

Late Maternal Folate Supplementation Rescues from Methyl Donor Deficiency-Associated Brain Defects by Restoring Let-7 and miR-34 Pathways.

PubMed

Geoffroy, Andréa; Kerek, Racha; Pourié, Grégory; Helle, Déborah; Guéant, Jean-Louis; Daval, Jean-Luc; Bossenmeyer-Pourié, Carine

2017-09-01

The micronutrients folate and vitamin B12 are essential for the proper development of the central nervous system, and their deficiency during pregnancy has been associated with a wide range of disorders. They act as methyl donors in the one-carbon metabolism which critically influences epigenetic mechanisms. In order to depict further underlying mechanisms, we investigated the role of let-7 and miR-34, two microRNAs regulated by methylation, on a rat model of maternal deficiency. In several countries, public health policies recommend periconceptional supplementation with folic acid. However, the question about the duration and periodicity of supplementation remains. We therefore tested maternal supply (3 mg/kg/day) during the last third of gestation from embryonic days (E) 13 to 20. Methyl donor deficiency-related developmental disorders at E20, including cerebellar and interhemispheric suture defects and atrophy of selective cerebral layers, were associated with increased brain expression (by 2.5-fold) of let-7a and miR-34a, with subsequent downregulation of their regulatory targets such as Trim71 and Notch signaling partners, respectively. These processes could be reversed by siRNA strategy in differentiating neuroprogenitors lacking folate, with improvement of their morphological characteristics. While folic acid supplementation helped restoring the levels of let-7a and miR-34a and their downstream targets, it led to a reduction of structural and functional defects taking place during the perinatal period. Our data outline the potential role of let-7 and miR-34 and their related signaling pathways in the developmental defects following gestational methyl donor deficiency and support the likely usefulness of late folate supplementation in at risk women.

Transcriptome dynamics of human pluripotent stem cell-derived contracting cardiomyocytes using an embryoid body model with fetal bovine serum.

PubMed

Jung, Kwang Bo; Son, Ye Seul; Lee, Hana; Jung, Cho-Rok; Kim, Janghwan; Son, Mi-Young

2017-07-25

Cardiomyocyte (CM) differentiation techniques for generating adult-like mature CMs remain imperfect, and the plausible underlying mechanisms remain unclear; however, there are a number of current protocols available. Here, to explore the mechanisms controlling cardiac differentiation, we analyzed the genome-wide transcription dynamics occurring during the differentiation of human pluripotent stem cells (hPSCs) into CMs using embryoid body (EB) formation. We optimized and updated the protocol to efficiently generate contracting CMs from hPSCs by adding fetal bovine serum (FBS) as a medium supplement, which could have a significant impact on the efficiency of cardiac differentiation. To identify genes, biological processes, and pathways involved in the cardiac differentiation of hPSCs, integrative and comparative analyses of the transcriptome profiles of differentiated CMs from hPSCs and of control CMs of the adult human heart (CM-AHH) were performed using gene ontology, functional annotation clustering, and pathway analyses. Several genes commonly regulated in the differentiated CMs and CM-AHH were enriched in pathways related to cell cycle and nucleotide metabolism. Strikingly, we found that current differentiation protocols did not promote sufficient expression of genes involved in oxidative phosphorylation to differentiate CMs from hPSCs compared to the expression levels in CM-AHH. Therefore, to obtain mature CMs similar to CM-AHH, these deficient pathways in CM differentiation, such as energy-related pathways, must be augmented prior to use for in vitro and in vivo applications. This approach opens up new avenues for facilitating the utilization of hPSC-derived CMs in biomedical research, drug evaluation, and clinical applications for patients with cardiac failure.

75 FR 66686 - Defense Federal Acquisition Regulation Supplement; Balance of Payments Program Exemption for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-29

... Federal Acquisition Regulation Supplement; Balance of Payments Program Exemption for Commercial... Balance of Payments Program for construction material that is commercial information technology. DATES..., Balance of Payments Program--Construction Material, and 252.225- 7045, Balance of Payments Program...

78 FR 59851 - Defense Federal Acquisition Regulation Supplement: Enhancement of Contractor Employee...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-30

...-AH97 Defense Federal Acquisition Regulation Supplement: Enhancement of Contractor Employee... contractor and subcontractor employees. DATES: Effective date: September 30, 2013. In accordance with FAR 1... Whistleblower Protections for Contractor Employees) made extensive changes to 10 U.S.C. 2409, entitled...

76 FR 52133 - Defense Federal Acquisition Regulation Supplement; Contractors Performing Private Security...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-19

... 0750-AH28 Defense Federal Acquisition Regulation Supplement; Contractors Performing Private Security..., entitled ``Contractors Performing Private Security Functions in Areas of Combat Operations or Other... of DoD and other Governmental private security contractors. A clause to cover the interagency...

Will the new Consumer Protection Act prevent harm to nutritional supplement users?

PubMed

Gabriels, Gary; Lambert, Mike; Smith, Pete; Hiss, Donavon

2011-07-25

BACKGROUND. There is no clear distinction between the regulation of food, supplements and medicines in South Africa. Consequently, grey areas exist in implementing the legislation, particularly in the supplement industry. The increase in supplement sales in South Africa can be attributed to aggressive marketing by manufacturers whose claims are not always supported by published peer-reviewed evidence. Such claims often go unchecked, resulting in consumers being mislead about the role of supplements. As a result of poor regulation, contaminants or adulterants in supplements may also cause insidious effects unrelated to the listed ingredients. AIM. To assess the regulations, legislation, and claims associated with nutritional supplement products in South Africa. METHOD. Peer-reviewed literature and the relevant South African statutes were consulted. RESULTS. The National Health Act incorporates the Medicine Control Council, which is charged with ensuring the safety, quality and effectiveness of medicines, and related matters, including complementary/alternative medicines. The South African Institute for Drug-Free Sport and Amendment Act provides for testing athletes for using banned substances, but currently does not concern itself with monitoring nutritional supplements for contaminants or adulterants that may cause a positive drug test, which has implications for sports participants and also the health of the general population. The implementation of the Consumer Protection Act 68 of 2008 (CPA) could protect consumer rights if it is administered and resourced appropriately. CONCLUSION. The CPA should promote greater levels of policy development, regulatory enforcement, and consumer education of South Africa's supplement industry.

43 CFR 7.32 - Supplemental definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Supplemental definitions. 7.32 Section 7... RESOURCES Department of the Interior Supplemental Regulations § 7.32 Supplemental definitions. For purposes of this subpart, the following definitions will be used: (a) Site of religious or cultural importance...

Osteogenic differentiation of stem cells derived from human periodontal ligaments and pulp of human exfoliated deciduous teeth.

PubMed

Chadipiralla, Kiranmai; Yochim, Ji Min; Bahuleyan, Bindu; Huang, Chun-Yuh Charles; Garcia-Godoy, Franklin; Murray, Peter E; Stelnicki, Eric J

2010-05-01

Multipotent stem cells derived from periodontal ligaments (PDLSC) and pulp of human exfoliated deciduous teeth (SHED) represent promising cell sources for bone regeneration. Recent studies have demonstrated that retinoic acid (RA) and dexamethasone (Dex) induce osteogenesis of postnatal stem cells. The objective of this study was to examine the effects of RA and Dex on the proliferation and osteogenic differentiation of SHED and PDLSC and to compare the osteogenic characteristics of SHED and PDLSC under RA treatment. SHED and PDLSC were treated with serum-free medium either alone or supplemented with RA or Dex for 21 days. The proliferation of SHED and PDLSC was significantly inhibited by both RA and Dex. RA significantly upregulated gene expression and the activity of alkaline phosphatase in SHED and PDLSC. Positive Alizarin red and von Kossa staining of calcium deposition was seen on the RA-treated SHED and PDLSC after 21 days of culture. The influences of RA on the osteogenic differentiation of SHED and PDLSC were significantly stronger than with Dex. Supplementation with insulin enhanced RA-induced osteogenic differentiation of SHED. Thus, RA is an effective inducer of osteogenic differentiation of SHED and PDLSC, whereas RA treatment in combination with insulin supplementation might be a better option for inducing osteogenic differentiation. Significantly higher cell proliferation of PDLSC results in greater calcium deposition after 3-week culture, suggesting that PDLSC is a better osteogenic stem cell source. This study provides valuable information for efficiently producing osteogenically differentiated SHED or PDLSC for in vivo bone regeneration.

The Brain–to–Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions

PubMed Central

Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C.; Ali, Almas; Tamarina, Natalia; Philipson, Louis H.; Enquist, Lynn W.; Myers, Martin G.

2016-01-01

The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. PMID:27207534

The Brain-to-Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions.

PubMed

Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C; Ali, Almas; Tamarina, Natalia; Philipson, Louis H; Enquist, Lynn W; Myers, Martin G; Rhodes, Christopher J

2016-09-01

The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. © 2016 by the American Diabetes Association.

The critical chemical and mechanical regulation of folic acid on neural engineering.

PubMed

Kim, Gloria B; Chen, Yongjie; Kang, Weibo; Guo, Jinshan; Payne, Russell; Li, Hui; Wei, Qiong; Baker, Julianne; Dong, Cheng; Zhang, Sulin; Wong, Pak Kin; Rizk, Elias B; Yan, Jiazhi; Yang, Jian

2018-04-03

The mandate of folic acid supplementation in grained products has reduced the occurrence of neural tube defects by one third in the U.S since its introduction by the Food and Drug Administration in 1998. However, the advantages and possible mechanisms of action of using folic acid for peripheral nerve engineering and neurological diseases still remain largely elusive. Herein, folic acid is described as an inexpensive and multifunctional niche component that modulates behaviors in different cells in the nervous system. The multiple benefits of modulation include: 1) generating chemotactic responses on glial cells, 2) inducing neurotrophin release, and 3) stimulating neuronal differentiation of a PC-12 cell system. For the first time, folic acid is also shown to enhance cellular force generation and global methylation in the PC-12 cells, thereby enabling both biomechanical and biochemical pathways to regulate neuron differentiation. These findings are evaluated in vivo for clinical translation. Our results suggest that folic acid-nerve guidance conduits may offer significant benefits as a low-cost, off-the-shelf product for reaching the functional recovery seen with autografts in large sciatic nerve defects. Consequently, folic acid holds great potential as a critical and convenient therapeutic intervention for neural engineering, regenerative medicine, medical prosthetics, and drug delivery. Copyright © 2018 Elsevier Ltd. All rights reserved.

Leptin potentiates Prevotella intermedia lipopolysaccharide-induced production of TNF-alpha in monocyte-derived macrophages.

PubMed

Kim, Sung-Jo

2010-06-01

In addition to regulating body weight, leptin is also recognized for its role in the regulation of immune function and inflammation. The purpose of this study was to investigate the effect of leptin on Prevotella (P.) intermedia lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha production in differentiated THP-1 cells, a human monocytic cell line. LPS from P. intermedia ATCC 25611 was prepared by the standard hot phenol-water method. THP-1 cells were incubated in the medium supplemented with phorbol myristate acetate to induce differentiation into macrophage-like cells. The amount of TNF-alpha and interleukin-8 secreted into the culture medium was determined by enzyme-linked immunosorbent assay (ELISA). TNF-alpha and Ob-R mRNA expression levels were determined by semi-quantitative reverse transcription-polymerase chain reaction analysis. Leptin enhanced P. intermedia LPS-induced TNF-alpha production in a dose-dependent manner. Leptin modulated P. intermedia LPS-induced TNF-alpha expression predominantly at the transcriptional level. Effect of leptin on P. intermedia LPS-induced TNF-alpha production was not mediated by the leptin receptor. The ability of leptin to enhance P. intermedia LPS-induced TNF-alpha production may be important in the establishment of chronic lesion accompanied by osseous tissue destruction observed in inflammatory periodontal disease.

Differential effects of Glycyrrhiza species on genotoxic estrogen metabolism: licochalcone A downregulates P450 1B1 whereas isoliquiritigenin stimulates

PubMed Central

Dunlap, Tareisha L.; Wang, Shuai; Simmler, Charlotte; Chen, Shao-Nong; Pauli, Guido F.; Dietz, Birgit M.; Bolton, Judy L.

2015-01-01

Estrogen chemical carcinogenesis involves 4-hydroxylation of estrone/estradiol (E1/E2) by P450 1B1, generating catechol and quinone genotoxic metabolites that cause DNA mutations and initiate/promote breast cancer. Inflammation enhances this effect by up-regulating P450 1B1. The present study tested the three authenticated medicinal species of licorice, [Glycyrrhiza glabra (GG), G. uralensis (GU), and G. inflata (GI)], used by women as dietary supplements, for their anti-inflammatory activities and their ability to modulate estrogen metabolism. The pure compounds, liquiritigenin (LigF), its chalcone isomer isoliquiritigenin (LigC), and the GI specific licochalcone A (LicA) were also tested. The licorice extracts and compounds were evaluated for anti-inflammatory activity by measuring inhibition of iNOS activity in macrophage cells: GI > GG > GU and LigC ≅ LicA > LigF. The Michael acceptor chalcone LicA, is likely responsible for the anti-inflammatory activity of GI. A sensitive LC-MS/MS assay was employed to quantify estrogen metabolism by measuring 2-MeOE1 as non-toxic and 4-MeOE1 as genotoxic biomarkers in the non-tumorigenic human mammary epithelial cell line, MCF-10A. GG, GU, and LigC increased 4-MeOE1, whereas GI and LicA inhibited 2- and 4-MeOE1 levels. GG, GU (5 μg/mL), and LigC (1 μM) also enhanced P450 1B1 expression and activities, which was further increased by inflammatory cytokines (TNF-α and IFN-γ). LicA (1 μM, 10 μM) decreased cytokine- and TCDD-induced, P450 1B1 gene expression and TCDD-induced xenobiotic response element luciferase reporter (IC50=12.3 μM), suggesting an antagonistic effect on the aryl hydrocarbon receptor, which regulates P450 1B1. Similarly, GI (5 μg/mL) reduced cytokine- and TCDD-induced P450 1B1 gene expression. Collectively, these data suggest that of the three licorice species that are used in botanical supplements, GI represents the most promising chemopreventive licorice extract for women’s health. Additionally, the differential effects of the Glycyrrhiza species on estrogen metabolism emphasize the importance of standardization of botanical supplements to species-specific bioactive compounds. PMID:26134484

Taking weight-loss supplements may elicit liberation from dietary control. A laboratory experiment.

PubMed

Chang, Yevvon Yi-Chi; Chiou, Wen-Bin

2014-01-01

Given that changes in diet and exercise habits are difficult to initiate and maintain, the use of weight-loss supplements has become an appealing alternative approach to weight management for many individuals. The current research examined whether the use of weight-loss supplements induced overly optimistic assessments of progress toward weight reduction, leading to psychological abdication of dietary regulation. Participants were randomly assigned to take either an identified placebo or a purported weight-loss supplement (actually the same placebo). Each participant reported perceived progress toward weight reduction following the manipulation. Consumption of snacks in a taste test and choice of sugary drinks were recorded. The results showed that participants receiving a purported supplement ate more in a taste task and preferred larger quantities of sugar in their reward drinks than did controls. Mediation analysis supported that the perception of progress toward weight reduction contributed to the liberating effect. Using weight-loss supplements may increase perceived progress toward weight reduction but decrease dietary self-regulation. These thought-provoking findings can serve as a basis for educating the public about the myth that they are free to feel liberated from the need to regulate their eating when using weight-loss supplements. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Biologically active food supplements: legislative and regulator basis. Report 2].

PubMed

Sukhanov, B P; Kerimova, M G

2004-01-01

The article presents the history of food supplements' origin. The main requirements to them are given an account of the main legislative and normative documents, regulating the composition and considered as an important instrument for improving the structure and quality of nutrition of the population.

78 FR 48331 - Defense Federal Acquisition Regulation Supplement: Release of Fundamental Research Information...

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2013-08-08

... Federal Acquisition Regulation Supplement: Release of Fundamental Research Information (DFARS Case 2012...) to provide guidance relating to the release of fundamental research information. This rule was... release of information on fundamental research projects and not safeguarding. This rule was initiated to...

76 FR 9680 - Defense Federal Acquisition Regulation Supplement; Limitations on Procurements With Non-Defense...

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2011-02-22

... Subjects in 48 CFR Part 217 Government procurement. Mary Overstreet, Editor, Defense Acquisition... Federal Acquisition Regulation Supplement; Limitations on Procurements With Non-Defense Agencies (DFARS...: Final rule. SUMMARY: DoD is adopting without change an interim rule amending the Defense Federal...

7 CFR 250.63 - Commodity Supplemental Food Program.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 4 2011-01-01 2011-01-01 false Commodity Supplemental Food Program. 250.63 Section 250.63 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE GENERAL REGULATIONS AND POLICIES-FOOD DISTRIBUTION DONATION OF FOODS FOR USE IN THE...

7 CFR 250.63 - Commodity Supplemental Food Program.

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2012-01-01

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7 CFR 250.63 - Commodity Supplemental Food Program.

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2010-01-01

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7 CFR 250.63 - Commodity Supplemental Food Program.

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2014-01-01

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7 CFR 250.63 - Commodity Supplemental Food Program.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 4 2013-01-01 2013-01-01 false Commodity Supplemental Food Program. 250.63 Section 250.63 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE GENERAL REGULATIONS AND POLICIES-FOOD DISTRIBUTION DONATION OF FOODS FOR USE IN THE...

15 CFR Supplement No. 15 to Part 760 - Interpretation

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2010-01-01

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75 FR 71564 - Defense Federal Acquisition Regulation Supplement; Contractor Insurance/Pension Review (DFARS...

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15 CFR Supplement No. 8 to Part 760 - Interpretation

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2011-01-01

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15 CFR Supplement No. 8 to Part 760 - Interpretation

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2010-01-01

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15 CFR Supplement No. 8 to Part 760 - Interpretation

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2013-01-01

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5 CFR 837.701 - Offset from supplemental annuity.

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2010-01-01

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48 CFR 731.205-71 - Salary supplements for Host Government employees.

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2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Salary supplements for... Contracts With Commercial Organizations 731.205-71 Salary supplements for Host Government employees. (a... fifty percent of its financial support from the government. (b) General. Salary supplement occurs when...

Regulation of Intestinal Epithelial Cells Properties and Functions by Amino Acids.

PubMed

Kong, Shanshan; Zhang, Yanhui H; Zhang, Weiqiang

2018-01-01

Intestinal epithelial cells (IECs) line the surface of intestinal epithelium, where they play important roles in the digestion of food, absorption of nutrients, and protection of the human body from microbial infections, and others. Dysfunction of IECs can cause diseases. The development, maintenance, and functions of IECs are strongly influenced by external nutrition, such as amino acids. Amino acids play important roles in regulating the properties and functions of IECs. In this article, we briefly reviewed the current understanding of the roles of amino acids in the regulation of IECs' properties and functions in physiological state, including in IECs homeostasis (differentiation, proliferation, and renewal), in intestinal epithelial barrier structure and functions, and in immune responses. We also summarized some important findings on the effects of amino acids supplementation (e.g., glutamine and arginine) in restoring IECs' and intestine functions in some diseased states. These findings will further our understanding of the important roles of amino acids in the homeostasis of IECs and could potentially help identify novel targets and reagents for the therapeutic interventions of diseases associated with dysfunctional IECs.

Resource reallocation patterns within Sagittaria trifolia inflorescences following differential pollination.

PubMed

Dai, Can; Luo, Wen-Jie; Gong, Yan-Bing; Liu, Fan; Wang, Zheng-Xiang

2018-04-30

Understanding resource allocation to reproduction, a key factor in life history tradeoffs, has long intrigued plant ecologists. Despite the recognized importance of understanding the movement of resources among flowers following variable pollination, the patterns of resource reallocation to plant reproductive organs have not been thoroughly addressed. In this study, we aimed to empirically explore how resources redistribute within inflorescences in response to differential pollination intensities. Using a common herb, Sagittaria trifolia, we conducted supplemental and controlled pollination for single, some, or all flowers in simple and complex inflorescences, and compared their resulting fruiting probabilities, seed production, and average seed masses. Pollen supplementation of a single flower significantly increased its fruiting probability; however, the same manipulation of an inflorescence did not increase its overall reproduction. Single pollen-supplemented flowers had a higher percentage fruit set than inflorescences receiving supplemental pollination. In complex inflorescences, supplemental pollination had no effect on the reproductive success of flowers on the lateral or main branches. We provided evidence of resource reallocation from controlled to pollen-supplemented flowers in simple inflorescences; however, resources were unlikely to be reallocated between the main and lateral branches in the complex inflorescences, suggesting that flowering branches represent integrated physiological units in S. trifolia. The results also demonstrated that single-flower supplemental pollination would exaggerate pollen limitation and lead to a biased understanding of a plant's reproductive status. © 2018 Botanical Society of America.

Sida rhomboidea.Roxb aqueous extract down-regulates in vivo expression of vascular cell adhesion molecules in atherogenic rats and inhibits in vitro macrophage differentiation and foam cell formation.

PubMed

Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Salunke, Sunita P; Devkar, Ranjitsinh V; Ramachandran, A V

2012-10-01

The present study evaluates efficacy of Sida rhomboidea.Roxb (SR) leaves extract in ameliorating experimental atherosclerosis using in vitro and in vivo experimental models. Atherogenic (ATH) diet fed rats recorded significant increment in the serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), very LDL (VLDL), autoantibody against oxidized LDL (Ox-LDL), markers of LDL oxidation and decrement in high-density lipoprotein (HDL) along with increment in aortic TC and TG. The ex vivo LDL oxidation assay revealed an increased susceptibility of LDL isolated from ATH rats to undergo copper mediated oxidation. These set of changes were minimized by simultaneous co-supplementation of SR extract to ATH diet fed rats. Histopathology of aorta and immunolocalization studies recorded pronounced atheromatous plaque formation, vascular calcification, significant elastin derangements and higher expression of macrophage surface marker (F4/80), vascular cell adhesion molecule-1 (VCAM-1) and p-selectin in ATH rats. Whereas, ATH+SR rats depicted minimal evidence of atheromatous plaque formation, calcium deposition, distortion/defragmentation of elastin and accumulation of macrophages along with lowered expression of VCAM-1 and P-selectin compared to ATH rats. Further, monocyte to macrophage differentiation and in vitro foam cell formation were significantly attenuated in presence of SR extract. In conclusion, SR extract has the potency of controlling experimental atherosclerosis and can be used as promising herbal supplement in combating atherosclerosis.

75 FR 76692 - Defense Federal Acquisition Regulation Supplement; Business Systems-Definition and Administration...

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..., and 252 RIN 0750-AG58 Defense Federal Acquisition Regulation Supplement; Business Systems--Definition... for Business Systems--Definition and Administration (DFARS Case 2009-D038) in the Federal Register on... improve the effectiveness of DoD oversight of contractor business systems. The comment period is being...

15 CFR Supplement No. 1 to Part 738 - Commerce Country Chart

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2013-01-01

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15 CFR Supplement No. 1 to Part 738 - Commerce Country Chart

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2012-01-01

... 15 Commerce and Foreign Trade 2 2012-01-01 2012-01-01 false Commerce Country Chart No. Supplement No. 1 to Part 738 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS...

15 CFR Supplement No. 1 to Part 738 - Commerce Country Chart

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2014-01-01

... 15 Commerce and Foreign Trade 2 2014-01-01 2014-01-01 false Commerce Country Chart No. Supplement No. 1 to Part 738 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS...

15 CFR Supplement No. 1 to Part 738 - Commerce Country Chart

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2011-01-01

... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Commerce Country Chart No. Supplement No. 1 to Part 738 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS...

77 FR 11367 - Defense Federal Acquisition Regulation Supplement; Extension of the Test Program for Negotiation...

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... Federal Acquisition Regulation Supplement; Extension of the Test Program for Negotiation of Comprehensive... Program for Negotiation of Comprehensive Small Business Subcontracting Plans. DATES: Effective Date... Fiscal Year 2012, (Pub. L. 112-81). Section 866 amends the DoD Test Program for Negotiation of...

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... Acquisition Regulation Supplement; Independent Research and Development Technical Descriptions (DFARS Case... (DFARS) to require contractors to report independent research and development (IR&D) projects generating... the address shown below on or before May 2, 2011, to be considered in the formation of the final rule...

75 FR 34942 - Defense Federal Acquisition Regulation Supplement; Multiyear Contract Authority for Electricity...

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2010-06-21

...-AG48 Defense Federal Acquisition Regulation Supplement; Multiyear Contract Authority for Electricity... years for the purchase of electricity from sources of renewable energy. DATES: Effective Date: June 21... contract for a period not to exceed 10 years for the purchase of electricity from sources of renewable...

76 FR 14589 - Defense Federal Acquisition Regulation Supplement; Repeal of Restriction on Ballistic Missile...

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2011-03-17

...-AH18 Defense Federal Acquisition Regulation Supplement; Repeal of Restriction on Ballistic Missile...). Section 222 repeals the restriction on purchase of Ballistic Missile Defense research, development, test... Ballistic Missile Defense research, development, test, and evaluation that was required by section 222 of...

78 FR 28790 - Defense Federal Acquisition Regulation Supplement; Forward Pricing Rate Proposal Adequacy...

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... Federal Acquisition Regulation Supplement; Forward Pricing Rate Proposal Adequacy Checklist (DFARS Case... (DFARS) to provide guidance to contractors for the submittal of forward pricing rate proposals to ensure the adequacy of forward pricing rate proposals submitted to the Government. DATES: Comments on the...

15 CFR Supplement Nos.1-3 to Part 746 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false [Reserved] Nos.1 Supplement Nos.1-3 to Part 746 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS EMBARGOES AND...

76 FR 35424 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

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...; Defense Federal Acquisition Regulation Supplement; Acquisition of Information Technology AGENCY: Defense... techniques or other forms of information technology. The Office of Management and Budget (OMB) has approved... Information Technology, and the associated clauses at DFARS 252.239-7000 and 252.239-7006; OMB Control Number...

75 FR 71563 - Defense Federal Acquisition Regulation Supplement; Services of Senior Mentors (DFARS Case 2010-D025)

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... mentoring, teaching, training, advice, and recommendations to senior military officers, staff, and students... Acquisition Regulation Supplement; Services of Senior Mentors (DFARS Case 2010-D025) AGENCY: Defense... policy on the services of senior mentors. DATES: Effective: November 24, 2010. FOR FURTHER INFORMATION...

75 FR 6185 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Rights in...

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...; Defense Federal Acquisition Regulation Supplement; Rights in Technical Data and Computer Software (OMB... 227.72, Rights in Computer Software and Computer Software Documentation, and related provisions and... rights in technical data and computer software. DoD needs this information to implement 10 U.S.C. 2320...

78 FR 48333 - Defense Federal Acquisition Regulation Supplement: Least Developed Countries That Are Designated...

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... Federal Acquisition Regulation Supplement: Least Developed Countries That Are Designated Countries (DFARS... least developed countries that are designated countries under the Trade Agreements Act of 1979. DATES... least developed countries as eligible countries under the Trade Agreements Act of 1979, allowing non...

75 FR 10190 - Defense Federal Acquisition Regulation Supplement; Payment of Costs Prior to Definitization...

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2010-03-05

... Acquisition Regulation Supplement; Payment of Costs Prior to Definitization-Definition of Contract Action... the definition of ``contract action'' at DFARS 217.7401. This is not a significant regulatory action... paragraph (a)(3) to read as follows: 217.7401 Definitions. * * * * * (a) * * * (2) It includes task orders...

77 FR 30368 - Defense Federal Acquisition Regulation Supplement; Utilization of Domestic Photovoltaic Devices...

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2012-05-22

... objective of the rule is to promote utilization of domestic photovoltaic devices under energy savings... 0750-AH43 Defense Federal Acquisition Regulation Supplement; Utilization of Domestic Photovoltaic... Authorization Act for Fiscal Year 2011. The section provides that photovoltaic devices to be utilized in...

75 FR 61511 - Intent To Prepare a Supplemental Environmental Impact Statement: Outer Continental Shelf, Alaska...

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2010-10-05

... DEPARTMENT OF THE INTERIOR Bureau of Ocean Energy Management, Regulation and Enforcement Intent To Prepare a Supplemental Environmental Impact Statement: Outer Continental Shelf, Alaska OCS Region, Chukchi Sea Planning Area, Oil and Gas Lease Sale 193 AGENCY: Bureau of Ocean Energy Management, Regulation...

77 FR 35879 - Defense Federal Acquisition Regulation Supplement: Title 41 Positive Law Codification-Further...

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... Acquisition Regulation Supplement: Title 41 Positive Law Codification--Further Implementation (DFARS Case 2012...) to conform statutory titles throughout the DFARS to the new Positive Law Codification of Title 41... the ``Service Contract Labor Standards statute''). A table providing the historical titles of the Acts...

15 CFR Supplement Nos. 2-3 to Part... - [Reserved

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2011-01-01

... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false [Reserved] Nos. Supplement Nos. 2-3 to Part 716 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS INITIAL...

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76 FR 38053 - Defense Federal Acquisition Regulation Supplement; Successor Entities to the Netherlands Antilles...

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78 FR 30233 - Defense Federal Acquisition Regulation Supplement; Government Support Contractor Access to...

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2011-11-18

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Dietary Green Pea Protects against DSS-Induced Colitis in Mice Challenged with High-Fat Diet.

PubMed

Bibi, Shima; de Sousa Moraes, Luís Fernando; Lebow, Noelle; Zhu, Mei-Jun

2017-05-18

Obesity is a risk factor for developing inflammatory bowel disease. Pea is unique with its high content of dietary fiber, polyphenolics, and glycoproteins, all of which are known to be health beneficial. We aimed to investigate the impact of green pea (GP) supplementation on the susceptibility of high-fat diet (HFD)-fed mice to dextran sulfate sodium (DSS)-induced colitis. Six-week-old C57BL/6J female mice were fed a 45% HFD or HFD supplemented with 10% GP. After 7-week dietary supplementation, colitis was induced by adding 2.5% DSS in drinking water for 7 days followed by a 7-day recovery period. GP supplementation ameliorated the disease activity index score in HFD-fed mice during the recovery stage, and reduced neutrophil infiltration, mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and inflammatory markers interleukin (IL)-6, cyclooxygenase-2 (COX-2), IL-17, interferon-γ (IFN-γ), and inducible nitric oxide synthase (iNOS) in HFD-fed mice. Further, GP supplementation increased mucin 2 content and mRNA expression of goblet cell differentiation markers including Trefoil factor 3 (Tff3), Krüppel-like factor 4 (Klf4), and SAM pointed domain ETS factor 1 (Spdef1) in HFD-fed mice. In addition, GP ameliorated endoplasmic reticulum (ER) stress as indicated by the reduced expression of Activating transcription factor-6 (ATF-6) protein and its target genes chaperone protein glucose-regulated protein 78 (Grp78), the CCAAT-enhancer-binding protein homologous protein (CHOP), the ER degradation-enhancing α-mannosidase-like 1 protein (Edem1), and the X-box binding protein 1 (Xbp1) in HFD-fed mice. In conclusion, GP supplementation ameliorated the severity of DSS-induced colitis in HFD-fed mice, which was associated with the suppression of inflammation, mucin depletion, and ER stress in the colon.

Supplementation with N-3 Long-Chain Polyunsaturated Fatty Acids or Olive Oil in Men and Women with Renal Disease Induces Differential Changes in the DNA Methylation of FADS2 and ELOVL5 in Peripheral Blood Mononuclear Cells

PubMed Central

Hoile, Samuel P.; Clarke-Harris, Rebecca; Huang, Rae-Chi; Calder, Philip C.; Mori, Trevor A.; Beilin, Lawrence J.; Lillycrop, Karen A.; Burdge, Graham C.

2014-01-01

Background Studies in animal models and in cultured cells have shown that fatty acids can induce alterations in the DNA methylation of specific genes. There have been no studies of the effects of fatty acid supplementation on the epigenetic regulation of genes in adult humans. Methods and Results We investigated the effect of supplementing renal patients with 4 g daily of either n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) or olive oil (OO) for 8 weeks on the methylation status of individual CpG loci in the 5′ regulatory region of genes involved in PUFA biosynthesis in peripheral blood mononuclear cells from men and women (aged 53 to 63 years). OO and n-3 LCPUFA each altered (>10% difference in methylation) 2/22 fatty acid desaturase (FADS)-2 CpGs, while n-3 LCPUFA, but not OO, altered (>10%) 1/12 ELOVL5 CpGs in men. OO altered (>6%) 8/22 FADS2 CpGs and (>3%) 3/12 elongase (ELOVL)-5 CpGs, while n-3 LCPUFA altered (>5%) 3/22 FADS2 CpGs and 2/12 (>3%) ELOVL5 CpGs in women. FADS1 or ELOVL2 methylation was unchanged. The n-3 PUFA supplementation findings were replicated in blood DNA from healthy adults (aged 23 to 30 years). The methylation status of the altered CpGs in FADS2 and ELOVL5 was associated negatively with the level of their transcripts. Conclusions These findings show that modest fatty acid supplementation can induce altered methylation of specific CpG loci in adult humans, contingent on the nature of the supplement and on sex. This has implications for understanding the effect of fatty acids on PUFA metabolism and cell function. PMID:25329159

Activating transcription factor 4 regulates stearate-induced vascular calcification.

PubMed

Masuda, Masashi; Ting, Tabitha C; Levi, Moshe; Saunders, Sommer J; Miyazaki-Anzai, Shinobu; Miyazaki, Makoto

2012-08-01

Previously, we reported that stearate, a saturated fatty acid, promotes osteoblastic differentiation and mineralization of vascular smooth muscle cells (VSMC). In this study, we examined the molecular mechanisms by which stearate promotes vascular calcification. ATF4 is a pivotal transcription factor in osteoblastogenesis and endoplasmic reticulum (ER) stress. Increased stearate by either supplementation of exogenous stearic acid or inhibition of stearoyl-CoA desaturase (SCD) by CAY10566 induced ATF4 mRNA, phosphorylated ATF4 protein, and total ATF4 protein. Induction occurred through activation of the PERK-eIF2α pathway, along with increased osteoblastic differentiation and mineralization of VSMCs. Either stearate or the SCD inhibitor but not oleate or other fatty acid treatments also increased ER stress as determined by the expression of p-eIF2α, CHOP, and the spliced form of XBP-1, which were directly correlated with ER stearate levels. ATF4 knockdown by lentiviral ATF4 shRNA blocked osteoblastic differentiation and mineralization induced by stearate and SCD inhibition. Conversely, treatment of VSMCs with an adenovirus containing ATF4 induced vascular calcification. Our results demonstrated that activation of ATF4 mediates vascular calcification induced by stearate.

Activating transcription factor 4 regulates stearate-induced vascular calcification

PubMed Central

Masuda, Masashi; Ting, Tabitha C.; Levi, Moshe; Saunders, Sommer J.; Miyazaki-Anzai, Shinobu; Miyazaki, Makoto

2012-01-01

Previously, we reported that stearate, a saturated fatty acid, promotes osteoblastic differentiation and mineralization of vascular smooth muscle cells (VSMC). In this study, we examined the molecular mechanisms by which stearate promotes vascular calcification. ATF4 is a pivotal transcription factor in osteoblastogenesis and endoplasmic reticulum (ER) stress. Increased stearate by either supplementation of exogenous stearic acid or inhibition of stearoyl-CoA desaturase (SCD) by CAY10566 induced ATF4 mRNA, phosphorylated ATF4 protein, and total ATF4 protein. Induction occurred through activation of the PERK-eIF2α pathway, along with increased osteoblastic differentiation and mineralization of VSMCs. Either stearate or the SCD inhibitor but not oleate or other fatty acid treatments also increased ER stress as determined by the expression of p-eIF2α, CHOP, and the spliced form of XBP-1, which were directly correlated with ER stearate levels. ATF4 knockdown by lentiviral ATF4 shRNA blocked osteoblastic differentiation and mineralization induced by stearate and SCD inhibition. Conversely, treatment of VSMCs with an adenovirus containing ATF4 induced vascular calcification. Our results demonstrated that activation of ATF4 mediates vascular calcification induced by stearate. PMID:22628618

Improvement of Cell Survival During Human Pluripotent Stem Cell Definitive Endoderm Differentiation

PubMed Central

Wang, Han; Luo, Xie; Yao, Li; Lehman, Donna M.

2015-01-01

Definitive endoderm (DE) is a vital precursor for internal organs such as liver and pancreas. Efficient protocol to differentiate human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) to DE is essential for regenerative medicine and for modeling diseases; yet, poor cell survival during DE differentiation remains unsolved. In this study, our use of B27 supplement in modified differentiation protocols has led to a substantial improvement. We used an SOX17-enhanced green fluorescent protein (eGFP) reporter hESC line to compare and modify established DE differentiation protocols. Both total live cell numbers and the percentages of eGFP-positive cells were used to assess differentiation efficiency. Among tested protocols, three modified protocols with serum-free B27 supplement were developed to generate a high number of DE cells. Massive cell death was avoided during DE differentiation and the percentage of DE cells remained high. When the resulting DE cells were further differentiated toward the pancreatic lineage, the expression of pancreatic-specific markers was significantly increased. Similar high DE differentiation efficiency was observed in H1 hESCs and iPSCs through the modified protocols. In B27 components, bovine serum albumin was found to facilitate DE differentiation and cell survival. Using our modified DE differentiation protocols, satisfactory quantities of quality DE can be produced as primary material for further endoderm lineage differentiation. PMID:26132288

77 FR 16761 - Supplemental Standards of Ethical Conduct for Employees of the Department of Housing and Urban...

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Comparison of different methods for erythroid differentiation in the K562 cell line.

PubMed

Shariati, Laleh; Modaress, Mehran; Khanahmad, Hossein; Hejazi, Zahra; Tabatabaiefar, Mohammad Amin; Salehi, Mansoor; Modarressi, Mohammad Hossein

2016-08-01

To compare methods for erythroid differentiation of K562 cells that will be promising in the treatment of beta-thalassemia by inducing γ-globin synthesis. Cells were treated separately with: RPMI 1640 medium without glutamine, RPMI 1640 medium without glutamine supplemented with 1 mM sodium butyrate, RPMI 1640 medium supplemented with 1 mM sodium butyrate, 25 µg cisplatin/ml, 0.1 µg cytosine arabinoside/ml. The highest differentiation (84 %) with minimum toxicity was obtained with cisplatin at 15 µg /ml. Real-time RT-PCR showed that expression of the γ-globin gene was significantly higher in the cells differentiated with cisplatin compared to undifferentiated cells (P < 0.001). Cisplatin is useful in the experimental therapy of ß-globin gene defects and can be considered for examining the basic mechanism of γ-reactivation.

Monograph - The Numerical Integration of Ordinary Differential Equations.

ERIC Educational Resources Information Center

Hull, T. E.

The materials presented in this monograph are intended to be included in a course on ordinary differential equations at the upper division level in a college mathematics program. These materials provide an introduction to the numerical integration of ordinary differential equations, and they can be used to supplement a regular text on this…

Nutrition in brain development and aging: role of essential fatty acids.

PubMed

Uauy, Ricardo; Dangour, Alan D

2006-05-01

The essential fatty acids (EFAs), particularly the n-3 long-chain polyunsaturated fatty acids (LCPs), are important for brain development during both the fetal and postnatal period. They are also increasingly seen to be of value in limiting the cognitive decline during aging. EFA deficiency was first shown over 75 years ago, but the more subtle effects of the n-3 fatty acids in terms of skin changes, a poor response to linoleic acid supplementation, abnormal visual function, and peripheral neuropathy were only discovered later. Both n-3 and n-6 LCPs play important roles in neuronal growth, development of synaptic processing of neural cell interaction, and expression of genes regulating cell differentiation and growth. The fetus and placenta are dependent on maternal EFA supply for their growth and development, with docosahexaenomic acid (DHA)-supplemented infants showing significantly greater mental and psychomotor development scores (breast-fed children do even better). Dietary DHA is needed for the optimum functional maturation of the retina and visual cortex, with visual acuity and mental development seemingly improved by extra DHA. Aging is also associated with decreased brain levels of DHA: fish consumption is associated with decreased risk of dementia and Alzheimer's disease, and the reported daily use of fish-oil supplements has been linked to improved cognitive function scores, but confirmation of these effects is needed.

Age-related change in the retinoid X receptor beta gene expression in peripheral blood mononuclear cells of healthy volunteers: effect of 13-cis retinoic acid supplementation.

PubMed

Brtko, J; Rock, E; Nezbedova, P; Krizanova, O; Dvorcakova, M; Minet-Quinard, R; Farges, M-C; Ribalta, J; Winklhofer-Roob, B M; Vasson, M-P; Macejova, D

2007-01-01

The regulation of cell growth and differentiation and also expression of a number of genes by retinoids are mediated by nuclear retinoid receptors (RARs and/or RXRs). In this study we investigated age-related alteration in both RAR and RXR receptor subtypes gene expression and tissue transglutaminase (tTG) activity before and after supplementation with 13-cis retinoic acid (13cRA) in human peripheral blood mononuclear cells (PBMCs). Healthy men (40) were divided in two groups according to their age (young group: 26.1+/-4.1 years and old group: 65.4+/-3.8 years). Each volunteer received 13cRA (Curacné), 0.5mg/(kgday)) during a period of 4 weeks. We have shown that RXRbeta expression was decreased significantly (p=0.0108) in PBMCs of elderly men when compared to that of young volunteers. Distribution of retinoic acid receptor subtype expression in PBMCs was found in the order: RXRbeta>RARgamma>RXRalpha>RARalpha. The tTG activity in PBMCs reflected a trend to be enhanced after 13-cis retinoic acid supplementation. In conclusion, we demonstrate a significant decrease in the expression of RXRbeta subtype of rexinoid receptors in PBMCs of healthy elderly men. Our data suggest that in healthy elderly men reduction of RXRbeta expression in PBMCs might be a common feature of physiological senescence.

Regulations applicable to plant food supplements and related products in the European Union.

PubMed

Silano, Vittorio; Coppens, Patrick; Larrañaga-Guetaria, Ainhoa; Minghetti, Paola; Roth-Ehrang, René

2011-12-01

This paper deals with the current regulatory and legal settings of traditional plant food supplements and herbal medicinal products in the European Union (EU). Marketing of botanicals in foods and food supplements in the EU is subject to several provisions of food law, which cover aspects of safety, production, labelling and product composition, including the use of additives and maximum levels of contaminants and residues. However, due to limited harmonization at the EU level, specific national regulations adopted at a Member State level also apply and mutual recognition is the mechanism through which such products can be marketed in EU countries other than those of origin. Unlike food supplements, marketing of traditional herbal medicinal products is regulated by an ad hoc Directive (i.e. Directive 2004/24/EC) covering in detail all the relevant aspects of these products, including a facilitated registration procedure at national level. However, by distinguishing traditional herbal medicinal products from plant food supplements and establishing selective marketing modalities for these two product categories, the EU has been confronted with implementation difficulties for traditional herbal medicinal products and a lack of homogeneity in the regulatory approaches adopted in different EU Member States. In fact, currently the nature of the commercial botanical products made available to consumers as traditional medicinal products or food supplements, depends largely on the EU Member State under consideration as a consequence of how competent National Authorities and manufacturing companies interpret and apply current regulations rather than on the intrinsic properties of the botanical products and their constituents. When the EU approach is compared with approaches adopted in some non-European countries to regulate these product categories, major differences become evident.

The safety and regulation of natural products used as foods and food ingredients.

PubMed

Abdel-Rahman, Ali; Anyangwe, Njwen; Carlacci, Louis; Casper, Steve; Danam, Rebecca P; Enongene, Evaristus; Erives, Gladys; Fabricant, Daniel; Gudi, Ramadevi; Hilmas, Corey J; Hines, Fred; Howard, Paul; Levy, Dan; Lin, Ying; Moore, Robert J; Pfeiler, Erika; Thurmond, T Scott; Turujman, Saleh; Walker, Nigel J

2011-10-01

The use of botanicals and dietary supplements derived from natural substances as an adjunct to an improved quality of life or for their purported medical benefits has become increasingly common in the United States. This review addresses the safety assessment and regulation of food products containing these substances by the U.S. Food and Drug Administration (FDA). The issue of safety is particularly critical given how little information is available on the toxicity of some of these products. The first section uses case studies for stevia and green tea extracts as examples of how FDA evaluates the safety of botanical and herbal products submitted for consideration as Generally Recognized as Safe under the Federal Food, Drug, and Cosmetics Act. The 1994 Dietary Supplement Health Education Act (DSHEA) created a regulatory framework for dietary supplements. The article also discusses the regulation of this class of dietary supplements under DSHEA and addresses the FDA experience in analyzing the safety of natural ingredients described in pre-market safety submissions. Lastly, we discuss an ongoing interagency collaboration to conduct safety testing of nominated dietary supplements.

77 FR 4637 - Defense Federal Acquisition Regulation Supplement: Shipping Instructions (DFARS Case 2011-D052)

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... #0;#0;Federal Register / Vol. 77 , No. 19 / Monday, January 30, 2012 / Proposed Rules#0;#0; [[Page...: Proposed rule. SUMMARY: DoD is proposing to amend the Defense Federal Acquisition Regulation Supplement... relocate the coverage within the DFARS. DATES: Comment Date: Comments on the proposed rule should be...

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75 FR 1271 - Technical Revisions to the Supplemental Security Income (SSI) Regulations on Income and Resources

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National Athletic Trainers' Association Position Statement: Evaluation of Dietary Supplements for Performance Nutrition

PubMed Central

Buell, Jackie L; Franks, Rob; Ransone, Jack; Powers, Michael E; Laquale, Kathleen M; Carlson-Phillips, Amanda

2013-01-01

Objectives To help athletic trainers promote a “food-first” philosophy to support health and performance, understand federal and sport governing body rules and regulations regarding dietary supplements and banned substances, and become familiar with reliable resources for evaluating the safety, purity, and efficacy of dietary supplements. Background The dietary supplement industry is poorly regulated and takes in billions of dollars per year. Uneducated athletes need to gain a better understanding of the safety, eligibility, and efficacy concerns associated with choosing to take dietary supplements. The athletic trainer is a valuable athletic team member who can help in the educational process. In many cases, athletic trainers are asked to help evaluate the legality, safety, and efficacy of dietary supplements. For this position statement, our mission is to provide the athletic trainer with the necessary resources for these tasks. Recommendations Proper nutrition and changes in the athlete's habitual diet should be considered first when improved performance is the goal. Athletes need to understand the level of regulation (or lack thereof) governing the dietary supplement industry at the international, federal, state, and individual sport-participation levels. Athletes should not assume a product is safe simply because it is marketed over the counter. All products athletes are considering using should be evaluated for purity (ie, truth in labeling), safety, and efficacy. PMID:23672334

The Effect of Selenium Supplementation on Glucose Homeostasis and the Expression of Genes Related to Glucose Metabolism.

PubMed

Jablonska, Ewa; Reszka, Edyta; Gromadzinska, Jolanta; Wieczorek, Edyta; Krol, Magdalena B; Raimondi, Sara; Socha, Katarzyna; Borawska, Maria H; Wasowicz, Wojciech

2016-12-13

The aim of the study was to evaluate the effect of selenium supplementation on the expression of genes associated with glucose metabolism in humans, in order to explain the unclear relationship between selenium and the risk of diabetes. For gene expression analysis we used archival samples of cDNA from 76 non-diabetic subjects supplemented with selenium in the previous study. The supplementation period was six weeks and the daily dose of selenium was 200 µg (as selenium yeast). Blood for mRNA isolation was collected at four time points: before supplementation, after two and four weeks of supplementation, and after four weeks of washout. The analysis included 15 genes encoding selected proteins involved in insulin signaling and glucose metabolism. In addition, HbA1c and fasting plasma glucose were measured at three and four time points, respectively. Selenium supplementation was associated with a significantly decreased level of HbA1c but not fasting plasma glucose (FPG) and significant down-regulation of seven genes: INSR , ADIPOR1 , LDHA , PDHA , PDHB , MYC , and HIF1AN . These results suggest that selenium may affect glycemic control at different levels of regulation, linked to insulin signaling, glycolysis, and pyruvate metabolism. Further research is needed to investigate mechanisms of such transcriptional regulation and its potential implication in direct metabolic effects.

Effects of quercetin, a natural phenolic compound, in the differentiation of human mesenchymal stem cells (MSC) into adipocytes and osteoblasts.

PubMed

Casado-Díaz, Antonio; Anter, Jaouad; Dorado, Gabriel; Quesada-Gómez, José Manuel

2016-06-01

Natural phenols may have beneficial properties against oxidative stress, which is associated with aging and major chronic aging-related diseases, such as loss of bone mineral mass (osteoporosis) and diabetes. The main aim of this study was to analyze the effect of quercetin, a major nutraceutical compound present in the "Mediterranean diet", on mesenchymal stem-cell (MSC) differentiation. Such cells were induced to differentiate into osteoblasts or adipocytes in the presence of two quercetin concentrations (0.1 and 10μM). Several physiological parameters and the expression of osteoblastogenesis and adipogenesis marker genes were monitored. Quercetin (10μM) inhibited cell proliferation, alkaline phosphatase (ALPL) activity and mineralization, down-regulating the expression of ALPL, collagen type I alpha 1 (COL1A1) and osteocalcin [bone gamma-carboxyglutamate protein (BGLAP)] osteoblastogenesis-related genes in MSC differentiating into osteoblasts. Moreover, in these cultures, CCAAT/enhancer-binding protein alpha (CEBPA) and peroxisome proliferator-activated receptor gamma 2 (PPARG2) adipogenic genes were induced, and cells differentiated into adipocytes were observed. Quercetin did not affect proliferation, but increased adipogenesis, mainly at 10-μM concentration in MSC induced to differentiate to adipocytes. β- and γ-catenin (plakoglobin) nuclear levels were reduced and increased, respectively, in quercetin-treated cultures. This suggests that the effect of high concentration of quercetin on MSC osteoblastic and adipogenic differentiation is mediated via Wnt/β-catenin inhibition. In conclusion, quercetin supplementation inhibited osteoblastic differentiation and promoted adipogenesis at the highest tested concentration. Such possible adverse effects of high quercetin concentrations should be taken into account in nutraceutical or pharmaceutical strategies using such flavonol. Copyright © 2016 Elsevier Inc. All rights reserved.

Fish oil and krill oil supplementations differentially regulate lipid catabolic and synthetic pathways in mice

PubMed Central

2014-01-01

Background Marine derived oils are rich in long-chain polyunsaturated omega-3 fatty acids, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have long been associated with health promoting effects such as reduced plasma lipid levels and anti-inflammatory effects. Krill oil (KO) is a novel marine oil on the market and is also rich in EPA and DHA, but the fatty acids are incorporated mainly into phospholipids (PLs) rather than triacylglycerols (TAG). This study compares the effects of fish oil (FO) and KO on gene regulation that influences plasma and liver lipids in a high fat diet mouse model. Methods Male C57BL/6J mice were fed either a high-fat diet (HF) containing 24% (wt/wt) fat (21.3% lard and 2.3% soy oil), or the HF diet supplemented with FO (15.7% lard, 2.3% soy oil and 5.8% FO) or KO (15.6% lard, 2.3% soy oil and 5.7% KO) for 6 weeks. Total levels of cholesterol, TAG, PLs, and fatty acid composition were measured in plasma and liver. Gene regulation was investigated using quantitative PCR in liver and intestinal epithelium. Results Plasma cholesterol (esterified and unesterified), TAG and PLs were significantly decreased with FO. Analysis of the plasma lipoprotein particles indicated that the lipid lowering effect by FO is at least in part due to decreased very low density lipoprotein (VLDL) content in plasma with subsequent liver lipid accumulation. KO lowered plasma non-esterified fatty acids (NEFA) with a minor effect on fatty acid accumulation in the liver. In spite of a lower omega-3 fatty acid content in the KO supplemented diet, plasma and liver PLs omega-3 levels were similar in the two groups, indicating a higher bioavailability of omega-3 fatty acids from KO. KO more efficiently decreased arachidonic acid and its elongation/desaturation products in plasma and liver. FO mainly increased the expression of several genes involved in fatty acid metabolism, while KO specifically decreased the expression of genes involved in the early steps of isoprenoid/cholesterol and lipid synthesis. Conclusions The data show that both FO and KO promote lowering of plasma lipids and regulate lipid homeostasis, but with different efficiency and partially via different mechanisms. PMID:24834104

Subtle Decreases in DNA Methylation and Gene Expression at the Mouse Igf2 Locus Following Prenatal Alcohol Exposure: Effects of a Methyl-Supplemented Diet

PubMed Central

Downing, Chris; Johnson, Thomas E; Larson, Colin; Leakey, Tatiana I; Siegfried, Rachel N; Rafferty, Tonya M; Cooney, Craig A

2010-01-01

C57BL/6J (B6) mice are susceptible to in utero growth retardation and a number of morphological malformations following prenatal alcohol exposure, while DBA/2J (D2) mice are relatively resistant. We have previously shown that genomic imprinting may play a role in differential sensitivity between B6 and D2 (Downing and Gilliam 1999). The best characterized mechanism mediating genomic imprinting is differential DNA methylation. In the present study we examined DNA methylation and gene expression, in both embryonic and placental tissue, at the mouse Igf2 locus following in utero ethanol exposure. We also examined the effects of a methyl-supplemented diet on methylation and ethanol teratogenesis. In embryos from susceptible B6 mice, we found small decreases in DNA methylation at four CpG sites in one of the differentially methylated regions of the Igf2 locus; only one of the four sites showed a statistically significant decrease. We observed no significant decreases in methylation in placentae. All Igf2 transcripts showed approximately 1.5 fold decreases following intrauterine alcohol exposure. Placing dams on a methyl-supplemented diet before pregnancy and throughout gestation brought methylation back up to control levels. Methyl-supplementation also resulted in lower prenatal mortality, greater prenatal growth, and decreased digit malformations; it dramatically reduced vertebral malformations. Thus, while prenatal alcohol had only small effects on DNA methylation at the Igf2 locus, placing dams on a methyl-supplemented diet partially ameliorated ethanol teratogenesis. PMID:20705422

Osteoblastic phenotype of rat marrow stromal cells cultured in the presence of dexamethasone, beta-glycerolphosphate, and L-ascorbic acid

NASA Technical Reports Server (NTRS)

Peter, S. J.; Liang, C. R.; Kim, D. J.; Widmer, M. S.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

1998-01-01

We investigated the effects of the time course of addition of osteogenic supplements dexamethasone, beta-glycerolphosphate, and L-ascorbic acid to rat marrow stromal cells, and the exposure time on the proliferation and differentiation of the cells. It was the goal of these experiments to determine the time point for supplement addition to optimize marrow stromal cell proliferation and osteoblastic differentiation. To determine this, two studies were performed; one study was based on the age of the cells from harvest, and the other study was based on the duration of exposure to supplemented medium. Cells were seen to proliferate rapidly at early time points in the presence and absence of osteogenic supplements as determined by 3H-thymidine incorporation into the DNA of replicating cells. These results were supported by cell counts ascertained through total DNA analysis. Alkaline phosphatase (ALP) activity and osteocalcin production at 21 days were highest for both experimental designs when the cells were exposed to supplemented medium immediately upon harvest. The ALP levels at 21 days were six times greater for cells maintained in supplements throughout than for control cells cultured in the absence of supplements for both studies, reaching an absolute value of 75 x 10(-7) micromole/min/cell. Osteocalcin production reached 20 x 10(-6) ng/cell at 21 days in both studies for cells maintained in supplemented medium throughout the study, whereas the control cells produced an insignificant amount of osteocalcin. These results suggest that the addition of osteogenic supplements to marrow-derived cells early in the culture period did not inhibit proliferation and greatly enhanced the osteoblastic phenotype of cells in a rat model.

Differential transcriptomic profiles effected by oil palm phenolics indicate novel health outcomes

PubMed Central

2011-01-01

Background Plant phenolics are important nutritional antioxidants which could aid in overcoming chronic diseases such as cardiovascular disease and cancer, two leading causes of death in the world. The oil palm (Elaeis guineensis) is a rich source of water-soluble phenolics which have high antioxidant activities. This study aimed to identify the in vivo effects and molecular mechanisms involved in the biological activities of oil palm phenolics (OPP) during healthy states via microarray gene expression profiling, using mice supplemented with a normal diet as biological models. Results Having confirmed via histology, haematology and clinical biochemistry analyses that OPP is not toxic to mice, we further explored the gene expression changes caused by OPP through statistical and functional analyses using Illumina microarrays. OPP showed numerous biological activities in three major organs of mice, the liver, spleen and heart. In livers of mice given OPP, four lipid catabolism genes were up-regulated while five cholesterol biosynthesis genes were down-regulated, suggesting that OPP may play a role in reducing cardiovascular disease. OPP also up-regulated eighteen blood coagulation genes in spleens of mice. OPP elicited gene expression changes similar to the effects of caloric restriction in the hearts of mice supplemented with OPP. Microarray gene expression fold changes for six target genes in the three major organs tested were validated with real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and the correlation of fold changes obtained with these two techniques was high (R2 = 0.9653). Conclusions OPP showed non-toxicity and various pleiotropic effects in mice. This study implies the potential application of OPP as a valuable source of wellness nutraceuticals, and further suggests the molecular mechanisms as to how dietary phenolics work in vivo. PMID:21864415

Differential transcriptomic profiles effected by oil palm phenolics indicate novel health outcomes.

PubMed

Leow, Soon-Sen; Sekaran, Shamala Devi; Sundram, Kalyana; Tan, YewAi; Sambanthamurthi, Ravigadevi

2011-08-25

Plant phenolics are important nutritional antioxidants which could aid in overcoming chronic diseases such as cardiovascular disease and cancer, two leading causes of death in the world. The oil palm (Elaeis guineensis) is a rich source of water-soluble phenolics which have high antioxidant activities. This study aimed to identify the in vivo effects and molecular mechanisms involved in the biological activities of oil palm phenolics (OPP) during healthy states via microarray gene expression profiling, using mice supplemented with a normal diet as biological models. Having confirmed via histology, haematology and clinical biochemistry analyses that OPP is not toxic to mice, we further explored the gene expression changes caused by OPP through statistical and functional analyses using Illumina microarrays. OPP showed numerous biological activities in three major organs of mice, the liver, spleen and heart. In livers of mice given OPP, four lipid catabolism genes were up-regulated while five cholesterol biosynthesis genes were down-regulated, suggesting that OPP may play a role in reducing cardiovascular disease. OPP also up-regulated eighteen blood coagulation genes in spleens of mice. OPP elicited gene expression changes similar to the effects of caloric restriction in the hearts of mice supplemented with OPP. Microarray gene expression fold changes for six target genes in the three major organs tested were validated with real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and the correlation of fold changes obtained with these two techniques was high (R2 = 0.9653). OPP showed non-toxicity and various pleiotropic effects in mice. This study implies the potential application of OPP as a valuable source of wellness nutraceuticals, and further suggests the molecular mechanisms as to how dietary phenolics work in vivo.

Bile acid-FXRα pathways regulate male sexual maturation in mice

PubMed Central

Vega, Aurélie; Sédes, Lauriane; Rouaisnel, Betty; de Haze, Angélique; Baron, Silvère; Schoonjans, Kristina; Caira, Françoise; Volle, David H.

2016-01-01

The bile acid receptor Farnesol-X-Receptor alpha (FRXα) is a member of the nuclear receptor superfamily. FRXα is expressed in the interstitial compartment of the adult testes, which contain the Leydig cells. In adult, short term treatment (12 hours) with FRXα agonist inhibits the expression of steroidogenic genes via the induction of the Small heterodimer partner (SHP). However the consequences of FRXα activation on testicular pathophysiology have never been evaluated. We demonstrate here that mice fed a diet supplemented with bile acid during pubertal age show increased incidence of infertility. This is associated with altered differentiation and increase apoptosis of germ cells due to lower testosterone levels. At the molecular level, next to the repression of basal steroidogenesis via the induction expression of Shp and Dax-1, two repressors of steroidogenesis, the main action of the BA-FRXα signaling is through lowering the Leydig cell sensitivity to the hypothalamo-pituitary axis, the main regulator of testicular endocrine function. In conclusion, BA-FRXα signaling is a critical actor during sexual maturation. PMID:26848619

Modulatory effects of Echinacea purpurea extracts on human dendritic cells: a cell- and gene-based study.

PubMed

Wang, Chien-Yu; Chiao, Ming-Tsang; Yen, Po-Jen; Huang, Wei-Chou; Hou, Chia-Chung; Chien, Shih-Chang; Yeh, Kuo-Chen; Yang, Wen-Ching; Shyur, Lie-Fen; Yang, Ning-Sun

2006-12-01

Echinacea spp. are popularly used as an herbal medicine or food supplement for enhancing the immune system. This study shows that plant extracts from root [R] and stem plus leaf [S+L] tissues of E. purpurea exhibit opposite (enhancing vs inhibitory) modulatory effects on the expression of the CD83 marker in human dendritic cells (DCs), which are known as professional antigen-presenting cells. We developed a function-targeted DNA microarray system to characterize the effects of phytocompounds on human DCs. Down-regulation of mRNA expression of specific chemokines (e.g., CCL3 and CCL8) and their receptors (e.g., CCR1 and CCR9) was observed in [S+L]-treated DCs. Other chemokines and regulatory molecules (e.g., CCL4 and CCL2) involved in the c-Jun pathway were found to be up-regulated in [R]-treated DCs. This study, for the first time, demonstrates that E. purpurea extracts can modulate DC differentiation and expression of specific immune-related genes in DCs.

Provider and patient expectations for dietary supplement discussions.

PubMed

Tarn, Derjung M; Guzmán, Jennifer R; Good, Jeffrey S; Wenger, Neil S; Coulter, Ian D; Paterniti, Debora A

2014-09-01

Dietary supplement use in the United States is common. Patients can procure supplements without a prescription, and often do not disclose supplement use to their healthcare providers. Providers and patients may be uncertain about what would be appropriate or helpful in discussions of supplements during routine office visits. To explore provider and patient expectations for discussions of dietary supplements. Semi-structured interviews were conducted with a purposeful sample of healthcare providers from three specialties and their patients who reported taking supplements. Thirty-five outpatient providers (14 primary care, six integrative medicine, and 15 complementary and alternative medicine (CAM) providers) and 107 of their patients. Qualitative analysis of transcripts using grounded theory and iterative review. Both providers and patients raised twelve common topics about dietary supplements that they felt were important to discuss during office visits, such as: supplements taken; supplement risks (interactions, safety/harm, side effects/adverse events); treatment benefits; efficacy; alternative treatments; and patient expectations/preferences for treatment. Some topics were mentioned more frequently by providers than patients, such as how to take, reason for taking, and evidence for use. Providers raised several topics that were mentioned infrequently by patients. Supplement costs and regulations were not brought up by any patients, even though consideration of these topics could influence patient decisions to take supplements. Complementary healthcare providers brought up topics not mentioned by primary care providers, such as the importance of supplement brands and supplement mega-dosing. Patients and providers have concordant views about the need to discuss patient supplement use and ensure patient safety. Patients may undervalue, be unaware of, or discount information about cost or regulations that could affect their decision-making about supplement use. Future studies could examine the value, acceptability, and influence of a more comprehensive approach to discussions to help patients appropriately evaluate supplements.

Effects of keratinocyte growth factor on skin epithelial differentiation of human amnion epithelial cells.

PubMed

Fatimah, Simat Siti; Tan, Geok Chin; Chua, Kienhui; Tan, Ay Eeng; Nur Azurah, Abdul Ghani; Hayati, Abdul Rahman

2013-08-01

The aim of the present study was to determine the effects of KGF on the differentiation of cultured human amnion epithelial cells (HAECs) towards skin keratinocyte. HAECs at passage 1 were cultured in medium HAM's F12: Dulbecco's Modified Eagles Medium (1:1) supplemented with different concentrations of KGF (0, 5, 10, 20, 30 and 50 ng/ml KGF). Dose-response of KGF on HAECs was determined by morphological assessment; growth kinetic evaluation; immunocytochemical analysis; stemness and epithelial gene expression quantification with two step real time RT-PCR. KGF promotes the proliferation of HAECs with maximal effect observed at 10 ng/ml KGF. However, KGF decreased the stemness genes expression: Oct-3/4, Sox-2, Nanog3, Rex-1, FGF-4, FZD-9 and BST-1. KGF also down-regulates epithelial genes expression: CK3, CK18, CK19, Integrin-β1, p63 and involucrin in cultured HAECs. No significant difference on the gene expression was detected for each Nestin, ABCG-2, CK1 and CK14 in KGF-treated HAECs. Immunocytochemical analysis for both control and KGF-treated HAECs demonstrated positive staining against CK14 and CK18 but negative staining against involucrin. The results suggested that KGF stimulates an early differentiation of HAECs towards epidermal cells. Differentiation of KGF-treated HAECs to corneal lineage is unfavourable. Therefore, further studies are needed to elucidate the roles of KGF in the differentiation of HAECs towards skin keratinocytes. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

Bergamottin Promotes Adipocyte Differentiation and Inhibits Tumor Necrosis Factor-α-induced Inflammatory Cytokines Induction in 3T3-L1 Cells.

PubMed

Mizuno, Hideya; Hatano, Tomoko; Taketomi, Ayako; Kawabata, Mami; Nakabayashi, Toshikatsu

2017-01-01

Nowadays, a lot of food ingredients are marketed as dietary supplements for health. Because the effectiveness and mechanisms of these compounds have not been fully characterized, they might have unknown functions. Therefore, we investigated the effect of several food ingredients (Bergamottin, Chrysin, L-Citrulline and β-Carotene) known as health foods on adipocyte differentiation by using 3T3-L1 preadipocytes. In this study, we found that Bergamottin, a furanocoumarin isolated from grapefruit juice, promotes adipocyte differentiation. In addition, Bergamottin increases the expression of adiponectin, an anti-inflammatory adipokine, and peroxisome proliferator activated receptor γ (PPARγ), a nuclear receptor regulating adipocyte differentiation. Furthermore, the anti-inflammatory activity of Bergamottin was demonstrated by its inhibition of the activation of nuclear factor-κB (NF-κB), an inflammatory transcription factor. Stimulation of mature 3T3-L1 adipocytes by tumor necrosis factor-α (TNF-α) decreased the expression of the endogeneous NF-κB inhibitor, IκBα. Treatment with Bergamottin further decreased the TNF-α-induced change in IκBα expression, suggesting that Bergamottin mediated the inhibition of NF-κB activation. In addition, Bergamottin decreased the TNF-α-induced increase in the mRNA levels of pro-inflammatory adipokines, monocyte chemoattractant protein-1 and interleukin-6. Taken together, our results show that Bergamottin treatment could inhibit inflammatory activity through promoting adipocyte differentiation, which in turn suggests that Bergamottin has the potential to minimize the risk factors of metabolic syndrome.

Inhibitory effect of transforming growth factor-. beta. (TGF-. beta. ) on insulin-like growth factor 1 (IGF-1)-induced proliferation and differentiation in primary cultures of pig preadipocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richardson, R.L.; Hausman, G.J.; Gaskins, H.R.

1990-02-26

The influence of serum, IGF-1 and TGF-{beta} on the differentiation of preadipocytes was examined in primary cultures of porcine adipose tissue cells. In serum-supplemented or serum-free, IGF-1 (1 and 10 nM) had no effect on total cell number. However, IGF-1 (10nM) increased adipocyte number only in serum-supplemented (1% pig serum) cultures, whereas TGF-{beta} (15 pm) reduced the adipocyte number in the presence and absence of IGF-1. Replication of preadipocytes was analyzed with a ({sup 3}H) thymidine assay. Preadipocyte proliferation (cpm in adipocyte fraction) was increased by IGF-1 (10nM) only in cultures containing pig serum. TGF-{beta} had no effect on preadipocytemore » proliferation specifically, but slightly increased total ({sup 3}H) thymidine incorporation in cultures with serum. Glycerol phosphate dehydrogenase (GPDH) specific activity was decreased by adding TGF-{beta} to serum-free cultures but TGF-{beta} had little effect in serum-supplemented cultures. Cellular secretion of IGF-1 was decreased when TGF-{beta} was added to serum-free or serum-supplemented cultures. These studies indicate that TGF-{beta} does not inhibit adipocyte development in the initial growth phase, but may inhibit differentiation and/or hypertrophy at a later stage of development.« less

15 CFR Supplement No. 1 to Part 774 - The Commerce Control List

Code of Federal Regulations, 2010 CFR

2015-01-01

... 15 Commerce and Foreign Trade 2 2015-01-01 2015-01-01 false The Commerce Control List No. Supplement No. 1 to Part 774 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS THE COMMERCE CONTROL LIST Pt. 774, Supp. 1...

76 FR 21812 - Defense Federal Acquisition Regulation Supplement; Ownership or Control by a Foreign Government...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-19

... (44 U.S.C. chapter 35). List of Subjects in 48 CFR Parts 209 and 252 Government procurement. Mary...-AG78 Defense Federal Acquisition Regulation Supplement; Ownership or Control by a Foreign Government...). ACTION: Final rule. SUMMARY: DoD is adopting as a final rule, without change, an interim rule that...

15 CFR Supplement No. 1 to Part 774 - The Commerce Control List

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false The Commerce Control List No. Supplement No. 1 to Part 774 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS THE COMMERCE CONTROL LIST Pt. 774, Supp. 1...

15 CFR Supplement No. 1 to Part 774 - The Commerce Control List

Code of Federal Regulations, 2013 CFR

2013-01-01

... 15 Commerce and Foreign Trade 2 2013-01-01 2013-01-01 false The Commerce Control List No. Supplement No. 1 to Part 774 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS THE COMMERCE CONTROL LIST Pt. 774, Supp. 1...

15 CFR Supplement No. 1 to Part 774 - The Commerce Control List

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false The Commerce Control List No. Supplement No. 1 to Part 774 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS THE COMMERCE CONTROL LIST Pt. 774, Supp. 1...

15 CFR Supplement No. 1 to Part 774 - The Commerce Control List

Code of Federal Regulations, 2012 CFR

2012-01-01

... 15 Commerce and Foreign Trade 2 2012-01-01 2012-01-01 false The Commerce Control List No. Supplement No. 1 to Part 774 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS THE COMMERCE CONTROL LIST Pt. 774, Supp. 1...

15 CFR Supplement No. 1 to Part 774 - The Commerce Control List

Code of Federal Regulations, 2014 CFR

2014-01-01

... 15 Commerce and Foreign Trade 2 2014-01-01 2014-01-01 false The Commerce Control List No. Supplement No. 1 to Part 774 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS THE COMMERCE CONTROL LIST Pt. 774, Supp. 1...

76 FR 71928 - Defense Federal Acquisition Regulation Supplement; Updates to Wide Area WorkFlow (DFARS Case 2011...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-21

... Defense Federal Acquisition Regulation Supplement; Updates to Wide Area WorkFlow (DFARS Case 2011-D027... Wide Area WorkFlow (WAWF) and TRICARE Encounter Data System (TEDS). WAWF, which electronically... civil emergencies, when access to Wide Area WorkFlow by those contractors is not feasible; (4) Purchases...

Identifying Hydrated Salts Using Simultaneous Thermogravimetric Analysis and Differential Scanning Calorimetry

ERIC Educational Resources Information Center

Harris, Jerry D.; Rusch, Aaron W.

2013-01-01

simultaneous thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) to characterize colorless, hydrated salts with anhydrous melting points less than 1100 degrees C. The experiment could be used to supplement the lecture discussing gravimetric techniques. It is…

Dietary supplements: What's in a name? What's in the bottle?

PubMed

Marcus, Donald M

2016-01-01

The Dietary Supplement Health and Education Act of 1994 (DSHEA), which arbitrarily classified herbals and other medicinal products as dietary supplements, obscured fundamental differences between two classes of products. Authentic supplements to the diet, such as multivitamins or calcium, have nutritional value and are safe. Herbals are used worldwide as medicines, they do not supplement the diet, they may cause severe adverse events, and they should be regulated as medicines. DSHEA also prevented the Food and Drug Administration (FDA) from effectively regulating herbal supplements as medicines. One consequence of weak FDA regulatory oversight is the poor quality of herbals. FDA inspections of manufacturing facilities have revealed violations of good manufacturing practices in over half of facilities inspected, including unsanitary conditions and lack of product specifications. Moreover, many "all natural" herbals marketed for weight loss, enhancement of sexual health and improving sports performance are adulterated with prescription and over-the-counter medications that have caused adverse cardiovascular events. New procedures to authenticate the identity of plants used in herbals will neither detect adulteration by medications nor provide assurance of appropriate pharmacological activity or safety. Nonvitamin, nonmineral "supplements" should be regulated as medicines, but revision or repeal of DSHEA faces strong opposition in Congress. The marketing of botanical supplements is based on unfounded claims that they are safe and effective. Health professionals need to inform patients and the public that there is no reason to take herbal medicines whose composition and benefits are unknown, and whose risks are evident. Copyright © 2015 John Wiley & Sons, Ltd.

Dietary Supplements are Not all Safe and Not all Food: How the Low Cost of Dietary Supplements Preys on the Consumer.

PubMed

Sax, Joanna K

2015-01-01

Dietary supplements are regulated as food, even though the safety and efficacy of some supplements are unknown. These products are often promoted as 'natural.' This leads many consumers to fail to question the supplements' safety, and some consumers even equate 'natural' with safe. But, 'natural' does not mean safe. For example, many wild berries and mushrooms are dangerous although they are natural. Another example is tobacco--a key ingredient in cigarettes: it is natural, but overwhelming studies have established the harm of cigarette smoke. The Food and Drug Administration (FDA) requires safety and efficacy testing prior to market entry for drugs. In contrast, the FDA only has limited ability to regulate the entry of new dietary supplements into the marketplace because supplements are treated as food. Two main arguments support the current regulatory structure of dietary supplements: (1) cost and (2) access. But lower cost and increased access to dietary supplements do not necessary have any relationship to safety and efficacy. Manufacturers' marketing techniques tout the health benefits of their supplements. Meanwhile, consumers are ingesting supplements without scientific studies indicating whether or not they are harmful. The FDA Food Safety and Modernization Act, signed into law on January 4, 2011, did not address the safety concerns regarding dietary supplements. This article discusses the regulatory deficiencies concerning dietary supplements and proposes novel solutions to address this specific sector of the food supply. This article advocates for the use of scientific data to support a multi-tiered classification system to ensure that dietary supplements on the market are safe.

Synergistic effect of defined artificial extracellular matrices and pulsed electric fields on osteogenic differentiation of human MSCs.

PubMed

Hess, Ricarda; Jaeschke, Anna; Neubert, Holger; Hintze, Vera; Moeller, Stephanie; Schnabelrauch, Matthias; Wiesmann, Hans-Peter; Hart, David A; Scharnweber, Dieter

2012-12-01

In vivo, bone formation is a complex, tightly regulated process, influenced by multiple biochemical and physical factors. To develop a vital bone tissue engineering construct, all of these individual components have to be considered and integrated to gain an in vivo-like stimulation of target cells. The purpose of the present studies was to investigate the synergistic role of defined biochemical and physical microenvironments with respect to osteogenic differentiation of human mesenchymal stem cells (MSCs). Biochemical microenvironments have been designed using artificial extracellular matrices (aECMs), containing collagen I (coll) and glycosaminoglycans (GAGs) like chondroitin sulfate (CS), or a high-sulfated hyaluronan derivative (sHya), formulated as coatings on three-dimensional poly(caprolactone-co-lactide) (PCL) scaffolds. As part of the physical microenvironment, cells were exposed to pulsed electric fields via transformer-like coupling (TC). Results showed that aECM containing sHya enhanced osteogenic differentiation represented by increases in ALP activity and gene-expression (RT-qPCR) of several bone-related proteins (RUNX-2, ALP, OPN). Electric field stimulation alone did not influence cell proliferation, but osteogenic differentiation was enhanced if osteogenic supplements were provided, showing synergistic effects by the combination of sHya and electric fields. These results will improve the understanding of bone regeneration processes and support the development of effective tissue engineered bone constructs. Copyright © 2012 Elsevier Ltd. All rights reserved.

5 CFR 2635.105 - Supplemental agency regulations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Section 2635.105 Administrative Personnel OFFICE OF GOVERNMENT ETHICS GOVERNMENT ETHICS STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE EXECUTIVE BRANCH General Provisions § 2635.105 Supplemental agency... supplement this part shall prepare and submit to the Office of Government Ethics, for its concurrence and...

78 FR 76836 - Agency Information Collection Activities; Proposed Collection; Comment Request; Current Good...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-19

... Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements... of FDA's regulations regarding current good manufacturing practice (CGMP) for dietary supplements..., or Holding Operations for Dietary Supplements--21 CFR Part 111 (OMB Control Number 0910-0606...

75 FR 40840 - Agency Information Collection Activities; Proposed Collection; Comment Request; Current Good...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-14

... Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements... regulations regarding current good manufacturing practice (CGMP) for dietary supplements. DATES: Submit either... in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements--21 CFR Part 111...

48 CFR 252.231-7000 - Supplemental cost principles.

Code of Federal Regulations, 2010 CFR

2010-10-01

... principles. 252.231-7000 Section 252.231-7000 Federal Acquisition Regulations System DEFENSE ACQUISITION... of Provisions And Clauses 252.231-7000 Supplemental cost principles. As prescribed in 231.100-70, use the following clause: Supplemental Cost Principles (DEC 1991) When the allowability of costs under...

Dietary supplements for athletes: emerging trends and recurring themes.

PubMed

Maughan, R J; Greenhaff, P L; Hespel, P

2011-01-01

Dietary supplements are widely used at all levels of sport. Changes in patterns of supplement use are taking place against a background of changes in the regulatory framework that governs the manufacture and distribution of supplements in the major markets. Market regulation is complicated by the increasing popularity of Internet sales. The need for quality control of products to ensure they contain the listed ingredients in the stated amount and to ensure the absence of potentially harmful substances is recognized. This latter category includes compounds prohibited under anti-doping regulations. Several certification programmes now provide testing facilities for manufacturers of both raw ingredients and end products to ensure the absence of prohibited substances. Athletes should carry out a cost-benefit analysis for any supplement they propose to use. For most supplements, the evidence is weak, or even completely absent. A few supplements, including caffeine, creatine, and bicarbonate, are supported by a strong research base. Difficulties arise when new evidence appears to support novel supplements: in recent years, β-alanine has become popular, and the use of nitrate and arginine is growing. Athletes seldom wait until there is convincing evidence of efficacy or of safety, but caution is necessary to minimize risk.

Long term exposure to L-arginine accelerates endothelial cell senescence through arginase-II and S6K1 signaling

PubMed Central

Xiong, Yuyani; Fru, Michael Forbiteh; Yu, Yi; Montani, Jean-Pierre; Ming, Xiu-Fen; Yang, Zhihong

2014-01-01

L-arginine supplementation is proposed to improve health status or as adjunct therapy for diseases including cardiovascular diseases. However, controversial results and even detrimental effects of L-arginine supplementation are reported. We investigate potential mechanisms of L-arginine-induced detrimental effects on vascular endothelial cells. Human endothelial cells were exposed to a physiological (0.1 mmol/L) or pharmacological (0.5 mmol/L) concentration of L-arginine for 30 minutes (acute) or 7 days (chronic). The effects of L-arginine supplementation on endothelial senescence phenotype, i.e., levels of senescence-associated beta-galactosidase, expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, eNOS-uncoupling, arginase-II expression/activity, and mTORC1-S6K1 activity were analyzed. While acute L-arginine treatment enhances endothelial NO production accompanied with superoxide production and activation of S6K1 but no up-regulation of arginase-II, chronic L-arginine supplementation causes endothelial senescence, up-regulation of the adhesion molecule expression, and eNOS-uncoupling (decreased NO and enhanced superoxide production), which are associated with S6K1 activation and up-regulation of arginase-II. Silencing either S6K1 or arginase-II inhibits up-regulation/activation of each other, prevents endothelial dysfunction, adhesion molecule expression, and senescence under the chronic L-arginine supplementation condition. These results demonstrate that S6K1 and arginase-II form a positive circuit mediating the detrimental effects of chronic L-arginine supplementation on endothelial cells. PMID:24860943

Differential Benefits of Attending Supplemental Instruction for Introductory, Large-Section, University U.S. History Courses

ERIC Educational Resources Information Center

Summers, Emily J.; Acee, Taylor W.; Ryser, Gail R.

2015-01-01

We investigated students' academic achievement in three high-enrollment, introductory-level history sections at a large, public, Hispanic-serving university. Using a conditional indirect-effects model, we analyzed supplemental instruction (SI) attendance and class absences as predictors of course success, after accounting for sex, ethnicity/race,…

Ozone-Induced Pulmonary Injury and Vascular Contractility are Differentially Impacted by Coconut, Fish, and Olive Oil-Rich Diets

EPA Science Inventory

Pulmonary and systemic effects of ozone (O3) are mediated by hypothalamus pituitary adrenal (HPA)-axis activation. Fish oil (FO) and olive oil (OO) dietary supplementation have several cardioprotective benefits, but it is not established if these supplements can protect against t...

Development of Safe and Effective Botanical Dietary Supplements

PubMed Central

2015-01-01

Regulated differently than drugs or foods, the market for botanical dietary supplements continues to grow worldwide. The recently implemented U.S. FDA regulation that all botanical dietary supplements must be produced using good manufacturing practice is an important step toward enhancing the safety of these products, but additional safeguards could be implemented, and unlike drugs, there are currently no efficacy requirements. To ensure a safe and effective product, botanical dietary supplements should be developed in a manner analogous to pharmaceuticals that involves identification of mechanisms of action and active constituents, chemical standardization based on the active compounds, biological standardization based on pharmacological activity, preclinical evaluation of toxicity and potential for drug–botanical interactions, metabolism of active compounds, and finally, clinical studies of safety and efficacy. Completing these steps will enable the translation of botanicals from the field to safe human use as dietary supplements. PMID:26125082

12 CFR 204.7 - Supplemental reserve requirement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 2 2010-01-01 2010-01-01 false Supplemental reserve requirement. 204.7 Section... RESERVE REQUIREMENTS OF DEPOSITORY INSTITUTIONS (REGULATION D) § 204.7 Supplemental reserve requirement... reserve requirement on every depository institution of not more than 4 percent of its total transaction...

48 CFR 1837.203 - Policy. (NASA supplements paragraph (c))

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Policy. (NASA supplements... Services 1837.203 Policy. (NASA supplements paragraph (c)) (c) Advisory and assistance services of... 3300.1, Appointment of Personnel To/From NASA, Chapter 4, Employment of Experts and Consultants). [62...

48 CFR 1837.203 - Policy. (NASA supplements paragraph (c))

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Policy. (NASA supplements... Services 1837.203 Policy. (NASA supplements paragraph (c)) (c) Advisory and assistance services of... 3300.1, Appointment of Personnel To/From NASA, Chapter 4, Employment of Experts and Consultants). [62...

48 CFR 1837.203 - Policy. (NASA supplements paragraph (c))

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Policy. (NASA supplements... Services 1837.203 Policy. (NASA supplements paragraph (c)) (c) Advisory and assistance services of... 3300.1, Appointment of Personnel To/From NASA, Chapter 4, Employment of Experts and Consultants). [62...

48 CFR 1837.203 - Policy. (NASA supplements paragraph (c))

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Policy. (NASA supplements... Services 1837.203 Policy. (NASA supplements paragraph (c)) (c) Advisory and assistance services of... 3300.1, Appointment of Personnel To/From NASA, Chapter 4, Employment of Experts and Consultants). [62...

48 CFR 1837.203 - Policy. (NASA supplements paragraph (c))

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Policy. (NASA supplements... Services 1837.203 Policy. (NASA supplements paragraph (c)) (c) Advisory and assistance services of... 3300.1, Appointment of Personnel To/From NASA, Chapter 4, Employment of Experts and Consultants). [62...

Head-group specificity for feedback regulation of CTP:phosphocholine cytidylyltransferase.

PubMed Central

Jamil, H; Vance, D E

1990-01-01

The specificity of the phospholipid head-group for feedback regulation of CTP: phosphocholine cytidylyltransferase was examined in rat hepatocytes. In choline-deficient cells there is a 2-fold increase in binding of cytidylyltransferase to cellular membranes, compared with choline-supplemented cells. Supplementation of choline-deficient cells with choline, dimethylethanolamine, monomethylethanolamine or ethanolamine resulted in an increase in the concentration of the corresponding phospholipid. Release of cytidylyltransferase into cytosol was only observed in hepatocytes supplemented with choline or dimethylethanolamine. The apparent EC50 values (concn. giving half of maximal effect) for cytidylyltransferase translocation were similar for choline and dimethylethanolamine (25 and 27 microM respectively). The maximum amount of cytidylyltransferase released into cytosol with choline supplementation (1.13 m-units/mg membrane protein) was twice that (0.62) observed with dimethylethanolamine. Supplementation of choline-deficient hepatocytes with NN'-diethylethanolamine, N-ethylethanolamine or 3-aminopropanol also did not cause release of cytidylyltransferase from cellular membranes. The translocation of cytidylyltransferase appeared to be mediated by the concentration of phosphatidylcholine in the membranes and not the ratio of phosphatidylcholine to phosphatidylethanolamine. The results provide further evidence for feedback regulation of phosphatidylcholine biosynthesis by phosphatidylcholine. PMID:2173550

The Silk-protein Sericin Induces Rapid Melanization of Cultured Primary Human Retinal Pigment Epithelial Cells by Activating the NF-κB Pathway

PubMed Central

Eidet, J. R.; Reppe, S.; Pasovic, L.; Olstad, O. K.; Lyberg, T.; Khan, A. Z.; Fostad, I. G.; Chen, D. F.; Utheim, T. P.

2016-01-01

Restoration of the retinal pigment epithelial (RPE) cells to prevent further loss of vision in patients with age-related macular degeneration represents a promising novel treatment modality. Development of RPE transplants, however, requires up to 3 months of cell differentiation. We explored whether the silk protein sericin can induce maturation of primary human retinal pigment epithelial (hRPE) cells. Microarray analysis demonstrated that sericin up-regulated RPE-associated transcripts (RPE65 and CRALBP). Upstream analysis identified the NF-κB pathway as one of the top sericin-induced regulators. ELISA confirmed that sericin stimulates the main NF-κB pathway. Increased levels of RPE-associated proteins (RPE65 and the pigment melanin) in the sericin-supplemented cultures were confirmed by western blot, spectrophotometry and transmission electron microscopy. Sericin also increased cell density and reduced cell death following serum starvation in culture. Inclusion of NF-κB agonists and antagonists in the culture medium showed that activation of the NF-κB pathway appears to be necessary, but not sufficient, for sericin-induced RPE pigmentation. We conclude that sericin promotes pigmentation of cultured primary hRPE cells by activating the main NF-κB pathway. Sericin’s potential role in culture protocols for rapid differentiation of hRPE cells derived from embryonic or induced pluripotent stem cells should be investigated. PMID:26940175

The Silk-protein Sericin Induces Rapid Melanization of Cultured Primary Human Retinal Pigment Epithelial Cells by Activating the NF-κB Pathway.

PubMed

Eidet, J R; Reppe, S; Pasovic, L; Olstad, O K; Lyberg, T; Khan, A Z; Fostad, I G; Chen, D F; Utheim, T P

2016-03-04

Restoration of the retinal pigment epithelial (RPE) cells to prevent further loss of vision in patients with age-related macular degeneration represents a promising novel treatment modality. Development of RPE transplants, however, requires up to 3 months of cell differentiation. We explored whether the silk protein sericin can induce maturation of primary human retinal pigment epithelial (hRPE) cells. Microarray analysis demonstrated that sericin up-regulated RPE-associated transcripts (RPE65 and CRALBP). Upstream analysis identified the NF-κB pathway as one of the top sericin-induced regulators. ELISA confirmed that sericin stimulates the main NF-κB pathway. Increased levels of RPE-associated proteins (RPE65 and the pigment melanin) in the sericin-supplemented cultures were confirmed by western blot, spectrophotometry and transmission electron microscopy. Sericin also increased cell density and reduced cell death following serum starvation in culture. Inclusion of NF-κB agonists and antagonists in the culture medium showed that activation of the NF-κB pathway appears to be necessary, but not sufficient, for sericin-induced RPE pigmentation. We conclude that sericin promotes pigmentation of cultured primary hRPE cells by activating the main NF-κB pathway. Sericin's potential role in culture protocols for rapid differentiation of hRPE cells derived from embryonic or induced pluripotent stem cells should be investigated.

A Closed Chondromimetic Environment within Magnetic-Responsive Liquified Capsules Encapsulating Stem Cells and Collagen II/TGF-β3 Microparticles.

PubMed

Correia, Clara R; Gil, Sara; Reis, Rui L; Mano, João F

2016-06-01

TGF-β3 is enzymatically immobilized by transglutaminase-2 action to poly(l-lactic acid) microparticles coated with collagen II. Microparticles are then encapsulated with stem cells inside liquified spherical compartments enfolded with a permselective shell through layer-by-layer adsorption. Magnetic nanoparticles are electrostatically bound to the multilayered shell, conferring magnetic-response ability. The goal of this study is to engineer a closed environment inside which encapsulated stem cells would undergo a self-regulated chondrogenesis. To test this hypothesis, capsules are cultured in chondrogenic differentiation medium without TGF-β3. Their biological outcome is compared with capsules encapsulating microparticles without TGF-β3 immobilization and cultured in normal chondrogenic differentiation medium containing soluble TGF-β3. Glycosaminoglycans quantification demosntrates that similar chondrogenesis levels are achieved. Moreover, collagen fibrils resembling the native extracellular matrix of cartilage can be observed. Importantly, the genetic evaluation of characteristic cartilage markers confirms the successful chondrogenesis, while hypertrophic markers are downregulated. In summary, the engineered capsules are able to provide a suitable and stable chondrogenesis environment for stem cells without the need of TGF-β3 supplementation. This kind of self-regulated capsules with softness, robustness, and magnetic responsive characteristics is expected to provide injectability and in situ fixation, which is of great advantage for minimal invasive strategies to regenerate cartilage. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

21 CFR 330.14 - Additional criteria and procedures for classifying OTC drugs as generally recognized as safe and...

Code of Federal Regulations, 2012 CFR

2012-04-01

... conditions regulated as a cosmetic or dietary supplement in a foreign country that would be regulated as OTC... without the personal involvement of a pharmacist; dietary supplement; or cosmetic). If the condition has... concerns about the condition's toxicity or other potentiality for harmful effect, the method of its use, or...

78 FR 35844 - Migratory Bird Hunting; Supplemental Proposals for Migratory Game Bird Hunting Regulations for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-14

... Migratory Game Bird Hunting Regulations for the 2013-14 Hunting Season; Notice of Meetings AGENCY: Fish and... migratory game birds for the 2013-14 hunting season. This supplement to the proposed rule provides the... migratory game birds under Sec. Sec. 20.101 through 20.107, 20.109, and 20.110 of subpart K. This document...

76 FR 36508 - Migratory Bird Hunting; Supplemental Proposals for Migratory Game Bird Hunting Regulations for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-22

... Game Bird Hunting Regulations for the 2011-12 Hunting Season; Notice of Meetings AGENCY: Fish and... migratory game birds for the 2011-12 hunting season. This supplement to the proposed rule provides the... migratory game birds under Sec. Sec. 20.101 through 20.107, 20.109, and 20.110 of subpart K. This document...

15 CFR Supplement No. 1 to Part 774 - The Commerce Control List

Code of Federal Regulations, 2010 CFR

2017-01-01

... 15 Commerce and Foreign Trade 2 2017-01-01 2017-01-01 false The Commerce Control List No. Supplement No. 1 to Part 774 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS THE COMMERCE CONTROL LIST Pt. 774, Supp. No. 1...

15 CFR Supplement No. 1 to Part 774 - The Commerce Control List

Code of Federal Regulations, 2010 CFR

2016-01-01

... 15 Commerce and Foreign Trade 2 2016-01-01 2016-01-01 false The Commerce Control List No. Supplement No. 1 to Part 774 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS THE COMMERCE CONTROL LIST Pt. 774, Supp. No. 1...

15 CFR Supplement No. 1 to Part 774 - The Commerce Control List

Code of Federal Regulations, 2010 CFR

2018-01-01

... 15 Commerce and Foreign Trade 2 2018-01-01 2018-01-01 false The Commerce Control List No. Supplement No. 1 to Part 774 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS THE COMMERCE CONTROL LIST Pt. 774, Supp. No. 1...

Excited, Proud, and Accomplished: Exploring the Effects of Feedback Supplemented with Web-Based Peer Benchmarking on Self-Regulated Learning in Marketing Classrooms

ERIC Educational Resources Information Center

Raska, David

2014-01-01

This research explores and tests the effect of an innovative performance feedback practice--feedback supplemented with web-based peer benchmarking--through a lens of social cognitive framework for self-regulated learning. The results suggest that providing performance feedback with references to exemplary peer output is positively associated with…

78 FR 69267 - Defense Federal Acquisition Regulation Supplement: Requirements Relating to Supply Chain Risk...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-18

... Regulation Supplement: Requirements Relating to Supply Chain Risk (DFARS Case 2012-D050) AGENCY: Defense... for FY 2013. This interim rule allows DoD to consider the impact of supply chain risk in specified... Information Relating to Supply Chain Risk,'' as amended by section 806 of the NDAA for FY 2013 (Pub. L. 112...

Nutritional Treatment for Inborn Errors of Metabolism: Indications, Regulations, and Availability of Medical Foods and Dietary Supplements Using Phenylketonuria as an Example

PubMed Central

Camp, Kathryn M.; Lloyd-Puryear, Michele A.; Huntington, Kathleen L.

2012-01-01

Medical foods and dietary supplements are used to treat rare inborn errors of metabolism (IEM) identified through state-based universal newborn screening. These products are regulated under Food and Drug Administration (FDA) food and dietary supplement statutes. The lack of harmony in terminology used to refer to medical foods and dietary supplements and the misuse of words that imply that FDA regulates these products as drugs have led to confusion. These products are expensive and, although they are used for medical treatment of IEM, third-party payer coverage of these products is inconsistent across the United States. Clinicians and families report termination of coverage in late adolescence, failure to cover treatment during pregnancy, coverage for select conditions only, or no coverage. We describe the indications for specific nutritional treatment products for IEM and their regulation, availability, and categorization. We conclude with a discussion of the problems that have contributed to the paradox of identifying individuals with IEM through newborn screening but not guaranteeing that they receive optimal treatment. Throughout the paper, we use the nutritional treatment of phenylketonuria as an example of IEM treatment. PMID:22854513

Improvement of neuronal differentiation by carbon monoxide: Role of pentose phosphate pathway.

PubMed

Almeida, Ana S; Soares, Nuno L; Sequeira, Catarina O; Pereira, Sofia A; Sonnewald, Ursula; Vieira, Helena L A

2018-05-15

Over the last decades, the silent-killer carbon monoxide (CO) has been shown to also be an endogenous cytoprotective molecule able to inhibit cell death and modulate mitochondrial metabolism. Neuronal metabolism is mostly oxidative and neurons also use glucose for maintaining their anti-oxidant status by generation of reduced glutathione (GSH) via the pentose-phosphate pathway (PPP). It is established that neuronal differentiation depends on reactive oxygen species (ROS) generation and signalling, however there is a lack of information about modulation of the PPP during adult neurogenesis. Thus, the main goal of this study was to unravel the role of CO on cell metabolism during neuronal differentiation, particularly by targeting PPP flux and GSH levels as anti-oxidant system. A human neuroblastoma SH-S5Y5 cell line was used, which differentiates into post-mitotic neurons by treatment with retinoic acid (RA), supplemented or not with CO-releasing molecule-A1 (CORM-A1). SH-SY5Y cell differentiation supplemented with CORM-A1 prompted an increase in neuronal yield production. It did, however, not alter glycolytic metabolism, but increased the PPP. In fact, CORM-A1 treatment stimulated (i) mRNA expression of 6-phosphogluconate dehydrogenase (PGDH) and transketolase (TKT), which are enzymes for oxidative and non-oxidative phases of the PPP, respectively and (ii) protein expression and activity of glucose 6-phosphate dehydrogenase (G6PD) the rate-limiting enzyme of the PPP. Likewise, whenever G6PD was knocked-down CO-induced improvement on neuronal differentiation was reverted, while pharmacological inhibition of GSH synthesis did not change CO's effect on the improvement of neuronal differentiation. Both results indicate the key role of PPP in CO-modulation of neuronal differentiation. Furthermore, at the end of SH-SY5Y neuronal differentiation process, CORM-A1 supplementation increased the ratio of reduced and oxidized glutathione (GSH/GSSG) without alteration of GSH metabolism. These data corroborate with PPP stimulation. In conclusion, CO improves neuronal differentiation of SH-S5Y5 cells by stimulating the PPP and modulating the GSH system. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Adipocyte differentiation-related protein promotes lipid accumulation in goat mammary epithelial cells.

PubMed

Shi, H B; Yu, K; Luo, J; Li, J; Tian, H B; Zhu, J J; Sun, Y T; Yao, D W; Xu, H F; Shi, H P; Loor, J J

2015-10-01

Milk fat originates from the secretion of cytosolic lipid droplets (CLD) synthesized within mammary epithelial cells. Adipocyte differentiation-related protein (ADRP; gene symbol PLIN2) is a CLD-binding protein that is crucial for synthesis of mature CLD. Our hypothesis was that ADRP regulates CLD production and metabolism in goat mammary epithelial cells (GMEC) and thus plays a role in determining milk fat content. To understand the role of ADRP in ruminant milk fat metabolism, ADRP (PLIN2) was overexpressed or knocked down in GMEC using an adenovirus system. Immunocytochemical staining revealed that ADRP localized to the surface of CLD. Supplementation with oleic acid (OA) enhanced its colocalization with CLD surface and enhanced lipid accumulation. Overexpression of ADRP increased lipid accumulation and the concentration of triacylglycerol in GMEC. In contrast, morphological examination revealed that knockdown of ADRP decreased lipid accumulation even when OA was supplemented. This response was confirmed by the reduction in mass of cellular TG when ADRP was knocked down. The fact that knockdown of ADRP did not completely eliminate lipid accumulation at a morphological level in GMEC without OA suggests that some other compensatory factors may also aid in the process of CLD formation. The ADRP reversed the decrease of CLD accumulation induced by adipose triglyceride lipase. This is highly suggestive of ADRP promoting triacylglycerol stability within CLD by preventing access to adipose triglyceride lipase. Collectively, these data provide direct in vitro evidence that ADRP plays a key role in CLD formation and stability in GMEC. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

An overview of herbal supplement utilization with particular emphasis on possible interactions with dental drugs and oral manifestations.

PubMed

Abebe, Worku

2003-01-01

Herbal medication in the United States is a popular form of therapy. This paper provides an overview of the utilization of herbal supplements with particular emphasis on possible interactions with oral health drugs and oral manifestations. Herbal supplements are regulated by the Dietary Supplement Health and Education Act (DSHEA), which limits their regulation by the U.S Food and Drug Administration (FDA). A number of studies indicate that there is a progressive increase in the utilization of herbal supplements. The majority of consumers of these products are white, middle-aged women who have some college education. Many of the consumers use pharmaceutical drugs concurrently, but most do not inform their health-care providers about their use of herbal supplements. Various herbal supplements have been reported or are suspected to interact with certain oral health drugs, the most important one being 1) bromelain, cayenne, chamomile, feverfew, dong quai, eleuthro/Seberian ginseng, garlic, ginkgo, ginger, ginseng and licorice interacting with aspirin; 2) aloe latex, ephedra, ginseng, rhubarb, cascara sagrada, licorice, and senna interacting with corticosteriods; 3) kava, St. John's wort, chamomile, and valerian interacting with central nervous system (CNS) depressant drugs; and 4) herbs acting on the gastrointestinal system, altering the absorption of several orally administered drugs. Further, the use of some herbal supplements has been reported to be associated with oral manifestations, including aphthous ulcers, lip and tongue irritation, and swelling with feverfew; gingival bleeding with feverfew and ginkgo; tongue numbness with echinacea; xerostomia with St. John's wort; oral and lingual dyskinesia with kava; and salivation with yohimbe. These potential effects of herbal supplements in conjunction with factors related to regulation restrictions suggest that the use of these products may be associated with various adverse reactions that can affect oral health and treatment. Dental hygienists should inform themselves about herbal supplements in order to offer appropriate oral health care to individuals who take these substances.

7 CFR 250.66 - Special Supplemental Nutrition Program for Women, Infants and Children.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 4 2010-01-01 2010-01-01 false Special Supplemental Nutrition Program for Women... (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE GENERAL REGULATIONS AND POLICIES-FOOD... ITS JURISDICTION Household Programs § 250.66 Special Supplemental Nutrition Program for Women, Infants...

7 CFR 250.66 - Special Supplemental Nutrition Program for Women, Infants and Children.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 4 2011-01-01 2011-01-01 false Special Supplemental Nutrition Program for Women... (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE GENERAL REGULATIONS AND POLICIES-FOOD... ITS JURISDICTION Household Programs § 250.66 Special Supplemental Nutrition Program for Women, Infants...

7 CFR 250.66 - Special Supplemental Nutrition Program for Women, Infants and Children.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 4 2013-01-01 2013-01-01 false Special Supplemental Nutrition Program for Women... (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE GENERAL REGULATIONS AND POLICIES-FOOD... ITS JURISDICTION Household Programs § 250.66 Special Supplemental Nutrition Program for Women, Infants...

7 CFR 250.66 - Special Supplemental Nutrition Program for Women, Infants and Children.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 4 2014-01-01 2014-01-01 false Special Supplemental Nutrition Program for Women... (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE GENERAL REGULATIONS AND POLICIES-FOOD... ITS JURISDICTION Household Programs § 250.66 Special Supplemental Nutrition Program for Women, Infants...

7 CFR 250.66 - Special Supplemental Nutrition Program for Women, Infants and Children.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 4 2012-01-01 2012-01-01 false Special Supplemental Nutrition Program for Women... (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE GENERAL REGULATIONS AND POLICIES-FOOD... ITS JURISDICTION Household Programs § 250.66 Special Supplemental Nutrition Program for Women, Infants...

7 CFR 4280.29 - Supplemental financing required for the Ultimate Recipient Project.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Supplemental financing required for the Ultimate Recipient Project. 4280.29 Section 4280.29 Agriculture Regulations of the Department of Agriculture... AND GRANTS Rural Economic Development Loan and Grant Programs § 4280.29 Supplemental financing...

48 CFR 1815.209 - Solicitation provisions and contract clauses. (NASA supplements paragraph (a))

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Solicitation provisions and contract clauses. (NASA supplements paragraph (a)) 1815.209 Section 1815.209 Federal Acquisition... provisions and contract clauses. (NASA supplements paragraph (a)) (a) The contracting officer shall insert...

48 CFR 1815.209 - Solicitation provisions and contract clauses. (NASA supplements paragraph (a))

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Solicitation provisions and contract clauses. (NASA supplements paragraph (a)) 1815.209 Section 1815.209 Federal Acquisition... provisions and contract clauses. (NASA supplements paragraph (a)) (a) The contracting officer shall insert...

78 FR 23199 - NASA FAR Supplement Regulatory Review No. 1

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-18

... 2700-AE01 NASA FAR Supplement Regulatory Review No. 1 AGENCY: National Aeronautics and Space Administration. ACTION: Proposed rule. SUMMARY: NASA is updating the NASA FAR Supplement (NFS) with the goal of... existing regulations. The revisions to this rule are part of NASA's retrospective plan under EO 13563...

48 CFR 852.236-88 - Contract changes-supplement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Contract changes....236-88 Contract changes—supplement. As prescribed in 836.578, insert the following clause: Contract Changes—Supplement (JUL 2002) The clauses entitled “Changes” in FAR 52.243-4 and “Differing Site...

29 CFR 1953.6 - Review and approval of plan supplements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 1953.6 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION...) OSHA shall review a supplement to determine whether it is at least as effective as the Federal program.... If the review reveals any defect in the supplement, or if more information is needed, OSHA shall...

29 CFR 1953.6 - Review and approval of plan supplements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 1953.6 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION...) OSHA shall review a supplement to determine whether it is at least as effective as the Federal program.... If the review reveals any defect in the supplement, or if more information is needed, OSHA shall...

31 CFR 315.93 - Supplements, amendments, or revisions.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... SAVINGS BONDS, SERIES A, B, C, D, E, F, G, H, J, AND K, AND U.S. SAVINGS NOTES Miscellaneous Provisions § 315.93 Supplements, amendments, or revisions. The Secretary of the Treasury may at any time, or from time to time, prescribe additional, supplemental, amendatory, or revised rules and regulations...

48 CFR 852.236-88 - Contract changes-supplement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract changes....236-88 Contract changes—supplement. As prescribed in 836.578, insert the following clause: Contract Changes—Supplement (JUL 2002) The clauses entitled “Changes” in FAR 52.243-4 and “Differing Site...

One-step generation of murine embryonic stem cell-derived mesoderm progenitors and chondrocytes in a serum-free monolayer differentiation system.

PubMed

Waese, Elaine Y L; Stanford, William L

2011-01-01

Cartilage defects have limited capacity for repair and are often replaced by fibrocartilage with inferior mechanical properties. To overcome the limitations of artificial joint replacement, high-throughput screens (HTS) could be developed to identify molecules that stimulate differentiation and/or proliferation of articular cartilage for drug therapy or tissue engineering. Currently embryonic stem cells (ESCs) can differentiate into articular cartilage by forming aggregates (embryoid body (EB), pellet, micromass), which are difficult to image. We present a novel, single-step method of generating murine ESC-derived chondrocytes in monolayer cultures under chemically defined conditions. Mesoderm induction was achieved in cultures supplemented with BMP4, activin A, or Wnt3a. Prolonged culture with sustained activin A, TGFβ3, or BMP4 supplementation led to robust chondrogenic induction. A short pulse of activin A or BMP4 also induced chondrogenesis efficiently while Wnt3a acted as a later inducer. Long-term supplementation with activin A or with activin A followed by TGFβ3 promoted articular cartilage formation. Thus, we devised a serum-free (SF) culture system to generate ESC-derived chondrocytes without the establishment of 3D cultures or the aid of cell sorting. Cultures were governed by the same signaling pathways as 3D ESC differentiation systems and limb bud mesenchyme or articular cartilage explant cultures. Copyright © 2010 Elsevier B.V. All rights reserved.

Differential effects of dietary fats on sympathetic nervous system activity in the rat.

PubMed

Young, J B; Walgren, M C

1994-01-01

Fat feeding stimulates sympathetic nervous system (SNS) activity in rats. To determine if fats vary in their potency as stimulants of the SNS, [3H]norepinephrine ([3H]NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of animals fed lab chow diets supplemented with safflower oil, coconut oil, or medium-chain triglycerides (MCT). At 5 days, all three fats accelerated [3H]NE turnover in heart and did so equally, but only when the fat supplement represented an increase in energy intake. However, after 14 days, safflower oil and coconut oil but not MCT increased [3H]NE turnover in heart compared with turnover rates obtained in animals fed isoenergetic amounts of chow. Furthermore, the stimulatory effect of safflower oil on [3H]NE turnover was statistically greater than that seen in animals fed equivalent amounts of coconut oil. In vivo synthesis of NE assessed by accumulation of dopamine (DA) in heart following inhibition of dopamine-beta-hydroxylase (D beta H) was likewise highest in safflower oil-fed rats and lowest in those fed MCT. Thus, sympathetic activation by dietary fat varies among different fats, suggesting a role for fatty acid intake in dietary regulation of the SNS.

Alpha-lipoic acid supplementation protects enzymes from damage by nitrosative and oxidative stress.

PubMed

Hiller, Sylvia; DeKroon, Robert; Hamlett, Eric D; Xu, Longquan; Osorio, Cristina; Robinette, Jennifer; Winnik, Witold; Simington, Stephen; Maeda, Nobuyo; Alzate, Oscar; Yi, Xianwen

2016-01-01

S-nitrosylation of mitochondrial enzymes involved in energy transfer under nitrosative stress may result in ATP deficiency. We investigated whether α-lipoic acid, a powerful antioxidant, could alleviate nitrosative stress by regulating S-nitrosylation, which could result in retaining the mitochondrial enzyme activity. In this study, we have identified the S-nitrosylated forms of subunit 1 of dihydrolipoyllysine succinyltransferase (complex III), and subunit 2 of the α-ketoglutarate dehydrogenase complex by implementing a fluorescence-based differential quantitative proteomics method. We found that the activities of these two mitochondrial enzymes were partially but reversibly inhibited by S-nitrosylation in cultured endothelial cells, and that their activities were partially restored by supplementation of α-lipoic acid. We show that protein S-nitrosylation affects the activity of mitochondrial enzymes that are central to energy supply, and that α-lipoic acid protects mitochondrial enzymes by altering S-nitrosylation levels. Inhibiting protein S-nitrosylation with α-lipoic acid seems to be a protective mechanism against nitrosative stress. Identification and characterization of these new protein targets should contribute to expanding the therapeutic power of α-lipoic acid and to a better understanding of the underlying antioxidant mechanisms.

Effects of dietary carbohydrates on rumen epithelial metabolism of nonlactating heifers.

PubMed

Argov-Argaman, N; Eshel, O; Moallem, U; Lehrer, H; Uni, Z; Arieli, A

2012-07-01

Ruminal wall metabolism was studied in nonlactating heifers by altering the carbohydrate (CHO) digestion site between rumen and intestine. The CHO digestion site was estimated from in situ and total-tract digestibility of control (CONT) diets and diets supplemented with corn (CRN), barley (BARL), or soy hulls (SOYH). Ruminal epithelial metabolism regulating gene expression, morphology, and nutrient delivery was assessed from a combination of rumen volatile fatty acid (VFA) concentration, biopsies for papilla morphology, and expression of putative metabolic regulatory genes encoding enzymes that facilitate VFA utilization. Digestible dry matter and CHO intake were 25 and 45% higher, respectively, in the supplemented diets than in CONT diets. Fiber supplementation increased the intestinal and decreased ruminal CHO digestion. Ruminal nonfiber CHO digestibility was 10% lower in CRN than with the high rumen-degradable supplement. The CONT heifers had lowest total ruminal VFA and highest acetate concentration relative to the other treatments. Total VFA concentration in BARL and CRN diets tended to be higher than in SOYH. The SOYH diet tended to reduce papilla dimension relative to CRN and BARL. The CRN diet tended to increase papilla surface area relative to BARL and SOYH. Gene expression of propionyl-coenzyme A carboxylase was higher in CRN and BARL than in SOYH diets, and tended to be higher in CRN than in BARL and SOYH diets. Lactate dehydrogenase and butyryl coenzyme A synthase gene transcripts tended to be higher in CONT than in the supplemented treatments. Thus, rumen epithelial expression of genes involved in VFA metabolism and ruminal wall-structure development are influenced by other regulatory mechanism that is not directly affected by local signals. The in situ methods used are a useful tool for differentiating ruminal from extraruminal nutrient supply. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

DCGL v2.0: an R package for unveiling differential regulation from differential co-expression.

PubMed

Yang, Jing; Yu, Hui; Liu, Bao-Hong; Zhao, Zhongming; Liu, Lei; Ma, Liang-Xiao; Li, Yi-Xue; Li, Yuan-Yuan

2013-01-01

Differential co-expression analysis (DCEA) has emerged in recent years as a novel, systematic investigation into gene expression data. While most DCEA studies or tools focus on the co-expression relationships among genes, some are developing a potentially more promising research domain, differential regulation analysis (DRA). In our previously proposed R package DCGL v1.0, we provided functions to facilitate basic differential co-expression analyses; however, the output from DCGL v1.0 could not be translated into differential regulation mechanisms in a straightforward manner. To advance from DCEA to DRA, we upgraded the DCGL package from v1.0 to v2.0. A new module named "Differential Regulation Analysis" (DRA) was designed, which consists of three major functions: DRsort, DRplot, and DRrank. DRsort selects differentially regulated genes (DRGs) and differentially regulated links (DRLs) according to the transcription factor (TF)-to-target information. DRrank prioritizes the TFs in terms of their potential relevance to the phenotype of interest. DRplot graphically visualizes differentially co-expressed links (DCLs) and/or TF-to-target links in a network context. In addition to these new modules, we streamlined the codes from v1.0. The evaluation results proved that our differential regulation analysis is able to capture the regulators relevant to the biological subject. With ample functions to facilitate differential regulation analysis, DCGL v2.0 was upgraded from a DCEA tool to a DRA tool, which may unveil the underlying differential regulation from the observed differential co-expression. DCGL v2.0 can be applied to a wide range of gene expression data in order to systematically identify novel regulators that have not yet been documented as critical. DCGL v2.0 package is available at http://cran.r-project.org/web/packages/DCGL/index.html or at our project home page http://lifecenter.sgst.cn/main/en/dcgl.jsp.

Metabolomic comparison between wild Ophiocordyceps sinensis and artificial cultured Cordyceps militaris.

PubMed

Chen, Lin; Liu, Yuetao; Guo, Qingfeng; Zheng, Qingxia; Zhang, Wancun

2018-05-11

A systematic study on the metabolome differences between wild Ophiocordyceps sinensis and artificial cultured Cordyceps militaris was conducted using liquid chromatography-mass spectrometry. Principal component analysis and orthogonal projection on latent structure-discriminant analysis results showed that C. militaris grown on solid rice medium (R-CM) and C. militaris grown on tussah pupa (T-CM) evidently separated and individually separated from wild O. sinensis, indicating metabolome difference among wild O. sinensis, R-CM and T-CM. The metabolome differences between R-CM and T-CM indicated that C. militaris could accommodate to culture medium by differential metabolic regulation. Hierarchical clustering analysis was further performed to cluster the differential metabolites and samples based on their metabolic similarity. The higher content of amino acids (pyroglutamic acid, glutamic acid, histidine, phenylalanine and arginine), unsaturated fatty acid (linolenic acid and linoleic acid), peptides, mannitol, adenosine and succinoadenosine in O. sinensis make it as an excellent choice as a traditional Chinese medicine for invigoration or nutritional supplementation. Similar compositions with O. sinensis and easy cultivation make artificially cultured C. militaris a possible alternative to O. sinensis. Copyright © 2018 John Wiley & Sons, Ltd.

Perlecan expression influences the keratin 15‐positive cell population fate in the epidermis of aging skin

PubMed Central

Dos Santos, Morgan; Michopoulou, Anna; André‐Frei, Valérie; Boulesteix, Sophie; Guicher, Christine; Dayan, Guila; Whitelock, John; Damour, Odile; Rousselle, Patricia

2016-01-01

The epidermis is continuously renewed by stem cell proliferation and differentiation. Basal keratinocytes append the dermal‐epidermal junction, a cell surface‐associated, extracellular matrix that provides structural support and influences their behaviour. It consists of laminins, type IV collagen, nidogens, and perlecan, which are necessary for tissue organization and structural integrity. Perlecan is a heparan sulfate proteoglycan known to be involved in keratinocyte survival and differentiation. Aging affects the dermal epidermal junction resulting in decreased contact with keratinocytes, thus impacting epidermal renewal and homeostasis. We found that perlecan expression decreased during chronological skin aging. Our in vitro studies revealed reduced perlecan transcript levels in aged keratinocytes. The production of in vitro skin models revealed that aged keratinocytes formed a thin and poorly organized epidermis. Supplementing these models with purified perlecan reversed the phenomenon allowing restoration of a well‐differentiated multi‐layered epithelium. Perlecan down‐regulation in cultured keratinocytes caused depletion of the cell population that expressed keratin 15. This phenomenon depended on the perlecan heparan sulphate moieties, which suggested the involvement of a growth factor. Finally, we found defects in keratin 15 expression in the epidermis of aging skin. This study highlighted a new role for perlecan in maintaining the self‐renewal capacity of basal keratinocytes. PMID:26996820

Morphogenesis in leaf and single-cell cultures of mature Juniperus oxycedrus.

PubMed

Gomez, M P; Segura, J

1996-08-01

Single cells were mechanically isolated from leaf-derived callus of mature Juniperus oxycedrus L. These cells divided and gave rise to callus when plated on medium containing growth regulators. Best plating efficiency was obtained on a modified Schenk and Hildebrandt medium supplemented with 0.6 micro M 2,4-dichlorophenoxyacetic acid and 100 mg l(-1) casein hydrolyzate. Although single-cell-derived callus showed poor morphogenic potential, both adventitious shoots and embryogenic tissues differentiated from the callus. We also achieved induction of somatic embryogenesis in leaf explants of mature J. oxycedrus trees cultured in the presence of 6.0 or 10.0 micro M 2,4-dichlorophenoxyacetic acid or picloram. Frequency of embryogenic callus ranged from 6 to 18%; however, under the culture conditions tested, isolated embryos failed to develop into plants.

75 FR 56961 - Defense Federal Acquisition Regulation Supplement; Material Inspection and Receiving Report...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-17

...DoD is issuing a proposed rule to update Defense Federal Acquisition Regulation Supplement (DFARS), Appendix F, Material Inspection and Receiving Report, to incorporate procedures for using the electronic Wide Area Workflow Receiving Report required for use in most contracts in lieu of the DD Form 250, Material Inspection and Receiving Report, which is now used mostly on an exception basis.

75 FR 22706 - Defense Federal Acquisition Regulation Supplement; Service Contract Surveillance (DFARS Case 2008...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

...DoD is issuing a final rule amending the Defense Federal Acquisition Regulation Supplement (DFARS) to ensure that the requirement for a quality assurance surveillance plan is addressed for each contract with a dollar value above the simplified acquisition threshold, and that contracts for services have appropriate performance management or surveillance plans prepared for the work being performed under the contract.

Recurrent neural tube defects, risk factors and vitamins.

PubMed Central

Wild, J; Read, A P; Sheppard, S; Seller, M J; Smithells, R W; Nevin, N C; Schorah, C J; Fielding, D W; Walker, S; Harris, R

1986-01-01

Data from our trial of periconceptional vitamin supplementation for the prevention of neural tube defects have been analysed to assess the influence of various factors on recurrence rates of neural tube defect. Our data suggest that the risk of recurrence of neural tube defect is influenced by the number of previous neural tube defects, area of residence, immediately prior miscarriage, and interpregnancy interval. None of these factors, however, contributed any significant differential risk between supplemented and unsupplemented mothers. Hence we conclude that the highly significant difference in recurrence rates of neural tube defect between supplemented and unsupplemented mothers was due to vitamin supplementation. PMID:3521496

Effects of a Spirulina-based dietary supplement on cytokine production from allergic rhinitis patients.

PubMed

Mao, T K; Van de Water, J; Gershwin, M E

2005-01-01

Spirulina represents a blue-green alga that is widely produced and commercialized as a dietary supplement for modulating immune functions, as well as ameliorating a variety of diseases. We have previously shown that the in vitro culture of Spirulina with human peripheral blood mononuclear cells (PBMCs) modulated the production of cytokines. In the present study, we evaluated the impact of a Spirulina-based dietary supplement (Earthrise Nutritionals, Inc., Irvine, CA) on patients with allergic rhinitis by assessing the production of cytokines [interleukin (IL)-4, interferon (IFN)-gamma, and IL-2] critical in regulating immunoglobulin E-mediated allergy. In a randomized double-blinded crossover study versus placebo, allergic individuals were fed daily with either placebo or Spirulina, at 1,000 mg or 2,000 mg, for 12 weeks. PBMCs isolated before and after the Spirulina feeding were stimulated with phytohemagglutinin (PHA) prior to determining the levels of cytokine from cell culture supernatants. Although Spirulina seemed to be ineffective at modulating the secretion of Th1 cytokines (IFN-gamma and IL-2), we discovered that Spirulina, administered at 2,000 mg/day, significantly reduced IL-4 levels by 32% from PHA-stimulated cells. These results indicate that Spirulina can modulate the Th profile in patients with allergic rhinitis by suppressing the differentiation of Th2 cells mediated, in part, by inhibiting the production of IL-4. To our knowledge, this is the first human feeding study that demonstrates the protective effects of Spirulina towards allergic rhinitis.

Socioeconomic differentials in supplementation of vitamin A: evidence from the Philippines.

PubMed

Choi, Yoonjoung; Bishai, David; Hill, Kenneth

2005-06-01

The efficacy of supplementation of vitamin A in child survival has been well-demonstrated. However, the effectiveness of a programme of vitamin A supplementation at the population level has been rarely examined. Understanding how programmes reach disadvantaged children can help improve the design of initiatives of vitamin A supplementation. The differentials in receipt of vitamin A by socioeconomic status were assessed using data from the Philippines. Factors associated with receipt of vitamin A during the last six months were examined using the Philippines Demographic and Health Surveys conducted in 1993 and 1998. In total, 6,970 and 6,118 children aged 12-59 months were included in 1993 and 1998 respectively. Logistic regression was used for identifying associations between the outcome and the household socioeconomic variables. The coverage of national-level vitamin A supplementation increased from 27% in 1993 to 79% in 1998. However, children whose mothers did not complete primary education and children living in poor households were less likely to receive supplementation. This disparity increased between the surveys: the adjusted odds of vitamin A intake by poor households compared to middle-class households declined from 0.73 [95% confidence interval (CI) 0.61-0.87) in 1993 to 0.52 (95% CI 0.42-0.63)] in 1998, resulting in an increased health inequity. The vitamin A programme in the Philippines was not uniformly successful in reaching the most vulnerable children. Approaches targeting vulnerable households or approaches not requiring mothers to travel to distribution centres may be more promising.

20 CFR 216.42 - How a private railroad pension affects a supplemental annuity.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false How a private railroad pension affects a supplemental annuity. 216.42 Section 216.42 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT ELIGIBILITY FOR AN ANNUITY Supplemental Annuity § 216.42 How a private railroad...

15 CFR Supplement No. 1 to Part 714 - Schedule 3 Chemicals

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Schedule 3 Chemicals No. Supplement No... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 3 CHEMICALS Pt. 714, Supp. 1 Supplement No. 1 to Part 714—Schedule 3 Chemicals...

15 CFR Supplement No. 1 to Part 713 - Schedule 2 Chemicals

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Schedule 2 Chemicals No. Supplement No... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 2 CHEMICALS Pt. 713, Supp. 1 Supplement No. 1 to Part 713—Schedule 2 Chemicals...

15 CFR Supplement No. 1 to Part 712 - Schedule 1 Chemicals

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Schedule 1 Chemicals No. Supplement No... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS Pt. 712, Supp. 1 Supplement No. 1 to Part 712—Schedule 1 Chemicals...

15 CFR Supplement No. 1 to Part 712 - Schedule 1 Chemicals

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Schedule 1 Chemicals no. Supplement no... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS Pt. 712, Supp. 1 Supplement no. 1 to Part 712—Schedule 1 Chemicals...

15 CFR Supplement No. 1 to Part 714 - Schedule 3 Chemicals

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Schedule 3 Chemicals No. Supplement No... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 3 CHEMICALS Pt. 714, Supp. 1 Supplement No. 1 to Part 714—Schedule 3 Chemicals...

15 CFR Supplement No. 1 to Part 713 - Schedule 2 Chemicals

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Schedule 2 Chemicals No. Supplement No... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 2 CHEMICALS Pt. 713, Supp. 1 Supplement No. 1 to Part 713—Schedule 2 Chemicals...

Supplemental Educational Services and Student Achievement in Waiver Districts: Anchorage and Hillsborough

ERIC Educational Resources Information Center

Socias, Miguel; deSousa, Juliette-Marie; Le Floch, Kerstin Carlson

2009-01-01

Under federal regulations, school districts that have been identified for improvement or corrective action are not eligible to be supplemental educational service providers. However, the U.S. Department of Education granted waivers to five such districts, on a pilot basis, to allow those districts to provide supplemental educational services. Two…

78 FR 42544 - Outer Continental Shelf (OCS), Gulf of Mexico (GOM), Oil and Gas Lease Sale, Western Planning...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-16

... Prepare a Supplemental Environmental Impact Statement (EIS) SUMMARY: Consistent with the regulations... 248; Central Planning Area (CPA) Lease Sales 227, 231, 235, 241, and 247, Final Environmental Impact... Supplemental Environmental Impact Statement (OCS EIS/EA BOEM 2013-0118) (WPA 233/CPA 231 Supplemental EIS). The...

15 CFR Supplement No. 2 to Part 715 - Examples of Unscheduled Discrete Organic Chemicals (UDOCs) and UDOC Production

Code of Federal Regulations, 2012 CFR

2012-01-01

... Organic Chemicals (UDOCs) and UDOC Production No. Supplement No. 2 to Part 715 Commerce and Foreign Trade... COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING UNSCHEDULED DISCRETE ORGANIC CHEMICALS (UDOCs) Pt. 715, Supp. 2 Supplement No. 2 to Part 715—Examples of Unscheduled Discrete Organic...

15 CFR Supplement No. 2 to Part 715 - Examples of Unscheduled Discrete Organic Chemicals (UDOCs) and UDOC Production

Code of Federal Regulations, 2013 CFR

2013-01-01

... Organic Chemicals (UDOCs) and UDOC Production No. Supplement No. 2 to Part 715 Commerce and Foreign Trade... COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING UNSCHEDULED DISCRETE ORGANIC CHEMICALS (UDOCs) Pt. 715, Supp. 2 Supplement No. 2 to Part 715—Examples of Unscheduled Discrete Organic...

15 CFR Supplement No. 2 to Part 715 - Examples of Unscheduled Discrete Organic Chemicals (UDOCs) and UDOC Production

Code of Federal Regulations, 2011 CFR

2011-01-01

... Organic Chemicals (UDOCs) and UDOC Production No. Supplement No. 2 to Part 715 Commerce and Foreign Trade... COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING UNSCHEDULED DISCRETE ORGANIC CHEMICALS (UDOCs) Pt. 715, Supp. 2 Supplement No. 2 to Part 715—Examples of Unscheduled Discrete Organic...

15 CFR Supplement No. 2 to Part 715 - Examples of Unscheduled Discrete Organic Chemicals (UDOCs) and UDOC Production

Code of Federal Regulations, 2014 CFR

2014-01-01

... Organic Chemicals (UDOCs) and UDOC Production No. Supplement No. 2 to Part 715 Commerce and Foreign Trade... COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING UNSCHEDULED DISCRETE ORGANIC CHEMICALS (UDOCs) Pt. 715, Supp. 2 Supplement No. 2 to Part 715—Examples of Unscheduled Discrete Organic...

15 CFR Supplement No. 1 to Part 714 - Schedule 3 Chemicals

Code of Federal Regulations, 2013 CFR

2013-01-01

... 15 Commerce and Foreign Trade 2 2013-01-01 2013-01-01 false Schedule 3 Chemicals No. Supplement No... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 3 CHEMICALS Pt. 714, Supp. 1 Supplement No. 1 to Part 714—Schedule 3 Chemicals...

15 CFR Supplement No. 1 to Part 714 - Schedule 3 Chemicals

Code of Federal Regulations, 2012 CFR

2012-01-01

... 15 Commerce and Foreign Trade 2 2012-01-01 2012-01-01 false Schedule 3 Chemicals No. Supplement No... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 3 CHEMICALS Pt. 714, Supp. 1 Supplement No. 1 to Part 714—Schedule 3 Chemicals...

15 CFR Supplement No. 1 to Part 713 - Schedule 2 Chemicals

Code of Federal Regulations, 2012 CFR

2012-01-01

... 15 Commerce and Foreign Trade 2 2012-01-01 2012-01-01 false Schedule 2 Chemicals No. Supplement No... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 2 CHEMICALS Pt. 713, Supp. 1 Supplement No. 1 to Part 713—Schedule 2 Chemicals...

15 CFR Supplement No. 1 to Part 712 - Schedule 1 Chemicals

Code of Federal Regulations, 2013 CFR

2013-01-01

... 15 Commerce and Foreign Trade 2 2013-01-01 2013-01-01 false Schedule 1 Chemicals No. Supplement No... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS Pt. 712, Supp. 1 Supplement No. 1 to Part 712—Schedule 1 Chemicals...

15 CFR Supplement No. 1 to Part 712 - Schedule 1 Chemicals

Code of Federal Regulations, 2012 CFR

2012-01-01

... 15 Commerce and Foreign Trade 2 2012-01-01 2012-01-01 false Schedule 1 Chemicals No. Supplement No... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS Pt. 712, Supp. 1 Supplement No. 1 to Part 712—Schedule 1 Chemicals...

15 CFR Supplement No. 1 to Part 713 - Schedule 2 Chemicals

Code of Federal Regulations, 2013 CFR

2013-01-01

... 15 Commerce and Foreign Trade 2 2013-01-01 2013-01-01 false Schedule 2 Chemicals No. Supplement No... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 2 CHEMICALS Pt. 713, Supp. 1 Supplement No. 1 to Part 713—Schedule 2 Chemicals...

15 CFR Supplement No. 1 to Part 712 - Schedule 1 Chemicals

Code of Federal Regulations, 2014 CFR

2014-01-01

... 15 Commerce and Foreign Trade 2 2014-01-01 2014-01-01 false Schedule 1 Chemicals No. Supplement No... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS Pt. 712, Supp. 1 Supplement No. 1 to Part 712—Schedule 1 Chemicals...

15 CFR Supplement No. 1 to Part 713 - Schedule 2 Chemicals

Code of Federal Regulations, 2014 CFR

2014-01-01

... 15 Commerce and Foreign Trade 2 2014-01-01 2014-01-01 false Schedule 2 Chemicals No. Supplement No... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 2 CHEMICALS Pt. 713, Supp. 1 Supplement No. 1 to Part 713—Schedule 2 Chemicals...

15 CFR Supplement No. 1 to Part 714 - Schedule 3 Chemicals

Code of Federal Regulations, 2014 CFR

2014-01-01

... 15 Commerce and Foreign Trade 2 2014-01-01 2014-01-01 false Schedule 3 Chemicals No. Supplement No... (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 3 CHEMICALS Pt. 714, Supp. 1 Supplement No. 1 to Part 714—Schedule 3 Chemicals...

48 CFR 1805.303 - Announcement of contract awards. (NASA supplements paragraph (a))

Code of Federal Regulations, 2013 CFR

2013-10-01

... awards. (NASA supplements paragraph (a)) 1805.303 Section 1805.303 Federal Acquisition Regulations System... ACTIONS Synopses of Contract Awards 1805.303 Announcement of contract awards. (NASA supplements paragraph (a)) (a)(i) In lieu of the $3.5 million threshold cited in FAR 5.303(a), NASA Headquarters public...

48 CFR 1837.104 - Personal services contracts. (NASA supplements paragraph (b))

Code of Federal Regulations, 2012 CFR

2012-10-01

... contracts. (NASA supplements paragraph (b)) 1837.104 Section 1837.104 Federal Acquisition Regulations System... Contracts-General 1837.104 Personal services contracts. (NASA supplements paragraph (b)) (b) Section 203(c)(9) of the National Aeronautics and Space Act of 1958 (42 U.S.C. 2473(c)(9)) authorizes NASA “to...

48 CFR 1837.104 - Personal services contracts. (NASA supplements paragraph (b))

Code of Federal Regulations, 2013 CFR

2013-10-01

... contracts. (NASA supplements paragraph (b)) 1837.104 Section 1837.104 Federal Acquisition Regulations System... Contracts-General 1837.104 Personal services contracts. (NASA supplements paragraph (b)) (b) Section 203(c)(9) of the National Aeronautics and Space Act of 1958 (42 U.S.C. 2473(c)(9)) authorizes NASA “to...

48 CFR 1837.104 - Personal services contracts. (NASA supplements paragraph (b))

Code of Federal Regulations, 2014 CFR

2014-10-01

... contracts. (NASA supplements paragraph (b)) 1837.104 Section 1837.104 Federal Acquisition Regulations System... Contracts-General 1837.104 Personal services contracts. (NASA supplements paragraph (b)) (b) Section 203(c)(9) of the National Aeronautics and Space Act of 1958 (42 U.S.C. 2473(c)(9)) authorizes NASA “to...

48 CFR 1837.104 - Personal services contracts. (NASA supplements paragraph (b))

Code of Federal Regulations, 2010 CFR

2010-10-01

.... (NASA supplements paragraph (b)) 1837.104 Section 1837.104 Federal Acquisition Regulations System... Contracts-General 1837.104 Personal services contracts. (NASA supplements paragraph (b)) (b) Section 203(c)(9) of the National Aeronautics and Space Act of 1958 (42 U.S.C. 2473(c)(9)) authorizes NASA “to...

48 CFR 1815.604 - Agency points of contact. (NASA supplements paragraph (a))

Code of Federal Regulations, 2011 CFR

2011-10-01

.... (NASA supplements paragraph (a)) 1815.604 Section 1815.604 Federal Acquisition Regulations System... NEGOTIATION Unsolicited Proposals 1815.604 Agency points of contact. (NASA supplements paragraph (a)) (a)(6... Internet at http://ec.msfc.nasa.gov/hq/library/unSol-Prop.html. A deviation is required for use of any...

48 CFR 1815.604 - Agency points of contact. (NASA supplements paragraph (a))

Code of Federal Regulations, 2013 CFR

2013-10-01

.... (NASA supplements paragraph (a)) 1815.604 Section 1815.604 Federal Acquisition Regulations System... NEGOTIATION Unsolicited Proposals 1815.604 Agency points of contact. (NASA supplements paragraph (a)) (a)(6... Internet at http://ec.msfc.nasa.gov/hq/library/unSol-Prop.html. A deviation is required for use of any...

48 CFR 1805.303 - Announcement of contract awards. (NASA supplements paragraph (a))

Code of Federal Regulations, 2012 CFR

2012-10-01

... awards. (NASA supplements paragraph (a)) 1805.303 Section 1805.303 Federal Acquisition Regulations System... ACTIONS Synopses of Contract Awards 1805.303 Announcement of contract awards. (NASA supplements paragraph (a)) (a)(i) In lieu of the $3.5 million threshold cited in FAR 5.303(a), NASA Headquarters public...