Chow diet in mouse aging studies: nothing regular about it.

Chow diet is used in the majority of rodent studies and, although assumed to be standardized for dietary source and nutritional contents, it varies widely across commercial formulations. Similarly, current approaches to study aging in rodents involve a single-diet formulation across the lifespan and overlook age-specific nutritional requirements, which may have long-term effects on aging processes. Together, these nutrition-based disparities represent major gaps in geroscience research, affecting the interpretation and reproducibility of the studies. This perspective aims to raise awareness on the importance of rodent diet formulation and proposes that geroscientists include detailed descriptions of all experimental diets and feeding protocols. Detailed reporting of diets will enhance rigor and reproducibility of aging rodent studies and lead to more translational outcomes in geroscience research

Mathematical modelling of fibre-enhanced perfusion inside\ud a tissue-engineering bioreactor

We develop a simple mathematical model for forced flow of culture medium through a porous scaffold in a tissue- engineering bioreactor. Porous-walled hollow fibres penetrate the scaffold and act as additional sources of culture medium. The model, based on Darcy’s law, is used to examine the nutrient and shear-stress distributions throughout the scaffold. We consider several configurations of fibres and inlet and outlet pipes. Compared with a numerical solution of the full Navier–Stokes equations within the complex scaffold geometry, the modelling approach is cheap, and does not require knowledge of the detailed microstructure of the particular scaffold being used. The potential of this approach is demonstrated through quantification of the effect the additional flow from the fibres has on the nutrient and shear-stress distribution

Extrahepatic tissue concentrations of vitamin K are lower in rats fed a high vitamin E diet

BACKGROUND: An adverse hematological interaction between vitamins E and K has been reported, primarily in patients on anticoagulants. However, little is known regarding circulating levels or tissue concentrations of vitamin K in response to vitamin E supplementation. The purpose of this study was to examine the effect of different levels of dietary α-tocopherol on phylloquinone and menaquinone-4 concentrations, while maintaining a constant intake of phylloquinone, in rat tissues. METHODS: Male 4-wk old Fischer 344 rats (n = 33) were fed one of 3 diets for 12 wk: control (n = 13) with 30 mg all-rac-α-tocopherol acetate/kg diet; vitamin E-supplemented (n = 10) with 100 mg all-rac-α-tocopherol acetate/kg diet; and vitamin E-restricted (n = 10) with <10 mg total tocopherols/kg diet. All 3 diets contained 470 ± 80 μg phylloquinone/kg diet. RESULTS: Phylloquinone concentrations were lower (P ≤ 0.05) in the vitamin E-supplemented compared to the vitamin E-restricted group (mean ± SD spleen: 531 ± 58 vs.735 ± 77; kidney: 20 ± 17 vs. 94 ± 31, brain: 53 ± 19 vs.136 ± 97 pmol/g protein respectively); no statistically significant differences between groups were found in plasma, liver or testis. Similar results were noted with menaquinone-4 concentrations in response to vitamin E supplementation. CONCLUSION: There appears to be a tissue-specific interaction between vitamins E and K when vitamin E is supplemented in rat diets. Future research is required to elucidate the mechanism for this nutrient-nutrient interaction

Adiposity, Cardiometabolic Risk, and Vitamin D Status: The Framingham Heart Study

OBJECTIVE: Because vitamin D deficiency is associated with a variety of chronic diseases, understanding the characteristics that promote vitamin D deficiency in otherwise healthy adults could have important clinical implications. Few studies relating vitamin D deficiency to obesity have included direct measures of adiposity. Furthermore, the degree to which vitamin D is associated with metabolic traits after adjusting for adiposity measures is unclear. RESEARCH DESIGN AND METHODS: We investigated the relations of serum 25-hydroxyvitamin D (25[OH]D) concentrations with indexes of cardiometabolic risk in 3,890 nondiabetic individuals; 1,882 had subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes measured by multidetector computed tomography (CT). RESULTS: In multivariable-adjusted regression models, 25(OH)D was inversely associated with winter season, waist circumference, and serum insulin (P < 0.005 for all). In models further adjusted for CT measures, 25(OH)D was inversely related to SAT (−1.1 ng/ml per SD increment in SAT, P = 0.016) and VAT (−2.3 ng/ml per SD, P < 0.0001). The association of 25(OH)D with insulin resistance measures became nonsignificant after adjustment for VAT. Higher adiposity volumes were correlated with lower 25(OH)D across different categories of BMI, including in lean individuals (BMI <25 kg/m2). The prevalence of vitamin D deficiency (25[OH]D <20 ng/ml) was threefold higher in those with high SAT and high VAT than in those with low SAT and low VAT (P < 0.0001). CONCLUSIONS: Vitamin D status is strongly associated with variation in subcutaneous and especially visceral adiposity. The mechanisms by which adiposity promotes vitamin D deficiency warrant further study.National Institutes of Health's National Heart, Lung, and Blood Institute (N01-HC-25195, R01-DK-80739): American Heart Associatio

MicroRNA 146a (miR-146a) Is Over-Expressed during Prion Disease and Modulates the Innate Immune Response and the Microglial Activation State

Increasing evidence supports the involvement of microRNAs (miRNAs) in inflammatory and immune processes in prion neuropathogenesis. MiRNAs are small, non-coding RNA molecules which are emerging as key regulators of numerous cellular processes. We established miR-146a over-expression in prion-infected mouse brain tissues concurrent with the onset of prion deposition and appearance of activated microglia. Expression profiling of a variety of central nervous system derived cell-lines revealed that miR-146a is preferentially expressed in cells of microglial lineage. Prominent up-regulation of miR-146a was evident in the microglial cell lines BV-2 following TLR2 or TLR4 activation and also EOC 13.31 via TLR2 that reached a maximum 24–48 hours post-stimulation, concomitant with the return to basal levels of transcription of induced cytokines. Gain- and loss-of-function studies with miR-146a revealed a substantial deregulation of inflammatory response pathways in response to TLR2 stimulation. Significant transcriptional alterations in response to miR-146a perturbation included downstream mediators of the pro-inflammatory transcription factor, nuclear factor-kappa B (NF-κB) and the JAK-STAT signaling pathway. Microarray analysis also predicts a role for miR-146a regulation of morphological changes in microglial activation states as well as phagocytic mediators of the oxidative burst such as CYBA and NOS3. Based on our results, we propose a role for miR-146a as a potent modulator of microglial function by regulating the activation state during prion induced neurodegeneration

ALMA 1.3 Millimeter Map of the HD 95086 System

Planets and minor bodies such as asteroids, Kuiper-belt objects and comets are integral components of a planetary system. Interactions among them leave clues about the formation process of a planetary system. The signature of such interactions is most prominent through observations of its debris disk at millimeter wavelengths where emission is dominated by the population of large grains that stay close to their parent bodies. Here we present ALMA 1.3 mm observations of HD 95086, a young early-type star that hosts a directly imaged giant planet b and a massive debris disk with both asteroid- and Kuiper-belt analogs. The location of the Kuiper-belt analog is resolved for the first time. The system can be depicted as a broad ($\Delta R/R \sim$0.84), inclined (30\arcdeg$\pm$3\arcdeg) ring with millimeter emission peaked at 200$\pm$6 au from the star. The 1.3 mm disk emission is consistent with a broad disk with sharp boundaries from 106$\pm$6 to 320$\pm$20 au with a surface density distribution described by a power law with an index of --0.5$\pm$0.2. Our deep ALMA map also reveals a bright source located near the edge of the ring, whose brightness at 1.3 mm and potential spectral energy distribution are consistent with it being a luminous star-forming galaxy at high redshift. We set constraints on the orbital properties of planet b assuming co-planarity with the observed disk.Comment: accepted for publication in A

The role of menaquinones (vitamin K2) in human health

Recent reports have attributed the potential health benefits of vitamin K beyond its function to activate hepatic coagulation factors. Moreover, several studies have suggested that menaquinones, also known as vitamin K2, may be more effective in activating extra-hepatic vitamin K-dependent proteins than phylloquinone, also known as vitamin K1. Nevertheless, present dietary reference values (DRV) for vitamin K are exclusively based on phylloquinone, and its function in coagulation. The present review describes the current knowledge on menaquinones based on the following criteria for setting DRV: optimal dietary intake; nutrient amount required to prevent deficiency, maintain optimal body stores and/or prevent chronic disease; factors influencing requirements such as absorption, metabolism, age and sex. Dietary intake of menaquinones accounts for up to 25% of total vitamin K intake and contributes to the biological functions of vitamin K. However, menaquinones are different from phylloquinone with respect to their chemical structure and pharmacokinetics, which affects bioavailability, metabolism and perhaps impact on health outcomes. There are significant gaps in the current knowledge on menaquinones based on the criteria for setting DRV. Therefore, we conclude that further investigations are needed to establish how differences among the vitamin K forms may influence tissue specificities and their role in human health. However, there is merit for considering both menaquinones and phylloquinone when developing future recommendations for vitamin K intak

Genome-Wide Association with Select Biomarker Traits in the Framingham Heart Study

BACKGROUND: Systemic biomarkers provide insights into disease pathogenesis, diagnosis, and risk stratification. Many systemic biomarker concentrations are heritable phenotypes. Genome-wide association studies (GWAS) provide mechanisms to investigate the genetic contributions to biomarker variability unconstrained by current knowledge of physiological relations. METHODS: We examined the association of Affymetrix 100K GeneChip single nucleotide polymorphisms (SNPs) to 22 systemic biomarker concentrations in 4 biological domains: inflammation/oxidative stress; natriuretic peptides; liver function; and vitamins. Related members of the Framingham Offspring cohort (n = 1012; mean age 59 ± 10 years, 51% women) had both phenotype and genotype data (minimum-maximum per phenotype n = 507–1008). We used Generalized Estimating Equations (GEE), Family Based Association Tests (FBAT) and variance components linkage to relate SNPs to multivariable-adjusted biomarker residuals. Autosomal SNPs (n = 70,987) meeting the following criteria were studied: minor allele frequency ≥ 10%, call rate ≥ 80% and Hardy-Weinberg equilibrium p ≥ 0.001. RESULTS: With GEE, 58 SNPs had p < 10-6: the top SNPs were rs2494250 (p = 1.00*10-14) and rs4128725 (p = 3.68*10-12) for monocyte chemoattractant protein-1 (MCP1), and rs2794520 (p = 2.83*10-8) and rs2808629 (p = 3.19*10-8) for C-reactive protein (CRP) averaged from 3 examinations (over about 20 years). With FBAT, 11 SNPs had p < 10-6: the top SNPs were the same for MCP1 (rs4128725, p = 3.28*10-8, and rs2494250, p = 3.55*10-8), and also included B-type natriuretic peptide (rs437021, p = 1.01*10-6) and Vitamin K percent undercarboxylated osteocalcin (rs2052028, p = 1.07*10-6). The peak LOD (logarithm of the odds) scores were for MCP1 (4.38, chromosome 1) and CRP (3.28, chromosome 1; previously described) concentrations; of note the 1.5 support interval included the MCP1 and CRP SNPs reported above (GEE model). Previous candidate SNP associations with circulating CRP concentrations were replicated at p < 0.05; the SNPs rs2794520 and rs2808629 are in linkage disequilibrium with previously reported SNPs. GEE, FBAT and linkage results are posted at . CONCLUSION: The Framingham GWAS represents a resource to describe potentially novel genetic influences on systemic biomarker variability. The newly described associations will need to be replicated in other studies.National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC25195); National Institutes of Health National Center for Research Resources Shared Instrumentation grant (1S10RR163736-01A1); National Institutes of Health (HL064753, HL076784, AG028321, HL71039, 2 K24HL04334, 1K23 HL083102); Doris Duke Charitable Foundation; American Diabetes Association Career Developement Award; National Center for Research Resources (GCRC M01-RR01066); US Department of Agriculture Agricultural Research Service (58-1950-001, 58-1950-401); National Institute of Aging (AG14759

Vitamin K Status and Lower Extremity Function in Older Adults: The Health Aging and Body Composition Study

While low vitamin K status has been associated with several chronic diseases that can lead to lower extremity disability, it is not known if low vitamin K status is associated with worse lower extremity function