A Low Dose of Dietary Resveratrol Partially Mimics Caloric Restriction and Retards Aging Parameters in Mice

Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg−1 day−1), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles. We report a striking transcriptional overlap of CR and resveratrol in heart, skeletal muscle and brain. Both dietary interventions inhibit gene expression profiles associated with cardiac and skeletal muscle aging, and prevent age-related cardiac dysfunction. Dietary resveratrol also mimics the effects of CR in insulin mediated glucose uptake in muscle. Gene expression profiling suggests that both CR and resveratrol may retard some aspects of aging through alterations in chromatin structure and transcription. Resveratrol, at doses that can be readily achieved in humans, fulfills the definition of a dietary compound that mimics some aspects of CR

General SU(2)L×SU(2)R×U(1)EMSU(2)_L\times SU(2)_R \times U(1)_{EM} Sigma Model With External Sources, Dynamical Breaking And Spontaneous Vacuum Symmetry Breaking

We give a general $SU(2)_L\times SU(2)_R$ $\times U(1)_{EM}$ sigma model with external sources, dynamical breaking and spontaneous vacuum symmetry breaking, and present the general formulation of the model. It is found that $\sigma$ and $\pi ^0$ without electric charges have electromagnetic interaction effects coming from their internal structure. A general Lorentz transformation relative to external sources $J_{gauge}$ $=(J_{A_\mu},J_{A_\mu ^\kappa})$ is derived, using the general Lorentz transformation and the four-dimensional current of nuclear matter of the ground state with $J_{gauge}$ = 0, we give the four-dimensional general relations between the different currents of nuclear matter systems with $J_{gauge}\neq 0$ and those with $J_{gauge}=0$. The relation of the density's coupling with external magnetic field is derived, which conforms well to dense nuclear matter in a strong magnetic field. We show different condensed effects in strong interaction about fermions and antifermions, and give the concrete scalar and pseudoscalar condensed expressions of $\sigma_0$ and $\pi_0$ bosons. About different dynamical breaking and spontaneous vacuum symmetry breaking, the concrete expressions of different mass spectra are obtained in field theory. This paper acquires the running spontaneous vacuum breaking value $\sigma_0^{\prime},$ and obtains the spontaneous vacuum breaking in terms of the running $\sigma_0^{\prime}$, which make nucleon, $\sigma$ and $\pi$ particles gain effective masses. We achieve both the effect of external sources and nonvanishing value of the condensed scalar and pseudoscalar paticles. It is deduced that the masses of nucleons, $\sigma$ and $\pi$ generally depend on different external sources.Comment: 12 page

Qualitative and quantitative measurement of the anterior and posterior meniscal root attachments of the New Zealand white rabbit

Background: The purpose of this study was to quantify the meniscal root anatomy of the New Zealand white rabbit to better understand this animal model for future in vitro and in vivo joint degeneration studies. Methods: Ten non-paired fresh frozen New Zealand white rabbit knee stifle joints were carefully disarticulated for this study. Measurements were made for all bony landmarks and ligamentous structure attachment sites on the tibial plateau. The following soft tissue structures were consistently identified in the rabbit stifle joint: the anterior root attachment of the lateral meniscus, the anterior root attachment of the medial meniscus, the anterior cruciate ligament, the posterior root attachment of the medial meniscus, the ligament of Wrisberg, the posterior cruciate ligament, and the posterior meniscotibial ligament. The following bony landmarks were consistently identified: the extensor digitorum longus groove, the medial tibial eminence, the center of the tibial tuberosity, and the lateral tibial eminence. Results: The center of the anterior cruciate ligament and the medial tibial eminence apex were found to be 3.4 ± 0.3 mm (2.9–3.6) and 6.1 ± 0.6 mm (5.1–7.0) respectively from the center of the medical anterior root attachment. The center of the anterior cruciate ligament and the lateral tibial eminence apex were found to be 2.1 ± 0.5 mm (1.2–2.7) and 7.0 ± 0.6 mm (6.4–8.2) respectively from the center of the lateral anterior root attachment. The center of the posterior cruciate ligament and the medial tibial eminence apex were found to be 2.0 ± 0.7 mm (0.5–2.6) and 1.8 ± 0.4 mm (1.2–2.4) respectively from the center of the medial posterior root attachment. Conclusions: This study augments our understanding of the comparative anatomy of the rabbit stifle joint. This information will be useful for future biomechanical, surgical, and in vitro studies utilizing the rabbit stifle as a model for human knee joint degenerative diseases

Medial Meniscus Radial Tear: A Transtibial 2-Tunnel Technique

Complete radial tears of the medial meniscus significantly decrease the meniscal tissue's ability to dissipate tibiofemoral loads and have been described as functionally similar to a total meniscectomy, predisposing patients to early osteoarthritis. At present, no consensus exists regarding the optimal surgical treatment of a radial meniscal tear. Current repair techniques have led to a reportedly high rate of incomplete healing or healing of the meniscus in a nonanatomic, gapped position, which compromises its ability to withstand hoop stresses. Improvement regarding the ability to repair and heal medial meniscus radial tears has the potential to result in enhanced preservation of the articular cartilage in the medial compartment of the knee. This technical description details a method for repairing radial tears of the medial meniscus using a transtibial 2-tunnel technique

Evaluation of Endothelial and Vascular-Derived Progenitor Cell Populations in the Proximal and Distal UCL of the Elbow: A Comparative Study

Background: Vascular-derived progenitor and endothelial cell populations (CD31, CD34, CD146) are capable of multipotent differentiation at the site of injured ligamentous tissue to aid in the intrinsic healing response. Proximal ulnar collateral ligament (UCL) tears have been reported to have better healing capability when compared with distal UCL tears. Purpose: To compare the vascular composition of the proximal and distal insertions of the anterior bundle of the UCL of the elbow via known markers of endothelial and vascular-derived progenitor cells (CD31, CD34, CD146). Study Design: Descriptive laboratory study. Methods: UCLs were harvested from 10 nonpaired fresh-frozen human cadaveric elbows and transected into proximal and distal portions. Endothelial and vascular-derived progenitor cell densities were assessed with 4 staining groups: CD31 (immunohistochemistry) and CD31/α-smooth muscle actin (α-SMA), CD34/α-SMA, and CD146/α-SMA (immunofluorescence). CD31 immunohistochemistry identified endothelial progenitor cells in the UCL. Later staining of the same slides with α-SMA demonstrated the relationship of progenitor cells to the surrounding vasculature. Fluorescent staining was quantified by calculating the proportion of positively stained nuclei versus the total number of nuclei in the proximal and distal UCL. Results: CD31+ cells were present in the proximal and distal sections of all 10 UCLs. Fluorescent staining revealed no significant differences in the ratio of CD31 to total nuclei between the distal (median, 36% [range, 23%-53%]) and proximal UCL (39% [22%-56%]) (P = .432, Wilcoxon signed-rank test). Similarly, no differences were seen between CD34 distal (39% [24%-64%]) and proximal regions (46% [28%-63%]) (P = .846, Wilcoxon signed-rank test) or CD146 distal (40% [12%-65%]) and proximal regions (40% [22%-51%]) (P ≥ .999, Wilcoxon signed-rank test). Conclusion: Analysis of UCL tissues demonstrated equal distributions of vascular endothelial and vascular-derived progenitor cell markers throughout the proximal and distal UCL. Unlike that of the medial collateral ligament of the knee, the microvascular composition of the proximal and distal UCL insertions was not different, suggesting a well-vascularized ligament throughout its course

CRISPR screens identify gene targets at breast cancer risk loci

Abstract Background Genome-wide association studies (GWAS) have identified > 200 loci associated with breast cancer risk. The majority of candidate causal variants are in non-coding regions and likely modulate cancer risk by regulating gene expression. However, pinpointing the exact target of the association, and identifying the phenotype it mediates, is a major challenge in the interpretation and translation of GWAS. Results Here, we show that pooled CRISPR screens are highly effective at identifying GWAS target genes and defining the cancer phenotypes they mediate. Following CRISPR mediated gene activation or suppression, we measure proliferation in 2D, 3D, and in immune-deficient mice, as well as the effect on DNA repair. We perform 60 CRISPR screens and identify 20 genes predicted with high confidence to be GWAS targets that promote cancer by driving proliferation or modulating the DNA damage response in breast cells. We validate the regulation of a subset of these genes by breast cancer risk variants. Conclusions We demonstrate that phenotypic CRISPR screens can accurately pinpoint the gene target of a risk locus. In addition to defining gene targets of risk loci associated with increased breast cancer risk, we provide a platform for identifying gene targets and phenotypes mediated by risk variants

Differential Regulation of Adiponectin Receptor Gene Expression by Adiponectin and Leptin in Myotubes Derived from Obese and Diabetic Individuals

Objective: This study aimed to investigate the regulation of adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) gene expression in primary skeletal muscle myotubes, derived from human donors, after exposure to globular adiponectin (gAd) and leptin. Research Methods and Procedures: Four distinct primary cell culture groups were established [ Lean, Obese, Diabetic, Weight Loss (Wt Loss); n = 7 in each] from rectus abdominus muscle biopsies obtained from surgical patients. Differentiated myotube cultures were exposed to gAd (0.1 g/mL) or leptin (2.5 g/mL) for 6 hours. AdipoR1 and AdipoR2 gene expression was measured by real-time polymerase chain reaction analysis. Results: AdipoR1 mRNA expression in skeletal muscle myotubes derived from Lean subjects (p < 0.05) was stimulated 1.8-fold and 2.5-fold with gAd and leptin, respectively. No increase in AdipoR1 gene expression was measured in myotubes derived from Obese, Diabetic, or Wt Loss subjects. AdipoR2 mRNA expression was unaltered after gAd and leptin exposure in all myotube groups. Discussion: Adiponectin and leptin are rapid and potent stimulators of AdipoR1 in myotubes derived from lean healthy individuals. This effect was abolished in myotubes derived from obese, obese diabetic subjects, and obese-prone individuals who had lost significant weight after bariatric surgery. The incapacity of skeletal muscle of obese and diabetic individuals to respond to exogenous adiponectin and leptin may be further suppressed as a result of impaired regulation of the AdipoR1 gene

Berberine protects against high fat diet-induced dysfunction in muscle mitochondria by inducing SIRT1-dependent mitochondrial biogenesis

Item does not contain fulltextBerberine (BBR) has recently been shown to improve insulin sensitivity in rodent models of insulin resistance. Although this effect was explained partly through an observed activation of AMP-activated protein kinase (AMPK), the upstream and downstream mediators of this phenotype were not explored. Here, we show that BBR supplementation reverts mitochondrial dysfunction induced by High Fat Diet (HFD) and hyperglycemia in skeletal muscle, in part due to an increase in mitochondrial biogenesis. Furthermore, we observe that the prevention of mitochondrial dysfunction by BBR, the increase in mitochondrial biogenesis, as well as BBR-induced AMPK activation, are blocked in cells in which SIRT1 has been knocked-down. Taken together, these data reveal an important role for SIRT1 and mitochondrial biogenesis in the preventive effects of BBR on diet-induced insulin resistance