Energy Balance, Myostatin, and GILZ: Factors Regulating Adipocyte Differentiation in Belly and Bone

Peroxisome proliferator-activated receptor gamma (PPAR-γ) belongs to the nuclear hormone receptor subfamily of transcription factors. PPARs are expressed in key target tissues such as liver, fat, and muscle and thus they play a major role in the regulation of energy balance. Because of PPAR-γ's role in energy balance, signals originating from the gut (e.g., GIP), fat (e.g., leptin), muscle (e.g., myostatin), or bone (e.g., GILZ) can in turn modulate PPAR expression and/or function. Of the two PPAR-γ isoforms, PPAR-γ2 is the key regulator of adipogenesis and also plays a role in bone development. Activation of this receptor favors adipocyte differentiation of mesenchymal stem cells, while inhibition of PPAR-γ2 expression shifts the commitment towards the osteoblastogenic pathway. Clinically, activation of this receptor by antidiabetic agents of the thiazolidinedione class results in lower bone mass and increased fracture rates. We propose that inhibition of PPAR-γ2 expression in mesenchymal stem cells by use of some of the hormones/factors mentioned above may be a useful therapeutic strategy to favor bone formation

Estimating Sample Sizes for Distance Sampling of Autumn Northern Bobwhite Calling Coveys

Point transect sampling of calling coveys has been advocated for estimating autumn abundance of northern bobwhite (Colinus virginianus; hereafter bobwhite). We conducted power analysis, over a range of expected bobwhite calling covey densities to determine levels of sampling required to obtain density estimates for calling coveys over a wide range of precision. We used distance/detection information for autumn bobwhite coveys from 701 observer-mornings on 39 farms in the Upper Coastal Plain of Georgia to construct a global detection function (Uniform with cosine adjustment) using Program DISTANCE. We used simulation models to determine the expected coefficient of variation (CV) on density in relation to number of points sampled. We generated 1,000 sets of random samples in increments of 10 at sample sizes of 10-1,000. At each sample size we generated the respective number of observations from a Poisson distribution with λ = 0.5-3.0 and computed the density and associated statistics using the global detection function. We report the mean CV on covey density at each sample size. As expected, the CV on density decreased with increasing sample size and expected number of detections per point. Assuming sufficient observations to estimate the detection function, a CV on density \u3c15% could be achieved with 50 points at densities with a mean detection of 1 covey/point or 20 points with a mean detection of 2 coveys/point. A mean CV \u3c10% required 100 points at 1 covey/point and 30 points at 2 coveys/point. These simulations demonstrate that distance-based autumn covey surveys can provide density estimates for calling coveys with reasonable precision given sufficient effort

What doesn't kill you makes you stranger: Dipeptidyl peptidase-4 (CD26) proteolysis differentially modulates the activity of many peptide hormones and cytokines generating novel cryptic bioactive ligands

Dipeptidyl peptidase 4 (DPP4) is an exopeptidase found either on cell surfaces where it is highly regulated in terms of its expression and surface availability (CD26) or in a free/circulating soluble constitutively available and intrinsically active form. It is responsible for proteolytic cleavage of many peptide substrates. In this review we discuss the idea that DPP4-cleaved peptides are not necessarily inactivated, but rather can possess either a modified receptor selectivity, modified bioactivity, new antagonistic activity, or even a novel activity relative to the intact parent ligand. We examine in detail five different major DPP4 substrates: glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), peptide tyrosine-tyrosine (PYY), and neuropeptide Y (NPY), and stromal derived factor 1 (SDF-1 aka CXCL12). We note that discussion of the cleaved forms of these five peptides are underrepresented in the research literature, and are both poorly investigated and poorly understood, representing a serious research literature gap. We believe they are understudied and misinterpreted as inactive due to several factors. This includes lack of accurate and specific quantification methods, sample collection techniques that are inherently inaccurate and inappropriate, and a general perception that DPP4 cleavage inactivates its ligand substrates. Increasing evidence points towards many DPP4-cleaved ligands having their own bioactivity. For example, GLP-1 can work through a different receptor than GLP-1R, DPP4-cleaved GIP can function as a GIP receptor antagonist at high doses, and DPP4-cleaved PYY, NPY, and CXCL12 can have different receptor selectivity, or can bind novel, previously unrecognized receptors to their intact ligands, resulting in altered signaling and functionality. We believe that more rigorous research in this area could lead to a better understanding of DPP4’s role and the biological importance of the generation of novel cryptic ligands. This will also significantly impact our understanding of the clinical effects and side effects of DPP4-inhibitors as a class of anti-diabetic drugs that potentially have an expanding clinical relevance. This will be specifically relevant in targeting DPP4 substrate ligands involved in a variety of other major clinical acute and chronic injury/disease areas including inflammation, immunology, cardiology, stroke, musculoskeletal disease and injury, as well as cancer biology and tissue maintenance in aging

Knockdown of SVCT2 impairs in-vitro cell attachment, migration and wound healing in bone marrow stromal cells

AbstractBone marrow stromal cell (BMSC) adhesion and migration are fundamental to a number of pathophysiologic processes, including fracture and wound healing. Vitamin C is beneficial for bone formation, fracture repair and wound healing. However, the role of the vitamin C transporter in BMSC adhesion, migration and wound healing is not known. In this study, we knocked-down the sodium-dependent vitamin C transporter, SVCT2, the only known transporter of vitamin C in BMSCs, and performed cell adhesion, migration, in-vitro scratch wound healing and F-actin re-arrangement studies. We also investigated the role of oxidative stress on the above processes. Our results demonstrate that both oxidative stress and down-regulation of SVCT2 decreased cell attachment and spreading. A trans-well cell migration assay showed that vitamin C helped in BMSC migration and that knockdown of SVCT2 decreased cell migration. In the in-vitro scratch wound healing studies, we established that oxidative stress dose-dependently impairs wound healing. Furthermore, the supplementation of vitamin C significantly rescued the BMSCs from oxidative stress and increased wound closing. The knockdown of SVCT2 in BMSCs strikingly decreased wound healing, and supplementing with vitamin C failed to rescue cells efficiently. The knockdown of SVCT2 and induction of oxidative stress in cells produced an alteration in cytoskeletal dynamics. Signaling studies showed that oxidative stress phosphorylated members of the MAP kinase family (p38) and that vitamin C inhibited their phosphorylation. Taken together, these results indicate that both the SVCT2 transporter and oxidative stress play a vital role in BMSC attachment, migration and cytoskeletal re-arrangement. BMSC-based cell therapy and modulation of SVCT2 could lead to a novel therapeutic approach that enhances bone remodeling, fracture repair and wound healing in chronic disease conditions

The Grizzly, September 9, 1996

A Busy Summer for Ursinus Professors • Forest Norris • Welfare Protesters Shot from Dorm with Paintball Gun • Opinions: Who am I?; President Clinton Bombs Iraq; Good, Evil and Other Such Nonsense • Men\u27s and Women\u27s Cross Country Go Down • Volleyball Drops First Match • Field Hockey Update • Disappointing Start for Women\u27s Soccer • Football Takes Opener • Men\u27s Soccer Off to 2-2 Starthttps://digitalcommons.ursinus.edu/grizzlynews/1383/thumbnail.jp

The crucial role of vitamin C and its transporter (SVCT2) in bone marrow stromal cell autophagy and apoptosis

AbstractVitamin C is an antioxidant that plays a vital role in various biological processes including bone formation. Previously, we reported that vitamin C is transported into bone marrow stromal cells (BMSCs) through the sodium dependent Vitamin C Transporter 2 (SVCT2) and this transporter plays an important role in osteogenic differentiation. Furthermore, this transporter is regulated by oxidative stress. To date, however, the exact role of vitamin C and its transporter (SVCT2) in ROS regulated autophagy and apoptosis in BMSCs is poorly understood. In the present study, we observed that oxidative stress decreased survival of BMSCs in a dose-dependent manner and induced growth arrest in the G1 phase of the cell cycle. These effects were accompanied by the induction of autophagy, confirmed by P62 and LC3B protein level and punctate GFP-LC3B distribution. The supplementation of vitamin C significantly rescued the BMSCs from oxidative stress by regulating autophagy. Knockdown of the SVCT2 transporter in BMSCs synergistically decreased cell survival even under low oxidative stress conditions. Also, supplementing vitamin C failed to rescue cells from stress. Our results reveal that the SVCT2 transporter plays a vital role in the mechanism of BMSC survival under stress conditions. Altogether, this study has given new insight into the role of the SVCT2 transporter in oxidative stress related autophagy and apoptosis in BMSCs

Climate-Related Hazards: A Method for Global Assessment of Urban and Rural Population Exposure to Cyclones, Droughts, and Floods

Global climate change (GCC) has led to increased focus on the occurrence of, and preparation for, climate-related extremes and hazards. Population exposure, the relative likelihood that a person in a given location was exposed to a given hazard event(s) in a given period of time, was the outcome for this analysis. Our objectives were to develop a method for estimating the population exposure at the country level to the climate-related hazards cyclone, drought, and flood; develop a method that readily allows the addition of better datasets to an automated model; differentiate population exposure of urban and rural populations; and calculate and present the results of exposure scores and ranking of countries based on the country-wide, urban, and rural population exposures to cyclone, drought, and flood. Gridded global datasets on cyclone, drought and flood occurrence as well as population density were combined and analysis was carried out using ArcGIS. Results presented include global maps of ranked country-level population exposure to cyclone, drought, flood and multiple hazards. Analyses by geography and human development index (HDI) are also included. The results and analyses of this exposure assessment have implications for country-level adaptation. It can also be used to help prioritize aid decisions and allocation of adaptation resources between countries and within a country. This model is designed to allow flexibility in applying cyclone, drought and flood exposure to a range of outcomes and adaptation measures

The Grizzly, September 23, 1996

Internet Censorship Issue Addressed by Stefan Presser • Opinions: Life in a Determinist World; Are Guns Necessary? • Study Abroad to Have Fun and Learn • Get Moving: A Guide to the Benefits of Exercise • Anthonisen Exhibit Captures the Human Spirit • Bears Handle Diplomats • Men\u27s Soccer Wins First Conference Game • Women\u27s Soccer Wins First Game • Volleyball Wins Two Straight • Field Hockey Begins Patriot League Seasonhttps://digitalcommons.ursinus.edu/grizzlynews/1385/thumbnail.jp