Tulane University

About: Tulane University is a education organization based out in New Orleans, Louisiana, United States. It is known for research contribution in the topics: Population & Blood pressure. The organization has 24478 authors who have published 47205 publications receiving 1944993 citations. The organization is also known as: University of Louisiana.

Muscle-specific expression of IGF-1 blocks angiotensin II–induced skeletal muscle wasting

Abstract: Advanced congestive heart failure is associated with activation of the renin-angiotensin system and skeletal muscle wasting. We previously showed that angiotensin II infusion in rats produces cachexia secondarily to increased muscle proteolysis and also decreases levels of circulating and skeletal muscle IGF-1. Here we show that angiotensin II markedly downregulates phospho-Akt and activates caspase-3 in skeletal muscle, leading to actin cleavage, an important component of muscle proteolysis, and to increased apoptosis. These changes are blocked by muscle-specific expression of IGF-1, likely via the Akt/mTOR/p70S6K signaling pathway. We also demonstrate that mRNA levels of the ubiquitin ligases atrogin-1 and muscle ring finger-1 are upregulated in angiotensin II-infused WT, but not in IGF-1-transgenic, mice. These findings strongly suggest that angiotensin II downregulation of IGF-1 in skeletal muscle is causally related to angiotensin II-induced wasting. Because the renin-angiotensin system is activated in many catabolic conditions, our findings have broad implications for understanding mechanisms of skeletal muscle wasting and provide a rationale for new therapeutic approaches.

Long-term in vitro expansion alters the biology of adult mesenchymal stem cells.

Abstract: Mesenchymal stem cells (MSC) derived from bone marrow stem cells (BMSC) and adipose tissue stem cells (ASC) of humans and rhesus macaques were evaluated for their cell cycle properties during protracted culture in vitro. Human ASCs (hASC) and rhesus BMSCs (rBMSC) underwent significantly more total population doublings than human BMSCs (hBMSC) and rhesus ASCs (rASC). The cell cycle profile of all MSCs was altered as cultures aged. hMSCs underwent an increase in the frequency of cells in the S phase at P20 and P30. However, rhesus MSCs from both sources developed a distinct polyploid population of cells at P20, which progressed to aneuploidy by P30. Karyotype analysis of MSCs revealed the development of tetraploid or aneuploid karyotypes in the rhesus cells at P20 or P30. Analysis of the transcriptome of the MSCs from early and late passages revealed significant alterations in the patterns of gene expression (8.8% of the genes were differentially expressed in hBMSCs versus hASCs, and 5.5% in rBMSCs versus rASCs). Gene expression changes were much less evident within the same cell type as aging occurred (0.7% in hMSCs and 0.9% in rMSC). Gene ontology analysis showed that functions involved in protein catabolism and regulation of pol II transcription were overrepresented in rASCs, whereas the regulation of I kappa B/nuclear factor-kappaB cascade were overrepresented in hBMSCs. Functional analysis of genes that were differentially expressed in rASCs and hBMSCs revealed that pathways involved in cell cycle, cell cycle checkpoints, protein-ubiquitination, and apoptosis were altered.

Escaping the symmetry dilemma through a pair-density interpretation of spin-density functional theory

Abstract: In the standard interpretation of spin-density functional theory, a self-consistent Kohn-Sham calculation within the local spin density (LSD) or generalized gradient approximation (GGA) leads to a prediction of the total energy E, total electron density n(r)=${\mathit{n}}_{\mathrm{\ensuremath{\uparrow}}}$(r)+${\mathit{n}}_{\mathrm{\ensuremath{\downarrow}}}$(r), and spin magnetization density m(r)=${\mathit{n}}_{\mathrm{\ensuremath{\uparrow}}}$(r)-${\mathit{n}}_{\mathrm{\ensuremath{\downarrow}}}$(r). This interpretation encounters a serious ``symmetry dilemma'' for ${\mathrm{H}}_{2}$, ${\mathrm{Cr}}_{2}$, and many other molecules. Without changing LSD or GGA calculational methods and results, we escape this dilemma through an alternative interpretation in which the third physical prediction is not m(r) but the on-top electron pair density P(r,r), a quantity more directly related to the total energy in the absence of an external magnetic field. This alternative interpretation is also relevant to antiferromagnetic solids. We argue that the nonlocal exchange-correlation energy functional, which must be approximated, is most nearly local in the alternative spin-density functional theory presented here, less so in the standard theory, and far less so in total-density functional theory. Thus, in LSD or GGA, predictions of spin magnetization densities and moments are not so robust as predictions of total density and energy. The alternative theory helps to explain the surprising accuracy of LSD and GGA energies, and suggests that the correct solution of the Kohn-Sham equations in LSD or GGA is the fully self-consistent broken-symmetry single determinant of lowest total energy.

Marketplace, Reseller, or Hybrid: Strategic Analysis of an Emerging E‐Commerce Model

Abstract: Traditionally, online retailers have acted as product resellers. Recently, these retailers have also started to serve as online marketplaces by providing a platform to directly connect sellers with buyers. Over and above re‐shaping the traditional e‐commerce market, conventional wisdom suggests that this new format will mitigate the double‐marginalization effect and benefit both the intermediary and suppliers through a revenue sharing scheme. However, we find that upstream competition between suppliers critically moderates this possibility. We also find that the interaction of order‐fulfillment costs and upstream competition intensity moderates the selection of an optimal mode for the intermediary. More specifically, when order‐fulfillment costs are large and when the supplier product offerings are similar (i.e., competition intensity is high), the pure reseller mode is the preferred choice; when order‐fulfillment costs are small and the supplier product offerings are highly differentiated (i.e., low competition intensity), the pure marketplace mode is the preferred choice. Finally, the hybrid mode is preferred when order‐fulfillment costs are moderate and suppliers’ products are somewhat similar (i.e., competition intensity is moderate). The intuition behind these results hinges on the trade‐off between transfer of pricing rights and the responsibility for order fulfillment. Our findings not only complement the emerging online marketplace literature but also provide testable empirical questions concerning the relationship and magnitude of different factors steering the mode choice.

Association of Hypoglycemia and Cardiac Ischemia: A study based on continuous monitoring

Abstract: OBJECTIVE —In some studies intensive diabetes treatment in patients with type 2 diabetes may be associated with increased cardiovascular events. It is not clear whether these events are related to hypoglycemic episodes. To determine whether episodes of hypoglycemia were more likely to be associated with cardiac ischemia than normoglycemia or hyperglycemia, we carried out a study in 21 patients with coronary artery disease (CAD) and type 2 diabetes treated with insulin who had good glycemic control. RESEARCH DESIGN AND METHODS —We carried out 72-h continuous glucose monitoring along with simultaneous cardiac Holter monitoring for ischemia. Patients also recorded symptoms of cardiac ischemia (chest pain) and symptoms of hypoglycemia. RESULTS —Satisfactory continuous glucose monitoring system recordings were obtained in 19 patients. We recorded 54 episodes of hypoglycemia (blood glucose 200 mg/dl; none symptomatic). Of the 54 episodes of hypoglycemia, 10 were associated with symptoms of chest pain, during 4 of which electrocardiographic abnormalities were documented. In contrast, only 1 episode of chest pain occurred during 59 episodes of hyperglycemia. No chest pain or electrocardiographic abnormalities occurred when the blood glucose was within the normal range. The difference between the frequency of ischemia during hypoglycemia and the frequency during both hyperglycemia and normoglycemia was statistically significant ( P 100 mg over a 60-min period, and ischemic symptoms occurred during 9 of these episodes ( P < 0.01 compared with stable normoglycemia or hyperglycemia). CONCLUSIONS —Hypoglycemia is more likely to be associated with cardiac ischemia and symptoms than normoglycemia and hyperglycemia, and it is particularly common in patients who experience considerable swings in blood glucose. These data may be important in the institution of insulin treatment and attempting near-normal glycemia in patients with known CAD. Further research is needed to determine strategies to prevent ischemia associated with hypoglycemia.