Existence of a Strong Correlation of Biomarkers and Mirna in Females With Metabolic Syndrome and Obesity in a Population of West Virginia

Objectives: Metabolic syndrome causes complications like cardiovascular disease and type 2 diabetes mellitus (T2DM). As metabolic syndrome develops, altered levels of cytokines and microRNAs (miRNA) are measurable in the circulation. We aimed to construct a panel detecting abnormal levels of cytokines and miRNAs in patients at risk for metabolic syndrome. Methods: Participants included 54 patients from a Family Medicine Clinic at Marshall University School of Medicine, in groups of: Control, Obese, and Metabolic Syndrome (MetS). Results: Serum levels of leptin, adiponectin, leptin: adiponectin ratio, IL-6, six miRNAs (320a, 197-3p, 23-3p, 221-3p, 27a-3p, and 130a-3p), were measured. Among the three groups, leptin, and leptin: adiponectin ratio, and IL-6 levels were highest in MetS, and levels in Obese were greater than Control (p\u3e0.05). Adiponectin levels were lower in Obese compared to Control, but lowest in MetS (p0.05). Conclusion: Our results support the clinical application of biomarkers in diagnosing early stage MetS, which will enable attenuation of disease progression before onset of irreversible complications. Since West Virginians are high-risk for developing MetS, our biomarker panel could reduce the disease burden on our population

Forty years of temporal analysis of products

A detailed understanding of reaction mechanisms and kinetics is required in order to develop and optimize catalysts and catalytic processes. While steady-state investigations are known to give a global view of the catalytic system, transient studies are invaluable since they can provide more comprehensive insight into elementary steps. For almost forty years temporal analysis of products (TAP) has been successfully utilized for transient studies of gas phase heterogeneous reactions, and there have been a number of advances in instrumentation and numerical modeling methods in that time. Since TAP is a complex methodology it is often viewed as a niche specialty. With the purpose to make TAP more relevant and approachable to a wider segment of the catalytic research community, part of the intention of this work is to highlight the significant contributions TAP has made to elucidating mechanistic and kinetic aspects of complex, multi-step heterogeneous reactions. With this in mind, an outlook is also disclosed for the technique in terms of what is needed to revitalize the field and make it more applicable to the recent advances in catalyst characterization (e.g. operando modes)

Vpu Antagonizes BST-2–Mediated Restriction of HIV-1 Release via β-TrCP and Endo-Lysosomal Trafficking

The interferon-induced transmembrane protein BST-2/CD317 (tetherin) restricts the release of diverse enveloped viruses from infected cells. The HIV-1 accessory protein Vpu antagonizes this restriction by an unknown mechanism that likely involves the down-regulation of BST-2 from the cell surface. Here, we show that the optimal removal of BST-2 from the plasma membrane by Vpu requires the cellular protein β-TrCP, a substrate adaptor for a multi-subunit SCF E3 ubiquitin ligase complex and a known Vpu-interacting protein. β-TrCP is also required for the optimal enhancement of virion-release by Vpu. Mutations in the DSGxxS β-TrCP binding-motif of Vpu impair both the down-regulation of BST-2 and the enhancement of virion-release. Such mutations also confer dominant-negative activity, consistent with a model in which Vpu links BST-2 to β-TrCP. Optimal down-regulation of BST-2 from the cell surface by Vpu also requires the endocytic clathrin adaptor AP-2, although the rate of endocytosis is not increased; these data suggest that Vpu induces post-endocytic membrane trafficking events whose net effect is the removal of BST-2 from the cell surface. In addition to its marked effect on cell-surface levels, Vpu modestly decreases the total cellular levels of BST-2. The decreases in cell-surface and intracellular BST-2 are inhibited by bafilomycin A1, an inhibitor of endosomal acidification; these data suggest that Vpu induces late endosomal targeting and partial degradation of BST-2 in lysosomes. The Vpu-mediated decrease in surface expression is associated with reduced co-localization of BST-2 and the virion protein Gag along the plasma membrane. Together, the data support a model in which Vpu co-opts the β-TrCP/SCF E3 ubiquitin ligase complex to induce endosomal trafficking events that remove BST-2 from its site of action as a virion-tethering factor

pNaKtide Attenuates Steatohepatitis and Atherosclerosis by Blocking Na/K-ATPase/ROS Amplification in C57BI6 and ApoE Knockout Mice Fed a Western Diet

We have previously reported that the alpha1 subunit of sodium potassium adenosine triphosphatase (Na/K-ATPase), acts as a receptor and an amplifier for reactive oxygen species, in addition to its distinct pumping function. On this background, we speculated that blockade of Na/K-ATPase-induced ROS amplification with a specific peptide, pNaKtide, might attenuate the development of steatohepatitis. To test this hypothesis, pNaKtide was administered to a murine model of NASH: the C57Bl6 mouse fed a western diet containing high amounts of fat and fructose. The administration of pNaKtide reduced obesity as well as hepatic steatosis, inflammation and fibrosis. Of interest, we also noted marked improvement in mitochondrial fatty acid oxidation, insulin sensitivity, dyslipidemia and aortic streaking in this mouse model. To further elucidate the effects of pNaKtide on atherosclerosis, similar studies were performed in ApoE knockout mice also exposed to the western diet. In these mice, pNaKtide not only improved steatohepatitis, dyslipidemia, and insulin sensitivity, but also ameliorated significant aortic atherosclerosis. Collectively, this study demonstrates that the Na/K-ATPase/ROS amplification loop contributes significantly to the development and progression of steatohepatitis and atherosclerosis. And furthermore, this study presents a potential treatment, the pNaKtide, for the metabolic syndrome phenotype

Highly Parallel and Short-Acting Amplification with Locus-Specific Primers to Detect Single Nucleotide Polymorphisms by the DigiTag2 Assay

The DigiTag2 assay enables analysis of a set of 96 SNPs using Kapa 2GFast HotStart DNA polymerase with a new protocol that has a total running time of about 7 hours, which is 6 hours shorter than the previous protocol. Quality parameters (conversion rate, call rate, reproducibility and concordance) were at the same levels as when genotype calls were acquired using the previous protocol. Multiplex PCR with 192 pairs of locus-specific primers was available for target preparation in the DigiTag2 assay without the optimization of reaction conditions, and quality parameters had the same levels as those acquired with 96-plex PCR. The locus-specific primers were able to achieve sufficient (concentration of target amplicon ≥5 nM) and specific (concentration of unexpected amplicons <2 nM) amplification within 2 hours, were also able to achieve detectable amplifications even when working in a 96-plex or 192-plex form. The improved DigiTag2 assay will be an efficient platform for screening an intermediate number of SNPs (tens to hundreds of sites) in the replication analysis after genome-wide association study. Moreover, highly parallel and short-acting amplification with locus-specific primers may thus facilitate widespread application to other PCR-based assays

Combined spatially resolved operando spectroscopy: New insights into kinetic oscillations of CO oxidation on Pd/γ-Al 2O3

Spatially resolved, combined energy dispersive EXAFS (EDE) and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) measurements have been performed over a fixed catalyst bed of Pd/γ-Al 2 O 3 during kinetic oscillations of CO oxidation. The kinetic oscillations of CO oxidation over Pd (or for that matter Pt or Rh) catalysts are a complicated phenomenon that require characterisation techniques with high time resolution and spatial resolution in order to make links between catalyst structure and surface reactivity. By measuring the extent of Pd oxidation at the nanoparticle surface, from Pd K-edge EDE, and matching this with the CO coverage, from DRIFTS spectra, at multiple positions of the fixed bed reactor it is found that the majority of the catalyst undergoes a sharp transition from the CO poisoned catalyst to the highly active, oxidised Pd surface. This transition occurs initially at the end of the catalyst bed, nearest the outlet, and propagates upstream with increasing temperature of the reactor. The oscillations in Pd surface oxide formation and CO coverage are observed only in the first ∼1 mm of the bed, which gives rise to oscillations in CO 2 and O 2 concentrations observed by end-pipe mass spectrometry after the light-off temperature. The catalyst initially exists as less active, CO poisoned metallic Pd nanoparticles before light-off which transition to a highly active state after light-off when the Pd nanoparticle surface becomes dominated by chemisorbed oxygen. Kinetic oscillations only occur at the front of the catalyst bed where there is sufficient concentration of CO in the gas phase to compete with O 2 for adsorption sites at the catalyst surface. We demonstrate the complex nature of the evolving catalyst structure and surface reactivity during catalytic operation and the need for spatially resolved operando methods for understanding and optimising catalyst technologies

Emerging Infectious Diseases: a 10-Year Perspective from the National Institute of Allergy and Infectious Diseases

Advances in infectious disease research over the past 10 years have allowed breakthroughs in th

Roles for the coactivators CBP and p300 and the APC/C E3 ubiquitin ligase in E1A-dependent cell transformation

Adenovirus early region 1A (E1A) possesses potent transforming activity when expressed in concert with activated ras or E1B genes in in vitro tissue culture systems such as embryonic human retinal neuroepithelial cells or embryonic rodent epithelial and fibroblast cells. Early region 1A has thus been used extensively and very effectively as a tool to determine the molecular mechanisms that underlie the basis of cellular transformation. In this regard, roles for the E1A-binding proteins pRb, p107, p130, cyclic AMP response element-binding protein (CBP)/p300, p400, TRRAP and CtBP in cellular transformation have been established. However, the mechanisms by which E1A promotes transformation through interaction with these partner proteins are not fully delineated. In this review, we focus on recent advances in our understanding of CBP/p300 function, particularly with regard to its relationship to the anaphase-promoting complex/cyclosome E3 ubiquitin ligase, which has recently been shown to interact and affect the activity of CBP/p300 through interaction domains that are evolutionarily conserved in E1A