1,453 research outputs found
Exploring Vanadium Chemical Transferrin Mimetic Compounds for Insulin Enhancement
Diabetes Mellitus (DM) is caused by a lack of insulin production (Type 1) or the body’s cells’ inability to properly receive it, also known as insulin resistance (Type 2), resulting in greatly elevated levels of blood glucose. Vanadium(IV) and vanadium(V) ions are believed to enhance insulin activity by inhibition of protein tyrosine phosphatase 1B (PTP1B). PTP1B is normally responsible for downregulating the insulin signaling, but in DM type 2, PTP1B activity is overexpressed leading to the insulin signaling blocking. The most promising V(IV) compounds are designed for oral delivery: they are absorbed into the gut and delivered into the bloodstream where they are bound by the iron transporting protein serum transferrin (sTf). STf delivers the compound into cells via endocytosis, where vanadium can bind PTP1B. A limitation of these compounds is their poor stability at the stomach acidic conditions in which they undergo a significant amount of dissociation, resulting in a very inefficient gut absorption. This study explores the use of a chemical transferrin mimetic (cTfm) ligand to create V(IV) and V(V) compounds featuring excellent acidic pH stability for improved gut absorption. The cTfm-V(IV,V) compounds are expected to be labile in the pH of the bloodstream and thus the vanadium species can be quickly ligand exchanged with sTF. The cTfm ligand N,N\u27-di(o-hydroxybenzyl)ethylenediamine-N,N\u27-diacetic acid (HBED) was used to synthesize VO(IV)HBED and VO(V)HBED which demonstrated great aqueous stability in the 1-4 pH range. The role of citrate as a vehicle for delivering vanadium to sTf to regulate the transport of vanadium is also examined
Asthma and gender impact accumulation of T cell subtypes
<p>Abstract</p> <p>Background</p> <p>The "Th2 hypothesis for asthma" asserts that an increased ratio of Th2:Th1 cytokine production plays an important pathogenic role in asthma. Although widely embraced, the hypothesis has been challenged by various empirical observations and has been described as overly simplistic. We sought to establish whether CD3+CD28-mediated and antigen-independent accumulation of type 1 and type 2 T cells differs significantly between nonasthmatic and asthmatic populations.</p> <p>Methods</p> <p>An ex vivo system was used to characterize the regulation of IFN-γ-producing (type 1) and IL-13-producing (type 2) T cell accumulation in response to CD3+CD28 and IL-2 stimulation by flow cytometry.</p> <p>Results</p> <p>IL-13-producing T cells increased in greater numbers in response to antigen-independent stimulation in peripheral blood lymphocytes from female atopic asthmatic subjects compared with male asthmatics and both male and female atopic non-asthmatic subjects. IFN-γ<sup>+ </sup>T cells increased in greater numbers in response to either antigen-independent or CD3+CD28-mediated stimulation in peripheral blood lymphocytes from atopic asthmatic subjects compared to non-asthmatic subjects, regardless of gender.</p> <p>Conclusions</p> <p>We demonstrate that T cells from asthmatics are programmed for increased accumulation of both type 2 and type 1 T cells. Gender had a profound effect on the regulation of type 2 T cells, thus providing a mechanism for the higher frequency of adult asthma in females.</p
Yields of oxidized volatile organic compounds during the OH radical initiated oxidation of isoprene, methyl vinyl ketone, and methacrolein under high-NO_x conditions
We present first-generation and total production yields of glyoxal, methylglyoxal, glycolaldehyde, and hydroxyacetone from the oxidation of isoprene, methyl vinyl ketone (MVK), and methacrolein (MACR) with OH under high NO_x conditions. Several of these first-generation yields are not included in commonly used chemical mechanisms, such as the Leeds Master Chemical Mechanism (MCM) v. 3.2. The first-generation yield of glyoxal from isoprene was determined to be 2.1 (±0.6)%. Inclusion of first-generation production of glyoxal, glycolaldehyde and hydroxyacetone from isoprene greatly improves performance of an MCM based model during the initial part of the experiments. In order to further improve performance of the MCM based model, higher generation glyoxal production was reduced by lowering the first-generation yield of glyoxal from C5 hydroxycarbonyls. The results suggest that glyoxal production from reaction of OH with isoprene under high NO_x conditions can be approximated by inclusion of a first-generation production term together with secondary production only via glycolaldehyde. Analogously, methylglyoxal production can be approximated by a first-generation production term from isoprene, and secondary production via MVK, MACR and hydroxyacetone. The first-generation yields reported here correspond to less than 5% of the total oxidized yield from isoprene and thus only have a small effect on the fate of isoprene. However, due to the abundance of isoprene, the combination of first-generation yields and reduced higher generation production of glyoxal from C5 hydroxycarbonyls is important for models that include the production of the small organic molecules from isoprene
Analysis of photochemical and dark glyoxal uptake: Implications for SOA formation
The dependence of glyoxal uptake onto deliquesced ammonium sulfate seed aerosol was studied under photochemical (light + hydroxyl radical (OH)) and dark conditions. In this study, the chemical composition of aerosol formed from glyoxal is identical in the presence or absence of OH. In addition, there was no observed OH dependence on either glyoxal uptake or glyoxal-driven aerosol growth for this study. These findings demonstrate that, for the system used here, glyoxal uptake is not affected by the presence of OH. In combination with previous studies, this shows that the exact nature of the type of seed aerosol, in particular the presence of a coating, has a large influence on fast photochemical uptake of glyoxal. Due to the challenge of relating this seed aerosol dependence to ambient conditions, this work highlights the resulting difficulty in quantitatively including SOA formation from glyoxal in models
Fingerprinting Chamaesiphon populations as an approach toassess the quality of running waters
"This is the peer reviewed version of the following article: Loza, V.; Morales, A.; Perona, E. and Muñoz-Martín, M. A."Fingerprinting Chamaesiphon populations as an approach toassess the quality of running waters" River Research and Applications 34 (2018): 595-605 which has been published in final form at https://doi.org/10.1002/rra.3277. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions."Cyanobacterial communities are highly diverse in freshwaters and respond rapidly tochanging environments. Previous studies have highlighted variations in the structureand composition of epilithic cyanobacterial communities in response to eutrophica-tion in watercourses. In the present study, changes in benthic cyanobacterial commu-nities from Guadalix River (Spain) biofilms were examined using temperature‐gradientgel electrophoresis (TGGE) in conjunction with microscopic examination of field‐fixedsamples, focusing on populations of one of the dominant cyanobacteria:Chamaesiphon. Environmental characteristics were determined in order to character-ize the trophic status of the sampling sites. The presence of cyanobacteria in the riverwas determined from complex TGGE patterns, band extraction, and subsequentsequencing of 16S rDNA gene fragments. The microscopic observations revealed thatthe unicellular genus Chamaesiphon and the filamentous genus Phormidium were dom-inant in the studied locations. Within the 2 genera, 4 Chamaesiphon populations wereidentified (Chamaesiphon fuscus, Chamaesiphon starmachii, Chamaesiphon subglobosus ,and Chamaesiphon polymorphus) and Phormidium was represented at the samplingsites by the Phormidium autumnale morphotype. TGGE banding patterns differedamong samplings sites as a function of water quality. The genetic analysis revealed4 phylotypes within the genus Chamaesiphon and 1 phylotype within the classicP. autumnale clade. Chamaesiphon phylotypes were not equally distributed in all thesampling locations. Some phylotypes were related to low nutrient concentrations,while others were associated with eutrophic conditions. Our results support the useof fingerprints of Chamaesiphon populations obtained by TGGE to examine changesin water quality.This work was supported by Grant CGL2013‐44870‐R from the Ministerio de Economía y Competitividad, Spai
α-pinene photooxidation under controlled chemical conditions – Part 2: SOA yield and composition in low- and high-NO_x environments
The gas-phase oxidation of α-pinene produces a large amount of secondary organic aerosol (SOA) in the atmosphere. A number of carboxylic acids, organosulfates and nitrooxy organosulfates associated with α-pinene have been found in field samples and some are used as tracers of α-pinene oxidation. α-pinene reacts readily with OH and O_3 in the atmosphere followed by reactions with both HO_2 and NO. Due to the large number of potential reaction pathways, it can be difficult to determine what conditions lead to SOA. To better understand the SOA yield and chemical composition from low- and high-NO_x OH oxidation of α-pinene, studies were conducted in the Caltech atmospheric chamber under controlled chemical conditions. Experiments used low O_3 concentrations to ensure that OH was the main oxidant and low α-pinene concentrations such that the peroxy radical (RO_2) reacted primarily with either HO_2 under low-NO_x conditions or NO under high-NO_x conditions. SOA yield was suppressed under conditions of high-NO_x. SOA yield under high-NO_x conditions was greater when ammonium sulfate/sulfuric acid seed particles (highly acidic) were present prior to the onset of growth than when ammonium sulfate seed particles (mildly acidic) were present; this dependence was not observed under low-NO_x conditions. When aerosol seed particles were introduced after OH oxidation, allowing for later generation species to be exposed to fresh inorganic seed particles, a number of low-NO_x products partitioned to the highly acidic aerosol. This indicates that the effect of seed acidity and SOA yield might be under-estimated in traditional experiments where aerosol seed particles are introduced prior to oxidation. We also identify the presence of a number of carboxylic acids that are used as tracer compounds of α-pinene oxidation in the field as well as the formation of organosulfates and nitrooxy organosulfates. A number of the carboxylic acids were observed under all conditions, however, pinic and pinonic acid were only observed under low-NO_x conditions. Evidence is provided for particle-phase sulfate esterification of multi-functional alcohols
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