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

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

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

Caracterización molecular y biológica del virus de la rabia que circula en zorrillos de México enfocado a la variante del gen de la fosfoproteína (P)

The objective of this work was to characterize molecularly rabies viruses from Mexican skunks, by comparison of a portion of the viral P gene sequence with corresponding regions from other skunk-adapted rabies virus variants and with other genotype 1 rabies viruses that circulate in the Americas. Furthermore, incubation period and histopathologic lesions after virus inoculation by the intra-cerebral route in mice was characterized. According to the results of phylogenetic studies the Mexican skunk strains (Antigenic Variant (AV) 8 and AV10) are evolutionarily quite distinct. The AV10 isolate from South Baja California is quite closely related to the viruses that circulate in Californian skunks, while the AV8 isolate from San Luis Potosí was most closely related to the South central skunk strain that circulates in southern states such as Texas. These variations were reflected in some biological properties of both strains in mice.El objetivo de este estudio fue la caracterización molecular y biológica del virus de la rabia en zorrillos de México, comparando una porción de la secuencia viral del gen P, con regiones correspondientes de variantes de virus rábico adaptadas en zorrillos y pertenecientes al genotipo 1 (virus de la rabia "clásica"), que circulan en América. Como parte de la caracterización biológica se incluyó el periodo de incubación y las lesiones histopatológicas después de la inoculación del virus por ví­a intracerebral en ratones. De acuerdo a los resultados de estudios filogenéticos, las cepas de zorrillo mexicano (variante antigénica (AV8 y AV10) son muy distintas en cuanto a su evolución. El aislado AV10 de Baja California Sur está muy relacionado con los virus que circulan en zorrillos de California, mientras que el aislado AV8 de San Luis Potosí­ tuvo mayor relación con la cepa del zorrillo del Centro/Sur que circula en los estados del sur, como Texas. Estas variantes se reflejaron en algunas propiedades biológicas de ambas cepas en ratones

Bio-AIMS collection of chemoinformatics web tools based on molecular graph information and artificial intelligence models

[Abstract] The molecular information encoding into molecular descriptors is the first step into in silico Chemoinformatics methods in Drug Design. The Machine Learning methods are a complex solution to find prediction models for specific biological properties of molecules. These models connect the molecular structure information such as atom connectivity (molecular graphs) or physical-chemical properties of an atom/group of atoms to the molecular activity (Quantitative Structure - Activity Relationship, QSAR). Due to the complexity of the proteins, the prediction of their activity is a complicated task and the interpretation of the models is more difficult. The current review presents a series of 11 prediction models for proteins, implemented as free Web tools on an Artificial Intelligence Model Server in Biosciences, Bio-AIMS (http://bio-aims.udc.es/TargetPred.php). Six tools predict protein activity, two models evaluate drug - protein target interactions and the other three calculate protein - protein interactions. The input information is based on the protein 3D structure for nine models, 1D peptide amino acid sequence for three tools and drug SMILES formulas for two servers. The molecular graph descriptor-based Machine Learning models could be useful tools for in silico screening of new peptides/proteins as future drug targets for specific treatments.Red Gallega de Investigación y Desarrollo de Medicamentos; R2014/025Instituto de Salud Carlos III; PI13/0028