Thioglycine and l-thiovaline: biologically active H2S-donors.

Thioglycine and l-thiovaline are stable under acidic and basic conditions but in the presence of bicarbonate they liberate the gasotransmitter H(2)S. In cells both thioamino acids were proven to enhance cGMP formation and promote vasorelaxation in mouse aortic rings. Given that H(2)S is known to lower arterial hypertension, reduce oxidative stress and exhibit cardioprotective effects in preclinical models, H(2)S donors hold promise as novel treatments for cardiovascular disease

Using the local density approximation and the LYP, BLYP, and B3LYP functionals within Reference--State One--Particle Density--Matrix Theory

For closed-shell systems, the local density approximation (LDA) and the LYP, BLYP, and B3LYP functionals are shown to be compatible with reference-state one-particle density-matrix theory, where this recently introduced formalism is based on Brueckner-orbital theory and an energy functional that includes exact exchange and a non-universal correlation-energy functional. The method is demonstrated to reduce to a density functional theory when the exchange-correlation energy-functional has a simplified form, i.e., its integrand contains only the coordinates of two electron, say r1 and r2, and it has a Dirac delta function -- delta(r1 - r2) -- as a factor. Since Brueckner and Hartree--Fock orbitals are often very similar, any local exchange functional that works well with Hartree--Fock theory is a reasonable approximation with reference-state one-particle density-matrix theory. The LDA approximation is also a reasonable approximation. However, the Colle--Salvetti correlation-energy functional, and the LYP variant, are not ideal for the method, since these are universal functionals. Nevertheless, they appear to provide reasonable approximations. The B3LYP functional is derived using a linear combination of two functionals: One is the BLYP functional; the other uses exact exchange and a correlation-energy functional from the LDA.Comment: 26 Pages, 0 figures, RevTeX 4, Submitted to Mol. Phy

Noncommutative Particles in Curved Spaces

We present a formulation in a curved background of noncommutative mechanics, where the object of noncommutativity $\theta^{\mu\nu}$ is considered as an independent quantity having a canonical conjugate momentum. We introduced a noncommutative first-order action in D=10 curved spacetime and the covariant equations of motions were computed. This model, invariant under diffeomorphism, generalizes recent relativistic results.Comment: 1+15 pages. Latex. New comments and results adde

Selection for Replicases in Protocells

PMCID: PMC3649988This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Lack of Matrilin-2 Favors Liver Tumor Development via Erk1/2 and GSK-3 beta Pathways In Vivo

Matrilin-2 (Matn2) is a multidomain adaptor protein which plays a role in the assembly of extracellular matrix (ECM). It is produced by oval cells during stem cell-driven liver regeneration. In our study, the impact of Matn2 on hepatocarcinogenesis was investigated in Matn2(-/-) mice comparing them with wild-type (WT) mice in a diethylnitrosamine (DEN) model. The liver tissue was analyzed macroscopically, histologically and immunohistochemically, at protein level by Proteome Profiler Arrays and Western blot analysis. Matn2(-/-) mice exhibited higher susceptibility to hepatocarcinogenesis compared to wild-type mice. In the liver of Matn2(-/-) mice, spontaneous microscopic tumor foci were detected without DEN treatment. After 15 mu g/g body weight DEN treatment, the liver of Matn2(-/-) mice contained macroscopic tumors of both larger number and size than the WT liver. In contrast with the WT liver, spontaneous phosphorylation of EGFR, Erk1/2 GSK-3 alpha/beta and retinoblastoma protein (p-Rb), decrease in p21/CIP1 level, and increase in beta-Catenin protein expression were detected in Matn2(-/-) livers. Focal Ki-67 positivity of these samples provided additional support to our presumption that the lack of Matn2 drives the liver into a pro-proliferatory state, making it prone to tumor development. This enhanced proliferative capacity was further increased in the tumor nodules of DEN-treated Matn2(-/-) livers. Our study suggests that Matn2 functions as a tumor suppressor in hepatocarcinogenesis, and in this process activation of EGFR together with that of Erk1/2, as well as inactivation of GSK-3 beta, play strategic roles

Alcohol reversibly disrupts TNF-α/TACE interactions in the cell membrane

BACKGROUND: Alcohol abuse has long been known to adversely affect innate and adaptive immune responses and pre-dispose to infections. One cellular mechanism responsible for this effect is alcohol-induced suppression of TNF-α (TNF) by mononuclear phagocytes. We have previously shown that alcohol in part inhibits TNF-α processing by TNF converting enzyme (TACE) in human monocytes. We hypothesized that the chain length of the alcohol is critical for post-transcriptional suppression of TNF secretion. METHODS: Due to the complex transcriptional and post-transcriptional regulation of TNF in macrophages, to specifically study TNF processing at the cell membrane we performed transient transfections of A549 cells with the TNF cDNA driven by the heterologous CMV promoter. TNF/TACE interactions at the cell surface were assessed using fluorescent resonance energy transfer (FRET) microscopy. RESULTS: The single carbon alcohol, methanol suppressed neither TNF secretion nor FRET efficiency between TNF and TACE. However, 2, 3, and 4 carbon alcohols were potent suppressors of TNF processing and FRET efficiency. The effect of ethanol, a 2-carbon alcohol was reversible. CONCLUSION: These data show that inhibition of TNF-α processing by acute ethanol is a direct affect of ethanol on the cell membrane and is reversible upon cessation or metabolism

Modulating signaling networks by CRISPR/Cas9-mediated transposable element insertion

In a recent past, transposable elements (TEs) were referred to as selfish genetic components only capable of copying themselves with the aim of increasing the odds of being inherited. Nonetheless, TEs have been initially proposed as positive control elements acting in synergy with the host. Nowadays, it is well known that TE movement into host genome comprises an important evolutionary mechanism capable of increasing the adaptive fitness. As insights into TE functioning are increasing day to day, the manipulation of transposition has raised an interesting possibility of setting the host functions, although the lack of appropriate genome engineering tools has unpaved it. Fortunately, the emergence of genome editing technologies based on programmable nucleases, and especially the arrival of a multipurpose RNA-guided Cas9 endonuclease system, has made it possible to reconsider this challenge. For such purpose, a particular type of transposons referred to as miniature inverted-repeat transposable elements (MITEs) has shown a series of interesting characteristics for designing functional drivers. Here, recent insights into MITE elements and versatile RNA-guided CRISPR/Cas9 genome engineering system are given to understand how to deploy the potential of TEs for control of the host transcriptional activity.Fil: Vaschetto, Luis Maria Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Diversidad Animal I; Argentin

Effects of growth rate, size, and light availability on tree survival across life stages: a demographic analysis accounting for missing values and small sample sizes.

The data set supporting the results of this article is available in the Dryad repository, http://dx.doi.org/10.5061/dryad.6f4qs. Moustakas, A. and Evans, M. R. (2015) Effects of growth rate, size, and light availability on tree survival across life stages: a demographic analysis accounting for missing values.Plant survival is a key factor in forest dynamics and survival probabilities often vary across life stages. Studies specifically aimed at assessing tree survival are unusual and so data initially designed for other purposes often need to be used; such data are more likely to contain errors than data collected for this specific purpose

Alcoholism and Strongyloides stercoralis: Daily Ethanol Ingestion Has a Positive Correlation with the Frequency of Strongyloides Larvae in the Stools

It has been reported that Strongyloides stercoralis infection is more prevalent in chronic alcoholic patients than in non alcoholics living in the same country. In a retrospective study on the prevalence of S. stercoralis infection in a large sample of alcoholic patients, we demonstrate that this prevalence is significantly higher than in non-alcoholic patients admitted at the same hospital. Moreover, the frequency of the parasite was in close relationship with the daily amount of ingested ethanol, even in the absence of liver cirrhosis, reinforcing the idea that chronic alcoholism is associated with increased susceptibility to Strongyloides infection. Beside the bad hygiene profile of alcoholic patients, which explains high risk for acquisition of the parasite, the high prevalence of S. stercoralis in alcoholics may be in relationship with other effects of ethanol on the intestinal motility, steroid metabolism and immune system, which could enhance the chance of autoinfection and the survival and fecundity of females in duodenum. In this way, the number of larvae in the stools is higher in alcoholic patients, increasing the chance of a positive result in a stool examination by sedimentation method