Hydrogen sulfide pathway and skeletal muscle: an introductory review.

The presence of the H2 S pathway in skeletal muscle (SKM) has recently been established. SKM expresses the three constitutive H2 S-generating enzymes in animals and humans, and it actively produces H2 S. The main, recognized molecular targets of H2 S, that is, potassium channels and PDEs, have been evaluated in SKM physiology in order to hypothesize a role for H2 S signalling. SKM dysfunctions, including muscular dystrophy and malignant hyperthermia, have also been evaluated as conditions in which the H2 S and transsulfuration pathways have been suggested to be involved. The intrinsic complexity of the molecular mechanisms involved in excitation-contraction (E-C) coupling together with the scarcity of preclinical models of SKM-related disorders have hampered any advances in the knowledge of SKM function. Here, we have addressed the role of the H2 S pathway in E-C coupling and the relative importance of cystathionine β-synthase, cistathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase in SKM diseases

Intracellular trafficking and cellular uptake mechanism of PHBV nanoparticles for targeted delivery in epithelial cell lines

Indexación: Web of Science; Scopus; Scielo.Background: Nanotechnology is a science that involves imaging, measurement, modeling and a manipulation of matter at the nanometric scale. One application of this technology is drug delivery systems based on nanoparticles obtained from natural or synthetic sources. An example of these systems is synthetized from poly(3-hydroxybutyrate-co-3-hydroxyvalerate), which is a biodegradable, biocompatible and a low production cost polymer. The aim of this work was to investigate the uptake mechanism of PHBV nanoparticles in two different epithelial cell lines (HeLa and SKOV-3). Results: As a first step, we characterized size, shape and surface charge of nanoparticles using dynamic light scattering and transmission electron microscopy. Intracellular incorporation was evaluated through flow cytometry and fluorescence microscopy using intracellular markers. We concluded that cellular uptake mechanism is carried out in a time, concentration and energy dependent way. Our results showed that nanoparticle uptake displays a cell-specific pattern, since we have observed different colocalization in two different cell lines. In HeLa (Cervical cancer cells) this process may occur via classical endocytosis pathway and some internalization via caveolin-dependent was also observed, whereas in SKOV-3 (Ovarian cancer cells) these patterns were not observed. Rearrangement of actin filaments showed differential nanoparticle internalization patterns for HeLa and SKOV-3. Additionally, final fate of nanoparticles was also determined, showing that in both cell lines, nanoparticles ended up in lysosomes but at different times, where they are finally degraded, thereby releasing their contents. Conclusions: Our results, provide novel insight about PHBV nanoparticles internalization suggesting that for develop a proper drug delivery system is critical understand the uptake mechanism.https://jnanobiotechnology.biomedcentral.com/articles/10.1186/s12951-016-0241-

Maternal Hyperleptinemia Increases Arterial Stiffening and Alters Vasodilatoy Responses to Insulin in Adult Male Mice Offspring

Cardiovascular disease (CVD) is the number one cause of death in the U.S., and exposure to adverse maternal environments has been associated with the development of CVD including hypertension. Gestational diabetes mellitus (GDM) is an adverse maternal environment that has been associated with metabolic and CVD outcomes in the offspring. Key features of GDM and CVD are maternal hyperleptinemia and vascular disfunction/remodeling, respectively. Yet, there is limited information on the effects of maternal hyperleptinemia has on the function and structure of the offspring’s resistance vasculature. We hypothesize that alterations in offspring’s resistance artery structure and function underlie programming mechanisms for cardiovascular disease that are associated with maternal hyperleptinemia and GDM. To test this hypothesis, we used Leprdb/+ mice dams, which exhibit maternal hyperleptinemia and wildtype (WT) as controls. Vascular function was assessed in WT male offspring of control and hyperleptinemic dams at 31 weeks of age, after half the offspring had been fed a high fat diet (HFD) for 6 weeks. On a standard diet (SD), offspring of hyperleptinemic dams had mesenteric arteries with larger internal diameters than those of WT dams (258.36±14.99 vs 233.65±9.36 μm, p<0.05) indicative of outwardly remodeled, and enhanced maximal vasodilatory responses to insulin (39.97±6.71 vs 32.23±5.07 %, p<0.05). In offspring of WT, but not hyperleptinemic dams, HFD increased vessel wall cross-sectional area (18590.01±1251.16 vs 12807.20±1060.70 μm2, p<0.05), and enhanced the maximal vasodilatory response to acetylcholine (33.74±4.92 vs 21.86±2.73 %, p<0.05). HFD reduced the maximal response to insulin in offspring of hyperleptinemic dams compared to their WT and lean controls (21.88±3.80 vs 37.42±7.84 and 39.97±6.71 % respectively, p<0.05). Offspring of hyperleptinemic dams fed a HFD had increased elastic moduli normalized as a function of the percolation of the internal elastic lamina compared to their WT and lean controls (0.53±0.038 vs 0.34±0.023 and 0.38±0.032 ×106 dynes/cm2 respectively, p<0.05). Offspring of hyperleptinemic dams also had stiffer arteries at high pressure under both dietary conditions (2.36±0.35 vs 1.45±0.11 ×106 dynes/cm2, p<0.05). We conclude that when mice were fed a SD, maternal hyperleptinemia had beneficial effects to offspring’s vascular health, but did not protect offspring fed a HFD. Furthermore, maternal hyperleptinemia induced arterial stiffness in offspring regardless of diet. These results suggest that GDM programs offspring vascular function and structure through mechanisms that may be in part dependent on circulating maternal leptin levels and are differentially affected by postnatal developmental exposures

Geno-and cytotoxicity induced on Cyprinus carpio by aluminum, iron, mercury and mixture thereof.

Metals such as Al, Fe and Hg are used in diverse anthropogenic activities. Their presence in water bodies is due mainly to domestic, agricultural and industrial wastewater discharges and constitutes a hazard for the organisms inhabiting these environments. The present study aimed to evaluate geno- and cyto- toxicity induced by Al, Fe, Hg and the mixture of these metals on blood of the common carp Cyprinus carpio. Specimens were exposed to the permissible limits in water for human use and consumption according to the pertinent official Mexican norm [official Mexican norm NOM-127-SSA1-1994] Al (0.2 mg L 1), Fe (0.3 mg L 1), Hg (0.001 mg L 1) and their mixture for 12, 24, 48, 72 and 96 h. Bio- markers of genotoxicity (comet assay and micronucleus test) and cytotoxicity (caspase-3 activity and TUNEL assay) were evaluated. Significant increases relative to the control group (po0.05) were observed in all biomarkers at all exposure times in all test systems; however, damage was greater when the metals were present as a mixture. Furthermore, correlations between metal concentrations and biomarkers of geno- and cytotoxicity were found only at certain exposure times. In conclusion, Al, Fe, Hg and the mixture of these metals induce geno- and cytotoxicity on blood of C. carpio.CONACyT-Mexico, Project 18154

Search for CP Violation in the decays D+ -> K_S pi+ and D+ -> K_S K+

A high statistics sample of photo-produced charm from the FOCUS(E831) experiment at Fermilab has been used to search for direct CP violation in the decays D+->K_S pi+ and D+ -> K_S K+. We have measured the following asymmetry parameters relative to D+->K-pi+pi+: A_CP(K_S pi+) = (-1.6 +/- 1.5 +/- 0.9)%, A_CP(K_S K+) = (+6.9 +/- 6.0 +/- 1.5)% and A_CP(K_S K+) = (+7.1 +/- 6.1 +/- 1.2)% relative to D+->K_S pi+. The first errors quoted are statistical and the second are systematic. We also measure the relative branching ratios: \Gamma(D+->\bar{K0}pi+)/\Gamma(D+->K-pi+pi+) = (30.60 +/- 0.46 +/- 0.32)%, \Gamma(D+->\bar{K0}K+)/\Gamma(D+->K-pi+pi+) = (6.04 +/- 0.35 +/- 0.30)% and \Gamma(D+->\bar{K0}K+)/\Gamma(D+->\bar{K0}pi+) = (19.96 +/- 1.19 +/- 0.96)%.Comment: 4 pages, 3 figure

Search for Λc+→pK+π−\Lambda_c^+ \to p K^+ \pi^- and Ds+→K+K+π−D_s^+ \to K^+ K^+ \pi^- Using Genetic Programming Event Selection

We apply a genetic programming technique to search for the double Cabibbo suppressed decays $\Lambda_c^+ \to p K^+ \pi^-$ and $D_s^+ \to K^+ K^+ \pi^-$. We normalize these decays to their Cabibbo favored partners and find $\text{BR}($\Lambda_c^+ \to p K^+ \pi^-$)/\text{BR}($\Lambda_c^+ \to p K^- \pi^+$) = (0.05 \pm 0.26 \pm 0.02)$ and $\text{BR}($D_s^+ \to K^+ K^+ \pi^-$)/\text{BR}($D_s^+ \to K^+ K^- \pi^+$) = (0.52\pm 0.17\pm 0.11)$ where the first errors are statistical and the second are systematic. Expressed as 90% confidence levels (CL), we find $< 0.46$ and $< 0.78$ respectively. This is the first successful use of genetic programming in a high energy physics data analysis.Comment: 10 page

A High Statistics Measurement of the Lambdac+ Lifetime

A high statistics measurement of the Lambdac+ lifetime from the Fermilab fixed-target FOCUS photoproduction experiment is presented. We describe the analysis technique with particular attention to the determination of the systematic uncertainty. The measured value of 204.6 +/- 3.4 (stat.) +/- 2.5 (syst.) fs from 8034 +/- 122 Lambdac -> pKpi decays represents a significant improvement over the present world average.Comment: Submitted to Physical Review Letter

Measurement of the relative branching ratio BR(\Xi_c^+ \to p^+ K^-\pi^+)\BR(\Xi_c^+ \to \Xi^- \pi^+ \pi^+)

We report the observation of the Cabibbo suppressed decay \Xi_c^+ \to p K^-\pi^+ using data collected with the FOCUS spectrometer during the 1996--97 Fermilab fixed target run. We find a \Xi_c^+ signal peak of 202\pm35 events. We have measured the relative branching ratios BR(\Xi^+_c\to p K^-\pi^+)/BR(\Xi^+_c\to\Xi^-\pi^+\pi^+)= 0.234 \pm 0.047 \pm 0.022 and BR(\Xi^+_c\to p \bar{K}^*(892)^0)/BR(\Xi^+_c\to p K^-\pi^+)= 0.54 \pm 0.09 \pm 0.05 .Comment: 9 pages, 4 figure

A Non-parametric Approach to Measuring the \kpi{} Amplitudes in \dpkkpi{} Decay

Using a large sample of \dpkkpi{} decays collected by the FOCUS photoproduction experiment at Fermilab, we present the first non-parametric analysis of the \kpi{} amplitudes in \dpkkpi{} decay. The technique is similar to the technique used for our non-parametric measurements of the \krzmndk{} form factors. Although these results are in rough agreement with those of E687, we observe a wider S-wave contribution for the \ksw{} contribution than the standard, PDG \cite{pdg} Breit-Wigner parameterization. We have some weaker evidence for the existence of a new, D-wave component at low values of the $K^- \pi^+$ mass.Comment: 13 pages 3 figure

The Target Silicon Detector for the FOCUS Spectrometer

We describe a silicon microstrip detector interleaved with segments of a beryllium oxide target which was used in the FOCUS photoproduction experiment at Fermilab. The detector was designed to improve the vertex resolution and to enhance the reconstruction efficiency of short-lived charm particles.Comment: 18 pages, 14 figure