Hydrogen sulfide:A novel component in Arabidopsis peroxisomes which triggers catalase inhibition

Plant peroxisomes have the capacity to generate different reactive oxygen and nitrogen species(ROS and RNS),such as H_2O_2,superoxide radical(O_2~-),nitric oxide and peroxynitrite(ONOO~-).These organelles have an active nitrooxidative metabolism which can be exacerbated by adverse stress conditions.Hydrogen sulfide(H_2S)is a new signaling gasotransmitter which can mediate the posttranslational modification(PTM)persulfidation.We used Arabidopsis thaliana transgenic seedlings expressing cyan fluorescent protein(CFP)fused to a canonical peroxisome targeting signal 1(PTS1)to visualize peroxisomes in living cells,as well as a specific fluorescent probe which showed that peroxisomes contain H_2S.H_2S was also detected in chloroplasts under glyphosate-induced oxidative stress conditions.Peroxisomal enzyme activities,including catalase,photorespiratory H_2O_2-generating glycolate oxidase(GOX)and hydroxypyruvate reductase(HPR),were assayed in vitro with a H_2S donor.In line with the persulfidation of this enzyme,catalase activity declined significantly in the presence of the H_2S donor.To corroborate the inhibitory effect of H_2S on catalase activity,we also assayed pure catalase from bovine liver and pepper fruit-enriched samples,in which catalase activity was inhibited.Taken together,these data provide evidence of the presence of H_2S in plant peroxisomes which appears to regulate catalase activity and,consequently,the peroxisomal H_2O_2 metabolism.     

Zero‐modified Poisson model: Bayesian approach,influence diagnostics,and an application to a Brazilian leptospirosis notification data

In this paper, a Bayesian method for inference is developed for the zero‐modified Poisson (ZMP) regression model. This model is very flexible for analyzing count data without requiring any information about inflation or deflation of zeros in the sample. A general class of prior densities based on an information matrix is considered for the model parameters. A sensitivity study to detect influential cases that can change the results is performed based on the Kullback–Leibler divergence. Simulation studies are presented in order to illustrate the performance of the developed methodology. Two real datasets on leptospirosis notification in Bahia State (Brazil) are analyzed using the proposed methodology for the ZMP model.     

PARP-1 Regulates Metastatic Melanoma through Modulation of Vimentin-induced Malignant Transformation

PARP inhibition can induce anti-neoplastic effects when used as monotherapy or in combination with chemo- or radiotherapy in various tumor settings; however, the basis for the anti-metastasic activities resulting from PARP inhibition remains unknown. PARP inhibitors may also act as modulators of tumor angiogenesis. Proteomic analysis of endothelial cells revealed that vimentin, an intermediary filament involved in angiogenesis and a specific hallmark of EndoMT (endothelial to mesenchymal transition) transformation, was down-regulated following loss of PARP-1 function in endothelial cells. VE-cadherin, an endothelial marker of vascular normalization, was up-regulated in HUVEC treated with PARP inhibitors or following PARP-1 silencing; vimentin over-expression was sufficient to drive to an EndoMT phenotype. In melanoma cells, PARP inhibition reduced pro-metastatic markers, including vasculogenic mimicry. We also demonstrated that vimentin expression was sufficient to induce increased mesenchymal/pro-metastasic phenotypic changes in melanoma cells, including ILK/GSK3-β-dependent E-cadherin down-regulation, Snail1 activation and increased cell motility and migration. In a murine model of metastatic melanoma, PARP inhibition counteracted the ability of melanoma cells to metastasize to the lung. These results suggest that inhibition of PARP interferes with key metastasis-promoting processes, leading to suppression of invasion and colonization of distal organs by aggressive metastatic cells.     

Distribution in tissue homogenates,and the nature of the linkage of injected proteins to subcellular particles

Intravenously injected labeled proteins were recovered mostly in particulate fractions of rat liver homogenate. Distribution showed changes depending on the time elapsed from the injection. ¹³¹I-albumin undergoes an intraparticulate hydrolysis which shows the highest activity in the gradient fractions associated with the highest level of acid phosphatase. The labeled albumin-bearing particles separated at 27,000 g × 10 minutes released their radioactive protein at the same rate as acid phosphatase appeared in the medium, under the effect of such agents as distilled water, salts, homogenization, sonication and pH changes. The substitution of sucrose for distilled water or salts showed that the particles behave as an osmotic system as do lysosomes. These experiments prove that secondary lysosomes involved in the hydrolysis of foreign proteins, whose existence was shown by other authors only at the histochemical level, may survive the distrupting action of conventional homogenization and maintain many properties characteristic of primary lysosomes in addition to the ability of hydrolysing “in vitro” the engulfed material.     

Stimulating action of methyl 12, 12, 12-trifluorofarnesoate on in vitro juvenile hormone III biosynthesis in blattella germanica

Methyl 12, 12, 12-trifluorofarnesoate (MTFF) at a dose of 10 μM, stimulated in vitro juvenile hormone (JH) release in corpora allata (CA) from 6-day-old, freshly ecdysed, and 8-day-old (period of ootheca transport) adult virgin females of Blattella germanica. In addition, MTFF also induced intraglandular accumulation of JH and MF in treated CA. Trifluorofarnesoic acid (TFFA) and trifluorofarnesol (TFF) exhibited the same properties, although to a lesser extent than MTFF. The detection of MTFF in TFFA-treated CA suggested that TFFA and TFF were biotransformed into MTFF by the CA enzymatic system and that this ester might be responsible for the activity observed. Equivalent experiments carried out with farnesoic acid (FA) resulted in a more significant stimulation of JH production. This is not surprising, because exogenous FA is readily epoxidized at C10-C11 double bond and methylated to afford JH. Conversely, analytical data have shown that the C6-C7 double bond of MTFF is epoxidized by the CA enzymatic system, whereas that at C10-C11 remains practically unaltered.     

THDP17 Decreases Ammonia Production through Glutaminase Inhibition. A New Drug for Hepatic Encephalopathy Therapy

Ammonia production is implicated in the pathogenesis of hepatic encephalopathy (HE), being intestinal glutaminase activity the main source for ammonia. Management of ammonia formation can be effective in HE treatment by lowering intestinal ammonia production. The use of glutaminase inhibitors represents one way to achieve this goal. In this work, we have performed a search for specific inhibitors that could decrease glutaminase activity by screening two different groups of compounds: i) a group integrated by a diverse, highly pure small molecule compounds derived from thiourea ranging from 200 to 800 Daltons; and ii) a group integrated by commonly use compounds in the treatment of HE. Results shown that THDP-17 (10 µM), a thiourea derivate product, could inhibit the intestinal glutaminase activity (57.4±6.7%). Inhibitory effect was tissue dependent, ranging from 40±5.5% to 80±7.8% in an uncompetitive manner, showing V_max and K_m values of 384.62 µmol min⁻¹, 13.62 mM with THDP-17 10 µM, respectively. This compound also decreased the glutaminase activity in Caco-2 cell cultures, showing a reduction of ammonia and glutamate production, compared to control cultures. Therefore, the THDP-17 compound could be a good candidate for HE management, by lowering ammonia production.     

A New Species of the Genus Paravelia Breddin 1898 from Argentina (Heteroptera: Veliidae)

A new species of the genus Paravelia (Heteroptera: Veliidae) is described, increasing the number of species of the genus known from Argentina to three: P. platensis Berg 1883, P. paxila Drake 1957, and the new sp. P. correntina. Some ecological and statistical notes are included. Scanning electron micrographs and illustrations are provided.     

Tunable Stochastic Pulsing in the Escherichia coli Multiple Antibiotic Resistance Network from Interlinked Positive and Negative Feedback Loops

Cells live in uncertain, dynamic environments and have many mechanisms for sensing and responding to changes in their surroundings. However, sudden fluctuations in the environment can be catastrophic to a population if it relies solely on sensory responses, which have a delay associated with them. Cells can reconcile these effects by using a tunable stochastic response, where in the absence of a stressor they create phenotypic diversity within an isogenic population, but use a deterministic response when stressors are sensed. Here, we develop a stochastic model of the multiple antibiotic resistance network of Escherichia coli and show that it can produce tunable stochastic pulses in the activator MarA. In particular, we show that a combination of interlinked positive and negative feedback loops plays an important role in setting the dynamics of the stochastic pulses. Negative feedback produces a pulsatile response that is tunable, while positive feedback serves to amplify the effect. Our simulations show that the uninduced native network is in a parameter regime that is of low cost to the cell (taxing resistance mechanisms are expressed infrequently) and also elevated noise strength (phenotypic variability is high). The stochastic pulsing can be tuned by MarA induction such that variability is decreased once stresses are sensed, avoiding the detrimental effects of noise when an optimal MarA concentration is needed. We further show that variability in the expression of MarA can act as a bet hedging mechanism, allowing for survival in time-varying stress environments, however this effect is tunable to allow for a fully induced, deterministic response in the presence of a stressor.