The enzymes LSD1 and Set1A cooperate with the viral protein HBx to establish an active hepatitis B viral chromatin state

Indexación: Web of ScienceWith about 350 million people chronically infected around the world hepatitis B is a major health problem. Template for progeny HBV synthesis is the viral genome, organized as a minichromosome (cccDNA) inside the hepatocyte nucleus. How viral cccDNA gene expression is regulated by its chromatin structure; more importantly, how the modulation of this structure impacts on viral gene expression remains elusive. Here, we found that the enzyme SetDB1 contributes to setting up a repressed cccDNA chromatin state. This repressive state is activated by the histone lysine demethylase-1 (LSD1). Consistently, inhibiting or reducing LSD1 levels led to repression of viral gene expression. This correlates with the transcriptionally repressive mark H3K9 methylation and reduction on the activating marks H3 acetylation and H3K4 methylation on viral promoters. Investigating the importance of viral proteins we found that LSD1 recruitment to viral promoters was dependent on the viral transactivator protein HBx. Moreover, the histone methyltransferase Set1A and HBx are simultaneously bound to the core promoter, and Set1A expression correlates with cccDNA H3K4 methylation. Our results shed light on the mechanisms of HBV regulation mediated by the cccDNA chromatin structure, offering new therapeutic targets to develop drugs for the treatment of chronically infected HBV patients.http://www.nature.com/articles/srep2590

The Perceived Benefits of Height: Strength, Dominance, Social Concern, and Knowledge among Bolivian Native Amazonians

Research in industrial countries suggests that, with no other knowledge about a person, positive traits are attributed to taller people and correspondingly, that taller people have slightly better socioeconomic status (SES). However, research in some non-industrialized contexts has shown no correlation or even negative correlations between height and socioeconomic outcomes. It remains unclear whether positive traits remain attributed to taller people in such contexts. To address this question, here we report the results of a study in a foraging-farming society of native Amazonians in Bolivia (Tsimane’)–a group in which we have previously shown little association between height and socioeconomic outcomes. We showed 24 photographs of pairs of Tsimane’ women, men, boys, and girls to 40 women and 40 men >16 years of age. We presented four behavioral scenarios to each participant and asked them to point to the person in the photograph with greater strength, dominance, social concern, or knowledge. The pairs in the photographs were of the same sex and age, but one person was shorter. Tsimane’ women and men attributed greater strength, dominance, and knowledge to taller girls and boys, but they did not attribute most positive traits to taller adults, except for strength, and more social concern only when women assessed other women in the photographs. These results raise a puzzle: why would Tsimane’ attribute positive traits to tall children, but not tall adults? We propose three potential explanations: adults’ expectations about the more market integrated society in which their children will grow up, height as a signal of good child health, and children’s greater variation in the traits assessed corresponding to maturational stages

Model of optimization of mining complex for the planning of flow of quarry production of limestone in multiple products and with elements for the analysis of the capacity

Activities in mining complexes contain multiple decisions that affect the operations of the system for the extraction, transformation, transport and storage of various subsoil components. The purpose of this research is the planning of continuous flow production systems for mixed products, in non-metallic mining extraction processes, considering bottlenecks and capacity planning. This paper presents a model for production, based on mathematical optimization, that facilitates the planning and management of operations in the area of extraction, crushing and transformation of a quarry of aggregates for construction, considering the resources and the constraints that allow to define effective strategies in the increase of the productivity of the lines of low production environment by scenarios. This research develops an analysis of bottlenecks and contrasts the nature of the production system by means of a mathematical model of optimization, which considers the capacities and balances in the flows of the Limestone production line. The mathematical model that maximizes profits can be adapted to systems of continuous flow production in mining complexes where their products are part of a reverse logistics process, analysis of alternatives of extraction, transformation and transport

Parameters for antimicrobial photodynamic therapy on periodontal pocket-Randomized clinical trial.

BACKGROUND: Antimicrobial photodynamic therapy (aPDT) has been investigated as an adjunctive to periodontal treatment but the dosimetry parameters adopted have discrepancies and represent a challenge to measure efficacy. There is a need to understand the clinical parameters required to obtain antimicrobial effects by using aPDT in periodontal pockets. The aim of this study was to investigate parameters relating to the antimicrobial effects of photodynamic therapy in periodontal pockets. MATERIAL AND METHODS: This randomized controlled clinical trial included 30 patients with chronic periodontitis. Three incisors from each patient were selected and randomized for the experimental procedures. Microbiological evaluations were performed to quantify microorganisms before and after treatments and spectroscopy was used to identify methylene blue in the pocket. A laser source with emission of radiation at wavelength of ʎ = 660 nm and output radiant power of 100 mW was used for 1, 3 and 5 min. One hundred μM methylene blue was used in aqueous solution and on surfactant vehicle. RESULTS: The results demonstrated the absence of any antimicrobial effect with aqueous methylene blue-mediated PDT. On the other hand, methylene blue in the surfactant vehicle produced microbial reduction in the group irradiated for 5 min (p < 0.05). Spectroscopy showed that surfactant vehicle decreased the dimer peak signal at 610 nm. CONCLUSION: Within the parameters used in this study, PDT mediated by methylene blue in a surfactant vehicle reached significant microbial reduction levels with 5 min of irradiation. The clinical use of PDT may be limited by factors that reduce the antimicrobial effect. Forms of irradiation and stability of the photosensitizers play an important role in clinical aPDT

Antimicrobial photodynamic therapy mediated by methylene blue in surfactant vehicle on periodontopathogens

Background: Periodontal disease (PD) is a chronic inflammatory disease caused by the presence of microbial biofilm. The aim of this study was to evaluate antimicrobial effect of antimicrobial photodynamic therapy (A-PDT) mediated by methylene blue (MB) in monomer form on A. actinomycetemcomitans and P. gingivalis. Methods: A. actinomycetemcomitans ATCC 29523 and P. gingivalis ATCC 33577 were cultured on anaerobic jars at 37 °C for 48 h, and we tested APDT in the presence of 0.25% sodium dodecyl sulfate (SDS) in phosphate-buffered saline (PBS) or in PBS alone. APDT was carried out with 100 μM MB under laser radiation (PhotolaseIII, DMC, Brazil) at ʎ =660 nm and parameters as following (P =100 mW; I =250 mW/cm2, and doses of 15, 45 and 75 J/cm2). Results: Following A-PDT, PBS groups of A. actinomycetemcomitans presented 4 Logs of microbial death after 5 min irradiation. However, there was no bacterial reduction in SDS groups. On the other hand, P. gingivalis was sensitive to APDT in the presence of 0.25% SDS with 2 logs reduction from dark toxicity. Conclusion: The presence of 0.25% SDS can lead to different responses depending on the different microbial species. © 2020 Elsevier B.V

Trisulfate disaccharide decreases calcium overload and protects liver injury secondary to liver ischemia/reperfusion

Background Ischemia and reperfusion (I/R) causes tissue damage and intracellular calcium levels are a factor of cell death. Sodium calcium exchanger (NCX) regulates calcium extrusion and Trisulfated Disaccharide (TD) acts on NCX decreasing intracellular calcium through the inhibition of the exchange inhibitory peptide (XIP). Objectives The aims of this research are to evaluate TD effects in liver injury secondary to I/R in animals and in vitro action on cytosolic calcium of hepatocytes cultures under calcium overload. Methods Wistar rats submitted to partial liver ischemia were divided in groups: Control: (n = 10): surgical manipulation with no liver ischemia; Saline: (n = 15): rats receiving IV saline before reperfusion; and TD: (n = 15): rats receiving IV TD before reperfusion. Four hours after reperfusion, serum levels of AST, ALT, TNF-α, IL-6, and IL-10 were measured. Liver tissue samples were collected for mitochondrial function and malondialdehyde (MDA) content. Pulmonary vascular permeability and histologic parameters of liver were determined. TD effect on cytosolic calcium was evaluated in BRL3A hepatic rat cell cultures stimulated by thapsigargin pre and after treatment with TD. Results AST, ALT, cytokines, liver MDA, mitochondrial dysfunction and hepatic histologic injury scores were less in TD group when compared to Saline Group (p<0.05) with no differences in pulmonary vascular permeability. In culture cells, TD diminished the intracellular calcium raise and prevented the calcium increase pre and after treatment with thapsigargin, respectively. Conclusion TD decreases liver cell damage, preserves mitochondrial function and increases hepatic tolerance to I/R injury by calcium extrusion in Ca2+ overload situations

Primary Xenografts of Human Prostate Tissue as a Model to Study Angiogenesis Induced by Reactive Stroma

Characterization of the mechanism(s) of androgen-driven human angiogenesis could have significant implications for modeling new forms of anti-angiogenic therapies for CaP and for developing targeted adjuvant therapies to improve efficacy of androgen-deprivation therapy. However, models of angiogenesis by human endothelial cells localized within an intact human prostate tissue architecture are until now extremely limited. This report characterizes the burst of angiogenesis by endogenous human blood vessels in primary xenografts of fresh surgical specimens of benign prostate or prostate cancer (CaP) tissue that occurs between Days 6–14 after transplantation into SCID mice pre-implanted with testosterone pellets. The wave of human angiogenesis was preceded by androgen-mediated up-regulation of VEGF-A expression in the stromal compartment. The neo-vessel network anastomosed to the host mouse vascular system between Days 6–10 post-transplantation, the angiogenic response ceased by Day 15, and by Day 30 the vasculature had matured and stabilized, as indicated by a lack of leakage of serum components into the interstitial tissue space and by association of nascent endothelial cells with mural cells/pericytes. The angiogenic wave was concurrent with the appearance of a reactive stroma phenotype, as determined by staining for α-SMA, Vimentin, Tenascin, Calponin, Desmin and Masson's trichrome, but the reactive stroma phenotype appeared to be largely independent of androgen availability. Transplantation-induced angiogenesis by endogenous human endothelial cells present in primary xenografts of benign and malignant human prostate tissue was preceded by induction of androgen-driven expression of VEGF by the prostate stroma, and was concurrent with and the appearance of a reactive stroma phenotype. Androgen-modulated expression of VEGF-A appeared to be a causal regulator of angiogenesis, and possibly of stromal activation, in human prostate xenografts

Terahertz photometer to observe solar flares in continuum

Solar observations at sub-THz frequencies detected a new flare spectral component peaking in the THz range, simultaneously with the well known microwaves component, bringing challenging constraints for interpretation. Higher THz frequencies observations are needed to understand the nature of the mechanisms occurring in flares. A THz photometer system was developed to observe outside the terrestrial atmosphere on stratospheric balloons or satellites, or at exceptionally transparent ground stations. The telescope was designed to observe the whole solar disk detecting small relative changes in input temperature caused by flares at localized positions. A Golay cell detector is preceded by low-pass filters to suppress visible and near IR radiation, a band-pass filter, and a chopper. A prototype was assembled to demonstrate the new concept and the system performance. It can detect temperature variations smaller than 1 K for data sampled at a rate of 10/second, smoothed for intervals larger than 4 seconds. For a 76 mm aperture, this corresponds to small solar burst intensities at THz frequencies. A system with 3 and 7 THz photometers is being built for solar flare observations on board of stratospheric balloon missions.Comment: 11 pages, 8 figures, accepted by Journal of Infrared, Millimeter, and Terahertz Waves, 9 December 201