Reduced Graphene Oxide-Polycarbonate Electrodes on Different Supports for Symmetric Supercapacitors

publishedVersionPeer reviewe

Structure and activation mechanism of the human liver-type glutaminase GLS2

\ua9 2021. Cancer cells exhibit an altered metabolic phenotype, consuming higher levels of the amino acid glutamine. This metabolic reprogramming depends on increased mitochondrial glutaminase activity to convert glutamine to glutamate, an essential precursor for bioenergetic and biosynthetic processes in cells. Mammals encode the kidney-type (GLS) and liver-type (GLS2) glutaminase isozymes. GLS is overexpressed in cancer and associated with enhanced malignancy. On the other hand, GLS2 is either a tumor suppressor or an oncogene, depending on the tumor type. The GLS structure and activation mechanism are well known, while the structural determinants for GLS2 activation remain elusive. Here, we describe the structure of the human glutaminase domain of GLS2, followed by the functional characterization of the residues critical for its activity. Increasing concentrations of GLS2 lead to tetramer stabilization, a process enhanced by phosphate. In GLS2, the so-called “lid loop” is in a rigid open conformation, which may be related to its higher affinity for phosphate and lower affinity for glutamine; hence, it has lower glutaminase activity than GLS. The lower affinity of GLS2 for glutamine is also related to its less electropositive catalytic site than GLS, as indicated by a Thr225Lys substitution within the catalytic site decreasing the GLS2 glutamine concentration corresponding to half-maximal velocity (K0.5). Finally, we show that the Lys253Ala substitution (corresponding to the Lys320Ala in the GLS “activation” loop, formerly known as the “gating” loop) renders a highly active protein in stable tetrameric form. We conclude that the “activation” loop, a known target for GLS inhibition, may also be a drug target for GLS2

Perspectives on the Trypanosoma cruzi-host cell receptor interaction

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets

HIPK2 and extrachromosomal histone H2B are separately recruited by Aurora-B for cytokinesis

Cytokinesis, the final phase of cell division, is necessary to form two distinct daughter cells with correct distribution of genomic and cytoplasmic materials. Its failure provokes genetically unstable states, such as tetraploidization and polyploidization, which can contribute to tumorigenesis. Aurora-B kinase controls multiple cytokinetic events, from chromosome condensation to abscission when the midbody is severed. We have previously shown that HIPK2, a kinase involved in DNA damage response and development, localizes at the midbody and contributes to abscission by phosphorylating extrachromosomal histone H2B at Ser14. Of relevance, HIPK2-defective cells do not phosphorylate H2B and do not successfully complete cytokinesis leading to accumulation of binucleated cells, chromosomal instability, and increased tumorigenicity. However, how HIPK2 and H2B are recruited to the midbody during cytokinesis is still unknown. Here, we show that regardless of their direct (H2B) and indirect (HIPK2) binding of chromosomal DNA, both H2B and HIPK2 localize at the midbody independently of nucleic acids. Instead, by using mitotic kinase-specific inhibitors in a spatio-temporal regulated manner, we found that Aurora-B kinase activity is required to recruit both HIPK2 and H2B to the midbody. Molecular characterization showed that Aurora-B directly binds and phosphorylates H2B at Ser32 while indirectly recruits HIPK2 through the central spindle components MgcRacGAP and PRC1. Thus, among different cytokinetic functions, Aurora-B separately recruits HIPK2 and H2B to the midbody and these activities contribute to faithful cytokinesis

Social representations of AIDS and their quotidian interfaces for people living with HIV

This qualitative descriptive study, guided by the Social Representations Theory, aimed to describe the content of the social representations regarding the Acquired Immunodeficiency Syndrome (AIDS) for seropositive individuals in outpatient monitoring of the public health network and to analyze the interface of the social representations of AIDS with the quotidian of the individuals living with human immunodeficiency virus (HIV), especially in the adherence to treatment process Interviews were conducted with 30 seropositive individuals and the manual content analysis technique was used. From the analysis, six categories emerged that re-translated the quotidian of seropositive people permeated by the stigma, prejudice, struggle for life and the need for the continuous use of antiretrovirals. AIDS was assimilated to chronic diseases such as diabetes, showing a trend of transformation of the social representation of AIDS, substituting the idea of death, with life. It is concluded that people living with HIV are more optimistic due to effective treatments for the control of the disease.Se trata de un estudio cualitativo descriptivo orientado por la Teoría de las Representaciones Sociales, que objetivó describir el contenido de las representaciones sociales acerca de la Síndrome de Inmunodeficiencia Adquirida (SIDA) para los usuarios seropositivos en acompañamiento de ambulatorio en la red pública de salud y analizar la interconexión de las representaciones sociales del Sida con lo cotidiano de los individuos que viven con el virus de la inmunodeficiencia humana (HIV), especialmente al proceso de adhesión al tratamiento. Se realizaron entrevistas con 30 individuos seropositivos. Se utilizó la técnica de análisis de contenido manual. Del análisis, emergieron seis categorías que tradujeron lo cotidiano de seropositivos impregnados por el estigma, prejuicio, lucha por la vida y la necesidad del uso continuo de antirretrovirales. El Sida fue comparado a enfermedades crónicas como la diabetes, evidenciando una tendencia de transformación de la representación social del Sida, substituyendo la idea de muerte, por la de vida. Se concluye que las personas que conviven con HIV están más optimistas debido a los tratamientos eficaces en el control de la enfermedad.Trata-se de estudo qualitativo descritivo, norteado pela teoria das representações sociais. Objetivou-se descrever o conteúdo das representações sociais acerca da síndrome de imunodeficiência adquirida (AIDS) para os usuários soropositivos, em acompanhamento ambulatorial da rede pública de saúde, e analisar a interface das representações sociais da AIDS com o cotidiano dos indivíduos que vivem com o vírus da imunodeficiência humana (HIV), especialmente no processo de adesão ao tratamento. Realizaram-se entrevistas com 30 indivíduos soropositivos. Utilizou-se a técnica de análise de conteúdo manual. Da análise, emergiram seis categorias que retraduziram o cotidiano de soropositivos, permeados pelo estigma, preconceito, luta pela vida e a necessidade do uso contínuo de antirretrovirais. A AIDS foi assimilada a doenças crônicas como diabetes, evidenciando tendência para transformação da representação social da AIDS, substituindo a ideia de morte, por vida. Conclui-se que as pessoas que convivem com HIV estão mais otimistas devido aos tratamentos eficazes no controle da doença

Inactivation of plant-pathogenic fungus Colletotrichum acutatum with natural plant-produced photosensitizers under solar radiation.

The increasing tolerance to currently used fungicides and the need for environmentally friendly antimicrobial approaches have stimulated the development of novel strategies to control plant-pathogenic fungi such as antimicrobial phototreatment (APT). We investigated the in vitro APT of the plant-pathogenic fungus Colletotrichum acutatum with furocoumarins and coumarins and solar radiation. The compounds used were: furocoumarins 8-methoxypsoralen (8-MOP) and 5,8-dimethoxypsoralen (isopimpinellin), coumarins 2H-chromen-2-one (coumarin), 7-hydroxycoumarin, 5,7-dimethoxycoumarin (citropten) and a mixture (3:1) of 7-methoxycoumarin and 5,7-dimethoxycoumarin. APT of conidia with crude extracts from 'Tahiti' acid lime, red and white grapefruit were also performed. Pure compounds were tested at 50μM concentration and mixtures and extracts at 12.5mgL(-1). The C. acutatum conidia suspension with or without the compounds was exposed to solar radiation for 1h. In addition, the effects of APT on the leaves of the plant host Citrus sinensis were determined. APT with 8-MOP was the most effective treatment, killing 100% of the conidia followed by the mixture of two coumarins and isopimpinellin that killed 99% and 64% of the conidia, respectively. APT with the extracts killed from 20% to 70% of the conidia, and the extract from 'Tahiti' lime was the most effective. No damage to sweet orange leaves was observed after APT with any of the compounds or extracts