The H+-ATPase purified from maize root plasma membranes retains fusicoccin in vivo activation

AbstractThe activity of ‘P-type’ ATPases is modulated through the C-terminal autoinhibitory domain. The molecular bases of this regulation are unknown. Their understanding demands functional and structural studies on the activated purified enzyme. In this paper the plasma membrane H+-ATPase from maize roots activated in vivo by fusicoccin was solubilised and fractionated by anion-exchange HPLC. Results showed that the H+-ATPase separated from fusicoccin receptors retained fusicoccin activation and that it was more evident after enzyme insertion into liposomes. These data suggest that fusicoccin stimulation does not depend on a direct action of the fusicoccin receptor on the H+-ATPase, but rather, fusicoccin brings about a permanent modification of the H+-ATPase which very likely represents a general regulatory mechanism for ‘P-type’ ATPases

The Yin and Yang of Current Antifungal Therapeutic Strategies: How Can We Harness Our Natural Defenses?

Fungal infections have aroused much interest over the last years because of their involvement in several human diseases. Immunocompromission due to transplant-related therapies and malignant cancer treatments are risk factors for invasive fungal infections, but also aggressive surgery, broad-spectrum antibiotics and prosthetic devices are frequently associated with infectious diseases. Current therapy is based on the administration of antifungal drugs, but the occurrence of resistant strains to the most common molecules has become a serious health-care problem. New antifungal agents are urgently needed and it is essential to identify fungal molecular targets that could offer alternatives for development of treatments. The fungal cell wall and plasma membrane are the most important structures that offer putative new targets which can be modulated in order to fight microbial infections. The development of monoclonal antibodies against new targets is a valid therapeutic strategy, both to solve resistance problems and to support the immune response, especially in immunocompromised hosts. In this review, we summarize currently used antifungal agents and propose novel therapeutic approaches, including new fungal molecular targets to be considered for drug development

DISPERSÃO GEOQUÍMICA NA BACIA HIDROGRÁFICA DO RIO SÃO DOMINGOS (RJ) CONTROLADO PELA MORFOLOGIA DA BACIA: Geochemical spread in São Domingos hydrographic basin (RJ) controlled by basin morphology

The São Domingos hydrographic basin are located in Ribeira Belt where are strongly structured than conditioned the drain network. It is on Rio de Janeiro state northwest that is a main farming area, when occur relief changes from crop demand like a result of deforestation process to livestock and logging. Used metals concentration in stream sediments and basement rocks correlated was possible identify different influences in metals concentrations in these sediments, as well as spread geochemistry of that. It was observed than metals concentration (Cd, Co, Cr, Cu, Ni, Pb, Sr, V e Zn) are distributed in four morphostructural zones, also defined by network drain structuring and whose source was characterized like anthropic and natural source. Are an anthropic contribution up hydrographic basin however, the most main contribution is coming from basement rocks in the measured concentration and, that contribution is intensify by drain structuring.A bacia hidrográfica do rio São Domingos está localizada na Faixa Ribeira em uma área com forte estruturação que condiciona o sistema de drenagem. Está situada no noroeste do estado do Rio de Janeiro em uma região predominantemente agrícola, onde ocorre mudança de relevo tanto para atender esta atividade quanto decorrente do processo de desmatamento para pecuária e extração doméstica de madeira. A partir da utilização do método de análise e de concentração de metais nos sedimentos de corrente e correlação com as rochas do embasamento, foi possível identificar as diferentes influências nas concentrações de metais observadas nestes sedimentos, bem como a dispersão geoquímica. Foram observadas que as concentrações de metais (Cd, Co, Cr, Cu, Ni, Pb, Sr, V e Zn) se distribuem em quatro zoneamentos morfoestruturais definidos, também, de acordo com a estruturação da drenagem e, cujas fontes foram caracterizadas como de origem antrópicas e naturais, sendo essa a mais expressiva contribuição que se origina das rochas do embasamento, intensificadas pela estruturação da drenagem através da erosão

Assessment of Body Composition in Health and Disease Using Bioelectrical Impedance Analysis (BIA) and Dual Energy X-Ray Absorptiometry (DXA): A Critical Overview

The measurement of body composition (BC) represents a valuable tool to assess nutritional status in health and disease. The most used methods to evaluate BC in the clinical practice are based on bicompartment models and measure, directly or indirectly, fat mass (FM) and fat-free mass (FFM). Bioelectrical impedance analysis (BIA) and dual energy X-ray absorptiometry (DXA) (nowadays considered as the reference technique in clinical practice) are extensively used in epidemiological (mainly BIA) and clinical (mainly DXA) settings to evaluate BC. DXA is primarily used for the measurements of bone mineral content (BMC) and density to assess bone health and diagnose osteoporosis in defined anatomical regions (femur and spine). However, total body DXA scans are used to derive a three-compartment BC model, including BMC, FM, and FFM. Both these methods feature some limitations: the accuracy of BIA measurements is reduced when specific predictive equations and standardized measurement protocols are not utilized whereas the limitations of DXA are the safety of repeated measurements (no more than two body scans per year are currently advised), cost, and technical expertise. This review aims to provide useful insights mostly into the use of BC methods in prevention and clinical practice (ambulatory or bedridden patients). We believe that it will stimulate a discussion on the topic and reinvigorate the crucial role of BC evaluation in diagnostic and clinical investigation protocols

A new humanized antibody is effective against pathogenic fungi in vitro

Invasive fungal infections mainly affect patients undergoing transplantation, surgery, neoplastic disease, immunocompromised subjects and premature infants, and cause over 1.5 million deaths every year. The most common fungi isolated in invasive diseases are Candida spp., Cryptococcus spp., and Aspergillus spp. and even if four classes of antifungals are available (Azoles, Echinocandins, Polyenes and Pyrimidine analogues), the side effects of drugs and fungal acquired and innate resistance represent the major hurdles to be overcome. Monoclonal antibodies are powerful tools currently used as diagnostic and therapeutic agents in different clinical contexts but not yet developed for the treatment of invasive fungal infections. In this paper we report the development of the first humanized monoclonal antibody specific for β-1,3 glucans, a vital component of several pathogenic fungi. H5K1 has been tested on C. auris, one of the most urgent threats and resulted efficient both alone and in combination with Caspofungin and Amphotericin B showing an enhancement effect. Our results support further preclinical and clinical developments for the use of H5K1 in the treatment of patients in need