Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

Peer reviewedPublisher PD

aHUS caused by complement dysregulation: new therapies on the horizon

Atypical hemolytic uremic syndrome (aHUS) is a heterogeneous disease that is caused by defective complement regulation in over 50% of cases. Mutations have been identified in genes encoding both complement regulators [complement factor H (CFH), complement factor I (CFI), complement factor H-related proteins (CFHR), and membrane cofactor protein (MCP)], as well as complement activators [complement factor B (CFB) and C3]. More recently, mutations have also been identified in thrombomodulin (THBD), an anticoagulant glycoprotein that plays a role in the inactivation of C3a and C5a. Inhibitory autoantibodies to CFH account for an additional 5–10% of cases and can occur in isolation or in association with mutations in CFH, CFI, CFHR 1, 3, 4, and MCP. Plasma therapies are considered the mainstay of therapy in aHUS secondary to defective complement regulation and may be administered as plasma infusions or plasma exchange. However, in certain cases, despite initiation of plasma therapy, renal function continues to deteriorate with progression to end-stage renal disease and renal transplantation. Recently, eculizumab, a humanized monoclonal antibody against C5, has been described as an effective therapeutic strategy in the management of refractory aHUS that has failed to respond to plasma therapy. Clinical trials are now underway to further evaluate the efficacy of eculizumab in the management of both plasma-sensitive and plasma-resistant aHUS

X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients

Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Removal of arsenic from drinking water and soil bioremediation

ABSTRACT: Various countries in America have reported the existence of people suffering chronic exposure to levels of arsenic in drinking water that are higher than those envisaged in international standards. This is the case in Canada, the United States, Chile, Peru, Bolivia, Mexico, El Salvador and Nicaragua. Some of these countries have solved, either fully or in part, the problem of technology availability, depending on whether the affected population lives in rural or urban areas. There are around 14 methods of removing arsenic from water, with efficiencies that range from 70 to 99%. Coagulation-flocculation and lime softening are the methods most used in large systems, and not only to remove arsenic. Small systems can use ion exchange, activated alumina, reverse osmosis, nanofiltration and reverse electrodialysis. New technologies include sand covered with iron oxides, granular ferric hydroxide, iron packets, iron modified by sulfur, zeolite filtration, iron addition with direct filtration and conventional removal of iron and manganese. In Latin America studies have concentrated on the use of chemical coagulation with aluminum sulfate, hydrated lime and sodium polyelectrolyte, and have achieved arsenic levels of 0.12-0.15 mg/l. Direct coagulation over filters and coagulation-flocculation have reached values below 0.05 mg/l. Removal through adsorption uses hematites and materials with a high iron content and positively charged surfaces (natural green clay, activated clays, natural and activated zeolite and bone charcoal). In Latin America, Chile is the most experienced country in treating water for urban areas since it has four plants for removing arsenic from the water supply (0.40 mg/l) which together treat 2000 l/s and produce drinking water with 0.040 mg As/l. Improving the system by adding reverse osmosis (post treatment) and desalination has also been evaluated. In Peru there is one plant for removing arsenic that treats the water with ferric chloride and sulfuric acid

Aspectos sanitários do cultivo da alface americana, irrigada com águas recptoras de efluentes urbanos Sanitary aspects of lectucce (Lactuca sativa L.) culture irrigated with receiving waters of urban effluent

Avaliou-se a influência da disposição de mangueiras gotejadoras nos canteiros e a injeção ou não de cloro na água de irrigação, nas condições sanitárias do solo e da alface americana irrigada (Lactuca sativa L.) com águas receptoras de efluentes urbanos. Foram realizadas análises microbiológicas de amostras de água do solo e da alface, no decorrer de todo o ciclo de cultivo. Objetivou-se determinar a possível existência de Salmonella spp. e de formas evolutivas de parasitos humanos e a quantidade de coliformes fecais, em pontos e épocas diferentes do experimento, impedindo assim o consumo da alface. Os resultados não indicaram a presença dos dois primeiros em nenhuma das amostras, mas sim de parasitos não humanos (nematóides) de vida livre no solo. Em relação à quantidade de coliformes fecais (NMP ml-1), o valor encontrado na cultura atende às exigências da Secretaria de Vigilância Sanitária do Ministério da Saúde brasileiro, porém a presença dos nematóides em quantidades superiores ao permitido pela Organização Mundial de Saúde (OMS) inviabiliza o seu consumo.<br>One evaluated the influence of drip tape arrangement and the use of chloride in the irrigation water, on soil sanitary conditions and growing lettuce (Lactuca sativa L.), irrigated with receiving urban waters. Water, soil and lettuce microbiological analyses were performed during crop cycle. The objective was to determine the presence of Salmonella spp., evolutive forms of human parasites and the amount of fecal coliforms in different locations and time, avoiding the lettuce consumption. Although results did not indicate the presence of Salmonella spp. and evolutive forms of human parasites in none of the samples but non human parasites (nematodes) of free life in soil. Total fecal coliforms count (NMP ml-1) met is according to the Brazilian Ministry of Health, Secretary of Health Surveillance requirements. Yet, the lettuce was not good for human consumption as the nematode presence was above the World Health Organization (WHO) guidelines