Cellular trafficking in trypanosomatids: a new target for therapies?

Pathogenic trypanosomatids cause a plethora of diseases marked by the lack of efficient vaccines and therapies. As a consequence, studies are being conducted that are geared towards the understanding of basic mechanisms and various biological aspects of these parasites that might be used as targets for new developments in these areas. One such aspect is the understanding of specific cellular trafficking mechanisms that might be attacked with the intention of disease control. In this paper, we give an overview of our current knowledge of cellular targeting mechanisms in trypanosomatids, with special emphasis on our data related to lysosomal targeting of cysteine proteinases in Leishmania.     

Genetic differentiation between sympatric populations of Bacillus cereus and Bacillus thuringiensis

Little is known about genetic exchanges in natural populations of bacteria of the spore-forming Bacillus cereus group, because no population genetics studies have been performed with local sympatric populations. We isolated strains of Bacillus thuringiensis and B. cereus from small samples of soil collected at the same time from two separate geographical sites, one within the forest and the other at the edge of the forest. A total of 100 B. cereus and 98 B. thuringiensis strains were isolated and characterized by electrophoresis to determine allelic composition at nine enzymatic loci. We observed genetic differentiation between populations of B. cereus and B. thuringiensis. Populations of a given Bacillus species--B. thuringiensis or B. cereus--were genetically more similar to each other than to populations of the other Bacillus species. Hemolytic activity provided further evidence of this genetic divergence, which remained evident even if putative clones were removed from the data set. Our results suggest that the rate of gene flow was higher between strains of the same species, but that exchanges between B. cereus and B. thuringiensis were nonetheless possible. Linkage disequilibrium analysis revealed sufficient recombination for B. cereus populations to be considered panmictic units. In B. thuringiensis, the balance between clonal proliferation and recombination seemed to depend on location. Overall, our data indicate that it is not important for risk assessment purposes to determine whether B. cereus and B. thuringiensis belong to a single or two species. Assessment of the biosafety of pest control based on B. thuringiensis requires evaluation of the extent of genetic exchange between strains in realistic natural conditions.     

Life cycle assessment of ethanol production from miscanthus: A comparison of production pathways at two European sites

Lignocellulosic ethanol represents a renewable alternative to petrol. Miscanthus, a perennial plant that grows on marginal land, is characterized by efficient use of resources and is considered a promising source of lignocellulosic biomass. A life cycle assessment (LCA) was performed to determine the environmental impacts of ethanol production from miscanthus grown on marginal land in Great Britain (Aberystwyth) and an average‐yield site in Germany (Stuttgart; functional unit: 1 GJ). As the conversion process has substantial influence on the overall environmental performance, the comparison examined three pretreatment options for miscanthus. Overall, results indicate lower impacts for the production in Stuttgart in comparison with the corresponding pathways in Aberystwyth across the analysed categories. Disparities between the sites were mainly attributed to differences in biomass yield. When comparing the conversion options, liquid hot water treatment resulted in the lowest impacts, followed by dilute sulphuric acid. Dilute sodium hydroxide pretreatment represented the least favourable option. Site‐dependent variation in biomass composition and degradability did not have substantial influence on the environmental performance of the analysed pathways. Additionally, implications of replacing petrol with miscanthus ethanol were examined. Ethanol derived from miscanthus resulted in lower impacts with respect to greenhouse gas emissions, fossil resource depletion, natural land transformation and ozone depletion. However, for other categories, including toxicity, eutrophication and agricultural land occupation, net scores were substantially higher than for the fossil reference. Nevertheless, the results indicate that miscanthus ethanol produced via dilute acid and liquid hot water treatment at the site in Stuttgart has the potential to comply with the requirements of the European Renewable energy directive for greenhouse gas emission reduction. For ethanol production at the marginal site, carbon sequestration needs to be considered in order to meet the requirements for greenhouse gas mitigation.     

Silencing the OCT4-PG1 pseudogene reduces OCT-4 protein levels and changes characteristics of the multidrug resistance phenotype in chronic myeloid leukemia

Molecular Biology Reports - Cancer stem cells show epigenetic plasticity and intrinsic resistance to anti-cancer therapy, rendering capable of initiating cancer relapse and progression....     

Modulation of ERG Genes Expression in Clinical Isolates of Candida tropicalis Susceptible and Resistant to Fluconazole and Itraconazole

Mycopathologia - Candida tropicalis is a non-albicans Candida specie that causes candidosis in several countries, including Brazil. However, little is known about the mechanisms of drug resistance...     

Detection and Molecular Characterization of <Emphasis Type=Italic>Yellow Fever Virus</Emphasis>, 2017, Brazil

At the end of 2016, Brazil experienced an unprecedented yellow fever (YF) outbreak. Clinical, molecular and ecological aspects of human and non-human primate (NHP) samples collected at the beginning of the outbreak are described in this study. Spatial distribution analyses demonstrated a strong overlap between human and NHP cases. Through molecular analyses, we showed that the outbreak had a sylvatic origin, caused by the South American genotype 1 YFV, which has already been shown to circulate in Brazil. As expected, the clusters of cases were identified in regions with a low vaccination coverage. Our findings highlight the importance of the synchronization of animal surveillance and health services to identify emerging YF cases, thereby promoting a better response to the vulnerable population.     

Effects of shear stress on articular chondrocyte metabolism

The articular cartilage of diarthrodial joints experiences a variety of stresses, strains and pressures that result from normal activities of daily living. In normal cartilage, the extracellular matrix exists as a highly organized composite of specialized macromolecules that distributes loads at the bony ends. The chondrocyte response to mechanical loading is recognized as an integral component in the maintenance of articular cartilage matrix homeostasis. With inappropriate mechanical loading of the joint, as occurs with traumatic injury, ligament instability, bony malalignment or excessive weight bearing, the cartilage exhibits manifestations characteristic of osteoarthritis. Breakdown of cartilage in osteoarthritis involves degradation of the extracellular matrix macromolecules and decreased expression of chondrocyte proteins necessary for normal joint function. Osteoarthritic cartilage often exhibits increased amounts of type I collagen and synthesis of proteoglycans characteristic of immature cartilage. The shift in cartilage phenotype in response to altered load yields a matrix that fails to support normal joint function. Mathematical modeling and experimental studies in animal models confirm an association between altered loading of diarthrotic joints and arthritic changes. Both types of studies implicate shear forces as a critical component in the destructive profile. The severity of cartilage destruction in response to altered loads appears linked to expression of biological factors influencing matrix integrity and cellular metabolism. Determining how shear stress alters chondrocyte metabolism is fundamental to understanding how to limit matrix destruction and stimulate cartilage repair and regeneration. At present, the precise biochemical and molecular mechanisms by which shear forces alter chondrocyte metabolism from a normal to a degenerative phenotype remain unclear. The results presented here address the hypothesis that articular chondrocyte metabolism is modulated by direct effects of shear forces that act on the cell through mechanotransduction processes. The purpose of this work is to develop critical knowledge regarding the basic mechanisms by which mechanical loading modulates cartilage metabolism in health and disease. This presentation will describe the effects of using fluid induced shear stress as a model system for stimulation of articular chondrocytes in vitro. The fluid induced shear stress was applied using a cone viscometer system to stimulate all the cells uniformly under conditions of minimal turbulence. The experiments were carried using high-density primary monolayer cultures of normal and osteoarthritic human and normal bovine articular chondrocytes. The analysis of the cellular response included quantification of cytokine release, matrix metalloproteinase expression and activation of intracellular signaling pathways. The data presented here show that articular chondrocytes exhibit a dose- and time-dependent response to shear stress that results in the release of soluble mediators and extracellular matrix macromolecules. The data suggest that the chondrocyte response to mechanical stimulation contributes to the maintenance of articular cartilage homeostasis in vivo.