Fucosylated Chondroitin Sulfate Inhibits Plasmodium Falciparum Cytoadhesion And Merozoite Invasion.

Sequestration of Plasmodium falciparum-infected erythrocytes (Pf-iEs) in the microvasculature of vital organs plays a key role in the pathogenesis of life-threatening malaria complications, such as cerebral malaria and malaria in pregnancy. This phenomenon is marked by the cytoadhesion of Pf-iEs to host receptors on the surfaces of endothelial cells, on noninfected erythrocytes, and in the placental trophoblast; therefore, these sites are potential targets for antiadhesion therapies. In this context, glycosaminoglycans (GAGs), including heparin, have shown the ability to inhibit Pf-iE cytoadherence and growth. Nevertheless, the use of heparin was discontinued due to serious side effects, such as bleeding. Other GAG-based therapies were hampered due to the potential risk of contamination with prions and viruses, as some GAGs are isolated from mammals. In this context, we investigated the effects and mechanism of action of fucosylated chondroitin sulfate (FucCS), a unique and highly sulfated GAG isolated from the sea cucumber, with respect to P. falciparum cytoadhesion and development. FucCS was effective in inhibiting the cytoadherence of Pf-iEs to human lung endothelial cells and placenta cryosections under static and flow conditions. Removal of the sulfated fucose branches of the FucCS structure virtually abolished the inhibitory effects of FucCS. Importantly, FucCS rapidly disrupted rosettes at high levels, and it was also able to block parasite development by interfering with merozoite invasion. Collectively, these findings highlight the potential of FucCS as a candidate for adjunct therapy against severe malaria.581862-7

Aqueous Biphasic Systems Composed of Ionic Liquids and Sodium Carbonate as Enhanced Routes for the Extraction of Tetracycline

Aqueous biphasic systems (ABS) using ionic liquids (ILs) offer an alternative approach for the extraction, recovery, and purification of biomolecules through their partitioning between two aqueous liquid phases. In this work, the ability of a wide range of ILs to form ABS with aqueous solutions of Na 2 CO 3 was evaluated. The ABS formed by IL 1 water 1 Na 2 CO 3 were determined at 25 C, and the respective solubility curves, tie-lines, and tie-line lengths are reported. The studied ILs share the common chloride anion, allowing the IL cation core, the cation isomerism, the presence of functionalized groups, and alkyl side chain length effects to be evaluated. An increase in the cation side alkyl chain length leads to a higher ability for liquid-liquid demixing whereas different positional isomers and the presence of an allyl group have no major influence in the phase diagrams behavior. Quaternary phosphoniumand ammonium-based fluids are more able to form an ABS when compared with imidazolium-, pyridinium-, pyrrolidinium-, and piperidium-based ILs. Moreover, the presence of an aromatic cation core has no major contribution to the formation of ABS when compared to the respective nonaromatic counterparts. Finally, to appraise on the systems applicability in downstream processing, selected systems were used for the partitioning of tetracyclines (neutral and salt forms) -a class of antibiotics produced by bacteria fermentation. Single-step extraction efficiencies for the IL-rich phase were always higher than 99% and confirm the great potential of ILs to be applied in the biotechnological field

Portuguese multidisciplinary recommendations for non-pharmacological and non-surgical interventions in patients with rheumatoid arthritis

BACKGROUND: Patients with rheumatoid arthritis (RA) report significant levels of disease impact, which are improved, but not fully abrogated by immunosuppressive therapy, even when remission is achieved. This imposes the need for adjuvant interventions targeting the uncontrolled domains of disease impact. Non-pharmacological interventions are widely used for this purpose, but they have not been the object of professional recommendations or guidelines. OBJECTIVE: To propose multidisciplinary recommendations to inform clinical care providers regarding the employment of non-pharmacological and non-surgical interventions in the management of patients with RA. METHODS: The EULAR standardized operating procedures for the development of recommendations were followed. First, a systematic literature review was performed. Then, a multidisciplinary Technical Expert Panel (TEP) met to develop and discuss the recommendations and research agenda. For each developed recommendation i) the level of evidence and grade of recommendation were determined, and ii) the level of agreement among TEP members was set. A recommendation was adopted if approved by ≥75% of the TEP members, and the level of agreement was considered high when ≥8. All relevant national societies were included in this construction process to attain their endorsement. RESULTS: Based on evidence and expert opinion, the TEP developed and agreed on five overarching principles and 12 recommendations for non-pharmacological and non-surgical interventions in patients with RA. The mean level of agreement between the TEP members ranged between 8.5 and 9.9. The recommendations include a broad spectrum of intervention areas, such as exercise, hydrokinesiotherapy, psychological interventions, orthoses, education, general management of comorbidities, among others; and they set the requirements for their application. CONCLUSIONS: These recommendations are based on the consensus judgment of clinical experts from a wide range of disciplines and patients' representatives from Portugal. Given the evidence for effectiveness, feasibility and safety, non-pharmacological and non-surgical interventions should be an integral part of standard care for people with RA. It is hoped that these recommendations should be widely implemented in clinical practice. The target audience for these recommendations includes all health professionals involved in the care of patients with RA. The target patient population includes adult Portuguese people with RA.publishersversionpublishe

Trypanosoma cruzi Gene Expression in Response to Gamma Radiation

Trypanosoma cruzi is an organism highly resistant to ionizing radiation. Following a dose of 500 Gy of gamma radiation, the fragmented genomic DNA is gradually reconstructed and the pattern of chromosomal bands is restored in less than 48 hours. Cell growth arrests after irradiation but, while DNA is completely fragmented, RNA maintains its integrity. In this work we compared the transcriptional profiles of irradiated and non-irradiated epimastigotes at different time points after irradiation using microarray. In total, 273 genes were differentially expressed; from these, 160 were up-regulated and 113 down-regulated. We found that genes with predicted functions are the most prevalent in the down-regulated gene category. Translation and protein metabolic processes, as well as generation of precursor of metabolites and energy pathways were affected. In contrast, the up-regulated category was mainly composed of obsolete sequences (which included some genes of the kinetoplast DNA), genes coding for hypothetical proteins, and Retrotransposon Hot Spot genes. Finally, the tyrosyl-DNA phosphodiesterase 1, a gene involved in double-strand DNA break repair process, was up-regulated. Our study demonstrated the peculiar response to ionizing radiation, raising questions about how this organism changes its gene expression to manage such a harmful stress

A global review and meta-analysis of applications of the freshwater Fish Invasiveness Screening Kit

The freshwater Fish Invasiveness Screening Kit (FISK) has been applied in 35 risk assessment areas in 45 countries across the six inhabited continents (11 applications using FISK v1; 25 using FISK v2). The present study aimed: to assess the breadth of FISK applications and the confidence (certainty) levels associated with the decision-support tool’s 49 questions and its ability to distinguish between taxa of low-to-medium and high risk of becoming invasive, and thus provide climate-specific, generalised, calibrated thresholds for risk level categorisation; and to identify the most potentially invasive freshwater fish species on a global level. The 1973 risk assessments were carried out by 70 + experts on 372 taxa (47 of the 51 species listed as invasive in the Global Invasive Species Database www.iucngisd.org/gisd/), which in decreasing order of importance belonged to the taxonomic Orders Cypriniformes, Perciformes, Siluriformes, Characiformes, Salmoniformes, Cyprinodontiformes, with the remaining ≈ 8% of taxa distributed across an additional 13 orders. The most widely-screened species (in decreasing importance) were: grass carp Ctenopharyngodon idella, common carp Cyprinus carpio, rainbow trout Oncorhynchus mykiss, silver carp Hypophthalmichthys molitrix and topmouth gudgeon Pseudorasbora parva. Nine ‘globally’ high risk species were identified: common carp, black bullhead Ameiurus melas, round goby Neogobius melanostomus, Chinese (Amur) sleeper Perccottus glenii, brown bullhead Ameiurus nebulosus, eastern mosquitofish Gambusia holbrooki, largemouth (black) bass Micropterus salmoides, pumpkinseed Lepomis gibbosus and pikeperch Sander lucioperca. The relevance of this global review to policy, legislation, and risk assessment and management procedures is discussed

Aboveground biomass of a "campina" ecosystem in Roraima, Northern of Brazilian Amazonia

The aboveground biomass of a "campina" ecosystem was estimated in Roraima, in the northern portion of Brazilian Amazonia. The biomass was determined from a phytosociological inventory (1 ha) and distributed between two categories: (1) grassy-woody, composed of "herbs+lichens" (Poaceae, Cyperaceae, Eriocaulaceae, Cladonia spp), Bromeliaceae, seedlings, fine and coarse litter and, (2) woody, composed of trees and bushes. The grassy-woody category was estimated by the direct method (cutting and weighing) in 10 1-m² plots, taking advantage of transects of the inventory. The category woody was estimated by the indirect method cutting 98 individuals of different species and diameters. A model was generated to express the relationship among total dry above-ground biomass (kg), base circumference (cm) and total height (m) for the individuals in this category. The equation was applied to the 3,966 ind.ha-1 observed in the inventory. The total biomass was estimated at 15.91 t.ha-1, of which 2.20 ± 0.23 t.ha-1 (13.8%) was in the grassy-woody category and 13.70 ± 7.13 t.ha-1 (86.2%) in woody category. The tree species with the highest biomass was Humiria balsamifera (Aubl.) St. Hill. (8.43 t.ha-1), followed by Pagamea guianensis Aubl. (1.14 t.ha-1). These results are important for refining the calculations of greenhouse-gas emissions from burning and decomposition of above-ground biomass in "campina" ecosystems in the Amazon region.Foi estimada a biomassa (viva + morta) acima do solo de um ecossistema de "campina" localizado em Roraima, norte da Amazônia brasileira. A biomassa foi determinada a partir de um inventário fitossociológico (1 ha amostral) e distribuída em dois estratos(1) gramíneo-lenhoso, composto de "ervas + liquens" (Poaceae, Cyperaceae, Eriocaulaceae, Cladonia spp), Bromeliaceae, plântulas, "litter" fino e grosso e, (2) arbóreo-arbustivo, composto por árvores e arbustos. O estrato gramíneo-lenhoso foi estimado pelo método direto (corte e pesagem) através de 10 quadras de 1m², aproveitando os transectos do inventário. O estrato arbóreo-arbustivo foi estimado pelo método indireto com o corte de 98 indivíduos de diferentes espécies e diâmetros. Foi gerado um modelo para expressar a relação entre a biomassa seca total (kg), a circunferência de base (cm) e a altura total (m) para os indivíduos deste estrato. A equação foi aplicada nos 3.966 indivíduos.ha-1 observados no inventário. A biomassa total foi estimada em 15,91 t.ha-1, sendo 2,20 ± 0,23 t.ha-1 (13,8%) do estrato gramíneo-lenhoso e 13,70 ± 7,13 t.ha-1 (86,2%) do arbóreo-arbustivo. A espécie arbórea de maior biomassa foi Humiria balsamifera (Aubl.) St. Hill. (8,43 t.ha-1), seguida de Pagamea guianensis Aubl. (1,14 t.ha-1). Estes resultados são importantes para refinar os cálculos de emissão de gases do efeito estufa pela queima e decomposição da biomassa acima do solo em ecossistemas de campinas na Amazônia