Structural basis of signal sequence surveillance and selection by the SRP–FtsY complex

Signal-recognition particle (SRP)-dependent targeting of translating ribosomes to membranes is a multistep quality-control process. Ribosomes that are translating weakly hydrophobic signal sequences can be rejected from the targeting reaction even after they are bound to the SRP. Here we show that the early complex, formed by Escherichia coli SRP and its receptor FtsY with ribosomes translating the incorrect cargo EspP, is unstable and rearranges inefficiently into subsequent conformational states, such that FtsY dissociation is favored over successful targeting. The N-terminal extension of EspP is responsible for these defects in the early targeting complex. The cryo-electron microscopy structure of this 'false' early complex with EspP revealed an ordered M domain of SRP protein Ffh making two ribosomal contacts, and the NG domains of Ffh and FtsY forming a distorted, flexible heterodimer. Our results provide a structural basis for SRP-mediated signal-sequence selection during recruitment of the SRP receptor

DNA-Containing Immunocomplexes Promote Inflammasome Assembly and Release of Pyrogenic Cytokines by CD14+ CD16+ CD64high CD32low Inflammatory Monocytes from Malaria Patients

High levels of circulating immunocomplexes (ICs) are found in patients with either infectious or sterile inflammation. We report that patients with either Plasmodium falciparum or Plasmodium vivax malaria have increased levels of circulating anti-DNA antibodies and ICs containing parasite DNA. Upon stimulation with malaria-induced ICs, monocytes express an NF-kappaB transcriptional signature. The main source of IC-induced proinflammatory cytokines (i.e., tumor necrosis factor alpha [TNF-alpha] and interleukin-1beta [IL-1beta])in peripheral blood mononuclear cells from acute malaria patients was found to be a CD14(+) CD16 (FcgammaRIIIA)(+) CD64 (FcgammaRI)(high) CD32 (FcgammaRIIB)(low) monocyte subset. Monocytes from convalescent patients were predominantly of the classical phenotype (CD14(+) CD16(-)) that produces high levels of IL-10 and lower levels of TNF-alpha and IL-1beta in response to ICs. Finally, we report a novel role for the proinflammatory activity of ICs by demonstrating their ability to induce inflammasome assembly and caspase-1 activation in human monocytes. These findings illuminate our understanding of the pathogenic role of ICs and monocyte subsets and may be relevant for future development of immunity-based interventions with broad applications to systemic inflammatory diseases. IMPORTANCE: Every year, there are approximately 200 million cases of Plasmodium falciparum and P. vivax malaria, resulting in nearly 1 million deaths, most of which are children. Decades of research on malaria pathogenesis have established that the clinical manifestations are often a consequence of the systemic inflammation elicited by the parasite. Recent studies indicate that parasite DNA is a main proinflammatory component during infection with different Plasmodium species. This finding resembles the mechanism of disease in systemic lupus erythematosus, where host DNA plays a central role in stimulating an inflammatory process and self-damaging reactions. In this study, we disclose the mechanism by which ICs containing Plasmodium DNA activate innate immune cells and consequently stimulate systemic inflammation during acute episodes of malaria. Our results further suggest that Toll-like receptors and inflammasomes have a central role in malaria pathogenesis and provide new insights toward developing novel therapeutic interventions for this devastating disease

Recent achievements of greenness metrics on paper-based electrochemical (bio) sensors for environmental and clinical analysis

This review proposes, for the first time, a recent overview of ecological information involving electrochemical paper-based analytical devices (ePADs) dedicated to sensing environmental and clinical situations. The options of manufacturing methods are screen printing, stencil printing, pencil drawing, laser scribing, inject-printing, and additive printing. We have covered ecological aspects such as resource efficiency, safety, and toxicity regarding using paper-based (bio) electrodes. To see the ecological impact of testing methods by using ePADs, the Analytical GREEnness (AGREE) approach was utilized as a greenness metric calculator model since the tool makes use of 12 principles of Green Analytical Chemistry. Positive and negative concepts from the revised values of AGREE metric of clinical and environmental analysis were introduced and discussed. Also, we finalize the present review informing the life cycle of ePAD and some challenges that can impact the next generation of disposable electrodes

Influência do AIA e AIB no enraizamento do mamoeiro hibrido Tainung 1.

Nesta pesquisa estudou-se a influência das concentrações dos ácidos 3-indolil acético (AIA) e idolbutírico (AIB) na indução de rizogênese em mamoeiro híbrido Tainung 1

Atributos microbianos do solo sob pastagens naturais com diferentes intensidades de pastejo

The soil microbial biomass is the living fraction of organic matter, being responsible for several biological and biochemical processes of the soil and influenced by the conditions imposed by the environment. To evaluate the effect of grazing on changes in soil microbial attributes we studied four grazing intensities based on natural grassland of Pampa Biome: 4, 8, 12 and 16 kg of dry matter per day per 100 kg of animal live weight, compared to an area without grazing. We used randomized block design with two replications. Samples were taken on 11/23/2011 and analyzed to determine the levels of soil organic matter (SOM), microbial biomass, nitrogen, respiration and metabolic quotient. The results showed that at intermediate grazing intensities, such as 12%, minor disturbances occur in soil microbial biomass compared to other intensities, emit less CO2 into the atmosphere for each animal unit produced. The levels of organic matter and soil microbial biomass systems are lower in grazed than in areas excluded from grazing for a long period.A biomassa microbiana do solo constitui a fração viva da matéria orgânica, sendo responsável por diversos processos biológicos e bioquímicos do solo e influenciada pelas condições impostas pelo meio. Visando avaliar o efeito do pastejo nas alterações dos atributos microbianos do solo, foram estudados 4 intensidades de pastejo baseados em pastagem natural do Bioma Pampa: 4, 8, 12 e 16% de oferta de forragem (kg de peso vivo em MS), comparados com uma área sem pastejo. Foi utilizado o delineamento em blocos casualizados com duas repetições. As amostras foram tomadas no dia 23/11/2011, sendo avaliados os teores de matéria orgânica do solo (MOS), biomassa microbiana, nitrogênio, respiração e quociente metabólico. Os resultados apontaram que em intensidades de pastejo intermediárias, como 12%, ocorrem menores distúrbios na biomassa microbiana do solo quando comparados às demais ofertas, emitindo menor quantidade de CO2 para a atmosfera para cada unidade animal produzida. Os teores de matéria orgânica e biomassa microbiana do solo em sistemas pastejados são inferiores àqueles de áreas excluídas do pastejo por um longo período

Effect of polysaccharide sources on the physicochemical properties of bromelainchitosan nanoparticles

Bromelain, a set of proteolytic enzymes potential pharmaceutical applications, was encapsulated in chitosan nanoparticles to enhance enzyme stability, and the effect of different chitosan sources was evaluated. Chitosan types (i.e., low molecular weight chitosan, chitosan oligosaccharide lactate, and chitosan from shrimp shells) produced nanoparticles with different physicochemical properties, however in all cases, particle size and zeta potential decreased, and polydispersity index increased after bromelain addition. Bromelain encapsulation was higher than 84% and 79% for protein content and enzymatic activity, respectively, with low molecular weight chitosan presenting the highest encapsulation efficiency. Nanoparticle suspension was also tested for accelerated stability and rheological behavior. For the chitosan–bromelain nanoparticles, an instability index below 0.3 was recorded and, in general, the loading of bromelain in chitosan nanoparticles decreased the cohesiveness of the final suspension.This research was granted by FAPESP (2016/03444-5,2017/05275-9,and2017/05333-9), CNPq and FAEPEX, and by the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER, under the project reference M-ERA-NET/0004/2015 (PAIRED) Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Curcumin encapsulation in nanostructures for cancer therapy: a 10-year overview

Journal pre-proofsCurcumin (CUR) is a phenolic compound present in some herbs, including Curcuma longa Linn. (turmeric rhizome), with a high bioactive capacity and characteristic yellow color. It is mainly used as a spice, although it has been found that CUR has interesting pharmaceutical properties, acting as a natural antioxidant, anti-inflammatory, antimicrobial, and antitumoral agent. Nonetheless, CUR is a hydrophobic compound with low water solubility, poor chemical stability, and fast metabolism, limiting its use as a pharmacological compound. Smart drug delivery systems (DDS) have been used to overcome its low bioavailability and improve its stability. The current work overviews the literature from the past 10 years on the encapsulation of CUR in nanostructured systems, such as micelles, liposomes, niosomes, nanoemulsions, hydrogels, and nanocomplexes, emphasizing its use and ability in cancer therapy. The studies highlighted in this review have shown that these nanoformulations achieved higher solubility, improved tumor cytotoxicity, prolonged CUR release, and reduced side effects, among other interesting advantages.This study was funded by the Coordination for Higher Level Graduate Improvements (CAPES/Brazil, finance code 001), National Council for Scientific and Technological Development (CNPq/Brazil, PIBIC process #123483/2020-4), State of São Paulo Research Foundation (FAPESP/Brazil, processes #2017/10789-1, #2018/10799-0, #2018/06475-4, #2018/07707-6, #2019/08549-8, and #2020/03727-2). This work was also supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and the project AgriFood XXI (NORTE-01-0145-FEDER-000041) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. Our Figures were created with BioRenderinfo:eu-repo/semantics/publishedVersio

Antibodies That Induce Phagocytosis of Malaria Infected Erythrocytes: Effect of HIV Infection and Correlation with Clinical Outcomes

HIV infection increases the burden of disease of malaria in pregnancy, in part by impairing the development of immunity. We measured total IgG and phagocytic antibodies against variant surface antigens of placental-type CS2 parasites in 187 secundigravidae (65% HIV infected). In women with placental malaria infection, phagocytic antibodies to CS2VSA were decreased in the presence of HIV (p = 0.011) and correlated positively with infant birth weight (coef = 3.57, p = 0.025), whereas total IgG to CS2VSA did not. Phagocytic antibodies to CS2VSA are valuable tools to study acquired immunity to malaria in the context of HIV co-infection. Secundigravidae may be an informative group for identification of correlates of immunity

Chemical and pharmacological investigation of Solanum species of Brazil: a search for solasodine and other potentially useful therapeutic agents

A systematic search for solasodine, an important staring material for the partial synthesis of steroidal hormones as well as other potentially bioactive constituents of various Solanum species of Brazil has been undertaken. Thus, the fruits of S. paludosum, S. asperum, S. sessiliforum and Solanum sp. were found to contain significant amounts of solasodine. The root bark of S. paludosum which showe durare like activity yelded tomatidenol and another yet unidentified alkaloid responsible for the biological activity. The fruits of S. asperum yelded a new spirosolane alkaloid, solaparnaine. The stem bark of S. pseudo-quina showed convulsive and exitatory activity from which (25S)-isosolafloridine was identified as the active principle. In addition, the latter alkaloid was also found to show antimicrobial activity

Micropropagação do abacaxizeiro em larga escala.

O laboratório de Biotecnologia da Embrapa Semi-Árido produziu mudas de abacaxi híbrido [Ananas comosus (L.) Merril], resultante do cruzamento entre as variedades Primavera e Roxo de Tefé, provenientes da Emepa-PB, objetivando avaliar sua micropropagação massal