T Helper 1–Inducing Adjuvant Protects against Experimental Paracoccidioidomycosis

Immunostimulatory therapy is a promising approach to improving the treatment of systemic fungal infections such as paracoccidioidomycosis (PCM), whose drug therapy is usually prolonged and associated with toxic side effects and relapses. The current study was undertaken to determine if the injection of a T helper (Th) 1–stimulating adjuvant in P. brasiliensis–infected mice could have a beneficial effect on the course of experimental PCM. For this purpose, mice were infected and treated with complete Freund's adjuvant (CFA), a well-established Th1 experimental inductor, or incomplete Freund's adjuvant (IFA - control group) on day 20 postinfection. Four weeks after treatment, the CFA-treated mice presented a mild infection in the lungs characterized by absence of epithelioid cell granulomas and yeast cells, whereas the control mice presented multiple sites of focal epithelioid granulomas with lymphomonocytic halos circumscribing a high number of viable and nonviable yeast cells. In addition, CFA administration induced a 2.4 log reduction (>99%) in the fungal burden when compared to the control group, and led to an improvement of immune response, reversing the immunosuppression observed in the control group. The immunotherapy with Th1-inducing adjuvant, approved to be used in humans, might be a valuable tool in the treatment of PCM and potentially useful to improve the clinical cure rate in humans

Lack of Galectin-3 Drives Response to Paracoccidioides brasiliensis toward a Th2-Biased Immunity

There is recent evidence that galectin-3 participates in immunity to infections, mostly by tuning cytokine production. We studied the balance of Th1/Th2 responses to P. brasiliensis experimental infection in the absence of galectin-3. The intermediate resistance to the fungal infection presented by C57BL/6 mice, associated with the development of a mixed type of immunity, was replaced with susceptibility to infection and a Th2-polarized immune response, in galectin-3-deficient (gal3−/−) mice. Such a response was associated with defective inflammatory and delayed type hypersensitivity (DTH) reactions, high IL-4 and GATA-3 expression and low nitric oxide production in the organs of infected animals. Gal3−/− macrophages exhibited higher TLR2 transcript levels and IL-10 production compared to wild-type macrophages after stimulation with P. brasiliensis antigens. We hypothesize that, during an in vivo P. brasiliensis infection, galectin-3 exerts its tuning role on immunity by interfering with the generation of regulatory macrophages, thus hindering the consequent Th2-polarized type of response

The Recognition of N-Glycans by the Lectin ArtinM Mediates Cell Death of a Human Myeloid Leukemia Cell Line

ArtinM, a d-mannose-binding lectin from Artocarpus heterophyllus (jackfruit), interacts with N-glycosylated receptors on the surface of several cells of hematopoietic origin, triggering cell migration, degranulation, and cytokine release. Because malignant transformation is often associated with altered expression of cell surface glycans, we evaluated the interaction of ArtinM with human myelocytic leukemia cells and investigated cellular responses to lectin binding. The intensity of ArtinM binding varied across 3 leukemia cell lines: NB4>K562>U937. The binding, which was directly related to cell growth suppression, was inhibited in the presence of Manα1-3(Manα1-6)Manβ1, and was reverted in underglycosylated NB4 cells. ArtinM interaction with NB4 cells induced cell death (IC50 = 10 µg/mL), as indicated by cell surface exposure of phosphatidylserine and disruption of mitochondrial membrane potential unassociated with caspase activation or DNA fragmentation. Moreover, ArtinM treatment of NB4 cells strongly induced reactive oxygen species generation and autophagy, as indicated by the detection of acidic vesicular organelles in the treated cells. NB4 cell death was attributed to ArtinM recognition of the trimannosyl core of N-glycans containing a ß1,6-GlcNAc branch linked to α1,6-mannose. This modification correlated with higher levels of N-acetylglucosaminyltransferase V transcripts in NB4 cells than in K562 or U937 cells. Our results provide new insights into the potential of N-glycans containing a β1,6-GlcNAc branch linked to α1,6-mannose as a novel target for anti-leukemia treatment

Estimación de la concentración media diaria de material particulado fino en la región del Complejo Industrial y Portuario de Pecém, Ceará, Brasil

A exposição ao material particulado fino (MP2,5) está associada a inúmeros desfechos à saúde. Desta forma, monitoramento da concentração ambiental do MP2,5 é importante, especialmente em áreas amplamente industrializadas, pois abrigam potenciais emissores do MP2,5 e de substâncias com potencial de aumentar a toxicidade de partículas já suspensas. O objetivo desta pesquisa é estimar a concentração diária do MP2,5 em três áreas de influência do Complexo Industrial e Portuário do Pecém (CIPP), Ceará, Brasil. Foi aplicado um modelo de regressão não linear para a estimativa do MP2,5, por meio de dados de profundidade óptica monitorados por satélite. As estimativas foram realizadas em três áreas de influência (Ai) do CIPP (São Gonçalo do Amarante – Ai I, Paracuru e Paraipaba – Ai II e Caucaia – Ai III, no período de 2006 a 2017. As médias anuais das concentrações estimadas foram inferiores ao estabelecido pela legislação nacional em todas as Ai (8µg m-3). Em todas as Ai, os meses referentes ao período de seca (setembro a fevereiro) apresentaram as maiores concentrações e uma predominância de ventos leste para oeste. Os meses que compreendem o período de chuva (março a agosto) apresentaram as menores concentrações e ventos menos definidos. As condições meteorológicas podem exercer um papel importante nos processos de remoção, dispersão ou manutenção das concentrações do material particulado na região. Mesmo com baixas concentrações estimadas, é importante avaliar a constituição das partículas finas dessa região, bem como sua possível associação a efeitos adversos à saúde da população local.Exposure to fine particulate matter (PM2.5) is associated with numerous negative health outcomes. Thus, monitoring the environmental concentration of PM2.5 is important, especially in heavily industrialized areas, since they harbor potential emitters of PM2.5 and substances with the potential to increase the toxicity of already suspended particles. This study aims to estimate daily concentrations of PM2.5 in three areas under the influence of the Industrial and Port Complex of Pecém (CIPP), Ceará State, Brazil. A nonlinear regression model was applied to estimate PM2.5, using satellitemonitored optical depth data. Estimates were performed in three areas of influence (Ai) of the CIPP (São Gonçalo do Amarante – AiI, Paracuru and Paraipaba – AiII, and Caucaia – AiIII), from 2006 to 2017. Estimated mean annual concentrations were lower than established by Brazil’s national legislation in all three Ai (8µg m-³). In all the Ai, the months of the dry season (September to February) showed the highest concentrations and a predominance of east winds, while the months of the rainy season (March to August) showed the lowest concentrations and less defined winds Weather conditions can play an important role in the removal, dispersal, or maintenance of concentrations of particulate matter in the region. Even at low estimated concentrations, it is important to assess the composition of fine participles in this region and their possible association with adverse health outcomes in the local population.La exposición al material particulado fino (MP2,5) está asociada a innumerables problemas de salud. Por ello, la supervisión de la concentración ambiental del MP2,5 es importante, especialmente en áreas ampliamente industrializadas, puesto que albergan potenciales emisores de MP2,5 y de sustancias con potencial de aumentar la toxicidad de partículas ya suspendidas. El objetivo de esta investigación es estimar la concentración diaria del MP2,5 en tres áreas de influencia del Complejo Industrial y Portuario de Pecém (CIPP), Ceará, Brasil. Se aplicó un modelo de regresión no lineal para la estimación del MP2,5, mediante datos de profundidad óptica supervisados por satélite. Las estimaciones fueron realizadas en tres áreas de influencia (Ai) del CIPP (São Gonçalo do Amarante – Ai I, Paracuru y Paraipaba – Ai II y Caucaia – Ai III en el período de 2006 a 2017. Las medias anuales de las concentraciones estimadas fueron inferiores a lo establecido por la legislación nacional en todas las Ai (8µg m-³). En todas las Ai, los meses referentes al período de sequía (de setiembre a febrero) presentaron las mayores concentraciones y una predominancia de vientos este a oeste, los meses que comprenden el período de lluvia (marzo a agosto) presentaron las menores concentraciones y vientos menos definidos. Las condiciones meteorológicas pueden ejercer un papel importante en los procesos de eliminación, dispersión o mantenimiento de las concentraciones del material particulado en la región. Incluso con bajas concentraciones estimadas es importante que se evalúe la constitución de las partículas finas de esta región, así como su posible asociación con efectos adversos para la salud de la población local

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta