Parasite Glycobiology:A Bittersweet Symphony

Human infections caused by parasitic protozoans and helminths are among the world's leading causes of death. More than a million people die each year from diseases like malaria and neglected tropical diseases like leishmaniasis, trypanosomiasis, and schistosomiasis. Patients also endure disabilities that cause lifelong suffering and that affect productivity and development [1]. More insidiously, parasites generate important economic losses, since they often also infect commercially valuable animals. Worldwide, exposure to parasites is increasing due to growing international travel and migrations, as well as climate changes, which affect the geographic distribution of the parasite vectors. The parasitic threat is also aggravated by the rise of the immunocompromised population, which is particularly sensitive to parasite infections (e.g., individuals with AIDS and other immunodeficiencies). A common feature of protozoan parasites and helminths is the synthesis of glycoconjugates and glycan-binding proteins for protection and to interact and respond to changes in their environment. To address the many challenges associated with the study of the structure, the biosynthesis, and the biology of parasitic glycans, the authors of this article have established GlycoPar, a European Marie Curie training program steered by some of the world's academic leaders in the field of parasite glycobiology, in close association with European industrial enterprises. The main scientific goal of this network is the description of novel paradigms and models by which parasite glycoconjugates play a role in the successful colonization of the different hosts. By means of a training-through-research program, the aim of the network is to contribute to the training of a generation of young scientists capable of tackling the challenges posed by parasite glycobiology

Metallogenetic potencial of the Paleoproterozoic mafic-ultramafic Hamutenha intrusion (SW Angola). New data from PLANAGEO project [Abstract]

ABSTRACT: In the SW sector of the Angolan shield occur the Kunene Anorthositic Complex (KAC), one of the most remarkable magmatic anorthositic suites worldwide. The KAC is considered a long-lived magmatic system that operated in the area intermittently during the Mesoproterozoic (1450 ± 2 Ma to 1371 ± 2.5 Ma). Smaller mafic-ultramafic intrusive bodies ranging in composition from dunite to harzbugite, pyroxenite, troctolite and gabbro are located in the KAC periphery (e.g. Epupa, Ombuku, Hamutenha, Oncócua). The Hamutenha body is a 3 km long oriented NW-SE, banded intrusion with internal zonation hosted in the Paleoproterozoic granitic rocks (1970 ± 2 Ma). The internal zone is composed by rocks with ultramafic nature, mostly harzburgites and dunites with diorites in the external zone.N/

New insights on the ultramafic intrusions surrounding the Kunene Anorthosite Complex (SW Angola) from gravity, magnetic and radiometric data [Abstract]

ABSTRACT: The Kunene Anorthosite Complex (KAC), located in SW Angola, is one of the largest anorthosite structures in the world. Dating from the Mesoproterozoic, its installation process is still not clear. Several mafic and ultramafic outcrops can be found surrounding the KAC. Once considered related with its emplacement, the study of these bodies may help us understand the history of this unique geological feature. While geochronological data show that they are synchronous, or possibly a bit younger, than the embedding granites and migmatites of Paleoproterozoic age, the question arises of whether they are intrusions installed in the host rock or if they are instead recycled remains of older Arch crust. The development of these outcrops in depth provides relevant clues regarding the origin of these bodies and their relationship with the Eburnean (~1.93-2.04 Ga) and Epupa-Namibe (~1.83-1.74 Ga) events. One of these mafic outcrops, designated the Hamutenha outcrop (Huíla Province) exhibits an elongated shape and a NW-SE orientation and is characterized by an internal zonation. Generally, the innermost part is composed of ultramafic rocks of (mostly harzburgites and dunites), with diorites outcropping in its NW and SE borders. The Hamutenha outcrop was previously identified for potentially bearing Cr, Ni and PGE mineralization.N/

EXTRATO DE MAMONA COMO MANIPULADOR DA FERMENTAÇÃO RUMINAL

Objetivou-se investigar os efeitos da adição do extrato de farelo de mamona (EFM) sobre o perfil da fermentação ruminal in vitro em dietas com alto e baixo teor de forragem. Utilizou-se ensaio de incubação ruminal in vitro com dois controles, um negativo (sem aditivo) e um positivo (monensina sódica) e EFM liofilizado (20, 40 e 60 mg/frasco). Em condições de alto teor de forragem na dieta, a adição do EFM aumentou o pH do meio e a concentração de acetato, reduziu a produção de gás, mas não afetou a produção de gás por unidade de matéria seca (MS) digerida em relação ao tratamento controle. Em comparação com monensina sódica, o EFM reduziu as concentrações de propionato e amônia e aumentou a produção de gás por unidade de MS digerida. Em condições de baixo teor de forragem, a adição do EFM reduziu o pH e potencial redox do meio em relação ao tratamento controle. Em comparação com a monensina sódica, o EFM reduziu o pH do meio e a produção total de gás, mas não afetou a produção de gás por unidade de MS digerida. O extrato de farelo de mamona destoxificado não apresenta potencial como manipulador da fermentação ruminal.Palavras-chave: amônia; digestibilidade; eficiência; metano. CASTOR BEAN EXTRACT AS A MANIPULATOR OF RUMINAL FERMENTATION ABSTRACT: Effects of the castorbean meal extract (CME) on ruminal in vitro were investigate in high and low forage diet conditions. For each dietary condition, one in vitro ruminal incubation experiment was conducted in a completely randomized design, with nine repetitions per treatment (three animal inoculum donators and three 48 hors-incubations). In high forage diet, CME increased ruminal pH acetate concentration, reduced gas production, but it did not affect the gas production per unit of digested dry matter (DM), in relation to control treatment. Compare to monensin sodium, CME reduced propionate and ammonia concentrations and increased gas production per unit of digested DM, indicating that CME reduces ruminal energetic efficiency. In low forage diet, CME reduced pH and redox potential compare to control. Compare to monensin sodium, CME reduced pH and gas production, but it did not affect gas production per unit of digested DM. Castorbean meal extract does not present potential as manipulator of the ruminal fermentation.Keywords: ammonia; digestibility; efficiency; methane

Cell-Free Antigens from Paracoccidioides brasiliensis Drive IL-4 Production and Increase the Severity of Paracoccidioidomycosis

The thermally dimorphic fungus Paracoccidioides brasiliensis (Pb) is the causative agent of paracoccidioidomycosis (PCM), one of the most frequent systemic mycosis that affects the rural population in Latin America. PCM is characterized by a chronic inflammatory granulomatous reaction, which is consequence of a Th1-mediated adaptive immune response. In the present study we investigated the mechanisms involved in the immunoregulation triggered after a prior contact with cell-free antigens (CFA) during a murine model of PCM. The results showed that the inoculation of CFA prior to the infection resulted in disorganized granulomatous lesions and increased fungal replication in the lungs, liver and spleen, that paralleled with the higher levels of IL-4 when compared with the control group. The role of IL-4 in facilitating the fungal growth was demonstrated in IL-4-deficient- and neutralizing anti-IL-4 mAb-treated mice. The injection of CFA did not affect the fungal growth in these mice, which, in fact, exhibited a significant diminished amount of fungus in the tissues and smaller granulomas. Considering that in vivo anti-IL-4-application started one week after the CFA-inoculum, it implicates that IL-4-CFA-induced is responsible by the mediation of the observed unresponsiveness. Further, the characterization of CFA indicated that a proteic fraction is required for triggering the immunosuppressive mechanisms, while glycosylation or glycosphingolipids moieties are not. Taken together, our data suggest that the prior contact with soluble Pb antigens leads to severe PCM in an IL-4 dependent manner

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Acesso a Tratamento Endovascular para Acidente Vascular Cerebral Isquémico em Portugal

Introduction: Since the publication of endovascular treatment trials and European Stroke Guidelines, Portugal has re-organized stroke healthcare. The nine centers performing endovascular treatment are not equally distributed within the country, which may lead to differential access to endovascular treatment. Our main aim was to perform a descriptive analysis of the main treatment metrics regarding endovascular treatment in mainland Portugal and its administrative districts. Material and Methods: A retrospective national multicentric cohort study was conducted, including all ischemic stroke patients treated with endovascular treatment in mainland Portugal over two years (July 2015 to June 2017). All endovascular treatment centers contributed to an anonymized database. Demographic, stroke-related and procedure-related variables were collected. Crude endovascular treatment rates were calculated per 100 000 inhabitants for mainland Portugal, and each district and endovascular treatment standardized ratios (indirect age-sex standardization) were also calculated. Patient time metrics were computed as the median time between stroke onset, first-door, and puncture. Results: A total of 1625 endovascular treatment procedures were registered. The endovascular treatment rate was 8.27/100 000 inhabitants/year. We found regional heterogeneity in endovascular treatment rates (1.58 to 16.53/100 000/year), with higher rates in districts closer to endovascular treatment centers. When analyzed by district, the median time from stroke onset to puncture ranged from 212 to 432 minutes, reflecting regional heterogeneity. Conclusion: The overall national rate of EVT in the first two years after the organization of EVT-capable centers is one of the highest among European countries, however, significant regional disparities were documented. Moreover, stroke-onset-to-first-door times and in-hospital procedural times in the EVT centers were comparable to those reported in the randomized controlled trials performed in high-volume tertiary hospitals.Introdução: A aprovação do tratamento endovascular para o acidente vascular cerebral isquémico obrigou à reorganização dos cuidados de saúde em Portugal. Os nove centros que realizam tratamento endovascular não estão distribuídos equitativamente pelo território, o que poderá causar acesso diferencial a tratamento. O principal objetivo deste estudo é realizar uma análise descritiva da frequência e métricas temporais do tratamento endovascular em Portugal continental e seus distritos. Material e Métodos: Estudo de coorte nacional multicêntrico, incluindo todos os doentes com acidente vascular cerebral isquémico submetidos a tratamento endovascular em Portugal continental durante um período de dois anos (julho 2015 a junho 2017). Foram colhidos dados demográficos, relacionados com o acidente vascular cerebral e variáveis do procedimento. Taxas de tratamento endovascular brutas e ajustadas (ajuste indireto a idade e sexo) foram calculadas por 100 000 habitantes/ano para Portugal continental e cada distrito. Métricas de procedimento como tempo entre instalação, primeira porta e punção foram também analisadas. Resultados: Foram registados 1625 tratamentos endovasculares, indicando uma taxa bruta nacional de tratamento endovascular de 8,27/100 000 habitantes/ano. As taxas de tratamento endovascular entre distritos variaram entre 1,58 e 16,53/100 000/ano, com taxas mais elevadas nos distritos próximos a hospitais com tratamento endovascular. O tempo entre sintomas e punção femural entre distritos variou entre 212 e 432 minutos. Conclusão: Portugal continental apresenta uma taxa nacional de tratamento endovascular elevada, apresentando, contudo, assimetrias regionais no acesso. As métricas temporais foram comparáveis com as observadas nos ensaios clínicos piloto