Metabolic Consequences of IgE- and Non-IgE-Mediated Mast Cell Degranulation.

Mast cells are important effector cells in the immune system and undergo activation (i.e., degranulation) by two major mechanisms: IgE-mediated and non-IgE-mediated mechanisms. Although IgE-mediated degranulation is well researched, the cellular mechanisms of non-IgE-mediated mast cell activation are poorly understood despite the potential to induce similar pathophysiological effects. To better understand non-IgE mast cell degranulation, we characterized and compared cellular metabolic shifts across several mechanisms of degranulation (allergen-induced [IgE-mediated], 20 nm of silver nanoparticle-mediated [non-IgE], and compound 48/80-mediated [non-IgE]) in murine bone marrow-derived mast cells. All treatments differentially impacted mitochondrial activity and glucose uptake, suggesting diverging metabolic pathways between IgE- and non-IgE-mediated degranulation. Non-IgE treatments depleted mast cells' glycolytic reserve, and compound 48/80 further inhibited the ability to maximize mitochondrial respiration. This cellular reprogramming may be indicative of a stress response with non-IgE treatments. Neither of these outcomes occurred with IgE-mediated degranulation, hinting at a separate programmed response. Fuel flexibility between the three primary mitochondrial nutrient sources was also eliminated in activated cells and this was most significant in non-IgE-mediated degranulation. Lastly, metabolomics analysis of bone marrow-derived mast cells following degranulation was used to compare general metabolite profiles related to energetic pathways. IgE-mediated degranulation upregulated metabolite concentrations for the TCA cycle and glycolysis compared with other treatments. In conclusion, mast cell metabolism varies significantly between IgE- and non-IgE-mediated degranulation suggesting novel cell regulatory mechanisms are potentially driving unexplored pathways of mast cell degranulation.

Orchid bees (Apidae, Euglossini) from Oil Palm Plantations in Eastern Amazon Have Larger but Not Asymmetrical Wings.

Phenotypic variation in both morphology and symmetry of individuals may appear due to environmental stress caused by land-use changes. Here, we evaluated fluctuating asymmetry (FA) and wing size variations of two orchid bee species, Euglossa ignita Smith, 1874 and Eulaema meriana (Olivier, 1789), comparing 11 wing traits. We sampled the individuals from legal reserves (LR), areas of permanent protection (APP), and oil palm plantations (PALM) in Eastern Amazonia. We calculated FA as the absolute difference between the wing measurements made in the right and left wings of specimens and both species' wing size. We corrected each FA measure for possible directional asymmetry bias by subtracting the mean value of the mean FA signed difference to each FA measure. We compared FA and the size of each wing trait of each species between land-use types using one-way ANOVAs. We found no effect of FA between land-use types, but we observed individuals of both species from PALM areas having larger wings than those from LR areas. Our results demonstrate that there seems to be a pressure exerted by land-use change associated with palm oil cultivation favoring individuals with larger wings, although both species had shown substantial permeability of oil palm.

Spatio-temporal dynamics of landscape use by the bumblebee Bombus pauloensis (Hymenoptera: Apidae) and its relationship with pollen provisioning.

Understanding how bees use resources at a landscape scale is essential for developing meaningful management plans that sustain populations and the pollination services they provide. Bumblebees are important pollinators for many wild and cultivated plants, and have experienced steep population declines worldwide. Bee foraging behavior can be influenced by resource availability and bees' lifecycle stage. To better understand these relationships, we studied the habitat selection of Bombus pauloensis by tracking 17 queen bumblebees with radio telemetry in blueberry fields in Entre Ríos province, Argentina. To evaluate land use and floral resources used by bumblebees, we tracked bees before and after nest establishment and estimated home ranges using minimum convex polygons and kernel density methods. We also classified the pollen on their bodies to identify the floral resources they used from the floral species available at that time. We characterized land use for each bee as the relative proportion of GPS points inside of each land use. Bumblebees differed markedly in their movement behavior in relation to pre and post nest establishment. Bees moved over larger areas, and mostly within blueberry fields, before nest establishment. In contrast, after establishing the nest, the bees preferred the edges near forest plantations and they changed the nutritional resources to prefer wild floral species. Our study is the first to track queen bumblebee movements in an agricultural setting and relate movement changes across time and space with pollen resource availability. This study provides insight into the way bumblebee queens use different habitat elements at crucial periods in their lifecycle, showing the importance of mass flowering crops like blueberry in the first stages of queen's lifecycle, and how diversified landscapes help support bee populations as their needs changes during different phases of their lifecycle.

Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019.

PURPOSE: Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services. METHODS: A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider). RESULTS: Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing-initial testing of priority genes followed by expanded testing-was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included BRCA2, BRCA1, and mismatch repair genes, with broader testing, such as ATM, for clinical trial eligibility. BRCA2 was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for BRCA2 carriers, with consideration in HOXB13, BRCA1, ATM, and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches. CONCLUSION: This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.

Biological role of excretory-secretory proteins in endemic parasites of Latin America and the Caribbean.

Neglected tropical diseases (NTDs) share certain traits: they are parasitic infections, prevailing in tropical environments and affecting marginalized sectors of the population. Six NTDs - ascariasis, cysticercosis, echinococcosis, hookworm infection, onchocerciasis and trichuriasis - all of them endemic in Latin America and the Caribbean (LAC), are analysed in this work. This review aims to discuss key information on the function of excretory/secretory (E/S) proteins from these parasites in their infectivity, pathogeny and diagnosis. The modulation of the host immune system to favour the permanence and survival of the parasite is also discussed. An updated knowledge on the function of E/S molecules in endemic parasitoses in LAC may lead to new approaches for the clinical management and diagnosis of these diseases. In turn, this could allow us to optimize their treatment and make it more affordable - a relevant goal given the economic constraints that the region is facing.

¿Funciona la ley de equilibrio de hardy-weinberg en autopoliploides igual que en diploides? / Does the hardy-weinberg law of equilibrium work in autopolyploids as it does in diploids?

La ley del equilibrio Hardy-Weinberg es la piedra angular de la genética de poblaciones y la genética cuantitativa; sin embargo, para su cálculo en autopoliploides hay que tener en cuenta que las frecuencias alélicas y gaméticas son diferentes, caso contrario que los diploides donde son iguales. Esto ocasiona que el cálculo de esta fórmula deba hacerse con las frecuencias alélicas o las gaméticas basadas en las alélicas, de otra forma se puede romper el equilibrio de la población y el sesgo que esto conlleva en cálculos de otras pruebas como los estadísticos F de Wright, la GST de Nei o modelos bayesianos que se basan en los desequilibrios que presentan las poblaciones. Por eso este ensayo desarrolla los modelos de un locus con dos alelos en genotipos autotetraploides y autooctoploides para poder realizar una generalización de la ley del equilibrio en poblaciones autopoliploides.

The law of equilibrium Hardy-Weinberg is the cornerstone of the population genetics and of the quantitative genetics; however, for its calculation in autopolyploids it is necessary take in account that the allelic and gametic frequencies are different, contrary to the diploids where they are the same. This causes that the calculations must be done with the allelic frequencies or gametic based on allelic frequencies. Otherwise the equilibrium is broken in the population and the bias that this entails in the calculation of other genetical test like Wright's F statistics, the Nei's GST or Bayesian models that are based on the disequilibrium that populations show. That is why in this work they developed models of one locus with two alleles in autotetraploid and autooctoploid genotypes to make a generalization of the law of equilibrium in autopolyploid populations.

Barriers and Solutions to Conducting Large International, Interdisciplinary Research Projects.

Global environmental problems such as climate change are not bounded by national borders or scientific disciplines, and therefore require international, interdisciplinary teamwork to develop understandings of their causes and solutions. Interdisciplinary scientific work is difficult enough, but these challenges are often magnified when teams also work across national boundaries. The literature on the challenges of interdisciplinary research is extensive. However, research on international, interdisciplinary teams is nearly non-existent. Our objective is to fill this gap by reporting on results from a study of a large interdisciplinary, international National Science Foundation Partnerships for International Research and Education (NSF-PIRE) research project across the Americas. We administered a structured questionnaire to team members about challenges they faced while working together across disciplines and outside of their home countries in Argentina, Brazil, and Mexico. Analysis of the responses indicated five major types of barriers to conducting interdisciplinary, international research: integration, language, fieldwork logistics, personnel and relationships, and time commitment. We discuss the causes and recommended solutions to the most common barriers. Our findings can help other interdisciplinary, international research teams anticipate challenges, and develop effective solutions to minimize the negative impacts of these barriers to their research.

Phase transitions and interface phenomena in the cryogenic temperature domain of a niobate nanostructured ceramic.

Powder neutron diffraction and dielectric spectroscopy were used to investigate both crystallographic and dielectric permittivity properties of a Sr2KNb5O15 single phase ferroelectric oxide with nanosized grains ranging from 35 nm to 90 nm. Measurements were carried out in the temperature range from 10 K (cryogenic) to 550 K. All neutron diffraction data were indexed on the basis of a tetragonal double unit cell. From 10 K to room temperature the space group of the Sr2KNb5O15 ferroelectric phase was considered to be P4bm. The refinement of the paraelectric phase (at 550 K) was determined in the centrosymmetric space group P4/mbm. Dielectric spectroscopy measurements were performed in a thermal cycle. A set of four phase transitions non-related to symmetry changing was detected from Rietveld analysis of neutron powder diffraction data. During a thermal cycle, in the cryogenic temperature domain, strong thermal hysteresis is developed. Both phase transition and thermal hysteresis were correlated. These phenomena are associated with Nb-cation atomic displacements in the NbO6 octahedra along the c-axis direction and of the domain with different frequencies involving grains as well as an excess of interfaces ascribed to the grain boundary. The bulk/grain boundary interfaces in nanostructured ceramics are correlated with the thermal stability phenomenon.

Revealing the properties of Mn2Au for antiferromagnetic spintronics.

The continuous reduction in size of spintronic devices requires the development of structures, which are insensitive to parasitic external magnetic fields, while preserving the magnetoresistive signals of existing systems based on giant or tunnel magnetoresistance. This could be obtained in tunnel anisotropic magnetoresistance structures incorporating an antiferromagnetic, instead of a ferromagnetic, material. To turn this promising concept into real devices, new magnetic materials with large spin-orbit effects must be identified. Here we demonstrate that Mn2Au is not a Pauli paramagnet as hitherto believed but an antiferromagnet with Mn moments of ~4 µB. The particularly large strength of the exchange interactions leads to an extrapolated Néel temperature well above 1,000 K, so that ground-state magnetic properties are essentially preserved up to room temperature and above. Combined with the existence of a significant in-plane anisotropy, this makes Mn2Au the most promising material for antiferromagnetic spintronics identified so far.

Experimental nodel of C6 brain tumors in athymic rats.

Malignant brain tumor experimental models tend to employ cells that are immunologically compatible with the receptor animal. In this study, we have proposed an experimental model of encephalic tumor development by injecting C6 cells into athymic Rowett rats, aiming at reaching a model which more closely resembles to the human glioma tumor. In our model, we observed micro-infiltration of tumor cell clusters in the vicinity of the main tumor mass, and of more distal isolated tumor cells immersed in normal encephalic parenchyma. This degree of infiltration is superior to that usually observed in other C6 models.

Experimental nodel of C6 brain tumors in athymic rats / Modelo experimental de tumor cerebral C6 em ratos atímicos

Malignant brain tumor experimental models tend to employ cells that are immunologically compatible with the receptor animal. In this study, we have proposed an experimental model of encephalic tumor development by injecting C6 cells into athymic Rowett rats, aiming at reaching a model which more closely resembles to the human glioma tumor. In our model, we observed micro-infiltration of tumor cell clusters in the vicinity of the main tumor mass, and of more distal isolated tumor cells immersed in normal encephalic parenchyma. This degree of infiltration is superior to that usually observed in other C6 models.

Modelos experimentais de tumores cerebrais malignos geralmente utilizam células imunologicamente compatíveis com o animal receptor. Neste estudo apresentamos um modelo experimental baseado na inoculação de células C6 em ratos atímicos Rowett, visando obter um tumor que se assemelhe mais àqueles observados nos seres humanos. Neste modelo observamos microinfiltração de ilhotas de células na periferia da massa tumoral principal e nas áreas mais distantes, células tumorais isoladas no tecido cerebral normal. Este grau de infiltração é superior àquele observado em outros modelos utilizando as células C6.

NUCEL (Cell and Molecular Therapy Center): a multidisciplinary center for translational research in Brazil.

Social and economical development is closely associated with technological innovation and a well-developed biotechnological industry. In the last few years, Brazil's scientific production has been steadily increasing; however, the number of patents is lagging behind, with technological and translational research requiring governmental incentive and reinforcement. The Cell and Molecular Therapy Center (NUCEL) was created to develop activities in the translational research field, addressing concrete problems found in biomedical and veterinary areas and actively searching for solutions by employing a genetic engineering approach to generate cell lines over-expressing recombinant proteins to be transferred to local biotech companies, aiming at furthering the development of a national competence for local production of biopharmaceuticals of widespread use and of life-saving importance. To this end, mammalian cell engineering technologies were used to generate cell lines over-expressing several different recombinant proteins of biomedical and biotechnological interest, namely, recombinant human Amylin/IAPP for diabetes treatment, human FVIII and FIX clotting factors for hemophilia, human and bovine FSH for fertility and reproduction, and human bone repair proteins (BMPs). Expression of some of these proteins is also being sought with the baculovirus/insect cell system (BEVS) which, in many cases, is able to deliver high-yield production of recombinant proteins with biological activity comparable to that of mammalian systems, but in a much more cost-effective manner. Transfer of some of these recombinant products to local Biotech companies has been pursued by taking advantage of the São Paulo State Foundation (FAPESP) and Federal Government (FINEP, CNPq) incentives for joint Research Development and Innovation partnership projects.