Preclinical development of a vaccine against oligomeric alpha-synuclein based on virus-like particles

Parkinson's disease (PD) is a progressive and currently incurable neurological disorder characterised by the loss of midbrain dopaminergic neurons and the accumulation of aggregated alpha-synuclein (a-syn). Oligomeric a-syn is proposed to play a central role in spreading protein aggregation in the brain with associated cellular toxicity contributing to a progressive neurological decline. For this reason, a-syn oligomers have attracted interest as therapeutic targets for neurodegenerative conditions such as PD and other alpha-synucleinopathies. In addition to strategies using small molecules, neutralisation of the toxic oligomers by antibodies represents an attractive and highly specific strategy for reducing disease progression. Emerging active immunisation approaches using vaccines are already being trialled to induce such antibodies. Here we propose a novel vaccine based on the RNA bacteriophage (Qbeta) virus-like particle conjugated with short peptides of human a-syn. High titres of antibodies were successfully and safely generated in wild-type and human a-syn over-expressing (SNCA-OVX) transgenic mice following vaccination. Antibodies from vaccine candidates targeting the C-terminal regions of a-syn were able to recognise Lewy bodies, the hallmark aggregates in human PD brains. Furthermore, antibodies specifically targeted oligomeric and aggregated a-syn as they exhibited 100 times greater affinity for oligomeric species over monomer a-syn proteins in solution. In the SNCA-OVX transgenic mice used, vaccination was, however, unable to confer significant changes to oligomeric a-syn bioburden. Similarly, there was no discernible effect of vaccine treatment on behavioural phenotype as compared to control groups. Thus, antibodies specific for oligomeric a-syn induced by vaccination were unable to treat symptoms of PD in this particular mouse model.</p

Tipos de plantio e fertilizante biológico no cafeeiro em função do índice térmico

The implantation phase of coffee is one of the most important stages of the crop. It is worth mentioning that the different implantation systems provide different conditions for the development of crops. In addition, in order to achieve a good initial development of the coffee, the producers have applied in newly transplanted crops organic fertilizers, which has the advantage of improving soil biota, as well as reducing costs with the acquisition of mineral fertilizers. Few researches have jointly tested the efficiency of the different systems of implantation and the biological fertilization in the coffee tree. The objective of this study was to test the efficacy of different types of planting and of the biological fertilizer on the initial growth of arabica coffee, as a function of the thermal index. The experiment was developed in southern Minas Gerais, Brazil. The experimental design was in randomized blocks, in a 3 x 2 factorial scheme with 4 replicates, in a total of 6 treatments. The following were used: a) three systems of implantation (conventional planting, no-tillage in the pit and minimum cultivation); and b) two doses of the biological fertilizer (presence and absence). The growth parameters and the first coffee crop were evaluated. The evaluations were carried out according to the degree days counted from the date of planting. The results were submitted to analysis of variance. The means were grouped by the Scott-Knott method. The coffee plants implanted in the planting system “in pits” showed the best results, both in vegetative parameters and in productivity. The use of the biological fertilization in the newly transplanted arabica coffee tree did not promote improvements in the vegetative growth and first coffee production.A fase de implantação do cafeeiro consiste em uma das etapas mais importantes da cultura. Vale ressaltar, que os diferentes sistemas de implantação proporcionam condições distintas de desenvolvimento das culturas. Além disso, visando um bom desenvolvimento inicial do cafeeiro, os produtores têm aplicado em lavouras recém-transplantadas adubos biológicos, que têm como vantagem a melhora da biota do solo, além da redução de custos com a aquisição de fertilizantes minerais. Poucas pesquisas têm testado de forma conjunta a eficiência dos diferentes sistemas de implantação e a adubação biológica no cafeeiro. Assim, objetivou-se testar a eficácia de diferentes tipos de plantio e do fertilizante biológico no crescimento inicial do cafeeiro arábica, cultivar Catucaí, em função do índice térmico. O experimento foi desenvolvido no Sul de Minas Gerais, Brasil. O delineamento experimental foi em blocos casualizados, em esquema fatorial 3 x 2 com 4 repetições, num total de 6 tratamentos. Foram utilizados: a) três sistemas de implantação (plantio convencional, o plantio direto na cova e cultivo mínimo); e b) duas doses do adubo biológico (presença e ausência). Foram avaliados os parâmetros de crescimento e a primeira safra do cafeeiro. As avaliações foram realizadas em função dos graus dias contabilizados a partir da data de plantio. Os resultados foram submetidos à análise de variância e as médias agrupadas pelo teste de Scott-Knott. As plantas de café implantadas no sistema de plantio “em covas” evidenciaram os melhores resultados, tanto nos parâmetros vegetativos como na produtividade. A utilização da adubação biológica no cafeeiro arábica recém-transplantado não promoveu melhorias no crescimento vegetativo e primeira produção do cafeeiro

Estudo do comportamento mecânico da dureza e da morfologia do compósito Al2O3-YAG

Os óxidos cerâmicos possuem alta resistência à oxidação e à corrosão em ambientes agressivos e em elevadas temperaturas, o que torna o seu emprego bastante atraente em relação a outros cerâmicos. Na década de 90, diversos pesquisadores mostraram o YAG como sendo o óxido de maior resistência à fluência em elevadas temperaturas. Nesta pesquisa, os pós reagentes, Al2O3 e Y2O3 foram misturados nas proporções em peso de 63,65 e 36,35% e 80,00 e 20,00%, respectivamente. Após, a mistura foi moída em moinho de bolas, por 5h, secos em estufa por 48 h, à 120 °C. Depois desaglomerados em gral e pistilo e peneiramento em peneiras de 120 mesh. Na etapa de compactação, os pós foram prensados em matriz e punção de aço, à 70 MPa, por 20 s de aplicação de carga. No processo de sinterização, foram realizados em forno em 1500 e 1600 °C, com 3 h de patamar, com taxa de aquecimento e resfriamento de 5 ºC/min, ao ar. Foram produzidos cinco corpos de prova para cada condição de sinterização. As amostras sinterizadas foram cortadas a fim de serem embutidas em baquelite. Após esta etapa as amostras foram lixadas em lixas diamantadas e foram polidas em pasta de diamante. As amostras foram avaliadas por dureza por microindentação Vickers e por Microscopia Eletrônica de Varredura (MEV). A amostra na composição eutética sinterizada à 1600°C apresentou maior dureza de 1200 HV.

Cross-sectional analysis of students and school workers reveals a high number of asymptomatic SARS-CoV-2 infections during school reopening in Brazilian cities

Brazil experienced one of the most prolonged periods of school closures, and reopening could have exposed students to high rates of SARS-CoV-2 infection. However, the infection status of students and school workers at the time of the reopening of schools located in Brazilian cities is unknown. Here we evaluated viral carriage by RT-PCR and seroprevalence of anti-SARS-CoV-2 antibodies (IgM and IgG) by immunochromatography in 2259 individuals (1139 students and 1120 school workers) from 28 schools in 28 Brazilian cities. We collected the samples within 30 days after public schools reopened and before the start of vaccination campaigns. Most students (n = 421) and school workers (n = 446) had active (qRT-PCR + IgM− IgG− or qRT-PCR + IgM + IgG−/+) SARS-CoV-2 infection. Regression analysis indicated a strong association between the infection status of students and school workers. Furthermore, while 45% (n = 515) of the students and 37% (n = 415) of the school workers were neither antigen nor antibody positive in laboratory tests, 16% of the participants (169 students and 193 school workers) were oligosymptomatic, including those reinfected. These individuals presented mild symptoms such as headache, sore throat, and cough. Notably, most of the individuals were asymptomatic (83.9%). These results indicate that many SARS-CoV-2 infections in Brazilian cities during school reopening were asymptomatic. Thus, our study highlights the need to promote a coordinated public health effort to guarantee a safe educational environment while avoiding exacerbating pre-existent social inequalities in Brazil, reducing social, mental, and economic losses for students, school workers, and their families

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost