Novel ocellatin peptides mitigate LPS-induced ROS formation and NF-kB activation in microglia and hippocampal neurons

© The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre-ative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not per-mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Cutaneous secretions of amphibians have bioactive compounds, such as peptides, with potential for biotechnological applications. Therefore, this study aimed to determine the primary structure and investigate peptides obtained from the cutaneous secretions of the amphibian, Leptodactylus vastus, as a source of bioactive molecules. The peptides obtained possessed the amino acid sequences, GVVDILKGAAKDLAGH and GVVDILKGAAKDLAGHLASKV, with monoisotopic masses of [M + H]± = 1563.8 Da and [M + H]± = 2062.4 Da, respectively. The molecules were characterized as peptides of the class of ocellatins and were named as Ocellatin-K1(1-16) and Ocellatin-K1(1-21). Functional analysis revealed that Ocellatin-K1(1-16) and Ocellatin-K1(1-21) showed weak antibacterial activity. However, treatment of mice with these ocellatins reduced the nitrite and malondialdehyde content. Moreover, superoxide dismutase enzymatic activity and glutathione concentration were increased in the hippocampus of mice. In addition, Ocellatin-K1(1-16) and Ocellatin-K1(1-21) were effective in impairing lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) formation and NF-kB activation in living microglia. We incubated hippocampal neurons with microglial conditioned media treated with LPS and LPS in the presence of Ocellatin-K1(1-16) and Ocellatin-K1(1-21) and observed that both peptides reduced the oxidative stress in hippocampal neurons. Furthermore, these ocellatins demonstrated low cytotoxicity towards erythrocytes. These functional properties suggest possible to neuromodulatory therapeutic applications.Alexandra Plácido is a recipient of a post-doctoral grant from the project FCT (PTDC/BII-BIO/31158/2017). Renato Socodato and Camila Cabral Portugal hold postdoctoral fellowships from FCT (Refs: SFRH/BPD/91833/2012 and FRH/BPD/91962/2012, respectively). This work was funded through project UID/QUI/50006/2013-POCI/01/0145/FEDER/007265 (LAQV/REQUIMTE) with financial support from FCT/MEC through national funds and co-financed by FEDER, under the Partnership Agreement PT 2020info:eu-repo/semantics/publishedVersio

Vaccine effectiveness of CoronaVac against COVID-19 among children in Brazil during the Omicron period.

Although severe COVID-19 in children is rare, they may develop multisystem inflammatory syndrome, long-COVID and downstream effects of COVID-19, including social isolation and disruption of education. Data on the effectiveness of the CoronaVac vaccine is scarce during the Omicron period. In Brazil, children between 6 to 11 years are eligible to receive the CoronaVac vaccine. We conducted a test-negative design to estimate vaccine effectiveness using 197,958 tests from January 21, 2022, to April 15, 2022, during the Omicron dominant period in Brazil among children aged 6 to 11 years. The estimated vaccine effectiveness for symptomatic infection was 39.8% (95% CI 33.7-45.4) at ≥14 days post-second dose. For hospital admission vaccine effectiveness was 59.2% (95% CI 11.3-84.5) at ≥14 days. Two doses of CoronaVac in children during the Omicron period showed low levels of protection against symptomatic infection, and modest levels against severe illness

Didactic Sequence for Teaching Exponential Function

This paper presents a methodological proposal for the teaching of exponential function, resulting from the application of a didactic sequence involving exponential function, where evidence of learning and the consolidation and application of mathematical concepts in problem solving were identified and analyzed. The Didactic Engineering of Michèle Artigue (1988) was used as a research methodology. As theoretical contributions that guided and enabled the development of the research, we chose the use of Mathematical Investigation in the classroom; Didactic Sequence in the conception of Zabala (1999); the Articulated Units of Conceptual Reconstruction proposed by Cabral (2017) and assumptions of Vygotsky\u27s theory. A didactic sequence composed of five UARC\u27s was elaborated to work the exponential function, with a view to minimizing the difficulties naturally imposed by the content to be explained. Microgenetic analysis of verbal interactions between teacher and students was used to analyze the results of the application. The results show that the students participating in the experiment showed evidence of learning, recorded during the process, and began to have a good understanding of the concepts and properties related to the topic, in addition to a good performance in carrying out the activities, facts that corroborate the potential of the didactic sequence proposed herein

Coefficient shifts in geographical ecology: an empirical evaluation of spatial and non-spatial regression

Copyright © 2009 The Authors. Copyright © ECOGRAPHY 2009.A major focus of geographical ecology and macro ecology is to understand the causes of spatially structured ecological patterns. However, achieving this understanding can be complicated when using multiple regressions, because the relative importance of explanatory variables, as measured by regression coefficients, can shift depending on whether spatially explicit or non-spatial modelling is used. However, the extent to which coefficients may shift and why shifts occur are unclear. Here, we analyze the relationship between environmental predictors and the geographical distribution of species richness, body size, range size and abundance in 97 multi-factorial data sets. Our goal was to compare standardized partial regression coefficients of non-spatial ordinary least squares regressions (i.e. models fitted using ordinary least squares without taking autocorrelation into account; “OLS models” hereafter) and eight spatial methods to evaluate the frequency of coefficient shifts and identify characteristics of data that might predict when shifts are likely. We generated three metrics of coefficient shifts and eight characteristics of the data sets as predictors of shifts. Typical of ecological data, spatial autocorrelation in the residuals of OLS models was found in most data sets. The spatial models varied in the extent to which they minimized residual spatial autocorrelation. Patterns of coefficient shifts also varied among methods and datasets, although the magnitudes of shifts tended to be small in all cases. We were unable to identify strong predictors of shifts, including the levels of autocorrelation in either explanatory variables or model residuals. Thus, changes in coefficients between spatial and non-spatial methods depend on the method used and are largely idiosyncratic, making it difficult to predict when or why shifts occur. We conclude that the ecological importance of regression coefficients cannot be evaluated with confidence irrespective of whether spatially explicit modelling is used or not. Researchers may have little choice but to be more explicit about the uncertainty of models and more cautious in their interpretation

CoronaVac vaccine is effective in preventing symptomatic and severe COVID-19 in pregnant women in Brazil: a test-negative case-control study.

BACKGROUND: More doses of CoronaVac have been administered worldwide than any other COVID-19 vaccine. However, the effectiveness of COVID-19 inactivated vaccines in pregnant women is still unknown. We estimated the vaccine effectiveness (VE) of CoronaVac against symptomatic and severe COVID-19 in pregnant women in Brazil. METHODS: We conducted a test-negative design study in all pregnant women aged 18-49 years with COVID-19-related symptoms in Brazil from March 15, 2021, to October 03, 2021, linking records of negative and positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) tests to national vaccination records. We also linked records of test-positive cases with notifications of severe, hospitalised or fatal COVID-19. Using logistic regression, we estimated the adjusted odds ratio and VE against symptomatic COVID-19 and against severe COVID-19 by comparing vaccine status in test-negative subjects to test-positive symptomatic cases and severe cases. RESULTS: Of the 19,838 tested pregnant women, 7424 (37.4%) tested positive for COVID-19 and 588 (7.9%) had severe disease. Only 83% of pregnant women who received the first dose of CoronaVac completed the vaccination scheme. A single dose of the CoronaVac vaccine was not effective at preventing symptomatic COVID-19. The effectiveness of two doses of CoronaVac was 41% (95% CI 27.1-52.2) against symptomatic COVID-19 and 85% (95% CI 59.5-94.8) against severe COVID-19. CONCLUSIONS: A complete regimen of CoronaVac in pregnant women was effective in preventing symptomatic COVID-19 and highly effective against severe illness in a setting that combined high disease burden and marked COVID-19-related maternal deaths

Whole-genome sequencing of 1,171 elderly admixed individuals from Brazil

As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enables identification of ~2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS

Effectiveness of CoronaVac, ChAdOx1 nCoV-19, BNT162b2, and Ad26.COV2.S among individuals with previous SARS-CoV-2 infection in Brazil: a test-negative, case-control study.

BACKGROUND: COVID-19 vaccines have proven highly effective among individuals without a previous SARS-CoV-2 infection, but their effectiveness in preventing symptomatic infection and severe outcomes among individuals with previous infection is less clear. We aimed to estimate the effectiveness of four COVID-19 vaccines against symptomatic infection, hospitalisation, and death for individuals with laboratory-confirmed previous SARS-CoV-2 infection. METHODS: Using national COVID-19 notification, hospitalisation, and vaccination datasets from Brazil, we did a test-negative, case-control study to assess the effectiveness of four vaccines (CoronaVac [Sinovac], ChAdOx1 nCoV-19 [AstraZeneca], Ad26.COV2.S [Janssen], and BNT162b2 [Pfizer-BioNtech]) for individuals with laboratory-confirmed previous SARS-CoV-2 infection. We matched cases with RT-PCR positive, symptomatic COVID-19 with up to ten controls with negative RT-PCR tests who presented with symptomatic illnesses, restricting both groups to tests done at least 90 days after an initial infection. We used multivariable conditional logistic regression to compare the odds of test positivity and the odds of hospitalisation or death due to COVID-19, according to vaccination status and time since first or second dose of vaccines. FINDINGS: Between Feb 24, 2020, and Nov 11, 2021, we identified 213 457 individuals who had a subsequent, symptomatic illness with RT-PCR testing done at least 90 days after their initial SARS-CoV-2 infection and after the vaccination programme started. Among these, 30 910 (14·5%) had a positive RT-PCR test consistent with reinfection, and we matched 22 566 of these cases with 145 055 negative RT-PCR tests from 68 426 individuals as controls. Among individuals with previous SARS-CoV-2 infection, vaccine effectiveness against symptomatic infection 14 or more days from vaccine series completion was 39·4% (95% CI 36·1-42·6) for CoronaVac, 56·0% (51·4-60·2) for ChAdOx1 nCoV-19, 44·0% (31·5-54·2) for Ad26.COV2.S, and 64·8% (54·9-72·4) for BNT162b2. For the two-dose vaccine series (CoronaVac, ChAdOx1 nCoV-19, and BNT162b2), effectiveness against symptomatic infection was significantly greater after the second dose than after the first dose. Effectiveness against hospitalisation or death 14 or more days from vaccine series completion was 81·3% (75·3-85·8) for CoronaVac, 89·9% (83·5-93·8) for ChAdOx1 nCoV-19, 57·7% (-2·6 to 82·5) for Ad26.COV2.S, and 89·7% (54·3-97·7) for BNT162b2. INTERPRETATION: All four vaccines conferred additional protection against symptomatic infections and severe outcomes among individuals with previous SARS-CoV-2 infection. The provision of a full vaccine series to individuals after recovery from COVID-19 might reduce morbidity and mortality. FUNDING: Brazilian National Research Council, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Oswaldo Cruz Foundation, JBS, Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Generalitat de Catalunya

Desafíos políticos de los países de inmigración

13 págs.-- Publicado en "Confluencia XXI. Revista de Pensamiento Político" (México), nº 3 (Oct-Dic 2008) bajo el título monográfico "Migrantes: ¿Por qué se van? ¿Por qué se quedan?".Las migraciones, una práctica tan antigua como la propia condición humana, se han convertido en un factor estructural de primer orden, en uno de los macrofenómenos más definitorios de nuestra época y en un complejo reto para las sociedades contemporáneas. En prácticamente todos los países del mundo, todo lo que concierne a este complejo fenómeno ocupa un lugar destacado en la agenda política. La gestión, el control y la integración de los movimientos internacionales de personas se presentan como un policy field de creciente y prioritaria relevancia. No se trata, sin embargo, de una cuestión de mera moda: el número de países implicados de manera significativa en las migraciones internacionales ha aumentado considerablemente, hasta el punto de que resulta realmente difícil encontrar algún Estado que no sea bien un país de inmigración, bien un país de emigración o bien ambas cosas a la vez, cuando no al menos un país de tránsito. No ha de extrañar entonces que la mayoría de los gobiernos haya tomado conciencia de la necesidad de ofrecer una respuesta en términos legales e institucionales a un fenómeno de carácter permanente que puede llegar a alterar la estructura demográfica, social, cultural, económica y laboral de un país. Dada la complejidad de la cuestión, y por cuestiones de economía argumentativa, aquí se abordará de manera fundamental desde la perspectiva de los países receptores, que, por lo demás, es también la adoptada en forma habitual por los países europeos que registran mayor inmigración. Sin embargo, el fenómeno migratorio es fundamentalmente transnacional y tiene fehacientes repercusiones en los países de emigración.Peer reviewe