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Gewebe sind nicht nur Baumaterialien, sondern Ausdruck der Bau- und Gestaltungsleistungen des Körpers. Erst durch ihren Gewebekontext erlangen die Stoffwechselleistungen der einzelnen Zellen Stoffwechselwirkung. Die tradierte Einteilung der Gewebe erschwert jedoch das Verständnis der eigenständigen systemischen Leistungen. Eine Neuordnung kann dazu beitragen, die in der osteopathischen, manualtherapeutischen Praxis erhobenen Palpationsbefunde quantitativ und qualitativ umfassend neu zu bewerten. Dieser Artikel argumentiert, warum es erforderlich ist, die klassische Einteilung zu überdenken, und plädiert für eine Betrachtung der Gewebe aus entwicklungsbiologischer Perspektive.

Major depressive disorder (MDD) is one of the most common neuropsychiatric disorders with high rates of prevalence and mortality. MDD is pathophysiologically complex, and treatment options are limited. Blueberries are rich in polyphenols and have neuroprotective potential. The aim of this study was to investigate the effects of blueberry extract on neuroinflammatory and neuroplasticity parameters, as well as Na

Obesity is a well-established risk factor for increased morbidity and mortality. Comprehensive lifestyle interventions, pharmacotherapy, and bariatric surgery are three effective treatment approaches for obesity. The Veterans Health Administration (VHA) offers all three domains but in different configurations across medical facilities. Study aim was to explore the relationship between configurations of three types of obesity treatments, context, and population impact across VHA using coincidence analysis. This was a cross-sectional analysis of survey data describing weight management treatment components linked with administrative data to compute population impact for each facility. Coincidence analysis was used to identify combinations of treatment components that led to higher population impact. Facilities with higher impact were in the top two quintiles for (1) reach to eligible patients and (2) weight outcomes. Sixty-nine facilities were included in the analyses. The final model explained 88% (29/33) of the higher-impact facilities with 91% consistency (29/32) and was comprised of five distinct pathways. Each of the five pathways depended on facility complexity-level plus factors from one or more of the three domains of weight management: comprehensive lifestyle interventions, pharmacotherapy, and/or bariatric surgery. Three pathways include components from multiple treatment domains. Combinations of conditions formed "recipes" that lead to higher population impact. Our coincidence analyses highlighted both the importance of local context and how combinations of specific conditions consistently and uniquely distinguished higher impact facilities from lower impact facilities for weight management.Obesity can contribute to increased rates of ill health and earlier death. Proven treatments for obesity include programs that help people improve lifestyle behaviors (e.g., being physically active), medications, and/or bariatric surgery. In the Veterans Health Administration (VHA), all three types of treatments are offered, but not at every medical center—in practice, individual medical centers offer different combinations of treatment options to their patients. VHA medical centers also have a wide range of population impact. We identified high-impact medical centers (centers with the most patients participating in obesity treatment who would benefit from treatment AND that reported the most weight loss for their patients) and examined which treatment configurations led to better population-level outcomes (i.e., higher population impact). We used a novel analysis approach that allows us to compare combinations of treatment components, instead of analyzing them one-by-one. We found that optimal combinations are context-sensitive and depend on the type of center (e.g., large centers affiliated with a university vs. smaller rural centers). We list five different “recipes” of treatment combinations leading to higher population-level impact. This information can be used by clinical leaders to design treatment programs to maximize benefits for their patients.

This brief background highlights Brazil as a 'climate-health hotspot', i.e. a country where climate affects local populations negatively through multiple pathways (Di Napoli et al. BMC Public Health 22(1):1-8, 2022). Knowledge gaps still need to be filled concerning the various climaterelated dimensions of tourism, vector-borne diseases, mortality and morbidity in urban centers in the country (Krüger et al. Int J Biometeorol 66(7):1297-1315, 2022). Motivated by this, the first Brazilian Symposium on Human Biometeorology (Simpósio Brasileiro de Biometeorologia Humana 2022) was organized and held at the Federal University of Rio Grande do Norte (UFRN) in Natal, northeastern Brazil, between July 4 and 8, 2022. The symposium was organized as a hybrid event by a committee composed of researchers acting in different regions of the country, and who had an ongoing research collaboration on matters related to human biometeorology. The event was partly sponsored by the ISB and partly self-supported by the organizers and institutions involved. The symposium aimed to promote the development of the research area on human biometeorology in Brazil in facing challenges imposed by a globally and locally changing climate. To achieve this, the symposium focused on five main topics of discussion: a) climate-driven diseases; b) thermal comfort, urban and architectural biometeorology; c) atmospheric pollution and health; d) climate change; e) climate, health and climate change. This summary highlights the main findings, future research directions, and policy implications in each topic from the presentations and panel discussions.

This work aims to analyze the relationship between meteorological conditions and the occurrence of hospital admissions for pneumonia in children under 5 years of age in the Metropolitan Region of Porto Alegre, Brazil, from 1998 to 2017. To this end, data from hospital admissions obtained from the Unified Health System database (DATASUS) were used and classified into two groups: acute respiratory infections (ARI) and asthma, according to the international classification of diseases, tenth edition (ICD-10). Data regarding meteorological variables were also used: temperature, relative humidity, atmospheric pressure and wind speed, at 12Z and 18Z, as well as the Thermal Comfort Index (TCI), Effective Temperature as a function of the wind (ETw) and Windchill (W). From the data obtained, a descriptive analysis of the diseases and a statistical analysis with the analysis of correlation and main components were performed. Results showed that pneumonia (catalogued in the ICD-10 as J12 to J18) was the main cause of hospitalizations in children. The annual, monthly and daily hospitalization frequency distributions showed higher rates of admissions occurring in the months of May to September. The peaks of admissions and high admissions (HA) occurred mainly in the winter months (June, July and August), and in 1998. Meanwhile, the correlation and principal component analysis showed an increase in hospital admissions due to pneumonia related to a decrease in temperature and ETw and W indices (negative anomalies) and an increase in atmospheric pressure and relative humidity (positive anomalies).

Resumo O objetivo deste ensaio clínico randomizado foi comparar a prevalência e a intensidade da dor pós-operatória em casos de retratamento endodôntico, utilizando instrumentos manuais ou reciprocantes (automatizados). O tempo necessário para desobturação e reinstrumentação do canal radicular também foi avaliado. Quarenta e oito indivíduos possuindo um dente unirradicular tratado endodonticamente e portador de periodontite apical assintomática foram incluídos no estudo. Os pacientes foram aleatoriamente distribuídos em dois grupos (n=24/grupo): retratamento com instrumentos manuais de aço inoxidável ou um sistema reciprocante de níquel-titânio (Reciproc; VDW, Munique, Alemanha). A reintervenção endodôntica foi realizada em duas consultas, sendo aplicada medicação intracanal à base de hidróxido de cálcio por 14 dias, antes da obturação. O tempo clínico gasto com os protocolos de desobturação e reinstrumentação do canal radicular foi registrado com um cronômetro digital. Após cada visita, a intensidade da dor pós-operatória foi avaliada em 12, 24, 48 horas e 7 dias por meio da escala de estimativa numérica (Numerical Rating Scale - NRS). Além do registro da dor, os pacientes foram questionados quanto ao uso de analgésicos. Os dados obtidos foram analisados por testes Qui-quadrado e Mann-Whitney (α=0.05). Não foi detectada diferença significativa entre os grupos quanto à prevalência e intensidade da dor ou uso de analgésicos em nenhum dos períodos avaliados. O tempo clínico foi significativamente menor no grupo reciprocante (18 versus 41 minutos). Pode-se concluir que os instrumentos manuais e reciprocantes foram equivalentes quanto à prevalência e intensidade de dor pós-operatória e uso de analgésicos, mas a desobturação e reinstrumentação do canal radicular foram duas vezes mais rápidas com o sistema reciprocante.

SUMMARY The aim of this laboratory study was to evaluate the pull-out force of a prefabricated fiberglass post (PP), relined fiberglass post (RP), or milled fiberglass post (MP) luted with Multilink N (MN), RelyX Unicem 2 (RXU2) or RelyX Ultimate (RU) to enlarged root canals. The thickness of the resin cements and the presence of voids in the resin cement film were observed. The root canals of 90 bovine incisors were enlarged, endodontically treated, and randomly divided into 9 groups (n=10) according to the post type and resin cement. The specimens were scanned using micro-CT to analyze the thickness of the resin cement and the presence of voids. The specimens were submitted to mechanical cyclic loading (500,000 cycles at 50 N load) and subjected to pull-out force testing. Two-way ANOVA and Tukey’s test analyzed the pull-out force and resin cement thickness data. Kruskal-Wallis and Bonferroni tests analyzed the void scores. The interaction between factors (post × resin cement) was significant (p=0.0001) for the pull-out force. Higher pull-out forces were obtained for RP and MP compared to PP. The post factor was significant (p=0.0001) for resin cement thickness, which was higher for PP (1054 μm), followed by MP (301 μm) and RP (194 μm). More void formation occurred for PP, being less for RP, differing significantly among the posts. Post customization (RP and MP) decreased resin cement thickness and void formation, favoring a higher pull-out force. Resin cements requiring an adhesive application (MN and RU) favored higher pull-out force than self-adhesive resin cement (RXU2).

Fluorescence reporter strains of human malaria parasites are powerful tools to study the interaction of the parasites with both human and mosquito hosts. However, low fluorescence intensity in transmission-relevant parasite stages and the choice of insertion loci that cause parasite developmental defects in the mosquito largely limits usefulness of currently available lines. To overcome these limitations, we used a CRISPR-Cas9-mediated approach to generatePfOBC13GFP, a novel selection marker-free reporter parasite in the background of the African NF54Plasmodium falciparumline. As docking site, we selected theOBC13locus that is dispensable for asexual and sexual developmentin vitro.PfOBC13GFPparasites encode GFP flanked byhsp70UTRs that drive strong fluorescence reporter expression throughout blood and mosquito stages, enabling parasite detection by such high throughput methods as flow cytometry. When compared to the parental line,PfOBC13GFPparasites showed normal development during blood and mosquito stages, and they efficiently infected the main African vectorAnopheles coluzzii,overcoming one of the limitations of the previously developed fluorescent reporter lines based on thePfs47locus.PfOBC13GFPconstitutes a potent tool enabling host-pathogen studies throughoutPlasmodiumlife cycle.ImportanceFluorescence reporter strains have been very useful in malaria research, however, up to date they had limitations in mosquito infectivity and fluorescence intensity. Here we report the generation ofPfOBC13GFP, a new fluorescent parasite strain of the human malaria parasiteP. falciparum.PfOBC13GFPparasites are highly fluorescent throughout the life cycle, making them an ideal tool for the study the parasite progression through blood and mosquito stages. They efficiently infect the African mosquitovector A. coluzzii, allowing the study of this African parasite in its biological background. Moreover, strong parasite fluorescence enables flow cytometry and live microscopy characterization of all parasite stages, especially those involved in transmission.

Restoration and rewetting of wetlands previously drained for agriculture, is currently used to decrease net greenhouse gas (GHG) emissions, while improving biodiversity. Wetland hydro(geo)logy is known to exert a key control on GHG-retention and on conditions facilitating improved biodiversity. Yet knowledge of the major hydrochemical processes that occur in wetlands prior to drainage and after restoration is limited, although links between wetland hydrochemistry, GHG-retention and biodiversity might well exist. To reduce the knowledge gap, we sample surface waters, precipitation, and shallow (

The persistence of leukemic stem cells (LSCs) represents a problem in the therapy of chronic myeloid leukemia (CML). Hence, it is of utmost importance to explore the underlying mechanisms to develop new therapeutic approaches to cure CML. Using the genetically engineered ScltTA/TRE-BCR::ABL1 mouse model for chronic phase CML, we previously demonstrated that the loss of the docking protein GAB2 counteracts the infiltration of mast cells (MCs) in the bone marrow (BM) of BCR::ABL1 positive mice. Here, we show for the first time that BCR::ABL1 drives the cytokine independent expansion of BM derived MCs and sensitizes them for FcεRI triggered degranulation. Importantly, we demonstrate that genetic mast cell deficiency conferred by the Cpa3Cre allele prevents BCR::ABL1 induced splenomegaly and impairs the production of pro-inflammatory cytokines. Furthermore, we show in CML patients that splenomegaly is associated with high BM MC counts and that upregulation of pro-inflammatory cytokines in patient serum samples correlates with tryptase levels. Finally, MC-associated transcripts were elevated in human CML BM samples. Thus, our study identifies MCs as essential contributors to disease progression and suggests considering them as an additional target in CML therapy.

A sexualidade está presente na vida de todos os seres humanos e que se manifesta de formas variadas nos diferentes ciclos de vida. Na infância, pode se expressar por meio de curiosidades, questionamentos, exploração do próprio corpo e reconhecimento das diferenças sexuais entre as pessoas (MAIA, 2014). Sendo assim, conhecer e entender os processos que envolvem a sexualidade torna-se essencial para desenvolver, plenamente, saúde física e mental.

Many butterfly populations respond negatively to land-use intensification in human-dominated landscapes. However, networks of protected sites have been established with the aim to halt species loss.We undertook annual surveys of all populations of 22 uncommon butterfly species in eastern Denmark during the period 2014-2019 and compared to a systematic atlas survey done 1989-1993, in order to assess trends in regional occupancy of species.Three out of 22 species went regionally extinct between 1993 and 2015. One species sustained a single population through the study period. Logistic regression for the remaining 18 species showed 10 to be in strong decline from 1993 to 2015, two showed a declining trend and six had stable trends. For all species except one, the declining trend continued 2015-2019. For five species, a sustained strong decline was evident.In 1993, the total count of populations for all 22 butterfly species was 565, which by 2019 had declined to 158 populations (a 72 % loss over 26 years). From 2015 to 2019, the total count of populations further shrank from 200 to 158 (a 21 % decline over just four years).Legal protection of areas (Natura 2000 and Danish Nature Protection Act §3) was, unexpectedly, not associated with lower probability of local extinction for butterfly population. The observed sustained decline across species suggests an overall low efficiency of the network of protected sites, probably due to a combination of misguided management regimes and payment of extinction debts from the past.

The gut microbiome is a diverse ecosystem, dominated by bacteria; however, fungi, phages/viruses, archaea, and protozoa are also important members of the gut microbiota. Up to recently, exploration of taxonomic compositions beyond bacteria as well as an understanding of the interaction between the bacteriome with the other members was limited due to 16S rDNA sequencing. Here, we developed MetaGut, a method enabling the simultaneous interrogation of the gut microbiome (bacteriome, mycobiome, archaeome, eukaryome, DNA virome) and of antibiotic resistance genes based on optimized long-read shotgun metagenomics protocols and custom bioinformatics. Using MetaGut we investigated the longitudinal composition of the gut microbiome in an exploratory clinical study in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT; n = 31). Pre-transplantation microbiomes exhibited a 3-cluster structure, associated withBacteroides/Phocaeicola, mixed composition andEnterococcusabundances. MetaGut revealed substantial inter-individual and temporal variabilities of microbial domain compositions, human DNA, and antibiotic resistance genes during the course of alloHSCT. Interestingly, viruses and fungi accounted for substantial proportions of microbiome content in individual samples (up to >50% and >20%, respectively). After leukopenia, strains were stable or newly acquired. Our results demonstrate the disruptive effect of alloHSCT on the gut microbiome and pave the way for future studies based on long-read metagenomics.

A adolescência é uma das etapas do desenvolvimento humano, onde ocorrem mudanças físicas estimuladas pela ação hormonal. São os atributos da puberdade que darão origens a inúmeros eventos psicológicos culminando na aquisição da identidade sexual, além de adaptação psicológica, familiar e social. É na adolescência que muitos iniciam sua vida sexual e podendo ocasionar em uma gravidez indesejada. Este estudo teve como objetivo identificar o conhecimento de adolescentes do Ensino Médio, sobre a sexualidade. A metodologia utilizada foi do tipo exploratório, descritivo, com abordagem de pesquisa quantitativa, com finalidade de coletar informações sobre o assunto abordado por meio de questionários. A partir dos resultados foi possível observar que a sexualidade ainda é um tema pouco discutido tanto no eixo familiar como escolar. Ainda, os adolescentes reconheceram seu atual período do desenvolvimento como uma fase difícil e conturbada e que, se tivessem maior abertura para dialogar com seus pais, se sentiriam mais seguros quanto as suas fragilidades. Os jovens também relataram a carência de ações educativas nas escolas e que estas poderiam contribuir com o aprendizado sobre o assunto. Percebe-se assim, que a sexualidade é um tema atemporal e de fundamental importância na maturação dos jovens. A educação sexual deve ser promovida e articulada em conjunto, através de ações, entre a atenção básica e educacional de modo a contribuir com a promoção da saúde e no desenvolvimento pessoal dos jovens.

To present our experience using a multiomic approach, which integrates genetic and biochemical testing as a first-line diagnostic tool for patients with inherited metabolic disorders (IMDs). A cohort of 3720 patients from 62 countries was tested using a panel including 206 genes with single nucleotide and copy number variant (SNV/CNV) detection, followed by semi-automatic variant filtering and reflex biochemical testing (25 assays). In 1389 patients (37%), a genetic diagnosis was achieved. Within this cohort, the highest diagnostic yield was obtained for patients from Asia (57.5%, mainly from Pakistan). Overall, 701 pathogenic/likely pathogenic unique SNVs and 40 CNVs were identified. In 620 patients, the result of the biochemical tests guided variant classification and reporting. Top five diagnosed diseases were: Gaucher disease, Niemann-Pick disease type A/B, phenylketonuria, mucopolysaccharidosis type I, and Wilson disease. We show that integrated genetic and biochemical testing facilitated the decision on clinical relevance of the variants and led to a high diagnostic yield (37%), which is comparable to exome/genome sequencing. More importantly, up to 43% of these patients (n = 610) could benefit from medical treatments (e.g., enzyme replacement therapy). This multiomic approach constitutes a unique and highly effective tool for the genetic diagnosis of IMDs.

Zusammenfassung Die mobilen Formationen der ukrainischen Hilfspolizei, genannt Schutzmannschaften (kurz Schuma), wurden bereits 1941 nach dem Einmarsch deutscher Truppen in die Ukrainische SSR gebildet. Im Kontext der Kriegswende, die sich im in dieser Studie untersuchten, zivil verwalteten »Generalbezirk Shitomir« ab 1943 immer stärker wahrnehmbar machte, und des Rückzugs der Wehrmacht durch diese Gebiete änderten sich die Aufgaben, die den Schutzmannschaften seitens der Besatzer zugeordnet wurden. Vor allem nahmen Einsätze im Partisanenkampf stark zu, der häufig auch Terror gegen die Zivilbevölkerung beinhaltete. Gleichzeitig schlug sich der allgemeine Trend einer Re-Sowjetisierung bei den Angehörigen der Hilfspolizei nieder, etwa in Form von Meutereien. Sie wurden gleichsam zu Evakuierten wie auch zu Evakuierenden und nahmen teils widersprüchliche Rollen ein, um ihre Überlebenschancen zu erhöhen.

This case focuses on how a startup can develop co-creation strategies along with its customers in times of crisis. It explores the case of Warren, which by forming a close relationship with its customers, has developed a simplified investment platform. The startup has grown and made innovations in the financial market. However, it has faced several challenges in the recent past owing to the crisis of COVID-19. This case study provides a detailed account of how firms can deal with crises, specifically in the context of startups. This case study is also useful for identifying the market opportunities in unstable scenarios. This will advance our understanding of how customer relationships can be used to develop innovative solutions.

Automotive and engine technology (2022). doi:10.1007/s41104-022-00106-8, Published by Springer International Publishing, [Cham, Switzerland]

This systematic review aims to give an overview of the diversity of research areas related to human biometeorology in Brazil. The main focus of this paper addresses research trends, represented by published papers with national and international authorship, main contributions and shortcomings, as well as challenges and prospects of research in this area of study. An extensive literature search was conducted in the Scopus, Web of Science, and Science Direct databases so as to identify relevant publication output up to July 2021 related to the research area. The screening resulted in 96 studies chosen for full-text reading. Overall, results indicated a reduced amount of articles on the subject matter published internationally, with noticeable gaps in research in some regions of the country, such as the Amazon region and in the Brazilian Midwest region. Research gaps in relevant areas have been identified with limited output in the climate dimensions of tourism, vector-borne diseases, mortality and morbidity in urban centers. Such gaps should further encourage researchers to engage in research focused on those areas.

This paper presents a preliminary analysis of meteorological variables and their relationship with respiratory morbidity in children under two years old of São Paulo city, taking into account the synoptical systems and their constructive structures of residences. Measurements of indoor air temperature and relative humidity were collected using a thermohygrographic across of 378 residences, between years 2003 to 2006. Outdoor meteorological variables have been obtained from meteorological station. A summary with four case studies is shown relating the thermal behavior in each residence and the onset of respiratory illness in children (wheezing). The results show associations of children respiratory crises and air temperature fall and increase of relative humidity, associated with maritime polar air masses and frontal systems (cold front). Specific residences have higher indoor humidity values than others, due to their constructive types and it is an important factor to bring out wheezing problems. Considering such results, acknowledging periods favorable to occurrences of wheezing in children, as well as the constructive type of residences, it is feasible to predict respiratory morbidity and to establish public policy in order to alert the population, minimizing weather/climate impacts on children's health

This study aims to evaluate the influence of meteorological factors on hospital admissions for pneumonia in children and elderly in Bauru and Pelotas cities, between 2009 to 2016. The health information was obtained from the Brazilian System Database and the daily average temperature and relative humidity from the meteorological stations of the National Institute of Meteorology and of the UNESP Meteorological Center. Descriptive analyses were performed to verify temporal trends and seasonal variations of meteorological variables and hospitalizations. Spearman correlation and Generalized Additive Model (GAM) Statistical methods were applied too. The results showed that Pelotas, presents the highest frequency of hospitalizations. It’s observed an increase in admissions in winter in both cities, except for children, in Bauru/SP, which occurs more frequently in the fall. The correlation was significant for low air temperature and high relative humidity. In addition, the GAM indicated a higher risk of hospitalizations with temperatures below 16°C and relative humidity above 40% (Bauru) and 80% in Pelotas. The increase in hospitalizations occurs in winter, and caused by the low temperatures and high relative humidity.

Additional file 3: Figure S3. Effects of more complex DIF mutations in BRAF on its heterodimerization with RAF1. HEK293T cells were transfected with either empty pLgBiT-N/pSmBiT-N control plasmidsor expression vectors encoding RAF1WT-SmBiT and the indicated BRAF-LgBiT proteins, either in combination with pMIG e.V.or pMIG KRASG12V. Cells were either treated with 10 µM Sorafenib or DMSO for 4 h prior to measurement. Shown is the mean of three to four biological replicates. HEK293T cells were transfected with either empty pLgBiT-N/pSmBiT-N control plasmids or expression vectors encoding RAF1WT-SmBiT and the indicated BRAF-LgBiT proteins, either in combination with pMIG e.V. or pMIG KRASG12V. Cells were either treated with 10 µM Sorafenib or DMSO) for 4 h prior to measurement. RAF1WT-SmBiT fusion proteins were immunoprecipitated using anti-Myc antibody. Following Western blotting, immunoprecipitatesand TCLs were probed with anti-HA and anti-Myc antibodies. Shown is a representative experiment from two biological replicates.

The objective of this paper was to evaluate the kinetics of the hydrolysis of soybean oil by the action of the Lipozyme® TL IM enzyme varying the operational conditions of molar ratio water/oil (9:1-60:1) and temperature (40-64 °C). To describe the experimental data, a mathematical model based on the kinetic mechanism of Ping-Pong Bi Bi (PPBB) was proposed, in which the following steps were not considered formation of the complex enzyme/oil substrate, and formation of the acylated enzyme/oil substrate complex. The results of enzymatic hydrolysis of soybean oil indicated a yield in free fatty acids of 76% at the molar ratio of 46:1 and temperature of 52 °C. Furthermore, based on the values of the determination coefficient and root mean square error, the mathematical model based on the kinetic mechanism of PPBB showed good agreement with the experimental data in a relatively wide temperature range. Thus, it can be a useful tool for the optimization and assessment of the mechanisms of enzymatic hydrolysis of vegetable oil.

Additional file 2: Figure S2. Side-by-side comparison of growth factor versus oncogenic KRASG12V induced BRAF-LgBiT/RAF1-SmBIT heterodimerization. HEK293T cells were transfected with either empty pMIGor pMIG/KRASG12V and the empty control vectors pLgBiT-N/pSmBit-N or the BRAF-LgBiT and RAF1-SmBiT expression vectors. Cells were either left untreated or stimulated with 100 ng/ml EGF for the indicated timepoints. Note the EGF induced increase in cells expressing BRAF-LgBiT/RAF1-SmBiT that is absent in cells transfected with the empty control vectors. Also note the consistent and highly significant increase in Nluc activity in unstimulated KRASG12V expressing cells compared to EGF stimulated cells transfected with pMIG e.V.

Additional file 1: Figure S1. Co-immunoprecipitation using anti-c-Myc antibodies confirms the enhanced heterodimerization between BRAF-LgBiT and RAF1-SmBiT as well as between RAF1-LgBiT and BRAF-SmBiT proteins in the presence of either KRASG12V or Sorafenib. HEK293T cells were co-transfected with the indicated plasmids and either pMIG empty vectoror pMIG/KRASG12V. Four hours prior to lysis, cells were treated with either 10 μM Sorafenib or the equivalent volume of DMSO. Myc-tagged RAF1-SmBiT or RAF1-LgBiT proteins were immuno-purified using anti-Myc antibody. Top: Immunoprecipitates were loaded on two gels. Purified RAF1 proteins were either detected using anti-Myc or RAF1 antibodies, while co-purified HA-tagged BRAF proteins were detected with anti-HA or anti-BRAF F7 antibodies. Note the expected increased BRAF/RAF1 heterodimerization by KRASG12V or sorafenib. Bottom: Analysis of total cellular lysates demonstrates expression of all Nluc components and confirms activation of the RAS/RAF/MEK/ERK-pathway by KRASG12V.

Additional file 4.

Durch die projizierte globale Erwärmung werden sich Hitzeextreme verschärfen. Vor allem in den Städten wird die Lebensqualität der Stadtbevölkerung unter sommerlichen Hitzewellen leiden. Im Projekt HeatResilientCity werden bewohnerorientierte Hitzeanpassungsmaßnahmen an Gebäuden und im städtischen Freiraum entwickelt und geprüft sowie Empfehlungen für die Umsetzung gegeben.The HeatResilientCity project applied insights from natural sciences, engineering and the social sciences to develop heat adaptation measures, test their effectiveness and partially implement them in two structurally different real-world laboratories in Dresden-Gorbitz and Erfurt-Oststadt. The present article discusses interventions to plant street trees and to refurbish two different residential buildings. We describe and analyse aspects of the implementation process to identify key factors that enable or constrain adaptation action among different groups of actors. We find that adaptation measures that are objectively effective and supported by residents are most appropriate for implementation. Where residents evince scepticism about adaptation measures, information about their effectiveness and usefulness should be disseminated. Early and targeted involvement of relevant stakeholders, careful communication and the establishment of climate adaptation as a permanent interdepartmental task at municipal level can promote successful implementation of heat adaptation measures.

The following work aims to present the effects of elaborating a radio show about science, intended to help the development of some middle schools, showing important topics as a means to curb the impact of the pandemic on the students in three primary and secondary public schools in Uruguaiana (RS). Due to the COVID-19 pandemic in 2020, the curricular activities had to be suspended at the federal level, resulting in drastic changes in teaching methods and forcing teachers and their students to adapt to this new reality. As a way to circumvent the difficulties faced in the Ensino Remoto Emergencial (Emergencial Remote Education, direct translation), the group of resident teachers from Ciências da Natureza – Licenciatura course from Unipampa (Universidade Federal do Pampa, Uruguaiana Campus) arose with an idea of presenting a radio program about topics from the Natural Sciences curriculum, which was aired in a local station. The show was named “Ciência na Residência” and had 18 episodes in total, seeking to give out important information for the students and their community, using simulated conversations as a method for its presentation, which were structured by the residents. Keywords: Oriented teaching. Teaching. Natural sciences. Remote learning. O presente trabalho tem por objetivo apresentar os resultados da elaboração de um programa de rádio sobre ciências voltado a desenvolver conteúdos pertinentes ao Ensino Fundamental II como forma de atenuar o impacto da pandemia sobre os alunos da educação básica de três escolas públicas de Uruguaiana (RS). Em decorrência da pandemia de COVID-19 no ano de 2020, as atividades curriculares presenciais tiveram de ser suspensas em nível nacional, provocando mudanças drásticas nos métodos de ensino e forçando professores e alunos a se adaptarem a esta nova realidade. Como forma de contornar as dificuldades encontradas no Ensino Remoto Emergencial, o grupo de residentes do curso de Ciências da Natureza – Licenciatura da Unipampa (Campus Uruguaiana) trouxe a proposta da apresentação de um programa de rádio sobre assuntos pertinentes ao estudo das Ciências da Natureza, que foi ao ar em uma rádio local. O programa, denominado “Ciência na Residência”, foi concluído com 18 episódios construídos com base no método de simulação de conversa do tipo improviso estruturado entre os participantes e visou entregar informações de qualidade para os alunos e para a comunidade em geral. Palavras-chave: Docência orientada. Ensino. Ciências da Natureza. Ensino Remoto.

A presente pesquisa objetivou investigar o impacto causado pela Fundação Municipal de Artes de Montenegro (Fundarte) no desenvolvimento da educação musical e cultural no Vale do Caí/RS. A instituição vem, há muitos anos, sendo referência no ensino de música na região e no estado. Em uma abordagem qualitativa, utilizou-se a pesquisa documental como método, sendo coletados documentos institucionais oficiais da Fundarte e reportagens em um jornal local, este, referência em comunicação da região, datadas de 2017 a 2020. O referencial teórico teve como base estudos de Kraemer (2000) e Swanwick (1999), considerando-se a educação musical e suas relações com diversos tempos, espaços e disciplinas. Como resultados, constatou-se que a Fundarte tem um papel importante na difusão e no desenvolvimento da arte e da cultura, oportunizando o ensino e a pesquisa na região do Vale do Caí/RS, bem como nas localidades do entorno. Como desdobramentos, almeja-se que esta pesquisa fomente outras investigações, não somente no que diz respeito à Fundarte, mas, também, de outras instituições da mesma natureza, que contribuem para a história e fortalecem ainda mais a área da educação musical.

We study the relation between board gender diversity and goodwill (GW). GW on the balance sheet is connected to both the firm’s risk-taking and its accounting conservatism which are two popular topics in how gender diversity affects the governance of firms. GW captures the firm’s decision to acquire another business for a price exceeding the received identifiable net assets and the subsequent valuation of the purchase. We propose that board decisions affecting GW could depict information about board gender diversity and its potential effects. Specifically, we examine Nordic listed firms in the period 2009–2018, to determine whether and how female representation on the board of directors is linked to the GW change. Big GW increases are associated with risk-taking and GW write-downs are signs of conservative accounting. Thus, we hypothesize and evidence that firms with substantial GW increases (decreases) are associated with fewer (more) women on the board. These results provide insight on board composition and potentially also on good governance and their consequences for strategic decision-making. Our findings contribute to the board diversity literature in accounting and corporate governance.

Contextualizacao: o presente trabalho relata parte das intervencoes do Laboratorio Metuia/Nucleo UFPB-Uncisal em parceria com as criancas de uma comunidade no municipio de Joao Pessoa/PB. Processo de Intervencao: foram desenvolvidas acoes virtuais, de forma individual e coletiva, com criancas entre 6 e 11 anos, a fim de dialogar, apreender suas demandas e tentar criar estrategias para lidar com as situacoes emergentes e intensificadas pelo contexto em que vivemos. Analise critica da pratica: mesmo diante da complexidade do debate em torno da utilizacao do meio virtual, para o desenvolvimento das atividades praticas em terapia ocupacional social, acredita-se ser possivel, apesar de nao ser o ideal, a utilizacao dos recursos tecnologicos para a intervencao com as criancas. Sintese das consideracoes: o estar com as criancas permitiu continuarmos apreendendo, a partir das suas historias e de suas familias, a intensificacao da desigualdade social causada pela pandemia da Covid-19 no Brasil. Palavras-chave: Terapia Ocupacional. Criancas. Pandemia. Territorio Sociocultural Abstract Contextualization: this work addresses part of an Laboratorio Metuia/Nucleo UFPB-Uncisal investigation in partnership with children from a community in the city of Joao Pessoa/PB. Intervention Process: virtual actions were developed, individually and collectively, with children between 6 and 11 years old, in order to dialogue, understand their demands and try to create strategies to deal with emergent situations, intensified by the context in which we live. Critical analysis of the practice : even given the complexity of the debate surrounding the use of the virtual work enviroment for the development of practical activities in social occupational therapy, it is believed that it is possible, although not ideal, to use such a method for the desired purposes. Summary of the considerations: being with the children allowed us to keep apprehending, based on their stories and their families, about the intensification of social inequality caused by the Covid-19 pandemic in Brazil. Keywords: Occupational Therapy. Children. Pandemic. Sociocultural Territory. Resumen Contextualizacion: el presente trabajo informa parte de las intervenciones del Laboratorio Metuia/Nucleo UFPB-Uncisal en conjunto con los ninos de una comunidad de la ciudad de Joao Pessoa/PB. Proceso de Intervencion: se desarrollaron acciones virtuales, de manera individual y colectiva, con ninos de entre 6 y 11 anos, con el fin de dialogar, comprender sus demandas e intentar generar estrategias para enfrentar situaciones emergentes e intensificadas por el contexto en el que vivimos. Analisis critico de la practica: incluso ante la complejidad del debate en torno al uso del espacio virtual para el desarrollo de actividades practicas en terapia ocupacional social, se cree que es posible, aunque no ideal, utilizar recursos tecnologicos para la intervencion con los ninos. Sintesis de las consideraciones: estar con los ninos nos permitio seguir aprehendiendo, a partir de sus historias y sus familias, la intensificacion de la desigualdad social provocada por la pandemia de Covid-19 en Brasil. Palabras clave: Terapia Ocupacional. Ninos. Pandemia. Territorio Sociocultural

This study investigated the effects of inosine on memory acquisition and consolidation, cholinesterases activities, redox status and Na+, K+-ATPase activity in a rat model of scopolamine-induced cognitive impairment. Adult male rats were divided into four groups: control (saline), scopolamine (1 mg/kg), scopolamine plus inosine (50 mg/kg), and scopolamine plus inosine (100 mg/kg). Inosine was pre-administered for 7 days, intraperitoneally. On day 8, scopolamine was administered pre (memory acquisition protocol) or post training (memory consolidation protocol) on inhibitory avoidance tasks. The animals were subjected to the step-down inhibitory avoidance task 24 hours after the training. Scopolamine induced impairment in the acquisition and consolidation phases; however, inosine was able to prevent only the impairment in memory consolidation. Also, scopolamine increased the activity of acetylcholinesterase and reduced the activity of Na+, K+-ATPase and the treatment with inosine protected against these alterations in consolidation protocol. In the animals treated with scopolamine, inosine improved the redox status by reducing the levels of reactive oxygen species and thiobarbituric acid reactive substances and restoring the activity of the antioxidant enzymes, superoxide dismutase and catalase. Our findings suggest that inosine may offer protection against scopolamine-induced memory consolidation impairment by modulating brain redox status, cholinergic signaling and ion pump activity. This compound may provide an interesting approach in pharmacotherapy and as a prophylactic against neurodegenerative mechanisms involved in Alzheimer’s disease.

Cold War History organised this roundtable to commemorate the thirtieth anniversary of the end of the Soviet Union – one of the two superpower poles that defined the Cold War confrontation and inte...