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Abstract The goal of designing safer, more effective drugs has led to tremendous interest in molecular mechanisms through which ligands can precisely manipulate the signaling of G-protein-coupled receptors (GPCRs), the largest class of drug targets. Decades of research have led to the widely accepted view that all agonists—ligands that trigger GPCR activation—function by causing rearrangement of the GPCR’s transmembrane helices, opening an intracellular pocket for binding of transducer proteins. Here we demonstrate that certain agonists instead trigger activation of free fatty acid receptor 1 by directly rearranging an intracellular loop that interacts with transducers. We validate the predictions of our atomic-level simulations by targeted mutagenesis; specific mutations that disrupt interactions with the intracellular loop convert these agonists into inverse agonists. Further analysis suggests that allosteric ligands could regulate the signaling of many other GPCRs via a similar mechanism, offering rich possibilities for precise control of pharmaceutically important targets.

In the growing market of the translation industry, where 90% of the global output consists of specialised translation, the acquisition of familiarity with different specialised genres is critical for translation trainees to confidently prepare for their future professional challenges. Not only do professionals report dealing with a high diversity of texts and domains but low familiarity may result in poor translation performances and low self-efficacy. Due to the general orientation of Specialised Translation master's programmes in Italy, it is often difficult to deliver genre-specific training, which translates to scattered tasks and avoidance of highly specialised genres and texts. This contribution describes training administered to final-year learners of a master's degree in Specialised Translation, and it was designed to delve into four specialised genres by analysing and translating authentic professional materials. Pre-test and post-test questionnaires employing an adaptation of Chen, Gully, and Eden's general self-efficacy scale (2001) were administered to explore learners' perceived difficulties and to investigate whether the training could enhance learners' self-efficacy about translation tasks.

Metabotropic glutamate receptors (mGluRs) are dimeric class C G-protein-coupled receptors that operate in glia and neurons. Glutamate affinity and efficacy vary greatly between the eight mGluRs. The molecular basis of this diversity is not understood. We used single-molecule fluorescence energy transfer to monitor the structural rearrangements of activation in the mGluR ligand binding domain (LBD). In saturating glutamate, group II homodimers fully occupy the activated LBD conformation (full efficacy) but homodimers of group III mGluRs do not. Strikingly, the reduced efficacy of Group III homodimers does not arise from differences in the glutamate binding pocket but, instead, from interactions within the extracellular dimerization interface that impede active state occupancy. By contrast, the functionally boosted mGluR II/III heterodimers lack these interface brakes to activation and heterodimer asymmetry in the flexibility of a disulfide loop connecting LBDs greatly favors occupancy of the activated conformation. Our results suggest that dimerization interface interactions generate substantial functional diversity by differentially stabilizing the activated conformation. This diversity may optimize mGluR responsiveness for the distinct spatio-temporal profiles of synaptic versus extrasynaptic glutamate.

Objetivo: Avaliar a eficácia e segurança de estatinas para pessoas com doença falciforme (DF). Métodos: Protocolo foi registrado na PROSPERO, seguindo o Cochrane Handbook e o relatório seguiu PRISMA. Incluíram-se ECRs com participantes de qualquer idade com diagnóstico de DF. Desfechos: crises de dor agudas, mortalidade relacionada à DF, complicações graves, transfusão sanguínea, eventos adversos e qualidade de vida. Foram buscados estudos em CENTRAL, Embase, MEDLINE, ClinicalTrials.gov e WHO International Clinical Trials Registry Platform, além de busca manual. Foram encontrados 261 artigos. Após excluir duplicatas, foram analisados títulos e resumos (246 excluídos) e textos completos (11 excluídos), restando 2 ECRs: um publicado como comentário e outro concluído sem desfechos disponíveis. Devido à ausência de dados, não foi possível realizar meta-análises. Resultados: O estudo Kenneth 2019 incluiu 13 participantes com atorvastatina 40 mg/dia por 6 semanas versus placebo. O estudo Abdelhalim 2021 incluiu 350 participantes com sinvastatina 20-40 mg/dia por 8-10 meses, associada ao tratamento tradicional versus placebo. Desfechos de Kenneth 2019: disfunção endotelial, relação albumina-creatinina, TFG, níveis de ET-1 e p-selectina solúvel, todos com p > 0,05. O risco de viés foi avaliado como incerto para várias categorias e baixo para relato seletivo dos desfechos. Não foi possível avaliar a certeza da evidência pelo GRADE devido à falta de desfechos de interesse e pequeno tamanho amostral, sugerindo evidência de certeza muito baixa. Discussão: A anemia falciforme apresenta alta prevalência e impacto psicossocial significativo devido ao seu caráter crônico, com agudizações recorrentes, episódios de dor frequentes e potencial risco de morte. Apesar disso, as opções de manejo atuais são limitadas. A revisão avaliou o uso de estatinas, amplamente utilizadas em risco cardiovascular, na DF. Na literatura, alguns estudos pré-clínicos demonstraram desfechos interessantes relacionados a adesão endotelial e função renal com o uso de estatinas na DF, os quais poderiam diminuir as crises de oclusão de vasos que levam a dor e danos a órgãos. Contudo, os resultados dessa revisão mostram que não houve diferença significativa em nenhum dos parâmetros analisados. A revisão destaca a lacuna na pesquisa clínica, sublinhando a necessidade de estudos mais robustos, randomizados e controlados por placebo para uma compreensão mais abrangente e confiável dos efeitos das estatinas na anemia falciforme, pois grande parte dos estudos analisados foram excluídos por serem de braço único ou com controle incorreto. Ademais, a ausência de investigações que avaliem parâmetros clínicos, em detrimento dos laboratoriais, impede decisões clínicas baseadas em evidências, sugerindo uma subutilização de recursos científicos. A pesquisa deve focar em desfechos que efetivamente impactem a vida dos pacientes. Além disso, ao trazer à tona a falta de investigações sobre qualidade de vida de adultos afetados pela DF, o estudo proporciona nova perspectiva sobre a necessidade de ampliação da atenção científica para tal população. Conclusão: Apesar de um ECR sobre o uso de estatinas na DF não revelar diferenças significativas nos parâmetros avaliados, a escassez de estudos disponíveis e a ausência de desfechos de interesse limitam a certeza das evidências. Para orientar a prática clínica, são necessárias futuras pesquisas clínicas rigorosas, explorando desfechos além dos laboratoriais.

Abstract Background Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann’s procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P

RESUMO O objetivo desta pesquisa foi infocar os fatores que afetam a qualidade da madeira. Tais fatores podem ser inerentes a própria madeira e também decorrente do ambiente em que as árvores se desenvolveram. A relação existente entre a característica silvicultural aplicada ao rápido crescimento e suas implicações nas propriedades tecnológicas do xilema secundário são avaliadas nesta revisão. O efeito produzido na madeira, tanto em espécies de coníferas como de folhosas, são também abordados, apontando possíveis práticas que visam minimizar tais efeitos.

RESUMO Este trabalho trata da influência das características anatômicas da madeira sobre a penetração e adesão de adesivos. Neste contexto, deu-se enfoque a diversidade estrutural e anatômica da madeira e seus papeis na performance de uma ligação adesiva.

Abstract Background Mammalian follicle development is characterized by extensive changes in morphology, endocrine responsiveness, and function, providing the optimum environment for oocyte growth, development, and resumption of meiosis. In cattle, the first signs of transcription activation in the oocyte are observed in the secondary follicle, later than during mouse and human oogenesis. While many studies have generated extensive datasets characterizing gene expression in bovine oocytes, they are mostly limited to the analysis of fully grown and matured oocytes. The aim of the present study was to apply single-cell RNA sequencing to interrogate the transcriptome of the growing bovine oocyte from the secondary follicle stage through to the mid-antral follicle stage. Results Single-cell RNA-seq libraries were generated from oocytes of known diameters ( 120 μm), and datasets were binned into non-overlapping size groups for downstream analysis. Combining the results of weighted gene co-expression network and Trendy analyses, and differently expressed genes (DEGs) between size groups, we identified a decrease in oxidative phosphorylation and an increase in maternal -genes and transcription regulators across the bovine oocyte growth phase. In addition, around 5,000 genes did not change in expression, revealing a cohort of stable genes. An interesting switch in gene expression profile was noted in oocytes greater than 100 μm in diameter, when the expression of genes related to cytoplasmic activities was replaced by genes related to nuclear activities (e.g., chromosome segregation). The highest number of DEGs were detected in the comparison of oocytes 100–109 versus 110–119 μm in diameter, revealing a profound change in the molecular profile of oocytes at the end of their growth phase. Conclusions The current study provides a unique dataset of the key genes and pathways characteristic of each stage of oocyte development, contributing an important resource for a greater understanding of bovine oogenesis.

Receptor activity-modifying proteins (RAMPs) modulate the activity of many Family B GPCRs. We show that RAMP2 directly interacts with the glucagon receptor (GCGR), a Family B GPCR responsible for blood sugar homeostasis, and broadly inhibits receptor-induced downstream signaling. HDX-MS experiments demonstrate that RAMP2 enhances local flexibility in select locations in and near the receptor extracellular domain (ECD) and in the 6th transmembrane helix, whereas smFRET experiments show that this ECD disorder results in the inhibition of active and intermediate states of the intracellular surface. We determined the cryo-EM structure of the GCGR-Gs complex at 2.9 Å resolution in the presence of RAMP2. RAMP2 apparently does not interact with GCGR in an ordered manner; however, the receptor ECD is indeed largely disordered along with rearrangements of several intracellular hallmarks of activation. Our studies suggest that RAMP2 acts as a negative allosteric modulator of GCGR by enhancing conformational sampling of the ECD.

Objective: The main objective of this study is to report on the implementation and results of the “Supporting Health-Related Judicial Decisions in Brazil” project conducted at the Health Technology Assessment Center, Hospital Sírio-Libanês through the “Programa de Apoio ao Desenvolvimento Institucional do Sistema Único de Saúde”, in Brazil. Methods: This study is an experience report of a project conducted at the Health Technology Assessment Center, Hospital Sírio-Libanês. Results: The activities of the project occurred in 2023 and included two online training courses on primary studies and systematic reviews, 11 one-day workshops with technical-scientific content for members of the Technical Support Centers for the Judiciary (NATJus), 40 online technical-scientific consultations for magistrates on a digital platform, 11 technical-scientific reports addressing the most legally claimed technologies in Brazil; two methodological tools, a national forum (hybrid event), 10 chat-based mentorships for NATJus members; and the maintenance of an open-access blog, by publishing news on relevant topics on law and health. Discussion and conclusion: This project has contributed to the improvement of the judicial decision-making process by providing a range of activities aimed at aiding the prioritization of health technologies that are clearly effective and safe over those that are ineffective, harmful, or have uncertain effects. Submission: 04/09/24| Review: 06/29/24| Approval: 08/18/24

Fat mass and obesity-related (FTO) gene single nucleotide polymorphisms (SNPs) interferes with food preferences that impact macronutrient intake. Few studies have investigated the relationship of this polymorphisms with the intake of micronutrients. Moreover, studies have shown multiple micronutrient deficiencies in patients with obesity. This work evaluated the effect of the FTO rs9939609 gene polymorphism on dietary nutritional quality and food intake of macronutrients and vitamins in of women with obesity candidates for metabolic surgery. The study included 106 women (24 to 60 years old) with BMIs of 36.1 to 64.8 kg/m2. A food frequency questionnaire validated for the local population was applied to obtain information about food intake. The Index of Nutritional Quality (INQ) was used to assess the adequacy of macronutrient and vitamin intake. Energy, protein and lipid intakes were higher in carriers of the A allele compared to TT in the younger age groups but were similar in the class of subjects aged ≥45 years. The INQ for protein was higher in carriers of the A allele than in carriers of the TT allele. The INQs for protein, carbohydrate, vitamins B2, B3 and B6 decreased, whereas the INQ for vitamin C increased with advancing age. The INQ for vitamin A was lower in AA than in TT, regardless of age, whereas vitamin E was higher in younger AA than in older AA. The INQ for vitamin B9 was higher in younger women than in older women. In conclusion, the FTO gene contributed to the intake of more energy, protein and lipids and interfered with the intake of vitamins B9, A and E. With the exception of vitamin A, the effect of the genotype was attenuated with ageing.

ABSTRACT The plywood panels and particleboards are examples of wood composites materials. Materials like MDF (“medium density fiberboard”), LVL (“laminated veneer lumber”) and the sidelong-glued panels constitute a new generation of wood based product. These products use a concept that joins new manufacture technologies to the rational use of the forest resources. This work had as objective to evaluate eucalypt “clear blocks” used as raw material for wood glued panels. Clear blocks are pieces of lumber with small dimensions without defects and imperfections. The results of an analysis of the laboratory production are presented.

RESUMO O objetivo deste trabalho foi avaliar a aptidão tecnológica de cinco espécies florestais, nativas e exóticas, combinadas com cimento Portland tipo CP II para o emprego na produção de painéis de cimento-madeíra, através do estudo do calor de hidratação desse compósito. A metodologia empregada para mensuração do tempo e temperatura de hidratação do cimento quando combinado ou não com as partículas das espécies foi a coleta, em intervalos de uma hora, da temperatura de hidratação de quatro amostras da mistura cimento, partículas e água, até no momento em que a mesma atingisse o valor máximo. Uma equação matemática foi utilizada para se determinar os índices de inibição para cada espécie. Os dados foram analisados comparando-se a temperatura máxima de hidratação, bem como o tempo necessário para se atingir essa temperatura e, ainda, os índices de inibição. Os resultados indicaram que as espécies com maior e menor aptidão ao uso em chapas minerais foram Eucalyptus citriodora e Leucaena leucocephala, respectivamente.

Resumo O presente estudo teve como objetivo avaliar o efeito da vaporização de toras no poder calorífico de Eucalyptus grandis. Para tanto, foram retirados madeira e casca dos topos das toras, antes e depois do processo de vaporização à 90ºC de temperatura durante 18horas. Posteriormente, determinou-se o poder calorífico superior da madeira e da casca pelo método da bomba calorimétrica. Os resultados mostraram que: (1) a vaporização reduziu o poder calorífico superior da madeira de 4752,54 para 4641,55Kcal/ Kg, porém sem prejudicar o potencial de combustão da espécie; e (2) o poder calorífico superior da casca sem tratamento e da vaporizada são iguais estatisticamente e na ordem de 3877,32 e 3862,79Kcal/ Kg.

RESUMO O estudo do efeito da cura a vapor sobre as propriedades mecânicas das chapas de cimento-madeira foi realizado com chapas produzidas com partículas de madeira da espécie Eucalyptus urophylla S. T. Blake combinada com aditivo acelerador cloreto de cálcio e o cimento Portland tipo ARI (Alta resistência inicial). Os painéis foram submetidos a três períodos de cura (7, 14 e 28 dias) combinando cura a vapor numa temperatura de 60 0C e cura em câmara climática (20 ± 3oC e 65 ± 1%). Buscou-se identificar se os métodos de cura aplicados geraram resistências equivalentes entre os três períodos de cura utilizados. Diante dos resultados alcançados pôde-se concluir que a variação do tempo de exposição dos painéis em câmara de vapor proporcionou efeitos satisfatórios especialmente nas propriedades módulo de elasticidade na flexão e compressão paralela dos painéis, não apresentando efeito sobre o módulo de ruptura e ligação interna.

Resumo Para atender a crescente demanda por madeira serrada, as serrarias de madeiras tropicais da região amazônica devem possuir um programa de controle de qualidade que inclui a realização de estudos sobre seu processo produtivo. Neste sentido, realizou-se através da metodologia denominada Amostragem do Trabalho (método estatístico), o estudo do tempo de trabalho em duas serras de fita em serrarias da Empresa Cikel Brasil Verde S/A. Esta metodologia é baseada em cálculos estatísticos para analisar o desempenho do trabalho e a utilização das máquinas por observação direta. Observou-se que as serras passaram 90% do tempo serrando toras de madeira das espécies Manilkara spp (maçaranduba) e Astronium lecointei (muiraquatiara). Os principais problemas que afetaram a eficiência das serras foram os de natureza mecânica, devido a exaustão durante o turno de trabalho. Os tempos de tolerância enquadraram-se dentro da normalidade, não interferindo na produção, haja vista, que os valores ficaram abaixo de 5 e 20%.

Replacing the native porphyrin cofactor in haem proteins has led to the development of novel designer proteins for a variety of applications. In most cases, haem analogues bind in a way that is comparable to the iron porphyrin, but this is not necessarily the case for complexes bearing non-exchangeable ligands. This study probes how a P[double bond, length as m-dash]O corrole binds to functionally disparate hemoproteins: a haem-dependent oxygen sensor (H-NOX) and a haem-scavenging protein (HasA). The results demonstrate that the protein-cofactor interactions are distinct from the native, haem-bound holoprotein. In H-NOX, the P[double bond, length as m-dash]O unit primarily hydrogen bonds with the haem-ligating histidine (H102), rather than the hydrogen-bonding network that stabilises the Fe(ii)-O2 complex in the native protein. In the absence of H102, the protein is still able to bind the corrole, albeit at reduced levels. Molecular dynamics simulations were utilised to determine the flexibility of apo H-NOX and revealed the coupled motion of key residues necessary for corrole binding. In the case of HasA, the P[double bond, length as m-dash]O unit does not primarily interact with either the haem-ligating histidine (H32) or tyrosine (Y75). Instead, histidine 83, the hydrogen-bonding partner for Y75, is critical for P[double bond, length as m-dash]O corrole binding. The conformation of HasA is interrogated by site-specifically labelling the protein and exploiting Förster resonance energy transfer (FRET) to determine the dye-cofactor distance. HasA reconstituted with the P[double bond, length as m-dash]O corrole exhibits an extended, apo-like conformation. Together, these results demonstrate that non-natural cofactors can bind to proteins in unexpected ways and highlight the need to uncover these interactions for the further development of designer haem proteins.

RESUMO O objetivo deste estudo foi determinar a variação das propriedades físicas (densidade básica e contração volumétrica) e dos caracteres anatômicos da madeira de Corymbia citriodora (Hook.) K.D. Hill & L.A.S. Johnson e suas correlações. Foram consideradas as variações entre duas posições (cerne e alburno) e cinco diferentes alturas do tronco (da base ao topo). As análises estatísticas indicaram diferenças significativas entre as combinações de posição/altura para todas as propriedades físicas e caracteres anatômicos, exceto para o diâmetro de lume de fibra. A posição apresentou correlações positivas com a densidade básica e o comprimento de fibra. A altura apresentou correlações negativas com a contração volumétrica e o comprimento de fibra. A largura de fibra apresentou correlações positivas com a espessura de parede e o diâmetro de lume, enquanto que a densidade básica apresentou uma correlação negativa com a espessura de parede.

Abstract Metabotropic glutamate receptors (mGluRs) are dimeric class C G-protein–coupled receptors that operate in glia and neurons. Glutamate affinity and efficacy vary greatly between the eight mGluRs. The molecular basis of this diversity is not understood. We used single-molecule fluorescence energy transfer to monitor the structural rearrangements of activation in the mGluR ligand binding domain (LBD). In saturating glutamate, group II homodimers fully occupy the activated LBD conformation (full efficacy) but homodimers of group III mGluRs do not. Strikingly, the reduced efficacy of Group III homodimers does not arise from differences in the glutamate binding pocket but, instead, from interactions within the extracellular dimerization interface that impede active state occupancy. By contrast, the functionally boosted mGluR II/III heterodimers lack these interface ‘brakes’ to activation and heterodimer asymmetry in the flexibility of a disulfide loop connecting LBDs greatly favors occupancy of the activated conformation. Our results suggest that dimerization interface interactions generate substantial functional diversity by differentially stabilizing the activated conformation. This diversity may optimize mGluR responsiveness for the distinct spatio-temporal profiles of synaptic versus extrasynaptic glutamate.

RESUMO A melhor utilização da madeira depende de suas propriedades químicas, físicas e anatômicas. Diversos fatores bióticos e abióticos podem interferir em maior ou menor magnitude nas propriedades da mesma e conseqüentemente, em sua qualidade. Esta pesquisa teve como objetivo o estudo da variação da densidade da madeira, visando obter subsídios face sua melhor aplicação. O material empregado, constituiu-se de amostras de madeira de 12 árvores de Pinus elliottii com diferentes idades de crescimento. Os Resultados obtidos mostraram haver variação da densidade nos sentidos longitudinal e radial e em função da idade de crescimento. A densidade aumentou da medula para a casca e com a idade de crescimento e diminuiu da base para o topo. Baseado nesta variação, foi possível distinguir regiões onde os valores de densidades são praticamente idênticos e regiões onde eles diferem entre si, permitindo assim, classificar a madeira em termos de densidade e sugerir seu melhor emprego.

Resumo O objetivo deste trabalho foi realizar uma avaliação comparativa da densidade e produtividade da madeira de cinco tratamentos de híbridos de Pinus caribaea var. hondurensis x P. tecunumannii com um seminal de P. caribaea var. hondurensis plantados no mesmo povoamento no município de Agudos-SP. Determinou-se a densidade básica de cada disco pelo método de imersão. A produtividade foi determinada por meio dos incrementos médios anuais de volume e de massa. Os resultados evidenciaram que os tratamentos híbridos tiveram produtividade em volume de até 23 % maior que o tratamento seminal, entretanto houve diminuição de aproximadamente 10 % na densidade.

RESUMO Os objetivos deste estudo foram determinar a variação das propriedades físicas da madeira de Eucalyptus pellita F. Muell; determinar a variação das dimensões dos elementos anatômicos da madeira pelo método de aquisição e análise de imagens digitais através do software CELLF (Olympus®); e determinar as correlações existentes entre as variáveis estudadas. Amostras não destrutivas (baguetas de 20 mm de diâmetro) foram retiradas de árvores com 15 anos de idade e dividas em três posições: cerne, transição cerne/alburno e alburno. As análises estatísticas não indicaram diferenças significativas entre as três posições para nenhuma das variáveis dependentes estudadas, provavelmente devido à predominância de madeira juvenil. A densidade básica mostrou estar mais relacionada às dimensões das fibras (comprimento, largura e espessura de parede) do que aos demais elementos anatômicos. A contração volumétrica tendeu a diminuir com o aumento da largura dos raios e com a redução do comprimento dos vasos, sendo pouco afetada pelos demais elementos anatômicos.

RESUMO O conhecimento da composição química da madeira possibilita o entendimento de seu comportamento como matéria-prima para diversos usos, principalmente para a indústria de polpa celulósica, indústria de painéis, além de conferir propriedades preservativas face aos agentes bióticos e abióticos. Dentre as espécies do gênero Eucalyptus, destaca-se o Eucalyptus urophylla por apresentar o maior potencial de crescimento em termos de área plantada e em função da resistência ao fungo Cryphonectria cubensis, causador do cancro do eucalipto. O objetivo da pesquisa em tela foi analisar a possibilidade de propor um modelo sistemático de identificação para madeiras do gênero Eucalyptus por Ressonância Magnética Nuclear do 13C (RMN 13C). Neste trabalho, utilizaram-se os extratos ciclo-hexano de madeiras de clones de E. urophylla, devido a uma vasta diferença em deslocamento químico dos carbonos moleculares. O estudo está sendo aplicado também a outras espécies do gênero Eucalyptus. Os dados de RMN 13C mostraram que os espectros dos extratos ciclo-hexano do cerne foram os mais representativos para o estudo de clones de E. urophylla, devido ao maior número de absorções existentes. Com esses resultados, foi possível traçar o perfil espectral comum para a espécie E. urophylla de cada região (alburno, zona de transição e cerne) da madeira.

RESUMO Para análise do crescimento do xilema de espécies tropicais é necessário muitas vezes lançar mão de ferramentas que auxiliam na identificação precisa dos anéis de crescimento. Para avaliar o crescimento de uma árvore a dendrocronologia, utiliza métodos e técnicas, divididos em dois grupos, ou seja, método estático, que utiliza das técnicas desenvolvidas na anatomia de madeira, datação por radiocarbono, mensuração da largura do anel de crescimento, etc. e o método dinâmico que utiliza das técnicas de investigação fenológica, mensuração do diâmetro de crescimento por dendrômetro de faixa e mensuração da atividade cambial por resistência elétrica com um sigometrômetro. Estes métodos associados às técnicas auxiliam na identificação da periodicidade das zonas de crescimento e possibilita estimar a idade real da árvore. Em árvores tropicais com falsos anéis, anéis incompletos ou perdidos, para se comprovar exata periodicidade do crescimento ambos os métodos e várias técnicas podem ser combinados entre si.

RESUMO A análise tomográfica de impulso é um método não destrutivo que permite analisar o interior do lenho de árvores pela passagem de ondas mecânicas, tornando possível realizar uma avaliação prévia e detectar a presença de defeitos na madeira. Utilizou-se o tomógrafo de impulso ARBOTOM para analisar o lenho de árvores de Tectona grandis, localizadas em Cáceres, MT. Os resultados possibilitaram detectar a presença de zonas distintas no lenho através da variação da velocidade de ondas mecânicas indicada por variadas zonas de cores reveladas na imagem tomográfica. Possivelmente, essas diferenças de cores são atribuídas às variações da densidade e umidade da madeira.

RESUMO O objetivo desta pesquisa foi avaliar três métodos de determinação da densidade da madeira a 12 % e densidade básica. Os métodos usados foram: estereometria por imersão e por medição direta e o método de atenuação por radiação gama. Para tal, foram coletados discos de árvores de Pinus elliottii, oriundos de reflorestamento submetidas ou não ao processo de resinagem, com idade de 8, 15, 25 e 35, nas posições da base, DAP, 25%, 50%, 75% e 100% da altura comercial. Os resultados obtidos mostraram que os métodos empregados não apresentaram diferenças estatisticamente significativas. Entretanto, o método de atenuação da radiação gama permitiu determinar a densidade no sentido medulacasca, de milímetro em milímetro e transformar a densidade obtida na umidade de equilíbrio, em torno de 12% em densidade básica e densidade anidra, sem saturação e secagem total da amostra, respectivamente.

RESUMO A análise tomográfica de impulso é um método não destrutivo que permite analisar o interior do lenho de árvores pela passagem de ondas produzidas mecanicamente, tornando possível realizar uma avaliação prévia e detectar a presença de defeitos na madeira. Neste estudo, utilizou-se o tomógrafo de impulso ARBOTOM para analisar o lenho de árvores de Pinus caribaea e associar o efeito da umidade na formação da imagem tomográfica. Os resultados mostraram que existe uma associação entre a umidade da madeira e a velocidade de propagação da onda mecânica gerada pelo tomógrafo de impulso, confirmando o seu efeito na formação da imagem tomográfica.

Abstract Background Health evidence needs to be communicated and disseminated in a manner that is clearly understood by decision-makers. As an inherent component of health knowledge translation, communicating results of scientific studies, effects of interventions and health risk estimates, in addition to understanding key concepts of clinical epidemiology and interpreting evidence, represent a set of essential instruments to reduce the gap between science and practice. The advancement of digital and social media has reshaped the concept of health communication, introducing new, direct and powerful communication platforms and gateways between researchers and the public. The objective of this scoping review was to identify strategies for communicating scientific evidence in healthcare to managers and/or population. Methods We searched Cochrane Library, Embase®, MEDLINE® and other six electronic databases, in addition to grey literature, relevant websites from related organizations for studies, documents or reports published from 2000, addressing any strategy for communicating scientific evidence on healthcare to managers and/or population. Results Our search identified 24 598 unique records, of which 80 met the inclusion criteria and addressed 78 strategies. Most strategies focused on risk and benefit communication in health, were presented by textual format and had been implemented and somehow evaluated. Among the strategies evaluated and appearing to yield some benefit are (i) risk/benefit communication: natural frequencies instead of percentages, absolute risk instead relative risk and number needed to treat, numerical instead nominal communication, mortality instead survival; negative or loss content appear to be more effective than positive or gain content; (ii) evidence synthesis: plain languages summaries to communicate the results of Cochrane reviews to the community were perceived as more reliable, easier to find and understand, and better to support decisions than the original summaries; (iii) teaching/learning: the Informed Health Choices resources seem to be effective for improving critical thinking skills. Conclusion Our findings contribute to both the knowledge translation process by identifying communication strategies with potential for immediate implementation and to future research by recognizing the need to evaluate the clinical and social impact of other strategies to support evidence-informed policies. Trial registration protocol is prospectively available in MedArxiv (doi.org/10.1101/2021.11.04.21265922).

The aim of this study was to analyze the growth rings and evaluate the effect of the urban environment on the growth of Terminalia catappa L. under intense industrial activity. At least two wood samples were obtained from each tree with an increment borer. The regions of Volta Redonda (Northwest and Southeast regions) and Resende (used as control) were established for the collection. The dendrochronological potential of T. catappa indicated sensitivity to precipitation and temperature in a more exposed urban and industrial steel pollution area because there were differences in growth when compared to an area less exposed to the same pollution. Thus, it was possible to conclude that this species has the potential to be used as a bioindicator of anthropogenic activities. In addition, the delimitation of the growth rings of the studied species contributes to the realization of future dendrochronological studies, expanding the understanding of the behavior of this species present in urban environments at different regional scales. This study reinforces the importance of rainfall and temperature in regulating radial growth in tropical forests.

Ubiquitin is a common posttranslational modification canonically associated with targeting proteins to the 26S proteasome for degradation and also plays a role in numerous other nondegradative cellular processes. Ubiquitination at certain sites destabilizes the substrate protein, with consequences for proteasomal processing, while ubiquitination at other sites has little energetic effect. How this site specificity-and, by extension, the myriad effects of ubiquitination on substrate proteins-arises remains unknown. Here, we systematically characterize the atomic-level effects of ubiquitination at various sites on a model protein, barstar, using a combination of NMR, hydrogen-deuterium exchange mass spectrometry, and molecular dynamics simulation. We find that, regardless of the site of modification, ubiquitination does not induce large structural rearrangements in the substrate. Destabilizing modifications, however, increase fluctuations from the native state resulting in exposure of the substrate's C terminus. Both of the sites occur in regions of barstar with relatively high conformational flexibility. Nevertheless, destabilization appears to occur through different thermodynamic mechanisms, involving a reduction in entropy in one case and a loss in enthalpy in another. By contrast, ubiquitination at a nondestabilizing site protects the substrate C terminus through intermittent formation of a structural motif with the last three residues of ubiquitin. Thus, the biophysical effects of ubiquitination at a given site depend greatly on local context. Taken together, our results reveal how a single posttranslational modification can generate a broad array of distinct effects, providing a framework to guide the design of proteins and therapeutics with desired degradation and quality control properties.

Cochrane devolves most editorial governance of the Cochrane Database of Systematic Reviews (CDSR), including title prioritization, protocol registration, peer-review, editorial oversight and subsequent review deposition, to specific Cochrane Review Group (CRG) editorial boards. Current Cochrane policy stipulates authors of reviews who are also members of the supporting CRG declare this non-financial conflict of interest and confirm no involvement in the review editorial process. The aim of this cross-sectional analysis was to assess adherence to Cochrane's editorial conflict of interest policy. All 260 published Cochrane reviews (CR) in issues 1 to 6 from 2019 of the CDSR were reviewed. A total of 133 (51.2%, 133/260) of CRs had at least one author that was also listed as an editor in the CRG. Of these, only five (3.8%, 5/133) appropriately declared the conflict according to Cochrane policy. In 6.5% (17/133) CRs, the contact author had a leading editorial position within the CRG and in only four of 17 was this declared according to Cochrane policy. No CR with the contact author who also had a leading editorial position described methods to prevent any potential issues related to this scenario during the editorial process in accordance with Cochrane policy. We propose a specific form to improve the transparency and reliability of editorial conflict of interest reporting in CRs. The suggested form can be adapted to other contexts.

Technological advances in the professional segment of Language Service Providers (LSPs) have deeply changed the activity of professionals operating in the language industry. As a result, a large part of the translation activities which were once performed by human translators is now assigned to automatized systems. Machine Translation (MT) and Post-Editing (MTPE) services have doubled in size among the services offered by Language Service Companies (LSCs) and are expected to keep growing in future projections such that they might eventually prevail over Human Translation (HT). In light of this evolution, translation training institutes and universities claim to implement and develop training programs adapted to the evolving market, but the mismatch between the ideal requirements and the actual content of translation training programs is a critical issue of the translator training scenario in Italy. This paper describes an exploratory study aiming to investigate translation trainees' perception of their translation vs. post-editing performance, in order to understand their attitude towards MTPE and their confidence in performing a MTPE task. Results show that, contrary to a confident translation performance supported by extensive training, not only did the lack of appropriate and dedicated MTPE training affect trainees’ ability to perform the task but it also hampered their capability to analyze the task and self-evaluate their performance, calling for the design of more targeted curricula.

The >800 human G protein-coupled receptors (GPCRs) are responsible for transducing diverse chemical stimuli to alter cell state- and are the largest class of drug targets. Their myriad structural conformations and various modes of signaling make it challenging to understand their structure and function. Here, we developed a platform to characterize large libraries of GPCR variants in human cell lines with a barcoded transcriptional reporter of G protein signal transduction. We tested 7800 of 7828 possible single amino acid substitutions to the beta-2 adrenergic receptor (β2AR) at four concentrations of the agonist isoproterenol. We identified residues specifically important for β2AR signaling, mutations in the human population that are potentially loss of function, and residues that modulate basal activity. Using unsupervised learning, we identify residues critical for signaling, including all major structural motifs and molecular interfaces. We also find a previously uncharacterized structural latch spanning the first two extracellular loops that is highly conserved across Class A GPCRs and is conformationally rigid in both the inactive and active states of the receptor. More broadly, by linking deep mutational scanning with engineered transcriptional reporters, we establish a generalizable method for exploring pharmacogenomics, structure and function across broad classes of drug receptors.

The research landscape of personalized 3D-printed concrete-based modules for construction and their impact on thermal performance through generative design methods is explored through a bibliometric analysis. Comprehensive analysis techniques, including bibliographic data and visualization with VoSviewer, are employed to unveil collaborative networks, influential articles, research trends, and emerging themes within this domain. Global contributions are showcased, with citations predominantly from the UK and USA, while Denmark and Australia demonstrate a significant impact relative to publication numbers. Prominent authors like Buswell, Mechtcherine, and Zhang are highlighted through co-authorship analysis, revealing evolving collaborative patterns over time. Seminal works and influential authors are identified through co-citation analysis, providing insights into intellectual networks. Source citation analysis emphasizes the importance of sustainability and advanced manufacturing methods through key journals in the field. Keyword co-occurrence analysis identifies the core themes, including 3D concrete printing, additive manufacturing, and sustainability. Emerging trends indicate a growing focus on sustainability and adopting advanced manufacturing technologies. These insights have implications for future research, guiding impactful contributions in this evolving field.

Hedgehog signalling is fundamental to embryonic development and postnatal tissue regeneration1. Aberrant postnatal Hedgehog signalling leads to several malignancies, including basal cell carcinoma and paediatric medulloblastoma2. Hedgehog proteins bind to and inhibit the transmembrane cholesterol transporter Patched-1 (PTCH1), which permits activation of the seven-transmembrane transducer Smoothened (SMO) via a mechanism that is poorly understood. Here we report the crystal structure of active mouse SMO bound to both the agonist SAG21k and to an intracellular binding nanobody that stabilizes a physiologically relevant active state. Analogous to other G protein-coupled receptors, the activation of SMO is associated with subtle motions in the extracellular domain, and larger intracellular changes. In contrast to recent models3-5, a cholesterol molecule that is critical for SMO activation is bound deep within the seven-transmembrane pocket. We propose that the inactivation of PTCH1 by Hedgehog allows a transmembrane sterol to access this seven-transmembrane site (potentially through a hydrophobic tunnel), which drives the activation of SMO. These results-combined with signalling studies and molecular dynamics simulations-delineate the structural basis for PTCH1-SMO regulation, and suggest a strategy for overcoming clinical resistance to SMO inhibitors.

"Biased" G protein-coupled receptor (GPCR) agonists preferentially activate pathways mediated by G proteins or β-arrestins. Here, we use double electron-electron resonance spectroscopy to probe the changes that ligands induce in the conformational distribution of the angiotensin II type I receptor. Monitoring distances between 10 pairs of nitroxide labels distributed across the intracellular regions enabled mapping of four underlying sets of conformations. Ligands from different functional classes have distinct, characteristic effects on the conformational heterogeneity of the receptor. Compared to angiotensin II, the endogenous agonist, agonists with enhanced Gq coupling more strongly stabilize an "open" conformation with an accessible transducer-binding site. β-arrestin-biased agonists deficient in Gq coupling do not stabilize this open conformation but instead favor two more occluded conformations. These data suggest a structural mechanism for biased ligand action at the angiotensin receptor that can be exploited to rationally design GPCR-targeting drugs with greater specificity of action.

ABSTRACT BACKGROUND: Imaging tests are important for diagnosis during the management of pulmonary nodules; however, biopsy is required to confirm the malignancy. OBJECTIVES: To compare the effects of different techniques used for the biopsy of a pulmonary nodule. DESIGN AND SETTING: Systematic review and meta-analysis were conducted using Cochrane methodology in São Paulo, São Paulo, Brazil. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) on minimally invasive techniques, including tomography-guided percutaneous biopsy (PERCUT), transbronchial biopsies with fluoroscopy (FLUOR), endobronchial ultrasound (EBUSR), and electromagnetic navigation (NAVIG). The primary outcomes were diagnostic yield, major adverse events, and need for another approach. RESULTS: Seven RCTs were included (913 participants; 39.2% female, mean age: 59.28 years). Little to no increase was observed in PERCUT over FLUOR (P = 0.84), PERCUT over EBUSR (P = 0.32), and EBUSR over NAVIG (P = 0.17), whereas a slight increase was observed in NAVIG over FLUOR (P = 0.17); however, the evidence was uncertain. EBUSR may increase the diagnostic yield over FLUOR (P = 0.34). PERCUT showed little to no increase in all bronchoscopic techniques, with uncertain evidence (P = 0.02). CONCLUSION: No biopsy method is definitively superior to others. The preferred approach must consider availability, accessibility, and cost, as safety and diagnostic yield do not differ. Further RCTs planned, conducted, and reported with methodological rigor and transparency are needed, and additional studies should assess cost and the correlation between nodule size and location, as well as their association with biopsy results. SYSTEMATIC REVIEW REGISTRATION: PROSPERO database, CRD42018092367 -https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=92367.