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Background Aortic conduit and reservoir functions can be directly measured by four-dimensional flow (4D flow) cardiovascular magnetic resonance (CMR).Methods Twenty healthy controls (10 young and 10 age-gender-matched old controls) and 20 patients with heart failure with preserved ejection fraction (HFpEF) were recruited. All had 4D flow CMR. Flow was quantified at the ascending and descending aorta levels. In addition, at the ascending aorta level, we quantified systolic flow displacement (FDs) and systolic flow reversal ratio (sFRR). The aortic conduit function was defined as the relative drop in systolic flow from the ascending to the descending aorta (∆Fs). Aortic reservoir function was defined as descending aortic diastolic stroke volume (DAo SVd).Results Both ∆Fs (R=0.51, p=0.001) and DAo SVd (R=−0.68, p=0.001) were significantly associated with ageing. Native T1 (R=0.51, p=0.001) and extracellular volume (R=0.51, p=0.001) showed maximum association with ∆Fs. ∆Fs significantly increased in HFpEF versus age-gender-matched controls (41±8% vs 52±12%, p=0.02). In multiple regression, only ∆Fs and DAo SVd were independent predictors of the estimated glomerular filtration rate (model R=0.77, p=0.0001). FDs was significantly associated with ∆Fs (R=0.4, p=0.01) and DAo SVd (R=−0.48, p=0.002), whereas sFRR was mainly associated with DAo SVd (R=−0.46, p=0.003).Conclusion Both aortic conduit and reservoir function decline with age and this decline in aortic function is also independently associated with renal functional decline. Ascending aortic turbulent flow signatures are associated with loss of aortic conduit and reservoir functions. Finally, in HFpEF, aortic conduit and reservoir function demonstrate progressive decline.Trials registration number NCT05114785.

Abstract 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. Exploration of taxonomic compositions beyond bacteria as well as an understanding of the interaction between the bacteriome with the other members is limited using 16S rDNA sequencing. Here, we developed a pipeline 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 our pipeline 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, characterized by Bacteroides spp. /Phocaeicola spp., mixed composition and Enterococcus abundances. We 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. In the course of HSCT, bacterial strains were stable or newly acquired. Our results demonstrate the disruptive potential of alloHSCTon the gut microbiome and pave the way for future comprehensive microbiome studies based on long-read metagenomics.

A current systematic literature review has stated several deficiencies and knowledge gaps in biometeorology research conducted in Brazil. This finding encouraged a group of local professionals in the field to foster research initiatives in topics and regions yet unexplored in the country. Motivated by that, the group organized the first Brazilian Symposium on Human Biometeorology between July 4 and 8, 2022, in Natal (RN), northeastern Brazil. This paper aims to summarize the main studies presented at the symposium and highlight a few ideas that could be pursued next in human biometeorology in future research initiatives.

O objetivo do artigo é o de contribuir para o debate acerca da participação civil no golpe de 1964 e na ditadura. A proposta é promover uma reflexão, com base nos balanços histográficos mais recentes, sobre a nomenclatura do golpe e do regime. O artigo será trabalhado a partir de três questões: o avanço das pesquisas sobre empresariado e classes trabalhadoras no golpe e na ditadura, seu impacto na qualificação da participação civil no processo e a consequente influência desses estudos na nomenclatura golpe e regime empresarial-militar, entendida como desdobramento dessa produção. Ao final, propusemos um recorte metodológico para subsidiar a interpretação dos protagonistas e dos coadjuvantes do processo, com o objetivo de complexificar a análise dos grupos que compuseram o cenário e justificar a escolha da adjetivação do golpe e do regime como empresarial-militar, passando a pensar a nomenclatura de forma estrutural e conceitual.

O objetivo deste artigo é contribuir para o debate sobre o papel do empresariado na transição política brasileira, particularmente durante o governo de Ernesto Geisel (1974-1979). A perspectiva analítica central é a de que os representantes da empresa privada, independentemente da origem de seus capitais, atuaram em defesa de seus negócios, agindo politicamente para garantir a estabilidade dos países sob a influência do capital e assegurar sua dominação de classe. A pesquisa se baseia em análise teórica e empírica sobre a relação entre empresariado e ditadura, partindo do debate historiográfico sobre a produção acerca do tema, sugerindo o reconhecimento desses estudos como uma linha historiográfica consolidada na última década. A partir das produções dessa linha, o artigo desdobra a análise acerca da configuração do regime instaurado em 1964 como empresarial-militar. A interpretação se divide em dois movimentos distintos. Primeiramente, aborda a dimensão teórica, explorando os desdobramentos do período iniciado com o golpe empresarial-militar de 1964 e sua relação com o sistema capitalista e os Estados Unidos. Além disso, examina o papel dos empresários no regime político brasileiro, com foco especial na conjuntura do governo Geisel e no processo de transição política. O segundo movimento é empírico, utilizando documentos dos acervos pessoais de Ernesto Geisel e Antônio Azeredo da Silveira para fornecer exemplos concretos que sustentem a interpretação apresentada. A pesquisa utiliza a metodologia qualitativa de análise de conteúdo em fontes primárias para interpretar os dados da documentação.

Abstract Background Differentiation of gastrointestinal cancer (GIC) from chronic inflammatory enteropathies (CIE) in cats can be challenging and often requires extensive diagnostic testing. MicroRNAs (miRNAs) have promise as non‐invasive biomarkers in serum and feces for diagnosis of GIC. Hypothesis/Objectives Cats with GIC will have serum and fecal miRNA profiles that differ significantly from healthy cats and cats with CIE. Identify serum and fecal miRNAs with diagnostic potential for differentiation between cats with GIC and CIE as compared to healthy cats. Animals Ten healthy cats, 9 cats with CIE, and 10 cats with GIC; all client‐owned. Methods Cats were recruited for an international multicenter observational prospective case‐control study. Serum and feces were screened using small RNA sequencing for miRNAs that differed in abundance between cats with GIC and CIE, and healthy cats. Diagnostic biomarker potential of relevant miRNAs from small RNA sequencing and the literature was confirmed using reverse transcription quantitative real‐time PCR (RT‐qPCR). Results Serum miR‐223‐3p was found to distinguish between cats with GIC and CIE with an area under the curve (AUC) of 0.9 (95% confidence interval [CI], 0.760‐1.0), sensitivity of 90% (95% CI, 59.6‐99.5%), and specificity of 77.8% (95% CI, 45.3‐96.1%). Serum miR‐223‐3p likewise showed promise in differentiating a subgroup of cats with small cell lymphoma (SCL) from those with CIE. No fecal miRNAs could distinguish between cats with GIC and CIE. Conclusion and Clinical Importance Serum miR‐223‐3p potentially may serve as a noninvasive diagnostic biomarker of GIC in cats, in addition to providing a much needed tool for the differentiation of CIE and SCL.

Abstract The dimerization of RAF kinases represents a key event in their activation cycle and in RAS/ERK pathway activation. Genetic, biochemical and structural approaches provided key insights into this process defining RAF signaling output and the clinical efficacy of RAF inhibitors (RAFi). However, methods reporting the dynamics of RAF dimerization in living cells and in real time are still in their infancy. Recently, split luciferase systems have been developed for the detection of protein–protein-interactions (PPIs), incl. proof-of-concept studies demonstrating the heterodimerization of the BRAF and RAF1 isoforms. Due to their small size, the Nanoluc luciferase moieties LgBiT and SmBiT, which reconstitute a light emitting holoenzyme upon fusion partner promoted interaction, appear as well-suited to study RAF dimerization. Here, we provide an extensive analysis of the suitability of the Nanoluc system to study the homo- and heterodimerization of BRAF, RAF1 and the related KSR1 pseudokinase. We show that KRASG12V promotes the homo- and heterodimerization of BRAF, while considerable KSR1 homo- and KSR1/BRAF heterodimerization already occurs in the absence of this active GTPase and requires a salt bridge between the CC-SAM domain of KSR1 and the BRAF-specific region. We demonstrate that loss-of-function mutations impairing key steps of the RAF activation cycle can be used as calibrators to gauge the dynamics of heterodimerization. This approach identified the RAS-binding domains and the C-terminal 14–3-3 binding motifs as particularly critical for the reconstitution of RAF mediated LgBiT/SmBiT reconstitution, while the dimer interface was less important for dimerization but essential for downstream signaling. We show for the first time that BRAFV600E, the most common BRAF oncoprotein whose dimerization status is controversially portrayed in the literature, forms homodimers in living cells more efficiently than its wildtype counterpart. Of note, Nanoluc activity reconstituted by BRAFV600E homodimers is highly sensitive to the paradox-breaking RAFi PLX8394, indicating a dynamic and specific PPI. We report the effects of eleven ERK pathway inhibitors on RAF dimerization, incl. third-generation compounds that are less-defined in terms of their dimer promoting abilities. We identify Naporafenib as a potent and long-lasting dimerizer and show that the split Nanoluc approach discriminates between type I, I1/2 and II RAFi. Video Abstract

Abstract Brazil is among the largest apple producers in the world (Malus domestica Bork, Rosaceae), with production concentrated mainly in the southern of the country. Panonychus ulmi (Koch) (Tetranychidae) have economic importance in apple and, recently, Aculus schlechtendali (Nalepa) (Eriophyidae), was reported in Brazil. This review aims to delineate the distribution of the acarofauna associated to apple, with emphasis on the main groups of economic importance and their potential natural enemies and highlight the problems related to phytophagous species and management possibilities. Searches were carried out in databases, and the principal keywords were Aculus schlechtendali, Malus domestica and Panonychus ulmi. After the exclusion criteria resulted 166 publications. The social and economic importance of the apple has been increasing on the world, however, due to environmental imbalance, phytophagous mites are increasing their populations and acquiring resistance against acaricides. Panonychus ulmi has been reported in America for decades, being of economic importance for Brazil and the record of A. schlechtendali alerts to the possibility of damage in orchards in the country. Therefore, it is important that the literature be evaluated, that the mite species are identified and that forms of conscious management are developed. Prioritizing the human and animal health and environmental balance.

Tumor-associated p53 mutations endow cells with malignant phenotypes, including chemoresistance. Amyloid-like oligomers of mutant p53 transform this tumor suppressor into an oncogene. However, the composition and distribution of mutant p53 oligomers are unknown and the mechanism involved in the conversion is sparse. Here, we report accumulation of a p53 mutant within amyloid-like p53 oligomers in glioblastoma-derived cells presenting a chemoresistant gain-of-function phenotype. Statistical analysis from fluorescence fluctuation spectroscopy, pressure-induced measurements, and thioflavin T kinetics demonstrates the distribution of oligomers larger than the active tetrameric form of p53 in the nuclei of living cells and the destabilization of native-drifted p53 species that become amyloid. Collectively, these results provide insights into the role of amyloid-like mutant p53 oligomers in the chemoresistance phenotype of malignant and invasive brain tumors and shed light on therapeutic options to avert cancer.

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.

Background: The bond capacity of universal adhesives should be comparable to a specific primer for zirconia. Thus, this study evaluated the bond strength to zirconia of four universal adhesives and a zirconia primer over long-term storage. Materials and Methods: The surfaces of 75 samples of zirconia were sandblasted with 50 μm aluminum oxide particles and then divided into groups (n = 15): G1 – Single Bond Universal (SBU); G2 – All Bond Universal; G3 – Peak Universal Bond; G4 – Ambar Universal (AU), and G5 – Z-Prime Plus (ZP). A cone of resin composite was constructed on the applied materials. The samples were submitted to a tensile bond strength test after 24 h using a universal testing machine. Then, the remaining materials were removed from the sample surfaces, and the surfaces were polished and sandblasted again as previously described to obtain the same groups. These new samples were stored in distilled water at 37°C for 12 months and then submitted to a tensile bond strength test. The data were analyzed by two-way analysis of variance and Tukey's test (α =0.05). Results: The material factor (P = 0.001) and the storage factor (P = 0.001) were significant, and the interaction was not significant (P = 0.117). According to Tukey's test, bond strength mean values (in MPa) followed by distinct letters were significantly different. After 24 h, G5 = 21.12 A, G1 = 20.55 A, G4 = 19.19 AB, G2 = 14.22 B, and G3 = 8.44 C. After 12 months, G1 = 7.37 A, G5 = 5.61 AB, G4 = 4.97 B, G2 = 3.32 C, and G3 = 1.93 D. After 12 months of storage, all groups' bond strength significantly decreased. Conclusions: SBU and AU had bond strengths comparable to ZP after 24 h. No material resisted water degradation.

The Search for Medieval Music in Africa and Germany, 1891-1961: Scholars, Singers, Missionaries, by Anna Maria Busse Berger. New Material Histories of Music. Chicago: University of Chicago Press, 2020. xii, [...]

Abstract Background Reliable biomarkers to differentiate gastrointestinal cancer (GIC) from chronic inflammatory enteropathy (CIE) in dogs are needed. Fecal and serum microRNAs (miRNAs) have been proposed as diagnostic and prognostic markers of GI disease in humans and dogs. Hypothesis/Objectives Dogs with GIC have fecal and serum miRNA profiles that differ from those of dogs with CIE. Aims: (a) identify miRNAs that differentiate GIC from CIE, (b) use high‐throughput reverse transcription quantitative real‐time PCR (RT‐qPCR) to establish fecal and serum miRNA panels to distinguish GIC from CIE in dogs. Animals Twenty‐four dogs with GIC, 10 dogs with CIE, and 10 healthy dogs, all client‐owned. Methods An international multicenter observational prospective case‐control study. Small RNA sequencing was used to identify fecal and serum miRNAs, and RT‐qPCR was used to establish fecal and serum miRNA panels with the potential to distinguish GIC from CIE. Results The best diagnostic performance for distinguishing GIC from CIE was fecal miR‐451 (AUC: 0.955, sensitivity: 86.4%, specificity: 100%), miR‐223 (AUC: 0.918, sensitivity: 90.9%, specificity: 80%), and miR‐27a (AUC: 0.868, sensitivity: 81.8%, specificity: 90%) and serum miR‐20b (AUC: 0.905, sensitivity: 90.5%, specificity: 90%), miR‐148a‐3p (AUC: 0.924, sensitivity: 85.7%, specificity: 90%), and miR‐652 (AUC: 0.943, sensitivity: 90.5%, specificity: 90%). Slightly improved diagnostic performance was achieved when combining fecal miR‐451 and miR‐223 (AUC: 0.973, sensitivity: 95.5%, specificity: 90%). Conclusions and Clinical Importance When used as part of a diagnostic RT‐qPCR panel, the abovementioned miRNAs have the potential to function as noninvasive biomarkers for the differentiation of GIC and CIE in dogs.