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Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is expected to soon surpass colorectal cancer as a leading cause of cancer mortality in both males and females in the US, only lagging behind lung cancer. The lethality of PDAC is driven by late diagnosis and inefficient therapies. The complex biology of PDAC involves various cellular components, including exosomes that carry molecular information between cells. Thus, recipient cells can be reprogrammed, impacting tumorigenesis. Rab27a is a GTPase responsible for the last step of exosomes biogenesis. Hence, dissecting the mechanisms that regulate the expression of Rab27a and that control exosomes biogenesis can provide fundamental insights into the molecular underpinnings regulating PDAC progression. Methods To assess the mechanism that regulates Rab27a expression in PDAC, we used PDAC cell lines. The biological significance of these findings was validated in PDAC genetically engineered mouse models (GEMMs) and human samples. Results In this work we demonstrate in human PDAC samples and GEMMs that Rab27a expression decreases throughout the development of the disease, and that Rab27a knockout promotes disease progression. What is more, we demonstrate that Rab27a expression is epigenetically regulated in PDAC. Treatment with demethylating agents increases Rab27a expression specifically in human PDAC cell lines. We found that SMC3, a component of the cohesin complex, regulates Rab27a expression in PDAC. SMC3 methylation is present in human PDAC specimens and treatment with demethylating agents increases SMC3 expression in human PDAC cell lines. Most importantly, high levels of SMC3 methylation are associated with a worse prognosis in PDAC. Mechanistically, we identified an enhancer region within the Rab27a gene that recruits SMC3, and modulates Rab27a expression. Conclusion Overall, we dissected a mechanism that regulates Rab27a expression during PDAC progression and impacts disease prognosis.

Abstract Dung serves as a critical resource for diverse organisms, including dung-inhabiting fungi, which play a key role in nutrient cycling. In this study, we examined the decomposition rates and half-lives of dung from ruminant and monogastric herbivores in a microcosm experiment, assessing the impact of autoclaving (fungal exclusion) on decomposition dynamics. Over six months, autoclaved dung decomposed more slowly, retaining greater biomass and highlighting the fungi’s role in matter cycling. Decomposition followed a Gaussian linear model, with constants k ranging from 0.02 to 0.03 and half-lives of 19–23 days. Nutrient mineralization varied significantly between the start and end of the experiment, underscoring the contribution of the fungi to nutrient release. Our findings emphasize the ecological importance of dung-inhabiting fungi and suggest areas for future research on factors influencing dung decomposition in terrestrial ecosystems.

IntroductionThe effectiveness of supraglottic airway devices (SGDs) as a strategy for blind endotracheal intubation (ETI) was compared in this study.MethodsA systematic review of clinical trials (CTs) involving SGDs for blind ETI in patients under general anesthesia or simulation manikins, was conducted. CTs that used SGDs for fiberoptic-guided ETI and those conducted in children were excluded. Searches were performed in Embase, MEDLINE (PubMed), Scopus, and LILACS. The primary outcomes examined were the success rate of blind ETI and intubation time. Secondary outcomes were first-attempt intubation success rate and perceived ease of use.ResultsA total of 567 records were identified from databases, and 16 were identified through citation searches. Ultimately, 27 CTs met the inclusion criteria. The Fastrach Intubating Laryngeal Mask Airway (LMA Fastrach), i-gel, Air-Q Intubating Laryngeal Airway, and Supraglottic Airway Laryngopharyngeal Tube (S.A.L.T.) were the most used SGDs for blind ETI. LMA Fastrach was the most frequently compared device in these CTs. Among the studies in patients, LMA Fastrach and i-gel were the devices that showed the shortest intubation time, although it may be influenced by the way intubation time is assessed. The SGDs with the highest overall success rate were i-gel, S.A.L.T., LMA Fastrach, and single-use LMA Fastrach, followed by Air-Q, and the Intubating Laryngeal Tube Suction-Disposable (iLTS-D2), all achieving success rates greater than 90%. AuraGain had the lowest first-attempt and overall success rates for blind ETI with SGDs.ConclusionNew SGDs have not surpassed the LMA Fastrach effectiveness for blind ETI. The single-use LMA Fastrach combines the efficacy of the reusable LMA Fastrach with the features of other SGDs and may be a suitable replacement for them. The I-gel is also a viable alternative for blind ETI, while the AuraGain may not be recommended for this purpose.

Rhodoliths occur extensively around the shores of Fuerteventura Island in the Canary Archipelago, with Lithothamnion cf. corallioides being the most prominent species. A large number of rhodoliths end up washed onshore, the debris from which contributes to the formation of sediments constituting modern beaches. In a previous study by one of the co-authors (MEJ), the northern coast of Fuerteventura was shown to comprise various types of rhodolith deposits such as beach, platform overwash, tidal pools, coastal dunes, and others. An extraordinary example of stranded rhodoliths is located near Caleta del Bajo de Mejillones, approximately 3 km west of Corralejo, on the north coast of the island. The deposit forms a supratidal beach 120 m long and 10 m wide that sits above the landward termination of an extensive wave-cut platform eroded in basalt and exposed at low tide to a width of 130 m perpendicular to shore. Here, rhodoliths are very small (

The continued scaling of genetic perturbation technologies combined with high-dimensional assays such as cellular microscopy and RNA-sequencing has enabled genome-scale reverse-genetics experiments that go beyond single-endpoint measurements of growth or lethality. Datasets emerging from these experiments can be combined to construct perturbative "maps of biology", in which readouts from various manipulations (e.g., CRISPR-Cas9 knockout, CRISPRi knockdown, compound treatment) are placed in unified, relatable embedding spaces allowing for the generation of genome-scale sets of pairwise comparisons. These maps of biology capture known biological relationships and uncover new associations which can be used for downstream discovery tasks. Construction of these maps involves many technical choices in both experimental and computational protocols, motivating the design of benchmark procedures to evaluate map quality in a systematic, unbiased manner. Here, we (1) establish a standardized terminology for the steps involved in perturbative map building, (2) introduce key classes of benchmarks to assess the quality of such maps, (3) construct 18 maps from four genome-scale datasets employing different cell types, perturbation technologies, and data readout modalities, (4) generate benchmark metrics for the constructed maps and investigate the reasons for performance variations, and (5) demonstrate utility of these maps to discover new biology by suggesting roles for two largely uncharacterized genes. Author summary: Due to the rapid advancements in genetic perturbation, laboratory robotics, sequencing, and computer vision, more researchers are now generating datasets that capture cellular responses to genetic perturbations. These datasets can be powerful discovery tools for examining known biological relationships and revealing new associations in an unbiased manner when paired with a computational pipeline that can assemble the data into a digestible format. However, the challenge arises from the variety of cellular models, assay designs, terminologies, codebases, and analysis methods involved. In this work we define a unified framework for building and benchmarking perturbative maps, benchmark four different datasets assembled into 18 different maps, explore the impact of different design decisions, and demonstrate how these maps can be used to elucidate gene functions. Our goal is to facilitate comparisons across various technologies and methods by introducing a shared language for the field. The open-source codebase, capable of incorporating new methods, aims to be a resource for researchers developing laboratory or computational methodology. While we caution against definitive recommendations due to numerous variables at play, we hope to stimulate studies directly comparing methods under controlled conditions. Our framework can also help evaluate combining maps across modalities as the field progresses. [ABSTRACT FROM AUTHOR]

O poder de punir do Estado, seja na esfera judicial, seja na administrativa, deve estar conforme as garantias constitucionais fundadas no binômio dignidade da pessoa humana e do devido processo legal, e que se cristalizaram em princípios erigidos sob à ideia de racionalidade do comportamento humano que deu origem ao Estado moderno. Os dois princípios vetores do exercício desse jus puniendi são a razoabilidade e a proporcionalidade, e que tem sofrido progressivo e inarredável controle judicial quando a administração pública exorbita da prerrogativa de punir seus servidores públicos.

Low-order streams located near urban areas usually receive domestic, industrial, and agricultural wastewaters that negatively affect river water quality. Additionally, water pollution is associated with land-use variations around the river, which is characterized by unplanned urbanization, intense agricultural activities, and deforestation. This work correlated land-use patterns with physicochemical quality and genotoxic potential of water at four points (P1 to P4) along the Extrema River, located in an industrial and agricultural area of Central Brazil. Physicochemical analyses indicated that the water collected from the Extrema River is inappropriate for human consumption. Using the Allium cepa model, no evidence of cytotoxicity was observed at any point; in contrast, the genotoxic potential of these water samples was observed. The correlation of these results with land use showed that the water collected at P3 was the most contaminated; this is probably due to the inflow of wastewater from municipal, industrial, and agriculture activities. Different results were observed for P2 and P4, where land-use analysis attributed the water quality to forest burns. We concluded that differential use of the land changed the characteristics of the associated river water, and A. cepa parameters were more related to land-use characteristics than to physicochemical parameters. This study highlighted the importance of associating land use with the cyto genotoxic potential of water.

Este artigo abordou sobre o desenho na Educação Infantil e a formação docente como categorias necessárias ao processo de desenvolvimento e construção de aprendizagens de crianças pequenas e bem pequenas. Para a construção deste artigo, fundamentou-se em autores como Aries (2018), Mazzamati (2012), Oliveira (2011), Mello (2007), Kuhlmann Jr (2002), Almeida (2003), Moreira (1993), dentre outros; e documentos oficiais legislam e orientam sobre a temática a exemplo do Constituição Federal (1988) ECA (1990), LDB (1996), RCNEI (1988), DCNEI (2009) e BNCC (2018). A pesquisa foi descritiva, de natureza exploratória e teve abordagem qualitativa. Os instrumentos de coletas de dados foram extraídos a partir da observação participante realizada em momentos de interações pedagógicas de crianças da pré-escola de uma Unidade de Educação Básica, situada na zona urbana de São Luís- MA. Os resultados alcançados reforçam o entendimento que as crianças tem muito a dizer e que é necessário a escuta atenta e sensível por parte do educador da infância.

Lettuce (Lactuca sativa L.) is one of the most produced and consumed leafy vegetables in Brazil and worldwide. One of the main problems faced by producers is identifying the best time for weed control. The objective of this work was to evaluate the occurrence of programmed weeding on production components of the ‘Lucy Brown’ American lettuce. The experiment was carried out between March and May 2017, at the Federal University of Roraima, Cauamé Campus, located in Boa Vista, Roraima, Brazil. The experimental design adopted was in randomized blocks, with 6 treatments and 4 repetitions. The treatments consisted of: 100% weed control (100% WC), weed control 5 days after transplanting (WC 5 DAT), weed control 10 days after transplanting (WC 10 DAT), weed control 15 days after transplanting (WC 15 DAT), weed control 20 days after transplanting (WC 20 DAT) and 100% without weed control (100% WWC). The variables evaluated were: shoot height, stem height, stem diameter, number of leaves, leaf length, leaf width, root length, shoot fresh weight, total fresh weight, shoot dry weight and productivity. It is concluded that the ‘Lucy Brown’ lettuce must be weed-free after 5 days of transplanting the seedlings in order to avoid yield loss. The lack of weed control in the cultivation of ‘Lucy Brown’ lettuce causes a 71.88% decrease in its productivity.

ABSTRACT: The objective was to estimate the physiological and productive performance of potato genotypes in two organic cultivation systems. Two trials were conducted, being one in a protected and on in an open-field environment. A randomized complete block design with four replicates and five treatments (genotypes ‘Agata’, ‘Atlantic’, ‘BRS Ana’, ‘BRSIPR Bel’ and ‘BRS Clara’) was used. Physiological, productive characteristics and defects associated with tubers were obtained. The protected environment is the most appropriate to produce organic potatoes under the evaluated conditions. Genotypes ‘BRSIPR Bel’ and ‘BRS Ana’ exhibit a high productive potential in organic conditions.

Muitos fatores podem interferir na estimativa do Intervalo Pós-Morte (IPM) que é o tempo entre a morte e o achado de corpo, dentre eles substâncias que alteram os padrões de desenvolvimento dos insetos colonizadores de carcaças. Neste estudo testamos a hipótese de que, se um recurso simulando um cadáver estiver contaminado pelo inseticida tiametoxam, moscas varejeiras da espécie Chrysomya megacephala (Fabricius) (Diptera: Calliphoridae) irão evitar explorá-lo e consumi-lo. Foram feitos testes de dupla escolha nos quais as moscas podiam optar por recurso contaminado ou não contaminado. Os resultados mostraram que estas moscas varejeiras não evitam carne contaminada com inseticida e, além disso consomem o recurso, contudo, ao fazerem isso executam comportamentos atípicos, como expor o ovipositor, e limpar-se frequentemente. Estes resultados sugerem que caso um cadáver seja contaminado com o inseticida tiametoxam, as moscas irão explorá-lo como recurso, no entanto, como esse produto altera o seu comportamento, seu ciclo de vida possivelmente será alterado, bem como a ordem de chegada das espécies, o que poderá afetar a estimativa do IPM, tendo importante impacto sobre as perícias forenses.