The anaphase-promoting complex/cyclosome (APC/C) is a large multiprotein E3 ubiquitin ligase involved in ubiquitin-dependent proteolysis of key cell cycle regulatory proteins, including the ...destruction of mitotic cyclins at the metaphase-to-anaphase transition. Despite its importance, the role of the APC/C in plant cells and the regulation of its activity during cell division remain poorly understood. Here, we describe the identification of a plant-specific negative regulator of the APC/C complex, designated SAMBA. In Arabidopsis thaliana , SAMBA is expressed during embryogenesis and early plant development and plays a key role in organ size control. Samba mutants produced larger seeds, leaves, and roots, which resulted from enlarged root and shoot apical meristems, and, additionally, they had a reduced fertility attributable to a hampered male gametogenesis. Inactivation of SAMBA stabilized A2-type cyclins during early development. Our data suggest that SAMBA regulates cell proliferation during early development by targeting CYCLIN A2 for APC/C-mediated proteolysis.
Tumors are composed of many different cell types including cancer cells, fibroblasts, and immune cells. Dissecting functional metabolic differences between cell types within a mixed population can be ...challenging due to the rapid turnover of metabolites relative to the time needed to isolate cells. To overcome this challenge, we traced isotope-labeled nutrients into macromolecules that turn over more slowly than metabolites. This approach was used to assess differences between cancer cell and fibroblast metabolism in murine pancreatic cancer organoid-fibroblast co-cultures and tumors. Pancreatic cancer cells exhibited increased pyruvate carboxylation relative to fibroblasts, and this flux depended on both pyruvate carboxylase and malic enzyme 1 activity. Consequently, expression of both enzymes in cancer cells was necessary for organoid and tumor growth, demonstrating that dissecting the metabolism of specific cell populations within heterogeneous systems can identify dependencies that may not be evident from studying isolated cells in culture or bulk tissue.
The Cerrado-Amazonia Ecotone is one of the largest ecosystems in Brazil and is internationally considered a biodiversity hotspot. The occurrence of fires is common in these areas, directly affecting ...biomass losses and the reduction of vegetative vigor of forest typologies. Information obtained through remote sensing and geoprocessing can assist in the evaluation of vegetation behavior and its relation to the occurrence of forest fires. In this context, the objective of the present study was to analyze temporal vegetation dynamics, as well as their relationship with rainfall and fire occurrence on Indigenous lands, located in the Cerrado-Amazonia Ecotone of Mato Grosso state, Brazil. Normalized Difference Vegetation Index (NDVI) images of the MOD13Q1 MODIS product and burnt area of the MCD45A1 MODIS product, and rainfall images from the Tropical Rainfall Measuring Mission (TRMM) sensor were used. The period analyzed was from 2007 to 2016. After pre-processing the NDVI, TRMM and burnt area images, correlation analyses were performed between the rainfall, vegetation index and burnt area images, considering different lags (−3 to 3), to obtain the best response time for the variables. The analyses of inter-annual vegetation index trends were carried out following Mann–Kendall monotonic trend and seasonal trend analysis methodologies. Significant correlations were observed between NDVI and rainfall (R = 0.84), in grass regions and between NDVI and burnt area (R = −0.74). The Mann–Kendall monotonic trend indicates vegetation index stability with positive variations in grass regions. The analysis of seasonal trends identified different vegetation responses, with this biome presenting a diverse phytophysiognomy and seasonal vegetation with different phases for amplitudes. This variation is evidenced by the various phytophysiognomies and their responses in relation to biomass gains and losses. The correlation and regression of the NDVI and rainfall in the vegetation type of grass areas show that the burnt area tends to increase with the reduction of NDVI. Finally, no defined pattern of vegetation cycles or phases was observed in terms of seasonality and the proposed methodology can be adapted to other world biomes.
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by neutrophil articular infiltration, joint pain and the progressive destruction of cartilage and bone. IL-22 is a key effector ...molecule that plays a critical role in autoimmune diseases. However, the function of IL-22 in the pathogenesis of RA remains controversial. In this study, we investigated the role of IL-22 in the early phase of antigen-induced arthritis (AIA) in mice.
AIA was induced in C57BL/6, IL-22(-/-), ASC(-/-) and IL-1R1(-/-) immunized mice challenged intra-articularly with methylated bovine serum albumin (mBSA). Expression of IL-22 in synovial membranes was determined by RT-PCR. Articular hypernociception was evaluated using an electronic von Frey. Neutrophil recruitment and histopathological analyses were assessed in inflamed knee joint. Joint levels of inflammatory mediators and mBSA-specific IgG concentration in the serum were measured by ELISA.
The IL-22 mRNA expression and protein levels in synovial tissue were increased during the onset of AIA. In addition, pharmacological inhibition (anti-IL-22 antibody) and genetic deficiency (IL-22(-/-) mice) reduced articular pain and neutrophil migration in arthritic mice. Consistent with these findings, recombinant IL-22 joint administration promoted articular inflammation per se in WT mice, restoring joint nociception and neutrophil infiltration in IL-22(-/-) mice. Moreover, IL-22-deficient mice showed reduced synovitis (inflammatory cell influx) and lower joint IL-1β levels, whereas the production of IL-17, MCP-1/CCL2, and KC/CXCL1 and the humoral immune response were similar, compared with WT mice. Corroborating these results, the exogenous administration of IL-22 into the joints induced IL-1β production in WT mice and reestablished IL-1β production in IL-22(-/-) mice challenged with mBSA. Additionally, IL-1R1(-/-) mice showed attenuated inflammatory features induced by mBSA or IL-22 challenge. Articular nociception and neutrophil migration induced by IL-22 were also reduced in ASC(-/-) mice.
These results suggest that IL-22 plays a pro-inflammatory/pathogenic role in the onset of AIA through an ASC-dependent stimulation of IL-1β production.
Recently, remote sensing image time series analysis has being widely used to investigate the dynamics of environments over time. Many studies have combined image time series analysis with machine ...learning methods to improve land use and cover change mapping. In order to support image time series analysis, analysis-ready data (ARD) image collections have been modeled and organized as multidimensional data cubes. Data cubes can be defined as sets of time series associated with spatially aligned pixels. Based on lessons learned in the research project e-Sensing, related to national demands for land use and cover monitoring and related to state-of-the-art studies on relevant topics, we define the requirements to build Earth observation data cubes for Brazil. This paper presents the methodology to generate ARD and multidimensional data cubes from remote sensing images for Brazil. We describe the computational infrastructure that we are developing in the Brazil Data Cube project, composed of software applications and Web services to create, integrate, discover, access, and process the data sets. We also present how we are producing land use and cover maps from data cubes using image time series analysis and machine learning techniques.
Colony stimulating factor 1 receptor (CSF1R) plays key roles in regulating development and function of the monocyte/macrophage lineage, including microglia and osteoclasts. Mono-allelic mutations of ...CSF1R are known to cause hereditary diffuse leukoencephalopathy with spheroids (HDLS), an adult-onset progressive neurodegenerative disorder. Here, we report seven affected individuals from three unrelated families who had bi-allelic CSF1R mutations. In addition to early-onset HDLS-like neurological disorders, they had brain malformations and skeletal dysplasia compatible to dysosteosclerosis (DOS) or Pyle disease. We identified five CSF1R mutations that were homozygous or compound heterozygous in these affected individuals. Two of them were deep intronic mutations resulting in abnormal inclusion of intron sequences in the mRNA. Compared with Csf1r-null mice, the skeletal and neural phenotypes of the affected individuals appeared milder and variable, suggesting that at least one of the mutations in each affected individual is hypomorphic. Our results characterized a unique human skeletal phenotype caused by CSF1R deficiency and implied that bi-allelic CSF1R mutations cause a spectrum of neurological and skeletal disorders, probably depending on the residual CSF1R function.
Inspiratory muscle training (IMT) is known to promote physiological benefits and improve physical performance in endurance sports activities. However, the metabolic adaptations promoted by different ...IMT prescribing strategies remain unclear. In this work, a longitudinal, randomized, double-blind, sham-controlled, parallel trial was performed to investigate the effects of 11 weeks (3 days·weeksup.−1) of IMT at different exercise intensities on the serum metabolomics profile and its main regulated metabolic pathways. Twenty-eight healthy male recreational cyclists (30.4 ± 6.5 years) were randomized into three groups: sham (6 cm·Hsub.2O of inspiratory pressure, n = 7), moderate-intensity (MI group, 60% maximal inspiratory pressure (MIP), n = 11) and high-intensity (HI group, 85–90% MIP, n = 10). Blood serum samples were collected before and after 11 weeks of IMT and analyzed by sup.1H NMR and UHPLC-HRMS/MS. Data were analyzed using linear mixed models and metabolite set enrichment analysis. The sup.1H NMR and UHPLC-HRMS/MS techniques resulted in 46 and 200 compounds, respectively. These results showed that ketone body metabolism, fatty acid biosynthesis, and aminoacyl-tRNA biosynthesis were upregulated after IMT, while alpha linolenic acid and linoleic acid metabolism as well as biosynthesis of unsaturated fatty acids were downregulated. The MI group presented higher MIP, Tryptophan, and Valine levels but decreased 2-Hydroxybutyrate levels when compared to the other two studied groups. These results suggest an increase in the oxidative metabolic processes after IMT at different intensities with additional evidence for the upregulation of essential amino acid metabolism in the MI group accompanied by greater improvement in respiratory muscle strength.
Background
This study evaluated the effects of Bifidobacterium animalis subsp. lactis HN019 (B. lactis HN019) in the development of periodontitis (PE), associated or not with metabolic syndrome, (MS) ...in rats.
Methods
Ninety‐six rats were grouped according to a food protocol: high‐fat diet for induction of MS or standard diet for the control groups (C). They were subdivided into groups with (+) and without (−) PE, receiving (*) or not (**) probiotic (PROB): C−**, CP−*, PE+**, PEP+*, MS− MSP−*, MSPE+**, and MSPEP+*. PROB administration started on the eighth week of the study and PE was induced on the 14th week by placing ligature on the animals' lower first molars. Euthanasia occurred in the 16th week. Biomolecular analyzes, immunoenzymatic assays, and microtomographic analyses were performed. The data obtained were analyzed statistically (P < 0.05).
Results
The PEP and MSPEP groups showed lower levels of alveolar bone loss when compared with the PE and MSPE groups, respectively (P < 0.05). The immunoenzymatic analysis showed higher levels of interleukin (IL)‐1β and a higher receptor activator of NF‐kappaB ligand (RANKL)/osteoprotegerin (OPG) ratio in the MSPE group when compared with the MSPEP group (P < 0.05). The PEP group showed lower levels of tumor necrosis factor (TNF)‐α and IL–6 when compared with the PE group. The use of PROB attenuated dyslipidemia parameters in animals with MS, with or without PE.
Conclusion
B. lactis HN019 reduced more significantly the severity of PE in rats with MS, modulating both systemic metabolic and immunoinflammatory parameters in periodontal tissues.
Aim: To present an updated database of fish species recorded on south-western Atlantic reef environments and to explore the ecological drivers of the structure, the latitudinal gradient of ...biodiversity and the centre of endemism in this peripheral province. Location: South-western Atlantic (SWA): Brazilian and Argentinian Provinces. Methods: A database composed of 733 fish species along 23 locations in the SWA (00°55' N to 43°00' S) was compiled based on primary data, literature and museum records. Cluster and beta diversity analyses were carried out to evaluate faunal overlaps among locations and subprovinces. "Target-area-distance effect" and "stepping stones dispersal" hypotheses for assemblage composition were tested through Mantel tests. Relationships between the distribution patterns and ecological traits of reef fish species were investigated through generalized linear mixed-effect models. Results: Out of the 733 fish species, 405 are SWA resident reef fishes, of which 111 (27%) are endemics and 78 are threatened with extinction. Cluster analysis detected six subprovinces in the SWA structured following the target-area-distance model, and with no evidence for a latitudinal gradient in diversity. The greatest overall richness and endemic species richness were found in the east-south-eastern region. Depth range, habitat use and body size were the main drivers of SWA reef fish assemblage structure. Main conclusions: The Brazilian and Argentinian coasts constitute different provinces structured by oceanographic barriers and environmental filters. Similarities among oceanic islands indicate connectivity driven by stochastic and ecological factors. Species richness and endemism indicate that peripheral provinces may also bear centres of origin and biodiversity, patterns driven by parapatric/ecological speciation and the overlap between tropical and subtropical reef fish species. Ecological drivers of reef fish distribution, such as habitat specialization and body size, support hypotheses of speciation in the periphery. New approaches for spatial planning, marine protected areas and off-reserve marine management are essential for the conservation and sustainability of SWA reef fishes.
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