77 research outputs found
Developmental pathways inferred from modularity, morphological integration and fluctuating asymmetry patterns in the human face
Facial asymmetries are usually measured and interpreted as proxies to developmental noise. However, analyses focused on its developmental and genetic architecture are scarce. To advance on this topic, studies based on a comprehensive and simultaneous analysis of modularity, morphological integration and facial asymmetries including both phenotypic and genomic information are needed. Here we explore several modularity hypotheses on a sample of Latin American mestizos, in order to test if modularity and integration patterns difer across several genomic ancestry backgrounds. To do so, 4104 individuals were analyzed using 3D photogrammetry reconstructions and a set of 34 facial landmarks placed on each individual. We found a pattern of modularity and integration that is conserved across sub-samples difering in their genomic ancestry background. Specifcally, a signal of modularity based on functional demands and organization of the face is regularly observed across the whole sample. Our results shed more light on previous evidence obtained from Genome Wide Association Studies performed on the same samples, indicating the action of diferent genomic regions contributing to the expression of the nose and mouth facial phenotypes. Our results also indicate that large samples including phenotypic and genomic metadata enable a better understanding of the developmental and genetic architecture of craniofacial phenotypes
Evidence that Proteasome-Dependent Degradation of the Retinoblastoma Protein in Cells Lacking A-Type Lamins Occurs Independently of Gankyrin and MDM2
A-type lamins, predominantly lamins A and C, are nuclear intermediate filaments believed to act as scaffolds for assembly of transcription factors. Lamin A/C is necessary for the retinoblastoma protein (pRB) stabilization through unknown mechanism(s). Two oncoproteins, gankyrin and MDM2, are known to promote pRB degradation in other contexts. Consequently, we tested the hypothesis that gankyrin and/or MDM2 are required for enhanced pRB degradation in Lmna-/- fibroblasts. Principal Findings. To determine if gankyrin promotes pRB destabilization in the absence of lamin A/C, we first analyzed its protein levels in Lmna-/- fibroblasts. Both gankyrin mRNA levels and protein levels are increased in these cells, leading us to further investigate its role in pRB degradation. Consistent with prior reports, overexpression of gankyrin in Lmna+/+ cells destabilizes pRB. This decrease is functionally significant, since gankyrin overexpressing cells are resistant to p16(ink4a)-mediated cell cycle arrest. These findings suggest that lamin A-mediated degradation of pRB would be gankyrin-dependent. However, effective RNAi-enforced reduction of gankyrin expression in Lmna-/- cells was insufficient to restore pRB stability. To test the importance of MDM2, we disrupted the MDM2-pRB interaction by transfecting Lmna-/- cells with p14(arf). p14(arf) expression was also insufficient to stabilize pRB or confer cell cycle arrest, suggesting that MDM2 also does not mediate pRB degradation in Lmna-/- cells.Our findings suggest that pRB degradation in Lmna-/- cells occurs by gankyrin and MDM2-independent mechanisms, leading us to propose the existence of a third proteasome-dependent pathway for pRB degradation. Two findings from this study also increase the likelihood that lamin A/C functions as a tumor suppressor. First, protein levels of the oncoprotein gankyrin are elevated in Lmna-/- fibroblasts. Second, Lmna-/- cells are refractory to p14(arf)-mediated cell cycle arrest, as was previously shown with p16(ink4a). Potential roles of lamin A/C in the suppression of tumorigenesis are discussed
The arabidopsis DNA polymerase δ has a role in the deposition of transcriptionally active epigenetic marks, development and flowering
DNA replication is a key process in living organisms. DNA polymerase α (Polα) initiates strand synthesis, which is performed by Polε and Polδ in leading and lagging strands, respectively. Whereas loss of DNA polymerase activity is incompatible with life, viable mutants of Polα and Polε were isolated, allowing the identification of their functions beyond DNA replication. In contrast, no viable mutants in the Polδ polymerase-domain were reported in multicellular organisms. Here we identify such a mutant which is also thermosensitive. Mutant plants were unable to complete development at 28°C, looked normal at 18°C, but displayed increased expression of DNA replication-stress marker genes, homologous recombination and lysine 4 histone 3 trimethylation at the SEPALLATA3 (SEP3) locus at 24°C, which correlated with ectopic expression of SEP3. Surprisingly, high expression of SEP3 in vascular tissue promoted FLOWERING LOCUS T (FT) expression, forming a positive feedback loop with SEP3 and leading to early flowering and curly leaves phenotypes. These results strongly suggest that the DNA polymerase δ is required for the proper establishment of transcriptionally active epigenetic marks and that its failure might affect development by affecting the epigenetic control of master genes.Fil: Iglesias, Francisco Manuel. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Bruera, Natalia Alejandra. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Dergan Dylon, Leonardo Sebastian. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Marino, Cristina Ester. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Lorenzi, Hernán. J. Craig Venter Institute; Estados UnidosFil: Mateos, Julieta Lisa. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina. Max Planck Institute for Plant Breeding Research; AlemaniaFil: Turck, Franziska. Max Planck Institute for Plant Breeding Research; AlemaniaFil: Coupland, George. Max Planck Institute for Plant Breeding Research; AlemaniaFil: Cerdan, Pablo Diego. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina. Universidad de Buenos Aires. Departamento de Ciencias Exactas; Argentin
Early-life gut dysbiosis linked to juvenile mortality in ostriches
Imbalances in the gut microbial community (dysbiosis) of vertebrates have been associated with several gastrointestinal and autoimmune diseases. However, it is unclear which taxa are associated with gut dysbiosis, and if particular gut regions or specific time periods during ontogeny are more susceptible. We also know very little of this process in non-model organisms, despite an increasing realization of the general importance of gut microbiota for health
Acompanhamento de pacientes submetidos à cirurgia bariátrica : aspectos laboratoriais nos perÃodos pré e pós-operatório
Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmácia, Florianópolis, 2017A obesidade é uma doença crônica e endócrino-metabólica caracterizada pelo acúmulo excessivo de triacilgliceróis no tecido adiposo, capaz de ser revertida ou amenizada através de intervenção cirúrgica. Epidemiologicamente têm sido descritas associações entre o excesso de peso, resistência à insulina e processo inflamatório crônico. Além disso, nas últimas décadas o sistema complemento foi associado a doenças metabólicas e cardiovasculares e intimamente relacionado com a obesidade e resistência à insulina. Sendo assim, a melhora do estado metabólico e a remissão da inflamação em pacientes obesos submetidos à cirurgia bariátrica foram avaliadas, bem como a associação dos fatores 3 e 4 (C3 e C4) do sistema complemento com a sensibilidade à insulina e a perda de peso após a cirurgia bariátrica. Para isso, a presença de comorbidades e as concentrações séricas de leptina, adiponectina, resistina e grelina foram avaliados em pacientes obesos mórbidos antes, 1, 3 e 6 meses após a cirurgia bariátrica. Também foram medidas as concentrações de IL-1ß, IL-6, TNF-a, proteÃna amiloide sérica A (SAA), proteÃna quimiotática de monócitos 1 (MCP-1), C3, C4, glicose, insulina, colesterol total, triacilglicerol, LDL- colesterol, HDL-colesterol e foi realizado o cálculo do modelo de avaliação da homeostase da resistência à insulina (HOMA-IR) durante o seguimento da cirurgia, bem como em comparação com um grupo de indivÃduos não-obesos. Como resultado, observou-se uma redução significativa de peso acompanhada de melhora do perfil lipÃdico, da sensibilidade à insulina e das comorbidades. Ainda, houve diminuição de leptina e aumento de adiponectina no perÃodo pós-cirúrgico. IL-1ß, IL-6, TNF-a, MCP-1 e SAA não mostraram diferença no acompanhamento da cirurgia, porém SAA correlacionou-se com o IMC e apresentou-se muito mais alto no grupo de pacientes obesos. Além disso, C3 e C4 foram significativamente maiores em indivÃduos obesos quando comparados aos indivÃduos não-obesos e C3 e C4 foram positivamente correlacionados com HOMA-IR e as concentrações de C3 foram significativamente diminuÃdas após a cirurgia. Com base nesses resultados, a cirurgia bariátrica mostrou melhorar o estado metabólico melhorando as comorbidades associadas à obesidade e os biomarcadores de adiposidade leptina e adiponectina, mas não os demais hormônios e citocinas inflamatórias e C3 e C4 foram fortemente associados à sensibilidade à insulina.Abstract: Obesity is a chronic and endocrine-metabolic disease characterized by triacylglycerol accumulation in the adipose tissue, which can be reversed or improved through surgical intervention. Epidemiologically, associations between overweight, insulin resistance and chronic inflammatory process have been described. Furthermore, in the last decades the complement system was associated with metabolic and cardiovascular diseases and related to obesity and insulin resistance. Thus, metabolic status improvement and inflammation remission in obese patients undergoing bariatric surgery were evaluated, as well as the association of complement system factors 3 and 4 (C3 and C4) with insulin sensitivity and weight loss after bariatric surgery. For this, comorbidities and leptin, adiponectin, resistin and ghrelin serum concentrations were evaluated in morbidly obese patients before, 1, 3 and 6 months after bariatric surgery. IL-1ß, IL-6, TNF-a, serum amyloid A protein (SAA), monocyte chemotactic protein 1 (MCP-1), C3, C4, glucose, insulin, total cholesterol, triacylglycerol, LDL-cholesterol, HDL-cholesterol concentrations and the calculation of the homeostasis model of insulin resistance (HOMA-IR) were performed during the surgery follow-up, as well in a group of non-obese individuals. As a result, significant weight loss followed by improvement in lipid profile, insulin sensitivity and comorbidities were observed. Still, there was a decrease in leptin and an increase in adiponectin in the postoperative period. IL-1ß, IL-6, TNF-a, MCP-1 and SAA showed no difference after surgery, but SAA correlated with BMI and was much higher in obese patients. In addition, both C3 and C4 were significantly higher in obese individuals when compared to lean individuals and positively correlated with HOMA-IR. C3 concentrations were significantly decreased after surgery. Based on these results, bariatric surgery has been shown to improve metabolic status by improving obesity-associated comorbidities and adiposity biomarkers leptin and adiponectin but not the other hormones and inflammatory cytokines and C3 and C4 were strongly associated with insulin sensitivity
Excess cerebral TNF causing glutamate excitotoxicity rationalizes treatment of neurodegenerative diseases and neurogenic pain by anti-TNF agents
Automatic profile generation for UAV operators using a simulation-based training environment
- …