Effect of uncoupling protein-1 expression on 3T3-L1 adipocyte gene expression

The mitochondrial respiratory uncoupling protein 1 (UCP1) partially uncouples substrate oxidation and oxidative phosphorylation to promote the dissipation of cellular biochemical energy as heat in brown adipose tissue. We have recently shown that expression of UCP1 in 3T3-L1 white adipocytes reduces the accumulation of triglycerides. Here, we investigated the molecular basis underlying UCP1 expression in 3T3-L1 adipocytes. Gene expression data showed that forced UCP1 expression down-regulated several energy metabolism pathways; but ATP levels were constant. A metabolic flux analysis model was used to reflect the gene expression changes onto metabolic processes and concordance was observed in the down-regulation of energy consuming pathways. Our data suggest that adipocytes respond to long-term mitochondrial uncoupling by minimizing ATP utilization.     

Apoptosis repressor with caspase recruitment domain (ARC) inhibits myogenic differentiation

Apoptosis repressor with caspase recruitment domain (ARC), an anti-apoptotic protein, is highly expressed in differentiated heart and skeletal muscle. Apoptosis and differentiation share numerous common pathways; therefore, we examined the impact of ARC on H9c2-myoblast differentiation. We demonstrate that ARC expression levels increase and stabilize upon differentiation. ARC-overexpression in pre-differentiated H9c2-cells suppresses differentiation; indicated by increased myotube formation, nuclear fusion and expression of the differentiation markers myogenin and troponin-T. ARC-overexpression inhibited myoblast differentiation associated caspase-3 activation, suggesting ARC inhibits myogenic differentiation through caspase inhibition. In summary, we show a novel role for ARC in the regulation of muscle differentiation.     

Manifold active-state conformations in GPCRs: agonist-activated constitutively active mutant AT1 receptor preferentially couples to Gq compared to the wild-type AT1 receptor

The angiotensin II type I (AT(1)) receptor mediates regulation of blood pressure and water-electrolyte balance by Ang II. Substitution of Gly for Asn(111) of the AT(1) receptor constitutively activates the receptor leading to Gq-coupled IP(3) production independent of Ang II binding. The Ang II-activated conformation of the AT1(N111G) receptor was proposed to be similar to that of the wild-type AT(1) receptor, although, various aspects of the Ang II-induced conformation of this constitutively active mutant receptor have not been systematically studied. Here, we provide evidence that the conformation of the active state of the wild-type and the constitutively active AT(1) receptors are different. Upon Ang II binding an activated conformation of the wild-type AT(1) receptor activates G protein and recruits beta-arrestin. In contrast, the agonist-bound AT1(N111G) mutant receptor preferentially couples to Gq and is inadequate in beta-arrestin recruitment.     

Robustness of neural codes and its implication on natural image processing

In this study, based on the view of statistical inference, we investigate the robustness of neural codes, i.e., the sensitivity of neural responses to noise, and its implication on the construction of neural coding. We first identify the key factors that influence the sensitivity of neural responses, and find that the overlap between neural receptive fields plays a critical role. We then construct a robust coding scheme, which enforces the neural responses not only to encode external inputs well, but also to have small variability. Based on this scheme, we find that the optimal basis functions for encoding natural images resemble the receptive fields of simple cells in the striate cortex. We also apply this scheme to identify the important features in the representation of face images and Chinese characters.

E. O. 威尔逊与岛屿生物地理学理论

20世纪伟大的博物学家和生物地理学家爱德华·奥斯本·威尔逊(Edward Osborne Wilson,1929-2021)与杰出的理论和数学生态学家罗伯特·赫尔默·麦克阿瑟(Robert Helmer MacA rthur,1930-1972)共同开创的岛屿生物地理学理论是他们青年时代的巅峰之作。