New insights into the pathological role of TNF-alpha in early cardiac dysfunction and subsequent heart failure after infarction in rats

A marked increase in plasma TNF-alpha has been described in patients with chronic heart failure (CHF). Nevertheless, little is known about the direct role of this cytokine early after myocardial infarction (MI) and its possible effects on the subsequent development of CHF. Wistar rats were subjected to permanent in vivo coronary artery ligation. At 5, 7, and 9 days after MI, cardiac function, passive compliance of the left ventricle (LV), and cardiac geometry were evaluated. The same model was used to perform pharmacological studies 7 days and 10 wk after MI in rats treated with monomeric recombinant human soluble TNF-alpha receptor type II (sTNF-RII, 40 microg/kg iv) or a placebo on day 3. Maximal alterations of cardiac function and geometry occurred 7 days after MI, which correlated chronologically with a peak of cardiac and serum TNF-alpha, as shown by immunohistochemistry and ELISA, respectively. sTNF-RII improved LV end-diastolic pressure under basal conditions and after volume overload 7 days and 10 wk after MI. Moreover, a significant leftward shift of the pressure-volume curve in the sTNF-RII-treated group 7 days after MI indicated a preservation of LV volume. Infarct expansion index was also significantly improved by sTNF-RII 7 days after MI (P < 0.01). Nevertheless, 10 wk after MI, geometric indexes and passive pressure-volume curves were not significantly improved by the treatment. In conclusion, TNF-alpha plays a major role in cardiac alterations 7 days after MI in rats and contributes to hemodynamic derangement, but not to cardiac remodeling, in subsequent CHF.     

Effects of iron and oxygen species scavengers on Listeria spp. chemiluminescence

Listeria monocytogenes and Listeria innocua are able, under certain conditions, to produce chemiluminescence (CL), which is amplified by luminol. Kinetic studies of CL by L. monocytogenes and L. innocua show a close parallelism between CL and growth curves during the exponential phase, with a maximum of CL reached just before entrance of bacteria into the stationary phase. CL is tightly correlated with the release of oxygen compounds. The reactive oxygen species scavengers tryptophan, mannitol, and tiron, as well as cellobiose and high temperature, were assessed with regard to CL in the two Listeria species. Only tiron strongly reduced the CL emitted by L. monocytogenes and L. innocua. On the other hand, charcoal pretreatment of the growth medium inhibited the CL, whereas ferric citrate strongly increased the CL of L. monocytogenes and L. innocua. These data suggest that iron and superoxide radical are implicated in the CL produced by these bacteria, but this phenomenon is not correlated to virulence.     

Environmentally induced changes in carotenoid-based coloration of female lizards: a comment on Vercken et al

Colouration may either reflect a discrete polymorphism potentially related to life-history strategies, a continuous signal related to individual quality or a combination of both. Recently, Vercken et al. [J. Evol. Biol. (2007) 221] proposed three discrete ventral colour morphs in female common lizards, Lacerta vivipara, and suggested that they reflect alternative reproductive strategies. Here, we provide a quantitative assessment of the phenotypic distribution and determinants of the proposed colour polymorphism. Based on reflectance spectra, we found no evidence for three distinct visual colour classes, but observed continuous variation in colour from pale yellow to orange. Based on a 2-year experiment, we also provide evidence for reversible colour plasticity in response to a manipulation of the adult population sex ratio; yet, a significant portion of the colour variation was invariant throughout an adult female's life. Our results are thus in agreement with continuous colour variation in adults determined by environmental factors and potentially also by genetic factors.     

Comparison of the genetic determinism of two key phenological traits,flowering and maturity dates,in three Prunus species: peach,apricot and sweet cherry

The present study investigates the genetic determinism of flowering and maturity dates, two traits highly affected by global climate change. Flowering and maturity dates were evaluated on five progenies from three Prunus species, peach, apricot and sweet cherry, during 3–8 years. Quantitative trait locus (QTL) detection was performed separately for each year and also by integrating data from all years together. High heritability estimates were obtained for flowering and maturity dates. Several QTLs for flowering and maturity dates were highly stable, detected each year of evaluation, suggesting that they were not affected by climatic variations. For flowering date, major QTLs were detected on linkage groups (LG) 4 for apricot and sweet cherry and on LG6 for peach. QTLs were identified on LG2, LG3, LG4 and LG7 for the three species. For maturity date, a major QTL was detected on LG4 in the three species. Using the peach genome sequence data, candidate genes underlying the major QTLs on LG4 and LG6 were investigated and key genes were identified. Our results provide a basis for the identification of genes involved in flowering and maturity dates that could be used to develop cultivar ideotypes adapted to future climatic conditions.     

低温对梨(Pyrus communis L.)果实后熟过程中乙烯合成和反应的影响(英文)

Passe Crassane梨果实采后需经过 6 0～ 80d的低温处理才能正常后熟。为了明确低温促进果实成熟的机理 ,对果实进行了低温和低温结合 1 MCP(1 甲基环丙烯 ,乙烯作用抑制剂 )和丙烯 (乙烯类似物 )处理。研究发现 :果实经低温处理后 ,乙烯合成前体———ACC含量大幅度升高 ,而未经低温处理的果实 ,无论贮藏在空气中或用丙烯 1 0 0 0μl/L处理 ,果实中ACC、M ACC含量均保持较低水平。但冷藏前用 1 MCP处理可抑制冷藏果实或冷藏后升温的果实ACC含量的增高。这说明果实的后熟过程与低温和依赖乙烯的ACC合成酶的活性和基因的表达密切相关。未经冷藏的果实于 2 0℃下用丙烯处理 ,果实不能自发合成乙烯 ,但当果实经过冷藏后再用丙烯处理 ,则果实对丙烯的反应能力随冷藏时间延长而增强。为了进一步了解低温诱导的乙烯反应过程。我们对乙烯受体基因进行了研究。定量PCR分析结果表明 ,与拟南芥ETR1同源的基因的表达不受低温的调节。但冷藏后升温 ,或在升温后用丙烯处理时 ,mRNA含量降低。这些结果说明 ,低温可能是通过影响乙烯信号转导途径下游的其它因子而调节依赖乙烯的ETR1基因和ACC合成酶基因的表达 ,从而影响果实的成熟过程     

GSK-3beta inhibition by lithium confers resistance to chemotherapy-induced apoptosis through the repression of CD95 (Fas/APO-1) expression

Lithium exerts neuroprotective actions that involve the inhibition of glycogen synthase kinase-3beta (GSK-3beta). Otherwise, recent studies suggest that sustained GSK-3beta inhibition is a hallmark of tumorigenesis. In this context, the present study was undertaken to examine whether lithium modulated cancer cell sensitivity to apoptosis induced by chemotherapy agents. We observed that, in different human cancer cell lines, lithium significantly reduced etoposide- and camptothecin-induced apoptosis. In HepG2 cells, lithium repressed drug induction of CD95 expression and clustering at the cell surface as well as caspase-8 activation. Lithium acted through deregulation of GSK-3beta signaling since (1) it provoked a rapid and sustained phosphorylation of GSK-3beta on the inhibitory serine 9 residue; (2) the GSK-3beta inhibitor SB-415286 mimicked lithium effects by repressing drug-induced apoptosis and CD95 membrane expression; and (3) lithium promoted the disruption of nuclear GSK-3beta/p53 complexes. Moreover, the overexpression of an inactivated GSK-3beta mutant counteracted the stimulatory effects of etoposide and camptothecin on a luciferase reporter plasmid driven by a p53-responsive sequence from the CD95 gene. In conclusion, we provide the first evidence that lithium confers resistance to apoptosis in cancer cells through GSK-3beta inhibition and subsequent repression of CD95 gene expression. Our study also highlights the concerted action of GSK-3beta and p53 on CD95 gene expression.     

Hydrophobic substrate utilisation by the yeast Yarrowia lipolytica, and its potential applications

The alkane-assimilating yeast Yarrowia lipolytica degrades very efficiently hydrophobic substrates such as n-alkanes, fatty acids, fats and oils for which it has specific metabolic pathways. An overview of the oxidative degradation pathways for alkanes and triglycerides in Y. lipolytica is given, with new insights arising from the recent genome sequencing of this yeast. This includes the interaction of hydrophobic substrates with yeast cells, their uptake and transport, the primary alkane oxidation to the corresponding fatty alcohols and then by different enzymes to fatty acids, and the subsequent degradation in peroxisomal beta-oxidation or storage into lipid bodies. Several enzymes involved in hydrophobic substrate utilisation belong to multigene families, such as lipases/esterases (LIP genes), cytochromes P450 (ALK genes) and peroxisomal acyl-CoA oxidases (POX genes). Examples are presented demonstrating that wild-type and genetically engineered strains of Y. lipolytica can be used for alkane and fatty-acid bioconversion, such as aroma production, for production of SCP and SCO, for citric acid production, in bioremediation, in fine chemistry, for steroid biotransformation, and in food industry. These examples demonstrate distinct advantages of Y. lipolytica for their use in bioconversion reactions of biotechnologically interesting hydrophobic substrates.     

Interaction of Sirt3 with OGG1 contributes to repair of mitochondrial DNA and protects from apoptotic cell death under oxidative stress

Sirtuin 3 (Sirt3), a major mitochondrial NAD⁺-dependent deacetylase, targets various mitochondrial proteins for lysine deacetylation and regulates important cellular functions such as energy metabolism, aging, and stress response. In this study, we identified the human 8-oxoguanine-DNA glycosylase 1 (OGG1), a DNA repair enzyme that excises 7,8-dihydro-8-oxoguanine (8-oxoG) from damaged genome, as a new target protein for Sirt3. We found that Sirt3 physically associated with OGG1 and deacetylated this DNA glycosylase and that deacetylation by Sirt3 prevented the degradation of the OGG1 protein and controlled its incision activity. We further showed that regulation of the acetylation and turnover of OGG1 by Sirt3 played a critical role in repairing mitochondrial DNA (mtDNA) damage, protecting mitochondrial integrity, and preventing apoptotic cell death under oxidative stress. We observed that following ionizing radiation, human tumor cells with silencing of Sirt3 expression exhibited deteriorated oxidative damage of mtDNA, as measured by the accumulation of 8-oxoG and 4977 common deletion, and showed more severe mitochondrial dysfunction and underwent greater apoptosis in comparison with the cells without silencing of Sirt3 expression. The results reported here not only reveal a new function and mechanism for Sirt3 in defending the mitochondrial genome against oxidative damage and protecting from the genotoxic stress-induced apoptotic cell death but also provide evidence supporting a new mtDNA repair pathway.     

A real-time spiking cerebellum model for learning robot control

We describe a neural network model of the cerebellum based on integrate-and-fire spiking neurons with conductance-based synapses. The neuron characteristics are derived from our earlier detailed models of the different cerebellar neurons. We tested the cerebellum model in a real-time control application with a robotic platform. Delays were introduced in the different sensorimotor pathways according to the biological system. The main plasticity in the cerebellar model is a spike-timing dependent plasticity (STDP) at the parallel fiber to Purkinje cell connections. This STDP is driven by the inferior olive (IO) activity, which encodes an error signal using a novel probabilistic low frequency model. We demonstrate the cerebellar model in a robot control system using a target-reaching task. We test whether the system learns to reach different target positions in a non-destructive way, therefore abstracting a general dynamics model. To test the system's ability to self-adapt to different dynamical situations, we present results obtained after changing the dynamics of the robotic platform significantly (its friction and load). The experimental results show that the cerebellar-based system is able to adapt dynamically to different contexts.