卵泡膜细胞的胰岛素抵抗对其雄激素合成的影响以及胰岛素增敏剂的调控机制

为探索卵泡膜细胞人工诱导胰岛素抵抗后其雄激素合成的变化,以及胰岛素增敏剂曲格列酮、二甲双胍对胰岛素抵抗卵泡膜细胞的调控作用,采用猪卵巢内卵泡膜细胞进行体外培养,地塞米松诱导,构建胰岛素抵抗的细胞模型,用曲格列酮和二甲双胍分别处理模型细胞,检测培养液中葡萄糖和激素水平的变化以及胰岛素信号分子和雄激素合成关键酶的mRNA表达变化.结果表明:卵巢内卵泡膜细胞发生胰岛素抵抗后能明显增进其雄激素合成能力:曲格列酮、二甲双胍均能降低胰岛素抵抗的卵泡膜细胞的糖代谢异常和雄激素水平.     

Isotopic evidence for Mesoarchaean anoxia and changing atmospheric sulphur chemistry

The evolution of the Earth's atmosphere is marked by a transition from an early atmosphere with very low oxygen content to one with an oxygen content within a few per cent of the present atmospheric level. Placing time constraints on this transition is of interest because it identifies the time when oxidative weathering became efficient, when ocean chemistry was transformed by delivery of oxygen and sulphate, and when a large part of Earth's ecology changed from anaerobic to aerobic. The observation of non-mass-dependent sulphur isotope ratios in sedimentary rocks more than approximately 2.45 billion years (2.45 Gyr) old and the disappearance of this signal in younger sediments is taken as one of the strongest lines of evidence for the transition from an anoxic to an oxic atmosphere around 2.45 Gyr ago. Detailed examination of the sulphur isotope record before 2.45 Gyr ago also reveals early and late periods of large amplitude non-mass-dependent signals bracketing an intervening period when the signal was attenuated. Until recently, this record has been too sparse to allow interpretation, but collection of new data has prompted some workers to argue that the Mesoarchaean interval (3.2-2.8 Gyr ago) lacks a non-mass-dependent signal, and records the effects of earlier and possibly permanent oxygenation of the Earth's atmosphere. Here we focus on the Mesoarchaean interval, and demonstrate preservation of a non-mass-dependent signal that differs from that of preceding and following periods in the Archaean. Our findings point to the persistence of an anoxic early atmosphere, and identify variability within the isotope record that suggests changes in pre-2.45-Gyr-ago atmospheric pathways for non-mass-dependent chemistry and in the ultraviolet transparency of an evolving early atmosphere.     

Maternal signals for progeny prevention against allergy and asthma

Allergy and asthma are chronic inflammatory diseases which result from complex gene–environment interactions. Recent evidence indicates the importance of prenatal and postnatal developmental processes in terms of maturation of balanced immune responses. According to the current view, gene–environment interactions during a restricted time frame are responsible for programming of the immune system in favor of allergic immune mechanisms later in life. The interaction between genes and environment is complex and only partially understood; however, heritable epigenetic modifications including chemical additions in and alternative packaging of the DNA have been shown to play a crucial role in this context. Novel data indicate that epigenetic mechanisms contribute to the development of T-helper cell function. Environmental factors, including diesel exhaust particles (DEP), vitamins and tobacco smoke, operate through such mechanisms. Furthermore, the role of environmental microbes provides another and maybe even more important group of exogenous exposures which operates in this critical time frame.     

Peirescs Nebel im Sternbild Orion—eine neue Textgrundlage für die Geschichte von M42

Nicolas Claude Fabri de Peiresc (1580–1637) gilt als Entdecker des Orion-Nebels (M42). Als solcher ist er seit neunzig Jahren bekannt. Der französische Astronom und Wissenschaftshistoriker Guillaume Bigourdan zog diesen Schluss aus Aufzeichnungen, die er in Peirescs unveröffentlichtem Journal des observations entdeckt und 1916 veröffentlicht hatte. Demnach soll Peiresc den Orion-Nebel im November 1610 beobachtet haben. Peirescs Zeitgenossen jedoch war diese Beobachtung verborgen geblieben, und niemandem sonst gelang sie so früh nach Einführung des Teleskops. Mittlerweile sind Zweifel an Peirescs Entdeckung angemeldet worden. Die von Bigourdan veröffentlichten Notizen sind bislang keiner eingehenden Prüfung unterzogen worden. Der vorliegende Aufsatz liefert eine neue Transkription sowie erstmals eine Übersetzung der lateinischen Handschrift. Im Vergleich dazu erweist sich die Bigourdansche Edition häufig als nicht korrekt. Peirescs Orion-Bericht, der hier erstmals in Gänze lesbar vorliegt, wirft neue Fragen auf. Denn aus ihm geht nicht hervor, welche Region im Sternbild Orion, welche Sterne und welche Nebelobjekte Peiresc 1610 beobachtete. Die vollständige Lektüre von Peirescs Notizen verlangt nach einer neuen Interpretation seiner Beobachtungen im Sternbild Orion. Nur so ließe sich klären, ob tatsächlich schon Peiresc den Orion-Nebel sehen konnte oder ob womöglich M42 erst später sichtbar wurde.     

DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis

Hypophosphatemia is a genetically heterogeneous disease. Here, we mapped an autosomal recessive form (designated ARHP) to chromosome 4q21 and identified homozygous mutations in DMP1 (dentin matrix protein 1), which encodes a non-collagenous bone matrix protein expressed in osteoblasts and osteocytes. Intact plasma levels of the phosphaturic protein FGF23 were clearly elevated in two of four affected individuals, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH)2D levels and suggesting that DMP1 may regulate FGF23 expression.     

Linking climate change to lemming cycles

The population cycles of rodents at northern latitudes have puzzled people for centuries, and their impact is manifest throughout the alpine ecosystem. Climate change is known to be able to drive animal population dynamics between stable and cyclic phases, and has been suggested to cause the recent changes in cyclic dynamics of rodents and their predators. But although predator-rodent interactions are commonly argued to be the cause of the Fennoscandian rodent cycles, the role of the environment in the modulation of such dynamics is often poorly understood in natural systems. Hence, quantitative links between climate-driven processes and rodent dynamics have so far been lacking. Here we show that winter weather and snow conditions, together with density dependence in the net population growth rate, account for the observed population dynamics of the rodent community dominated by lemmings (Lemmus lemmus) in an alpine Norwegian core habitat between 1970 and 1997, and predict the observed absence of rodent peak years after 1994. These local rodent dynamics are coherent with alpine bird dynamics both locally and over all of southern Norway, consistent with the influence of large-scale fluctuations in winter conditions. The relationship between commonly available meteorological data and snow conditions indicates that changes in temperature and humidity, and thus conditions in the subnivean space, seem to markedly affect the dynamics of alpine rodents and their linked groups. The pattern of less regular rodent peaks, and corresponding changes in the overall dynamics of the alpine ecosystem, thus seems likely to prevail over a growing area under projected climate change.     

Robust trading rule selection and forecasting accuracy

Trading rules performing well on a given data set seldom lead to promising out-of-sample results, a problem which is a consequence of the in-sample data snooping bias. Efforts to justify the selection of trading rules by assessing the out-of-sample performance will not really remedy this predica- ment either, because they are prone to be trapped in what is known as the out-of-sample data-snooping bias. Our approach to curb the data-snooping bias consists of constructing a framework for trading rule selection using a-priori robustness strategies, where robustness is gauged on the basis of time- series bootstrap and multi-objective criteria. This approach focuses thus on building robustness into the process of trading rule selection at an early stage, rather than on an ex-post assessment of trading rule fitness. Intra-day FX market data constitute the empirical basis of the proposed investigations. Trading rules are selected from a wide universe created by evolutionary computation tools. The authors show evidence of the benefit of this approach in terms of indirect forecasting accuracy when investing in FX markets.     

Using a heterogeneous multinomial probit model with a neural net extension to model brand choice

The multinomial probit model introduced here combines heterogeneity across households with flexibility of the (deterministic) utility function. To achieve flexibility deterministic utility is approximated by a neural net of the multilayer perceptron type. A Markov Chain Monte Carlo method serves to estimate heterogeneous multinomial probit models which fulfill economic restrictions on signs of (marginal) effects of predictors (e.g., negative for price). For empirical choice data the heterogeneous multinomial probit model extended by a multilayer perceptron clearly outperforms all the other models studied. Moreover, replacing homogeneous by heterogeneous reference price mechanisms and thus allowing price expectations to be formed differently across households also leads to better model performance. Mean utility differences and mean elasticities w.r.t. price and price deviation from reference price demonstrate that models with linear utility and nonlinear utility approximated by a multilayer perceptron lead to very different implications for managerial decision making. Copyright © 2007 John Wiley & Sons, Ltd.