Immunochemical relationships among lysosomal acid phosphohydrolases: DNase II and nonspecific phosphodiesterase

Zusammenfassung Immunopräcipitationsreaktionen mit Schweinemilz, Desoxyribonuklease II, unspezifische Phosphodiesterase und Rindermilz-DNase II zeigen, dass eine engere immunologische Beziehung zwischen den Nukleasen beider Spezies besteht, als zwischen den beiden Schweinephosphohydrolasen.     

UDP-glucose ceramide glucosyltransferase activates AKT,promoted proliferation,and doxorubicin resistance in breast cancer cells

The UDP-glucose ceramide glucosyltransferase (UGCG) is a key enzyme in the synthesis of glycosylated sphingolipids, since this enzyme generates the precursor for all complex glycosphingolipids (GSL), the GlcCer. The UGCG has been associated with several cancer-related processes such as maintaining cancer stem cell properties or multidrug resistance induction. The precise mechanisms underlying these processes are unknown. Here, we investigated the molecular mechanisms occurring after UGCG overexpression in breast cancer cells. We observed alterations of several cellular properties such as morphological changes, which enhanced proliferation and doxorubicin resistance in UGCG overexpressing MCF-7 cells. These cellular effects seem to be mediated by an altered composition of glycosphingolipid-enriched microdomains (GEMs), especially an accumulation of globotriaosylceramide (Gb3) and glucosylceramide (GlcCer), which leads to an activation of Akt and ERK1/2. The induction of the Akt and ERK1/2 signaling pathway results in an increased gene expression of multidrug resistance protein 1 (MDR1) and anti-apoptotic genes and a decrease of pro-apoptotic gene expression. Inhibition of the protein kinase C (PKC) and phosphoinositide 3 kinase (PI3K) reduced MDR1 gene expression. This study discloses how changes in UGCG expression impact several cellular signaling pathways in breast cancer cells resulting in enhanced proliferation and multidrug resistance.     

The origin,diversity, and structure function relationships of insect luciferases

Luciferases are the enzymes that catalyze the reactions that produce light in bioluminescence. Whereas the oxidative mechanism which leads to light emission is similar for most luciferases, these enzymes and their substrates are evolutionarily unrelated. Among all bioluminescent groups, insects constitute one of the most diverse in terms of biochemistry. In the fungus-gnats (Mycetophilidae: Diptera), for example, bioluminescence is generated by two biochemically distinct systems. Despite the diversity, investigations on insect luciferases and biochemistry have been conducted mostly with fireflies. The luciferases from the related phengodid beetles, which can produce green to red bioluminescence using the same chemistry as firefly luciferases, have been recently investigated. Beetle luciferases originated from ancestral acyl-CoA ligases. Present data suggest that conserved motifs among this class of ligases are involved in substrate adenylation. The three-dimensional structure of firefly luciferase was recently solved and mutagenesis studies have been performed identifying putative residues involved in luciferin binding and bioluminescence color determination in several beetle luciferases. The knowledge gained through these studies is helping in the development of useful reporter gene tools for biotechnological and biomedical purposes. Received 4 March 2002; received after revision 13 May 2002; accepted 21 May 2002     

Mechanisms,the interventionist theory,and the ability to use causal relationships

In the area of social science, in particular, although we have developed methods for reliably discovering the existence of causal relationships, we are not very good at using these to design effective social policy. Cartwright argues that in order to improve our ability to use causal relationships, it is essential to develop a theory of causation that makes explicit the connections between the nature of causation, our best methods for discovering causal relationships, and the uses to which these are put. I argue that Woodward's interventionist theory of causation is uniquely suited to meet Cartwright's challenge. More specifically, interventionist mechanisms can provide the bridge from ‘hunting causes’ to ‘using them’, if interventionists (i) tell us more about the nature of these mechanisms, and (ii) endorse the claim that it is these mechanisms—or whatever constitutes them—that make causal claims true. I illustrate how having an understanding of interventionist mechanisms can allow us to put causal knowledge to use via a detailed example from organic chemistry.     

Scientists and their cultural heritage: Knowledge,politics and ambivalent relationships

For many years, scientific heritage has received attention from multiple actors from different spheres of activity—archives, museums, scientific institutions. Beyond the heterogeneity revealed when examining the place of scientific heritage in different places, an authentic patrimonial configuration emerges and takes the form of a nebula of claims and of accomplishments that result, in some cases, in institutional and political recognition at the national level, in various country all around the world. At the international level, the creation of the international committee dedicated to University Museums and Collections (UMAC) within the International Council of Museums (ICOM) certainly testified from this raising interest in academic heritage and the existence of a specific community concern with it.This article presents numerous initiatives for the preservation of scientific heritage in France, with the goal of analysing the relationship scientists have with their heritage. We argue that scientific communities have a special relationship with heritage, which is characterized by a number of ambiguities. We show that such ambivalences allow analysis of identity, discipline, professional, and social issues operative in defining heritage and being redefined by heritage. To explore these dimensions, we have chosen to present three different case studies. The first traces the institutional uses of heritage by a scientific institution, the Commissariat à l’énergie atomique (CEA), through the transformation of the first French atomic reactor (ZOE) into a museum. The second example describes the initiatives of French astronomers from the mid-1990s to construct a national programme for the protection of astronomy heritage. Lastly, we recount the case of universities, with the example of the Université de Strasbourg.     

Intrinsic links among sex,emotion, and reproduction

Species survival is dependent on successful reproduction. This begins with a desire to mate, followed by selection of a partner, copulation and in monogamous mammals including humans, requires emotions and behaviours necessary to maintain partner bonds for the benefit of rearing young. Hormones are integral to all of these stages and not only mediate physiological and endocrine processes involved in reproduction, but also act as neuromodulators within limbic brain centres to facilitate the expression of innate emotions and behaviours required for reproduction. A significant body of work is unravelling the roles of several key hormones in the modulation of mood states and sexual behaviours; however, a full understanding of the integration of these intrinsic links among sexual and emotional brain circuits still eludes us. This review summarises the evidence to date and postulates future directions to identify potential psycho-neuroendocrine frameworks linking sexual and emotional brain processes with reproduction.     

应力、应力纤维、Rho三者关系的研究进展

应力影响细胞的形状和骨架结构并因此控制许多与组织发展有关的关键行为，因此应力作用下细胞的种种响应问题成为生物力学目前最热的研究领域，应力纤维、Rho在研究应力信号如何被细胞感受过程中占据核心地位并已成为研究者关注的重点。本文依据国内外近几年进行的细胞对应力响应的研究进展对应力、应力纤维、Rho三者的相互关系进行了综述。     

Hybridization in the mexican and 13-lined ground squirrels,Spermophilus mexicanus andSpermophilus tridecemlineatus

Summary Evidence of hybridization between the ground squirrels,Spermophilus tridecemlineatus andS. mexicanus is presented on the basis of chromosomal and protein data. The hybrids produced appear to be completely interfertile. Based on the evidence of hybridization and the recent reestablishment of contact between these two species, they are considered to be semispecies.Supported by Faculty Research Grant No. 34925 from North Texas State University awarded toZimmerman.     

Observations on the toxicity and metabolic relationships of polygodial,the chemical defense of the nudibranchDendrodoris limbata

Summary Polygodial (1), the defense metabolite stored in the skin of the nudibranchDendrodoris limbata, is toxic for the mollusc itself when injected into the hepatopancreas. Biosynthetic experiments using labeled mevalonic acid were devised to investigate a possible metabolic relationship between1 and the mixture of sesquiterpenoidic esters2, stored in the hepatopancreas. The results suggest that1 and2 are biosynthesized by independent pathways.Thanks are due to G. Villani for supplyingDendrodoris limbata and to A. Trabucco for technical assistance.     

行业、战略、资源能力与企业间绩效差异关系研究综述

本文对近年来国外学者在企业间绩效差异来源方面的相关研究进行了梳理,并从全样本与样本分组两个视角出发,对行业、战略、资源能力与企业间绩效差异关系的相关研究成果进行了分类总结与比较分析.在此基础上,还得出应逐步加强对“效应有效性条件”问题进行研究的结论.     

Short-range linkage relationships, genomic organisation and sequence comparisons of a cluster of five HSP70 genes in Fugu rubripes

Twelve cosmids containing sequences resembling genes encoding members of the 70-kDa heat-shock protein family, HSP70, have been isolated from Fugu rubripes. They can be broadly divided into three groups of overlapping cosmids. Restriction analysis and sequencing of one set of five cosmids have revealed five intronless Fugu HSP70 genes spanning 42 kb, arranged in a combined head-to-head, tail-to-tail and head-to-tail orientation. The levels of DNA and amino acid identity are very high with respect to one another, and are most similar to HSP70 sequences linked to the major histocompatibility complex (MHC) region in other species. Putative heat-shock consensus elements are identified. Non-HSP70 sequences with homology to known genes have been found physically linked to this Fugu HSP70 cluster: the Drosophila melanogaster SOL gene, the Drosophila melanogaster nemo gene, the Caenorhabditis elegans T17E9.1 gene and the sequence encoding the serine protease domain. The linkage relationships described here so far bear no resemblance to those of HSP70 in other organisms. Convergence of mammalian HSP70 and MHC class I and II loci probably occurred after fish had diverged. Received 17 November 1998; received after revision 25 February 1999; accepted 26 February 1999     

Differences in cardiac myosin light chain LC1 among human,monkey and sheep

Summary The atrial and ventricular myosin light chains of human, monkey and sheep hearts were compared by dodecylsulfate polyacrylamide gel electrophoresis. The atrial light chain 2 and ventricular light chain 2 are similar among these mammals. However, the atrial light chain 1 of monkey has different electrophoretic mobility from those of human and sheep. The monkey ventricular light chain 1 has same mobility as that of sheep but different from that of human.Acknowledgments. This work was supported by MRC of Canada No. MA-8559. Dr G. Jackowski is a scholar of the Medical Research Council of Canada, and is the author to whom all correspondence should be addressed.     

Differences in cardiac myosin light chain LC1 among human, monkey and sheep

The atrial and ventricular myosin light chains of human, monkey and sheep hearts were compared by dodecylsulfate polyacrylamide gel electrophoresis. The atrial light chain 2 and ventricular light chain 2 are similar among these mammals. However, the atrial light chain 1 of monkey has different electrophoretic mobility from those of human and sheep. The monkey ventricular light chain 1 has same mobility as that of sheep but different from that of human.