Mineralogy of the mid-ocean-ridge basalt source from neodymium isotopic composition of abyssal peridotites

Inferring the melting process at mid-ocean ridges, and the physical conditions under which melting takes place, usually relies on the assumption of compositional similarity between all mid-ocean-ridge basalt sources. Models of mantle melting therefore tend to be restricted to those that consider the presence of only one lithology in the mantle, peridotite. Evidence from xenoliths and peridotite massifs show that after peridotite, pyroxenite and eclogite are the most abundant rock types in the mantle. But at mid-ocean ridges, where most of the melting takes place, and in ophiolites, pyroxenite is rarely found. Here we present neodymium isotopic compositions of abyssal peridotites to investigate whether peridotite can indeed be the sole source for mid-ocean-ridge basalts. By comparing the isotopic compositions of basalts and peridotites at two segments of the southwest Indian ridge, we show that a component other than peridotite is required to explain the low end of the (143)Nd/(144)Nd variations of the basalts. This component is likely to have a lower melting temperature than peridotite, such as pyroxenite or eclogite, which could explain why it is not observed at mid-ocean ridges.     

Genetic analysis of the mouse brain proteome

Proteome analysis is a fundamental step in systematic functional genomics. Here we have resolved 8,767 proteins from the mouse brain proteome by large-gel two-dimensional electrophoresis. We detected 1,324 polymorphic proteins from the European collaborative interspecific backcross. Of these, we mapped 665 proteins genetically and identified 466 proteins by mass spectrometry. Qualitatively polymorphic proteins, to 96%, reflect changes in conformation and/or mass. Quantitatively polymorphic proteins show a high frequency (73%) of allele-specific transmission in codominant heterozygotes. Variations in protein isoforms and protein quantity often mapped to chromosomal positions different from that of the structural gene, indicating that single proteins may act as polygenic traits. Genetic analysis of proteomes may detect the types of polymorphism that are most relevant in disease-association studies.     

Thyroid hormone controls carnitine status through modifications of γ-butyrobetaine hydroxylase activity and gene expression

The carnitine system plays a key role in β-oxidation of long-chain fatty acids by permitting their transport into the mitochondrial matrix. The effects of hypothyroidism and hyperthyroidism were studied on γ-butyrobetaine hydroxylase (BBH), the enzyme responsible for carnitine biosynthesis in the rat. In rat liver, BBH activity was decreased in the hypothyroid state and increased in hyperthyroid animals. The modifications in BBH activity correlated with changes in the enzyme Vmax values. These changes were shown to be related to hepatic BBH mRNA abundance. Thyroid hormones are known to interact with lipid metabolism, in particular by increasing long-chain fatty acid oxidation through activation of carnitine-dependent fatty acid import into mitochondria. Our study showed that thyroid hormones also increased carnitine bioavailability. Received 23 October 2001; received after revision 11 January 2002; accepted 15 January 2002     

Differential multiplicity of MDR alcohol dehydrogenases: enzyme genes in the human genome versus those in organisms initially studied

Screens were made for alcohol dehydrogenase (ADH) of the classical type (the MDR superfamily) in translations of human and other relevant genomes, corresponding to the organism types from which the enzyme was initially purified. Considerable multiplicities were detected in the dimeric enzymes from higher eukaryotes: seven forms in the human (plus three pseudogenes), all genes on chromosome 4, in the order class IV --> class Igamma --> class Ibeta --> class Ialpha --> class V --> class II --> class III, and eight forms in Arabidopsis thaliana (plus one pseudogene). These multiplicity patterns, and the species variability in the animal (human/mouse) and plant (Arabidopsis/pea) lines, suggest parallel but separate duplicatory events, giving rise to three families of dimeric MDR-ADH: class III, the animal non-class III, and the plant non-class III enzymes, with functions in formaldehyde elimination, in alcohol/aldehyde detoxication and in special pathways in higher eukaryotes. Multiplicity, although to a lesser extent, was also noted in tetrameric MDR-ADH, suggesting functional divergence between the dimeric and tetrameric enzymes. Combining these observations, at least five levels of divergence are reflected in the present ADH forms, corresponding to nodes at the SDR/MDR, the dimer/tetramer, the class III/non-class III, the class I/P, and the more recent class splits, each branch associated with separate functional patterns.     

Immunotherapy against antigenic tumors: a game with a lot of players

Our understanding of how immune responses are generated and regulated drives the design of possible immunotherapies for cancer patients. For that reason, we first describe briefly the actual immunological theories and their common perspectives about cancer vaccine development. Second, we describe cancer vaccines that are able to induce tumor-specific immune responses in cancer patients. However, these responses are not always followed by tumor rejection. At the end of the review, we discuss two possible reasons that might explain this dichotomy of cancer immunology. First, the immune response generated, although detectable, may not be quantitatively sufficient to reject the tumor. Second, the tumor microenvironment may modulate tumor cell susceptibility to the systemic immune response induced by the immunization. Finally, we discuss what, in our opinion, might be the best way to improve cancer vaccine strategies and how the relationship between the tumor and its surroundings might be studied in more details. Received 21 June 2001; received after revision 15 August 2001; accepted 15 August 2001     

Association of different mobile elements to generate novel integrative elements

Among the more important problems in modern hospitals is the prevalence of bacterial pathogens expressing resistance to multiple antimicrobial agents. The frequency of multiresistance suggests mechanisms by which bacterial species can concentrate and efficiently exchange a variety of resistance determinants. Mechanisms by which this occurs include insertion of transposons within transposons, coalescence through the activity of insertion sequences and the employment of integrons. In some instances, more than one of these mechanisms is involved in creating large multiresistance genetic elements. The association of the elements with transferable elements or transposons may promote rapid dissemination among clinical strains, and create further opportunities for inclusion of additional resistance determinants.     

Polyisoprenyl phosphates: natural antiinflammatory lipid signals

Lipoxins (LX) and aspirin-triggered 15-epimer LX are leukocyte-derived eicosanoids generated during host defense that serve as down-regulatory signals. The specific intracellular events that govern cellular responses to inhibitory extracellular signals are of wide interest in order to understand pivotal intracellular events in diseases characterized by enhanced inflammatory responses, such as asthma, rheumatoid arthritis and atherosclerosis. We recently uncovered a novel role for polyisoprenyl phosphates, in particular presqualene diphosphate (PSDP), as natural down-regulatory signals in human neutrophils that directly inhibit phospholipase D and superoxide anion generation. Activation of LXA₄ receptors (ALXR) reverses proinflammatory receptor-initiated decrements in PSDP and inhibits cellular responses. These findings represent evidence for a novel paradigm for lipid-protein interactions in the control of cellular responses, namely receptor-initiated degradation of repressor lipids that is subject to regulation by aspirin treatment via the actions of aspirin-triggered 15-epimer LX at the ALXR, and identify new templates for antiinflammatory drugs by design.     

Immunomodulatory properties of cystatins

Cystatins are natural tight-binding reversible inhibitors of cysteine proteases. Because these cysteine proteases exist in all living organisms and because they are involved in various biological and pathological processes, the control of these protease functions by cystatins is of cardinal importance. Cystatins are found in mammals but cystatin-like molecules are also present in mammals and parasites. In the immune system, cystatins modulate cathepsin activities and antigen presentation. They also induce tumor necrosis factor α and interleukin 10 synthesis, and they stimulate nitric oxide production by interferon γ-activated murine macrophages. In turn, nitric oxide has inhibitory activity on cysteine proteases, especially those from parasitic protozoa. Cystatins isolated from parasitic nematodes also have immunomodulatory activities that are distinguishable from those induced by lipopolysacharide-like molecules from endosymbiotic bacteria. On the whole, cystatins and cystatin-like molecules belong to a new category of immunomodulatory molecules. Doubtless increasing data will improve our knowledge of this property, leading to practical applications in immunotherapy. Received 11 April 2002; accepted 18 April 2002 RID="*" ID="*"Corresponding author.