Ethanol as a ‘food’ forDrosophila melanogaster: Influence of theEbony gene

Summary The survival time of adultDrosophila melanogaster flies without food is greater in the presence of ethanol, especially for flies of strains or lines with a higher alcohol dehydrogenase activity. It seems that theebony gene can act in some populations as a selective factor favoring the ADH^F allele, as well as the minor genes enhancing the alcohol dehydrogenase activity level.Chargé de Recherches au F. N. R. S.     

Genetic variation at the alcohol dehydrogenase locus inDrosophila melanogaster: A third ubiquitous allele

Summary A 3rd allele at theAdh locus,Adh ^FCh.D., has been found at polymorphic frequencies in natural populations ofD. melanogaster. The ADH-FChD enzyme has properties distinct from those of the 2 more common forms of ADH. TheAdh polymorphism should now be analyzed as a triallelic system.     

Mosaicism for sulfoiduronate sulfatase deficiency in carriers of Hunter's syndrome

Summary Using an assay for sulfoiduronate sulfatase based on the degradation of³⁵S mucopolysaccharides in a cellfree system, two clonal populations have been demonstrated in fibroblasts of heterozygotes for Hunter's syndrome. The locus responsible for sulfoiduronate sulfatase deficiency in thisX-linked mucopolysaccharidosis is therefore subjected to dosage compensation in females.Acknowledgments. The technical assistance of Mr.Antonio De Falco and Mrs.Carmela Salzano is gratefully acknowledged. The authors are indebted to Dr.H. Kresse (Münster, BRD) for helpful suggestions.     

Dystrophic mutation (dy2J) affecting regulation of lactate dehydrogenase (LDH) and pyruvate kinase (PK) in C57BL/6J mice

Summary The genotype difference (dystrophic vs nondystrophic) in the LDH isozymes is observed in kidney. These differences are evident only at birth and at early developmental stages (before the expression of dystrophic symptoms). The tissue specific genotype differences for PK are limited to the thigh muscle (M form) and heart (L form), after the onset of the condition. These differences may reflect the pleiotropic effect of the dy^2J locus during the temporal regulation of these and other enzymes implicated in muscular dystrophy (MD).This research was financed by a Natural Sciences and Engineering Research Council Canada grant to S.M.S.     

Lactate dehydrogenase polymorphism inMus musculus L. andMus spretus Lataste

Summary First variation at theLdh-A locus and a new allele at theLdh-B locus are reported in aM. musculus population dimorphic at theLdh-A locus and in aM. spretus population trimorphic at theLdh-B locus.Acknowledgments. This study was achieved with the technical assistance of J. Catalan. We thank N. Pasteur and F. Bonhomme for useful comments. This work was supported by the Université Montpellier 2 (service électrophorèse du Centre de Recherche sur l'Evolution et ses Mécanismes), the Ecole Pratique des Hautes Etudes and the Centre National de la Recherche Scientifique (ERA 261).     

Unstable genetic system inDrosophila melanogaster: I. Instability at theCinnabar locus

Summary A mutant strain containing acinnabar allele (cn ^rbr ,rojo brillante) is reported, that produces wild-type revertants at thecinnabar (cn) locus. Incn ^rbr /cn heterozygotes the rate of mutation is highly increased. The presence of a mutator agent acting premeiotically is indicated.D.L. Lindsley and E.H. Grell, Genetic variations ofDrosophila melanogaster. Carnegie Institution of Washington, Washington, 1968; Publication No. 627.     

Dominance for enzyme activity inDrosophila melanogaster

Summary A regulatory element tightly linked to theGpdh locus inDrosophila melanogaster has been isolated from a natural population. Flies homozygous for second chromosomes bearing the element,H31, have half the GPDH activity of normal homozygotes. Heterozygotes betweenH31 andF orS alleles exhibit dominance in GPDH activity. Heterozygotes betweenH31, F orS andDf(2L) GdhA have half the diploid level. The contribution of theS allele to the activity inS/H31 heterozygotes is more than four times that ofH31. The regulatory element distinguishingH31 is tightly linked to theGpdh ⁺ locus.     

Expression profiling of Tas2r genes reveals a complex pattern along the mouse GI tract and the presence of Tas2r131 in a subset of intestinal Paneth cells

The chemical variability of the intestinal lumen requires the presence of molecular receptors detecting the various substances naturally occurring in the diet and as a result of the activity of the microbiota. Despite their early discovery, intestinal bitter taste receptors (Tas2r) have not yet been assigned an unambiguous physiological function. Recently, using a CRE-recombinant approach we showed that the Tas2r131 gene is expressed in a subset of mucin-producing goblet cells in the colon of mice. Moreover, we also demonstrated that the expression of the Tas2r131 locus is not restricted to this region. In the present study we aimed at characterizing the presence of positive cells also in other gastrointestinal regions. Our results show that Tas2r131⁺ cells appear in the jejunum and the ileum, and are absent from the stomach and the duodenum. We identified the positive cells as a subpopulation of deep-crypt Paneth cells in the ileum, strengthening the notion of a defensive role for Tas2rs in the gut. To get a broader perspective on the expression of bitter taste receptors in the alimentary canal, we quantified the expression of all 35 Tas2r genes along the gastrointestinal tract by qRT-PCR. We discovered that the number and expression level of Tas2r genes profoundly vary along the alimentary canal, with the stomach and the colon expressing the largest subsets.     

The genetics of phytotoxin production by plant pathogenic fungi

Little is known about the genetic control of phytotoxin production by plant pathogenic fungi. The production of host-selective toxins known to play a role in disease development has been genetically analyzed in three species ofCochliobolus. InC. heterostrophus, a single genetic locus with two alleles has been identified controlling the production of HMT-toxin. This locus appears to be at or near the breakpoint of a chromosome rearrangement. Single genetic loci have also been identified controlling the production of HC-toxin byC. carbonum and HV-toxin byC. victoriae. The locus inC. carbonum may be a cluster of tightly linked genes.     

Familial hypobetalipoproteinemia: genetics and metabolism

Familial hypobetalipoproteinemia (FHBL), an autosomal dominant disorder, is defined as <5^th percentile LDL-cholesterol or apolipoprotein (apo) B in the plasma. FHBL subjects are generally heterozygous and asymptomatic. Three genetic forms exist: (i) premature stop codon specifying mutations of APOB; (ii) FHBL linked to a susceptibility locus on the chromosome 3p21; and (iii) FHBL linked neither to APOB nor to the chromosome 3p21. In heterozygous apoB-defective FHBL, the hepatic VLDL export system is defective because apoB 100, the product of the normal allele, is produced at ∼25% of normal rate, and truncated apoB is cleared too rapidly. The reduced capacity for hepatic triglyceride export increases hepatic fat three-fold. Indexes of adiposity and insulin action are similar to controls. ‘Knock-in’ mouse models of apoB truncations resemble human FHBL phenotypes. Liver fat in the chromosome 3p21-linked FHBL is normal. Elucidation of the genetic basis of the non-apoB FHBL could uncover attractive targets for lipid-lowering therapy. (See note added in proof.)Received 27 October 2004; received after revision 1 February 2005; accepted 22 February 2005     

Cadmium in the atmosphere

Summary Cadmium is present naturally in the air mainly as a result of volcanic emissions and release by vegetation. Anthropogenic sources, which overall give rise to emissions one order of magnitude greater than natural sources, are largely primary non-ferrous metals production and waste incineration. Measured concentrations of airborne cadmium are typically < 1 ng m^–3 at remote sites, 0.1–10 ng m^–3 at rural sites and 1–100 ng m^–3 at urban and industrial sites, dependent upon the nature and proximity of local sources. Particle sizes are generally <2 m, and often considerably smaller, consistent with an anthropogenic source and a long atmospheric life-time. Cadmium deposition to the land occurs with fluxes varying from 0.05 ng cm^–2 month^–1 in Greenland to circa 1000 ng cm^–2 month^–1 in the vicinity of major industrial sources. The possible significance of a motor vehicular source of airborne cadmium is also reviewed.     

The regulation of ion channels and transporters by glycolytically derived ATP

Glycolysis is an evolutionary conserved metabolic pathway that provides small amounts of energy in the form of ATP when compared to other pathways such as oxidative phosphorylation or fatty acid oxidation. The ATP levels inside metabolically active cells are not constant and the local ATP level will depend on the site of production as well as the respective rates of ATP production, diffusion and consumption. Membrane ion transporters (pumps, exchangers and channels) are located at sites distal to the major sources of ATP formation (the mitochondria). We review evidence that the glycolytic complex is associated with membranes; both at the plasmalemma and with membranes of the endo/sarcoplasmic reticular network. We examine the evidence for the concept that many of the ion transporters are regulated preferentially by the glycolytic process. These include the Na⁺/K⁺-ATPase, the H⁺-ATPase, various types of Ca²⁺-ATPases, the Na⁺/H⁺ exchanger, the ATP-sensitive K⁺ channel, cation channels, Na⁺ channels, Ca²⁺ channels and other channels involved in intracellular Ca²⁺ homeostasis. Regulation of these pumps, exchangers and ion channels by the glycolytic process has important consequences in a variety of physiological and pathophysiological processes, and a better understanding of this mode of regulation may have important consequences for developing future strategies in combating disease and developing novel therapeutic approaches. Received 20 July 2007; received after revision 30 July 2007; accepted 17 August 2007     

Developmental changes of aldehyde dehydrogenase isozymes in human livers: Mitochondrial ALDH2 isozyme is expressed in fetal livers

Summary Previous reports suggested that the major cytosolic aldehyde dehydrogenase (ALDH₁) was present in fetal and infant livers, but the major mitochondrial isozyme (ALDH₂) was absent or severely diminished. Re-examination by means of starch gel electrophoresis followed by enzyme activity staining, and by means of dot blot immuno-hybridization of liver samples with known genotypes of theALDH ₂ locus, indicated that bothALDH ₁ andALDH ₂ genes are expressed in fetal and infant livers. In addition, ALDH₄ isozyme was also observed. The results imply that a fetus with the usual homozygousALDH ₂ ¹ /ALDH ₂ ¹ genotype, but not one with the atypicalALDH ₂ ¹ /ALDH ₂ ² orALDH ₂ ² /ALDH ₂ ² , is capable of detoxifying acetaldehyde transferred from the mother.     

Structural variations in wheat HKT1;5 underpin differences in Na<Superscript>+</Superscript> transport capacity

An important trait associated with the salt tolerance of wheat is the exclusion of sodium ions (Na⁺) from the shoot. We have previously shown that the sodium transporters TmHKT1;5-A and TaHKT1;5-D, from Triticum monoccocum (Tm) and Triticum aestivum (Ta), are encoded by genes underlying the major shoot Na⁺-exclusion loci Nax1 and Kna1, respectively. Here, using heterologous expression, we show that the affinity (K _m) for the Na⁺ transport of TmHKT1;5-A, at 2.66 mM, is higher than that of TaHKT1;5-D at 7.50 mM. Through 3D structural modelling, we identify residues D⁴⁷¹/a gap and D⁴⁷⁴/G⁴⁷³ that contribute to this property. We identify four additional mutations in amino acid residues that inhibit the transport activity of TmHKT1;5-A, which are predicted to be the result of an occlusion of the pore. We propose that the underlying transport properties of TmHKT1;5-A and TaHKT1;5-D contribute to their unique ability to improve Na⁺ exclusion in wheat that leads to an improved salinity tolerance in the field.     

Ketoconazole,an inhibitor of calcium transport in skeletal muscle sarcoplasmic reticulum

Summary Ketoconazole, an antimycotic agent, inhibits calcium binding and accumulation, and induces calcium release in sarcoplasmic reticulum. The Mg²⁺-ATPase and the (Ca²⁺+Mg²⁺)-ATPase activities are stimulated at low but inhibited at high concentrations of ketoconazole.The author wishes to thank Dr K. S. Cheah for discussion and Mr C. C. Ketteridge for preparing the sarcoplasmic reticulum and carrying out the ATPase assays.     

The FHIT gene product: tumor suppressor and genome “caretaker”

The FHIT gene at FRA3B is one of the earliest and most frequently altered genes in the majority of human cancers. It was recently discovered that the FHIT gene is not the most fragile locus in epithelial cells, the cell of origin for most Fhit-negative cancers, eroding support for past claims that deletions at this locus are simply passenger events that are carried along in expanding cancer clones, due to extreme vulnerability to DNA damage rather than to loss of FHIT function. Indeed, recent reports have reconfirmed FHIT as a tumor suppressor gene with roles in apoptosis and prevention of the epithelial–mesenchymal transition. Other recent works have identified a novel role for the FHIT gene product, Fhit, as a genome “caretaker.” Loss of this caretaker function leads to nucleotide imbalance, spontaneous replication stress, and DNA breaks. Because Fhit loss-induced DNA damage is “checkpoint blind,” cells accumulate further DNA damage during subsequent cell cycles, accruing global genome instability that could facilitate oncogenic mutation acquisition and expedite clonal expansion. Loss of Fhit activity therefore induces a mutator phenotype. Evidence for FHIT as a mutator gene is discussed in light of these recent investigations of Fhit loss and subsequent genome instability.     

Behavioral phenomenology of sleep (somatic and vegetative)

Conclusions The foregoing analysis of behavioral sleep phenomenology shows that the most significant factual and theoretical aspects of sleep can be logically organized only according to several criteria, it being impossible to choose a singli one as truly paradigmatic. For this reason an ordinal classification of sleep phases was preferred. This fact does not detract from the usefulness of classifications based consistently on 1 criterion at a time (e.g.: synchronized-desynchronized; quiet-active; orthodoxical-paradoxical; NREM-REM; homeostatic-poikilostatic; spindle wave-slow wave-fast wave; external appetitive-internal appetitive-internal consummatory; and so on). In this respect, the bioelectrical classification is surely the best as it allows an analytical subdivision of the evolution of sleep with high resolving power^137–139. In particular, the electroencephalographic activity of late phase II (stage 4 in man¹³⁹ and slow wave¹¹ or deep slow wave¹⁴⁰ sleep in the cat) appears to be related to the triggering mechanisms and to the quantitative regulation of the circadian amount of phase III^3,5,11,140. However, in extending the field of functional implications of sleep phenomenology other criteria may be more significant. In fact, the somatic and vegetative events of sleep also lend themselves to an analysis according to the behavioral model of ethology^6,141–144 and the theory of homeostasis^{3–5, 145}, respectively. As an example, a number of classifying criteria are indicated in the table, where others, particularly neurochemical ones^146,147, could be added. At any rate, the difficulty of organizing sleep events into a satisfactory operational scheme is due to the fact that sleep is still an open problem as far as its mechanisms and functional significance are concerned.     

Allozyme polymorphism and linkage disequilibrium ofAdh and α-Gpdh loci in wine cellar and field populations ofDrosophila melanogaster

Summary Over three years, theAdh and -Gpdh loci have been studied in two cellar populations ofDrosophila melanogaster and in two field populations which were each near to one of the cellars. Analyses of gene frequencies indicate that the divergence among subpopulations is greater in theAdh locus than in the -Gpdh locus. Selection for or againstAdh ^S allele acting on theIn(2L)t inversion influences of the -Gpdh alleles. This phenomenon may contribute to explain the maintenance of theAdh and -Gpdh polymorphism and of theIn(2L)t inversion.     

Stability analysis of the bacteriophage ϕKMV lysin gp36C and its putative role during infection

The kinetic, thermodynamic and structural stability of gp36C, the virion-associated peptidoglycan hydrolase domain of bacteriophage ϕKMV, is analyzed. Recombinant gp36C is highly thermoresistant (k = 0.595 h⁻¹ at 95°C), but not thermostable (T_m = 50.2°C, ΔH_cal = 6.86 × 10⁴ cal mol⁻¹). However, aggregation influences kinetic stability in an unusual manner since aggregation is more pronounced at 55°C than at higher temperatures. Furthermore, gp36C reversibly unfolds in a two-state endothermic transition, and circular dichroism analysis shows that gp36C almost completely refolds after a 3-h heat treatment at 85°C. These properties are in agreement with gp36C being part of the extensible tail which is ejected in an unfolded state during phage infection. Received 24 April 2006; received after revision 26 May 2006; accepted 10 June 2006