Showing papers by "Aix-Marseille University published in 2005"

T-box genes in vertebrate development.

Abstract: The myriad developmental roles served by the T-box family of transcription factor genes defy easy categorization. Present in all metazoans, the T-box genes are involved in early embryonic cell fate decisions, regulation of the development of extraembryonic structures, embryonic patterning, and many aspects of organogenesis. They are unusual in displaying dosage sensitivity in most instances. In humans, mutations in T-box genes are responsible for developmental dysmorphic syndromes, and several T-box genes have been implicated in neoplastic processes. T-box transcription factors function in many different signaling pathways, notably bone morphogenetic protein and fibroblast growth factor pathways. The few downstream target genes that have been identified indicate a wide range of downstream effectors.

Circulating endothelial cells Biomarker of vascular disease

Abstract: Recent research has recognised new populations of non-hematopoietic cells in the blood. One of these, circulating endothelial cells (CECs), often defined by the expression of membrane glycoprotein CD146, are rarely found in the blood in health, but raised numbers are present in a wide variety of human conditions, including inflammatory, immune, infectious, neoplastic and cardiovascular disease, and seem likely to be evidence of profound vascular insult. An additional population are endothelial progenitor cells, defined by the co-expression of endothelial and immaturity cell surface molecules and also by the ability to form colonies in vitro. Although increased numbers of CECs correlate with other markers of vascular disease, questions remain regarding the precise definition, cell biology and origin of CECs. For example, they may be damaged, necrotic or apopototic, or alive, and could possess procoagulant and/or proinflammatory properties. However, since these cells seem to be representative of in situ endothelium, their phenotype may provide useful information. Indeed, whatever their phenotype, there is growing evidence that CECs may well be a novel biomarker, the measurement of which will have utility in various clinical settings related to vascular injury. Despite this promise, progress is impeded by the diversity of methodologies used to detect these cells. Accordingly, results are sometimes inconclusive and even conflicting. Nevertheless, increased CECs predict adverse cardiovascular events in acute coronary syndromes, suggesting they may move from being simply a research index to having a role in the clinic. The objective of the present communication is to condense existing data on CECs, briefly compare them with progenitor cells, and summarise possible mechanism(s) by which they may contribute to vascular pathology.

Word Sense Disambiguation: The State of the Art

Abstract: ANIMATE, HUMAN, etc. and encode type restrictions on nouns and adjectives and on the arguments of verbs. Subject codes use another set of primitives to classify senses of words by subject (ECONOMICS, ENGINEERING, etc.). Guthrie et al. (1991) demonstrate a typical use of this information: in addition to using the Lesk-based method of counting overlaps between definitions and contexts, they impose a correspondence of subject codes in an iterative process. No quantitative evaluation of this method is available, but Cowie et al. (1992) improve the method using simulated annealing and report results of 47% for sense distinctions and 72% for homographs. The use of LDOCE box codes, however, is problematic: the codes are not systematic (see, for example, Fontenelle, 1990); in later work, Braden-Harder (1993) showed that simply matching box or subject codes is not sufficient for disambiguation. For example, in I tipped the driver, the codes for several senses of the words in the sentence satisfy the necessary constraints (e.g. tip-money + human object or tip-tilt + movable solid object). In many ways, the supplemen7 Note that the assumptions underlying this method are very similar to Quillian’s: Thus one may think of a full concept analogically as consisting of all the information one would have if he looked up what will be called the “patriarch” word in a dictionary, then looked up every word in each of its definitions, then looked up every word found in each of these, and so on, continually branching outward[...] (Quillian, 1968, p. 238). However, Quillian’s network also keeps track of semantic relationships among the words encountered along the path between two words, which are encoded in his semantic network; the neural network avoids the overhead of creating the semantic network but loses this relational information. 13 tary information in the LDOCE, and in particular the subject codes, are similar to those in a thesaurus, which, however, are more systematically structured. Inconsistencies in dictionaries, noted earlier, are not the only and perhaps not the major source of their limitations for WSD. While dictionaries provide detailed information at the lexical level, they lack pragmatic information that enters into sense determination (see, e.g., Hobbs, 1987). For example, the link between ash and tobacco, cigarette or tray in a network such as Quillian’s is very indirect, whereas in the Brown Corpus, the word ash co-occurs frequently with one of these words. It is therefore not surprising that corpora have become a primary source of information for WSD; this development is outlined below in section 2.3. 2.3.2 Thesauri. Thesauri provide information about relationships among words, most notably synonymy. Roget's International Thesaurus, which was put into machine-tractable form in the 1950's8 and has been used in a variety of applications including machine translation (Masterman, 1957), information retrieval (Sparck Jones, 1964, 1986), and content analysis (Sedelow and Sedelow, 1969; see also Sedelow and Sedelow, 1986, 1992), also supplies an explicit concept hierarchy consisting of up to eight increasingly refined levels. Typically, each occurrence of the same word under different categories of the thesaurus represent different senses of that word; i.e., the categories correspond roughly to word senses (Yarowsky, 1992). A set of words in the same category are semantically related. The earliest known use of Roget’s for WSD is the work of Masterman (1957), described above in section 2.1. Several years later, Patrick (1985) used Roget’s to discriminate among verb senses, by examining semantic clusters formed by “e-chains” derived from the thesaurus (Bryan, 1973, 1974; see also Sedelow and Sedelow, 1986). He uses “word-strong neighborhoods,” comprising word groups in low-level semicolon groups, which are the most closely related semantically in the thesaurus, and words connected to the group via chains. He is able to discriminate the correct sense of verbs such as inspire (to raise the spirits vs. to inhale, breathe in, sniff, etc.), question (to doubt vs. to ask a question) with “high reliability.” Bryan's earlier work had already demonstrated that homographs can be distinguished by applying a metric based on relationships defined by his chains (Bryan, 1973, 1974). Similar work is described in Sedelow and Mooney (1988). Yarowsky (1992) derives classes of words by starting with words in common categories in Roget's (4th ed.). A 100-word context of each word in the category is extracted from a corpus (the 1991 electronic text of Grolier's Encyclopedia), and a mutual-information-like statistic is used to identify words most likely to co-occur with the category 8 The work of Masterman (1957) and Sparck Jones (1964) relied on a version of Roget’s that was hand-punched onto cards in the 1950’s; the Sedelow’s (1969) work relied on a machine readable version of the 3rd Edition. Roget’s is now widely available via anonymous ftp from various sites.

The GALEX-VVDS measurement of the evolution of the far-ultraviolet luminosity density and the cosmic star formation rate

Abstract: In a companion paper (Arnouts et al. 2004) we presented new measurements of the galaxy luminosity function at 1500 Angstroms out to z~1 using GALEX-VVDS observations (1039 galaxies with NUV 0.2) and at higher z using existing data sets. In this paper we use the same sample to study evolution of the FUV luminosity density. We detect evolution consistent with a (1+z)^{2.5+/-0.7} rise to z~1 and (1+z)^{0.5+/-0.4} for z>1. The luminosity density from the most UV-luminous galaxies (UVLG) is undergoing dramatic evolution (x30) between 025%) of the total FUV luminosity density at z<1. We measure dust attenuation and star formation rates of our sample galaxies and determine the star formation rate density as a function of redshift, both uncorrected and corrected for dust. We find good agreement with other measures of the SFR density in the rest ultraviolet and Halpha given the still significant uncertainties in the attenuation correction.

Analysis of the periodically fragmented environment model: I--species persistence.

Abstract: This paper is concerned with the study of the stationary solutions of the equation where the diffusion matrix A and the reaction term f are periodic in x. We prove existence and uniqueness results for the stationary equation and we then analyze the behaviour of the solutions of the evolution equation for large times. These results are expressed by a condition on the sign of the first eigenvalue of the associated linearized problem with periodicity condition. We explain the biological motivation and we also interpret the results in terms of species persistence in periodic environment. The effects of various aspects of heterogeneities, such as environmental fragmentation are also discussed.

The VIMOS-VLT deep survey - Evolution of the galaxy luminosity function up to z = 2 in first epoch data

Abstract: We investigate the evolution of the galaxy luminosity function from the VIMOS-VLT Deep Survey (VVDS) from the present to z=2 in five (U, B, V, R and I) rest-frame band-passes. We use the first epoch VVDS deep sample of 11,034 spectra selected at 17.5 <= I_{AB} <= 24.0, on which we apply the Algorithm for Luminosity Function (ALF), described in this paper. We observe a substantial evolution with redshift of the global luminosity functions in all bands. From z=0.05 to z=2, we measure a brightening of the characteristic magnitude M* included in the magnitude range 1.8-2.5, 1.7-2.4, 1.2-1.9, 1.1-1.8 and 1.0-1.6 in the U, B, V, R and I rest-frame bands, respectively. We confirm this differential evolution of the luminosity function with rest-frame wavelength, from the measurement of the comoving density of bright galaxies (M < M*(z=0.1)). This density increases by a factor of around 2.6, 2.2, 1.8, 1.5, 1.5 between z=0.05 and z=1 in the U, B, V, R, I bands, respectively. We also measure a possible steepening of the faint-end slope of the luminosity functions, with \\Delta\\alpha ~ -0.3 between z=0.05 and z=1, similar in all bands.

Stable sea surface temperatures in the western Pacific warm pool over the past 1.75 million years

Abstract: The first high-resolution record of Pleistocene climate changes from the western Pacific warm pool provides important information about climate change in the region, and will have implications for our understanding of how Earth's climate went into the mode of glacial/interglacial transition that has persisted for the past 800,000 years. The record uses Mg/Ca ratios in planktonic foraminifera as a proxy of sea surface temperatures during the past 1.75 million years. The results reveal a long period of stability in the region, which is not consistent with a gradual decrease in atmospheric CO2 as the trigger for glaciation. Rather, redistribution of Pacific sea surface temperatures by changes in zonal circulation could have affected the global climate, supporting recent concerns about the responses of the tropics to future changes. About 850,000 years ago, the period of the glacial cycles changed from 41,000 to 100,000 years. This mid-Pleistocene climate transition has been attributed to global cooling, possibly caused by a decrease in atmospheric carbon dioxide concentrations1,2. However, evidence for such cooling is currently restricted to the cool upwelling regions in the eastern equatorial oceans3,4, although the tropical warm pools on the western side of the ocean basins are particularly sensitive to changes in radiative forcing5,6. Here we present high-resolution records of sea surface temperatures spanning the past 1.75 million years, obtained from oxygen isotopes and Mg/Ca ratios in planktonic foraminifera from the western Pacific warm pool. In contrast with the eastern equatorial regions, sea surface temperatures in the western Pacific warm pool are relatively stable throughout the Pleistocene epoch, implying little long-term change in the tropical net radiation budget. Our results challenge the hypothesis of a gradual decrease in atmospheric carbon dioxide concentrations as a dominant trigger of the longer glacial cycles since 850,000 years ago. Instead, we infer that the temperature contrast across the equatorial Pacific Ocean increased, which might have had a significant influence on the mid-Pleistocene climate transition.

Consensus statement: medical management of acromegaly

Abstract: In November 2003, the Pituitary Society and the European Neuroendocrine Association sponsored a consensus workshop in Seville to address challenging issues in the medical management of acromegaly. Participants comprised 70 endocrinologists and neurosurgeons with international expertise in managing patients with acromegaly. All participants participated in the workshop proceedings, and the final document written by the scientific committee reflects the consensus opinion of the interactive deliberations. The meeting was supported by an unrestricted educational grant from Ipsen. No pharmaceutical representatives participated in the program planning or in the scientific deliberations.

Higher-level classification of the Archaea: evolution of methanogenesis and methanogens.

Abstract: We used a phylogenetic approach to analyze the evolution of methanogenesis and methanogens. We show that 23 vertically transmitted ribosomal proteins do not support the monophyly of methanogens, and propose instead that there are two distantly related groups of extant archaea that produce methane, which we have named Class I and Class II. Based on this finding, we subsequently investigated the uniqueness of the origin of methanogenesis by studying both the enzymes of methanogenesis and the proteins that synthesize its specific coenzymes. We conclude that hydrogenotrophic methanogenesis appeared only once during evolution. Genes involved in the seven central steps of the methanogenic reduction of carbon dioxide (CO2) are ubiquitous in methanogens and share a common history. This suggests that, although extant methanogens produce methane from various substrates (CO2, formate, acetate, methylated C-1 compounds), these archaea have a core of conserved enzymes that have undergone little evolutionary change. Furthermore, this core of methanogenesis enzymes seems to originate (as a whole) from the last ancestor of all methanogens and does not appear to have been horizontally transmitted to other organisms or between members of Class I and Class II. The observation of a unique and ancestral form of methanogenesis suggests that it was preserved in two independent lineages, with some instances of specialization or added metabolic flexibility. It was likely lost in the Halobacteriales, Thermoplasmatales and Archaeoglobales. Given that fossil evidence for methanogenesis dates back 2.8 billion years, a unique origin of this process makes the methanogenic archaea a very ancient taxon.

The GALEX VIMOS-VLT Deep Survey Measurement of the Evolution of the 1500 Å Luminosity Function

Abstract: We present the first measurement of the galaxy luminosity function (LF) at 1500 A in the range 0.2 =alpha>=-1.65, with a marginally significant hint of increase at higher z. (3) We split the sample in three rest-frame (B-I) intervals, providing an approximate spectral type classification: Sb-Sd, Sd-Irr, and unobscured starbursts. We find that the bluest class evolves less strongly in luminosity than the two other classes. On the other hand, their number density increases sharply with z (~15% in the local universe to ~55% at z~1), while that of the reddest classes decreases.

Mouse model of SCN5A-linked hereditary lenègre's disease : Age-related conduction slowing and myocardial fibrosis

Abstract: Background— We have previously linked hereditary progressive cardiac conduction defect (hereditary Lenegre’s disease) to a loss-of-function mutation in the gene encoding the main cardiac Na+ channel, SCN5A. In the present study, we investigated heterozygous Scn5a-knockout mice (Scn5a+/− mice) as a model for hereditary Lenegre’s disease. Methods and Results— In Scn5a+/− mice, surface ECG recordings showed age-related lengthening of the P-wave and PR- and QRS-interval duration, coinciding with previous observations in patients with Lenegre’s disease. Old but not young Scn5a+/− mice showed extensive fibrosis of their ventricular myocardium, a feature not seen in wild-type animals. In old Scn5a+/− mice, fibrosis was accompanied by heterogeneous expression of connexin 43 and upregulation of hypertrophic markers, including β-MHC and skeletal α-actin. Global connexin 43 expression as assessed with Western blots was similar to wild-type mice. Decreased connexin 40 expression was seen in the atria. Using pangen...

Revisiting the craniosynostosis-radial ray hypoplasia association: Baller-Gerold syndrome caused by mutations in the RECQL4 gene

Abstract: Baller-Gerold syndrome (BGS) is a rare autosomal recessive condition with radial aplasia/hypoplasia and craniosynostosis (OMIM 218600). Of >20 cases reported so far, a few appear atypical and have been reassigned to other nosologic entities, including Fanconi anaemia, Roberts SC phocomelia, and Pfeiffer syndromes after demonstration of corresponding cytogenetic or molecular abnormalities. Clinical overlap between BGS, Rothmund-Thomson syndrome (RTS), and RAPADILINO syndrome is noticeable. Because patients with RAPADILINO syndrome and a subset of patients with RTS have RECQL4 mutations, we reassessed two previously reported BGS families and found causal mutations in RECQL4 in both. In the first family, four affected offspring had craniosynostosis and radial defect and one of them developed poikiloderma. In this family, compound heterozygosity for a R1021W missense mutation and a g.2886delT frameshift mutation of exon 9 was found. In the second family, the affected male had craniosynostosis, radial ray defect, poikiloderma, and short stature. He had a homozygous splice site mutation (IVS17-2A>C). In both families, the affected offspring had craniosynostosis, radial defects, and growth retardation, and two developed poikiloderma. Our results confirm that BGS in a subgroup of patients is due to RECQL4 mutations and could be integrated into a clinical spectrum that encompasses RTS and RAPADILINO syndrome.

Fgf10 expression identifies parabronchial smooth muscle cell progenitors and is required for their entry into the smooth muscle cell lineage.

Abstract: Lineage formation in the lung mesenchyme is poorly understood. Using a transgenic mouse line expressing LacZ under the control of Fgf10 regulatory sequences, we show that the pool of Fgf10 -positive cells in the distal lung mesenchyme contains progenitors of the parabronchial smooth muscle cells. Fgf10 gene expression is slightly repressed in this transgenic line. This allowed us to create a hypomorphic Fgf10 phenotype by expressing the LacZ transgene in a heterozygous Fgf10 background. Hypomorphic Fgf10 mutant lungs display a decrease inβ -galactosidase-positive cells around the bronchial epithelium associated with an accumulation of β-galactosidase-expressing cells in the distal mesenchyme. This correlates with a marked reduction of α smooth muscle actin expression, thereby demonstrating that FGF10 is mostly required for the entry of mesenchymal cells into the parabronchial smooth muscle cell lineage. The failure of exogenous FGF10 to phosphorylate its known downstream targets ERK and AKT in lung mesenchymal cultures strongly suggests that FGF10 acts indirectly on the progenitor population via an epithelial intermediate. We provide support for a role of epithelial BMP4 in mediating the formation of parabronchial smooth muscle cells.

Natural killer cell and macrophage cooperation in MyD88-dependent innate responses to Plasmodium falciparum

Abstract: IFN-γ secretion by natural killer (NK) cells is pivotal to several tumor and viral immune responses, during which NK and dendritic cells cooperation is required. We show here that macrophages are mandatory for NK cell IFN-γ secretion in response to erythrocytes infected with Plasmodium falciparum (Pf), a causative agent of human malaria. In addition, direct sensing of Pf infection by NK cells induces their production of the proinflammatory chemokine CXCL8, without triggering their granule-mediated cytolytic programs. Despite their reported role in Pf recognition, Toll-like receptor (TLR) 2, TLR9, and TLR11 are individually dispensable for NK cell activation induced by Pf-infected erythrocytes. However, IL-18R expression on NK cells, IL-18 production by macrophages, and MyD88 on both cell types are essential components of this previously undescribed pathway of NK cell activation in response to a parasite infection.

Nanoarchaea: representatives of a novel archaeal phylum or a fast-evolving euryarchaeal lineage related to Thermococcales?

Abstract: Cultivable archaeal species are assigned to two phyla - the Crenarchaeota and the Euryarchaeota - by a number of important genetic differences, and this ancient split is strongly supported by phylogenetic analysis. The recently described hyperthermophile Nanoarchaeum equitans, harboring the smallest cellular genome ever sequenced (480 kb), has been suggested as the representative of a new phylum - the Nanoarchaeota - that would have diverged before the Crenarchaeota/Euryarchaeota split. Confirming the phylogenetic position of N. equitans is thus crucial for deciphering the history of the archaeal domain. We tested the placement of N. equitans in the archaeal phylogeny using a large dataset of concatenated ribosomal proteins from 25 archaeal genomes. We indicate that the placement of N. equitans in archaeal phylogenies on the basis of ribosomal protein concatenation may be strongly biased by the coupled effect of its above-average evolutionary rate and lateral gene transfers. Indeed, we show that different subsets of ribosomal proteins harbor a conflicting phylogenetic signal for the placement of N. equitans. A BLASTP-based survey of the phylogenetic pattern of all open reading frames (ORFs) in the genome of N. equitans revealed a surprisingly high fraction of close hits with Euryarchaeota, notably Thermococcales. Strikingly, a specific affinity of N. equitans and Thermococcales was strongly supported by phylogenies based on a subset of ribosomal proteins, and on a number of unrelated molecular markers. We suggest that N. equitans may more probably be the representative of a fast-evolving euryarchaeal lineage (possibly related to Thermococcales) than the representative of a novel and early diverging archaeal phylum.

Imaging experimental cerebral malaria in vivo: Significant role of ischemic brain edema

Abstract: The first in vivo magnetic resonance study of experimental cerebral malaria is presented. Cerebral involvement is a lethal complication of malaria. To explore the brain of susceptible mice infected with Plasmodium berghei ANKA, multimodal magnetic resonance techniques were applied (imaging, diffusion, perfusion, angiography, spectroscopy). They reveal vascular damage including blood-brain barrier disruption and hemorrhages attributable to inflammatory processes. We provide the first in vivo demonstration for blood-brain barrier breakdown in cerebral malaria. Major edema formation as well as reduced brain perfusion was detected and is accompanied by an ischemic metabolic profile with reduction of high-energy phosphates and elevated brain lactate. In addition, angiography supplies compelling evidence for major hemodynamics dysfunction. Actually, edema further worsens ischemia by compressing cerebral arteries, which subsequently leads to a collapse of the blood flow that ultimately represents the cause of death. These findings demonstrate the coexistence of inflammatory and ischemic lesions and prove the preponderant role of edema in the fatal outcome of experimental cerebral malaria. They improve our understanding of the pathogenesis of cerebral malaria and may provide the necessary noninvasive surrogate markers for quantitative monitoring of treatment.

Elliptic Eigenvalue Problems with Large Drift and Applications to Nonlinear Propagation Phenomena

Abstract: This paper is concerned with the asymptotic behaviour of the principal eigenvalue of some linear elliptic equations in the limit of high first-order coefficients. Roughly speaking, one of the main results says that the principal eigenvalue, with Dirichlet boundary conditions, is bounded as the amplitude of the coefficients of the first-order derivatives goes to infinity if and only if the associated dynamical system has a first integral, and the limiting eigenvalue is then determined through the minimization of the Dirichlet functional over all first integrals. A parabolic version of these results, as well as other results for more general equations, are given. Some of the main consequences concern the influence of high advection or drift on the speed of propagation of pulsating travelling fronts.

Patellofemoral arthroplasty: an update.

Abstract: UNLABELLED The rationale for presenting this updated study is to report long-term clinical and survival results of patellofemoral arthroplasty and to ascertain whether the preoperative diagnosis influenced outcomes and therefore indications. We retrospectively updated a previous evaluation of 66 patients who had unilateral patellofemoral arthroplasty between 1972 and 1990. The mean age of the patients at the initial surgery was 57 years (range, 21-82 years). The patients had an average followup of 16.2 years (range, 12-20 years). Preoperative diagnosis included instability, fracture, and primary arthritis. Revision surgery was done in 14 patients for femorotibial osteoarthritis, in 11 for loosening, and in four for stiffness. Survivorship was 58% at 16 years. The knee function score improved from 40 points preoperatively to 81 points at last followup. The best results were in patients with preoperative instability and corrected alignment of the extensor mechanism. Stiffness occurred only in those patients with osteoarthritis from previous fracture. Progressive degeneration of the tibiofemoral joint was noted mainly in the primary osteoarthritis etiologic group. This long-term evaluation of patellofemoral arthroplasty showed the importance of patient selection while excluding knees with significant frontal tibiofemoral malalignment. LEVEL OF EVIDENCE Therapeutic study, Level IV-1 (case series). See the Guidelines for Authors for a complete description of levels of evidence.

Heterogeneity in Consumer Price Stickiness: A Microeconometric Investigation

Abstract: This paper examines heterogeneity in price stickiness using a large, original, set of individual price data collected at the retail level for the computation of the French CPI. To that end, we estimate, at a very high level of disaggregation, competing-risks duration models that distinguish between price increases, price decreases and product replacements. The main findings are the following: i) cross-product and cross-outlet-type heterogeneity in both the shape of the hazard function and the impact of covariates is pervasive ii) at the product-outlet type level, the baseline hazard function of a price spell is non-decreasing iii) there is strong evidence of state dependence, especially for price increases.

Effect of numerics on navier-stokes computations of hypersonic double-cone flows

Abstract: A systematic study of the effects of the numerics on the simulation of a steady hypersonic flow past a sharp double cone is presented. Previous studies have shown that the double-cone flow is challenging to compute, making it useful for testing both numerical schemes and physical models. We focus on the numerical aspects only and show that the results are very sensitive to the numerical flux evaluation method and slope limiter used

Dopaminergic Contribution to the Regulation of Emotional Perception

Abstract: Dopamine (DA) acts as a key neurotransmitter in the brain. Numerous studies have shown its regulatory role in motor and cognitive function. However, the impairment of emotional processes in neurologic and psychiatric pathologies involving the dopaminergic system (Parkinson disease, schizophrenia, autism, Attention Deficit Hyperactivity Disorder, Huntington disease, frontal lobe lesions), as well as the influence that administration of dopaminergic agonists/antagonists exert on the processing of emotion, suggest a role for DA in emotional processes. Moreover, emotional processes are dependent upon a variety of structures, the majority of which form part of the limbic system and are subject to DA innervation. In reviewing the literature, the amygdala emerges as a brain structure critical for emotional processing. It may also be implicated in deficits in emotional recognition found in two major disorders where DA's implication is clear: Parkinson disease and schizophrenia. In addition, the amygdala's response to emotional tasks is likely to be altered by the administration of both agonist and antagonist dopaminergic drugs. Experimental studies reinforce the idea of a dopaminergic contribution to emotional response, as suggested by biochemical, pharmacologic, and lesion experiments. Although the implication of the dopaminergic system in emotional processing appears to be clearly documented, the contribution of specific DA receptor subtypes, or of the DA cotransmitters cholecystokinin and neurotensin, or even glutamate, is, however, still unclear. Altogether, these observations suggest that DA has, undoubtedly, a direct and/or indirect role in the full emotional process.

Aldosterone increases T-type calcium channel expression and in vitro beating frequency in neonatal rat cardiomyocytes.

Abstract: Objective : Although aldosterone has been implicated in the pathogenesis of cardiac hypertrophy and heart failure, its cellular mechanism of action on cardiomyocyte function is not yet completely elucidated. This study was designed to investigate the effect of aldosterone on calcium channel expression and cardiomyocyte contraction frequency. Methods : Cultured neonatal rat ventricular cardiomyocytes were stimulated in vitro with 1 μmol/L aldosterone for 24 h. Calcium currents were then measured with the patch clamp technique, while calcium channel expression was assessed by real-time RT-PCR. Results : In the present study, we show that aldosterone increases Ca2+ currents by inducing channel expression. Indeed, aldosterone led to a substantial increase of L- and T-type Ca2+ current amplitudes, and we found a concomitant 55% increase of the mRNA coding for α1C and β2 subunits of cardiac L channels. Although T-type currents were relatively small under control conditions, they increased 4-fold and T channel α1H isoform expression rose in the same proportion after aldosterone treatment. Because T channels have been implicated in the modulation of membrane electrical activity, we investigated whether aldosterone affects the beating frequency of isolated cardiomyocytes. In fact, aldosterone dose-dependently increased the spontaneous beating frequency more than 4-fold. This effect of aldosterone was prevented by actinomycin D and spironolactone and reduced by RU486, suggesting a mixed mineralocorticoid/glucocorticoid receptor-dependent transcriptional mechanism. Moreover, inhibition of T currents with Ni2+ or mibefradil significantly reduced beating frequency towards control values, while conditions affecting L-type currents completely blocked contractions. Conclusion : Aldosterone modulates the expression of cardiac voltage-operated Ca2+ channels and accelerates beating in cultured neonatal rat ventricular myocytes. This chronotropic action of aldosterone appears to be linked to increased T channel activity and could contribute to the deleterious effect of an excess of this steroid in vivo on cardiac function.

Myc interacts genetically with Tip48/Reptin and Tip49/Pontin to control growth and proliferation during Drosophila development.

Abstract: The transcription factor dMyc is the sole Drosophila ortholog of the vertebrate c-myc protooncogenes and a central regulator of growth and cell-cycle progression during normal development. We have investigated the molecular basis of dMyc function by analyzing its interaction with the putative transcriptional cofactors Tip48/Reptin (Rept) and Tip49/Pontin (Pont). We demonstrate that Rept and Pont have conserved their ability to bind to Myc during evolution. All three proteins are required for tissue growth in vivo, because mitotic clones mutant for either dmyc, pont,or rept suffer from cell competition. Most importantly, pont shows a strong dominant genetic interaction with dmyc that is manifested in the duration of development, rates of survival and size of the adult animal and, in particular, of the eye. The molecular basis for these effects may be found in the repression of certain target genes, such as mfas, by dMyc:Pont complexes. These findings indicate that dMyc:Pont complexes play an essential role in the control of cellular growth and proliferation during normal development.

Three-dimensional anatomy of the hip in osteoarthritis after developmental dysplasia

Abstract: Using radiography and computer tomography (CT) we studied the morphology of 83 hips in 69 Caucasian adults with osteoarthritis secondary to developmental dysplasia of the hip (DDH). A previously published series of 310 hips with primary osteoarthritis was used as a control group. According to the Crowe classification, 33 of the dysplastic hips were graded as class I, 27 as class II and 23 as class III or class IV.The intramedullary femoral canal had reduced mediolateral and anteroposterior dimensions in all groups compared with the control group. Only in Crowe class II hips was the femoral neck-shaft angle increased. The proximal femur had more anteversion in all the developmental dysplasia of the hip groups, ranging from 2° to 80°. Templated measurement of acetabular dimensions for plain radiography closely matched measurements taken by CT.The results of our study confirm the observations previously confined to the Japanese population.