A crosstalk between hSiah2 and Pias E3-ligases modulates Pias-dependent activation.

Protein inhibitor of activated STAT (Pias) and human homologues of seven in absentia (hSiah) proteins both exhibit properties of ubiquitin-family peptides conjugating enzymes. Pias present E3-ligase activity for small ubiquitin-related modifiers (Sumo) covalent attachment to their targets. This post-translational modification is responsible for the activation of different transcription factors such as AP1. HSiah proteins possess ubiquitin-E3-ligase activity that triggers their partners to proteasomal-dependent degradation. The present study identifies Pias as a new hSiah2-interacting protein. We demonstrate that hSiah2 regulates specifically the proteasome-dependent degradation of Pias proteins. On reverse, Pias does not prevent hSiah2 degradation. We provide evidences for hSiah2-dependent degradation of Pias as being a mechanism in the regulation of c-jun N-terminal kinase-activating pathways. This report describes a new interconnection between sumoylation and ubiquitination pathways by regulating the levels of the E3-ligases available for these processes.

Fibroblast growth factor (FGF) soluble receptor 1 acts as a natural inhibitor of FGF2 neurotrophic activity during retinal degeneration.

Fibroblast growth factors (FGF) 1 and 2 and their tyrosine kinase receptor (FGFR) are present throughout the adult retina. FGFs are potential mitogens, but adult retinal cells are maintained in a nonproliferative state unless the retina is damaged. Our work aims to find a modulator of FGF signaling in normal and pathological retina. We identified and sequenced a truncated FGFR1 form from rat retina generated by the use of selective polyadenylation sites. This 70-kDa form of soluble extracellular FGFR1 (SR1) was distributed mainly localized in the inner nuclear layer of the retina, whereas the full-length FGFR1 form was detected in the retinal Muller glial cells. FGF2 and FGFR1 mRNA levels greatly increased in light-induced retinal degeneration. FGFR1 was detected in the radial fibers of activated retinal Muller glial cells. In contrast, SR1 mRNA synthesis followed a biphasic pattern of down- and up-regulation, and anti-SR1 staining was intense in retinal pigmented epithelial cells. The synthesis of SR1 and FGFR1 specifically and independently regulated in normal and degenerating retina suggests that changes in the proportion of various FGFR forms may control the bioavailability of FGFs and thus their potential as neurotrophic factors. This was demonstrated in vivo during retinal degeneration when recombinant SR1 inhibited the neurotrophic activity of exogenous FGF2 and increased damaging effects of light by inhibiting endogenous FGF. This study highlights the significance of the generation of SR1 in normal and pathological conditions.

Genetic analysis of a selection experiment on the growth curve of chickens.

A selection experiment on the shape of the growth curve was performed on meat-type chickens through combined selection on juvenile and adult BW. Line X-+ was selected for low BW at 8 wk (BW8) and high BW at 36 wk (BW36). Line X+- was selected for high BW8 and low BW36. Line X++ was selected for high BW8 and BW36, and X-- was selected for low BW8 and BW36. Line X00 was maintained as an unselected control. Data on the first 14 generations (i.e., 38,693 birds) were used. The growth curve was modeled using a Gompertz function on 7,143 birds that were weighed regularly. Selection for higher BW8 increased BW from 4 to 16 wk, initial specific growth rate, and maturation rate and decreased age at inflection. Selection for higher BW36 resulted in increased BW36, asymptotic BW, and estimated BW at hatching. Body weights were more modified in Lines X++ and X--, but the growth curve parameters changed more in Lines X-+ and X-- than in Lines X++ and X+-.

[Depression and functional EEG asymmetry]. / Dépression et asymétrie fonctionnelle EEG.

A new quantified EEG index (Alpha Burst Occurrence Variability Index: alpha BVI) has been devised in order to characterize sequential variations of alpha bursts in EEG. This index makes it possible to quantify slope variations of a cumulative graph (periodogram) where the rank of alpha bursts is traced as a function of their instant of arrival. Such quantitative analysis was applied to spontaneous EEG segments which were recorded in the parieto-occipital regions (P3-Fz and P4-Fz) during a rest period, in three groups of depressed patients, one being characterized by psychomotor retardation (PRM group), another one by an emotional blunting (EB group) and a group of impulsive depressed patients (I group). The patients were compared to a group of healthy control subjects. In the three patient groups, before treatment, it was observed that the right and left alpha BVI were significantly lower than those of the control subjects. The right hemisphere was involved in all cases, but the left hemisphere was involved only in severe cases. In the EB and I groups, two strong "electro-clinical" correlations were observed, each one being specific for each hemisphere, one relating the reduction of the right alpha BVI to the depressive mood, the other relating the reduction of the left alpha BVI to the degree of speech ("ideoverbal") retardation. These results emphasize the role of the right hemisphere in the probable pathogenesis of depression.

Computer-aided staging of lymphoma patients with FDG PET/CT imaging based on textural information.

We have designed a computer-aided diagnosis system to discriminate between hypermetabolic cancer lesions and hypermetabolic inflammatory or physiological but noncancerous processes in FDG PET/CT exams of lymphoma patients. Detection performance of the support vector machine (SVM) classifier was assessed based on feature sets including 105 positron emission tomography (PET) and Computed tomography (CT) characteristics derived from the clinical practice and from more sophisticated texture analysis. An original feature selection method based on combining different filter methods was proposed. The evaluation database consisted of 156 lymphomatous and 32 suspicious but nonlymphomatous regions of interest. Different types of training databases including either the PET and CT features or the PET features only, with or without feature selection, were evaluated to assess the added value of multimodality and texture information on classification performance. An optimization study was conducted for each classifier separately to select the best combination of parameters. Promising classification performance was achieved by the SVM classifier combined with the 12 most discriminant PET and CT features with a value of the area under the receiver operating curve of 0.91.

Short-term changes in median nerve neural tension after a suboccipital muscle inhibition technique in subjects with cervical whiplash: a randomised controlled trial.

OBJECTIVES: To assess the immediate effect of a suboccipital muscle inhibition (SMI) technique on: (a) neck pain, (b) elbow extension range of motion during the upper limb neurodynamic test of the median nerve (ULNT-1), and (c) grip strength in subjects with cervical whiplash; and determine the relationships between key variables. DESIGN: Randomised, single-blind, controlled clinical trial. SETTING: Faculty of Nursing, Physiotherapy and Podiatry, University of Seville, Spain. PARTICIPANTS: Forty subjects {mean age 34 years [standard deviation (SD) 3.6]} with Grade I or II cervical whiplash and a positive response to the ULNT-1 were recruited and distributed into two study groups: intervention group (IG) (n=20) and control group (CG) (n=20). INTERVENTIONS: The IG underwent the SMI technique for 4minutes and the CG received a sham (placebo) intervention. Measures were collected immediately after the intervention. MAIN OUTCOME MEASURES: The primary outcome was elbow range of motion during the ULNT-1, measured with a goniometer. The secondary outcomes were self-perceived neck pain (visual analogue scale) and free-pain grip strength, measured with a digital dynamometer. RESULTS: The mean baseline elbow range of motion was 116.0° (SD 10.2) for the CG and 130.1° (SD 7.8) for the IG. The within-group comparison found a significant difference in elbow range of motion for the IG [mean difference -15.4°, 95% confidence interval (CI) -20.1 to -10.6; P=0.01], but not for the CG (mean difference -4.9°, 95% CI -11.8 to 2.0; P=0.15). In the between-group comparison, the difference in elbow range of motion was significant (mean difference -10.5°, 95% CI -18.6 to -2.3; P=0.013), but the differences in grip strength (P=0.06) and neck pain (P=0.38) were not significant. CONCLUSION: The SMI technique has an immediate positive effect on elbow extension in the ULNT-1. No immediate effects on self-perceived cervical pain or grip strength were observed.

PET-CT and diagnostic CT: the synergy of metabolic and morphological data in onco-haematology.

PURPOSE: Our goal was to determine how interpreting diagnostic CT together with PET-CT could improve the assessment of morphology in onco-haematology. PATIENTS AND METHODS: Fifty-nine patients with aggressive lymphoma were retrospectively included. The diagnostic CT scan was interpreted by two radiologists, followed by a combined analysis of the CT and the PET-CT carried out by two specialists in metabolic and morphological imaging. The diagnostic performances were assessed in terms of sensitivity and specificity, then concordance and discordance rates (kappa) were studied. RESULTS: A combined interpretation of CT and PET-CT showed better diagnostic performances than those of interpretations of CT only in the assessment of nodal sites (826 sites, sensitivity of 99% versus 85%, P<0.05), extranodal sites (649 sites, sensitivity of 88% versus 78%) and bone sites (one analysed per patient, sensitivity of 50% versus 27%). The combined interpretation also improved inter-observer agreement and led to an upgraded Ann Arbor staging in 15% of patients, with a change of treatment in 10%. CONCLUSION: Interpretation of diagnostic CT in onco-haematology can be improved by combining it with an assessment of PET-CT. The synergy between metabolic and morphological information leads to improved diagnostic capabilities and renders interpretations more reproducible.

[The relationship between heart rate and type of growth in the domestic fowl]. / Note sur les relations entre le rythme cardiaque et le type de croissance chez la poule domestique.

The heart rate at 6 and 24 weeks of age and the relative weight of the heart at 8 and 24 weeks were studied in four strains of domestic fowl, differing in growth and, in this study, in body weight. Heart rate at 6 weeks of age was not related to sex, body weight, absolute or relative heart weight. Heart rate at 24 weeks of age was related to relative heart weight at 24 weeks, to absolute heart weight at 6 and 24 weeks, and to body weight at 6 weeks. There was a marked sex effect at 24 weeks. No within-species relationship between heart rate and body weight was found, but a negative correlation existed between heart rate and relative heart weight.

Effects of selection for high and low plasma glucose concentration in chickens.

1. Two lines of broilers exhibiting low (LG) or high (HG) plasma glucose concentrations were selected from a pure line of White Rock chickens. 2. Realised heritabilities were close to 0.25 in both lines. 3. The LG line was significantly fatter than the HG line; this difference was more pronounced in females than in males. 4. Food was utilised less efficiently by the LG line than by the HG one.

Dynamic simulation of the mouse prion protein.

Conformational flexibility in the prion protein is believed to play a role in prion diseases. Here we examine the dynamic structure of the mouse cellular prion protein using two one-nanosecond molecular dynamics simulations from different initial conditions. The two simulations produce similar results. The overall structure remains close to that determined by nmr spectroscopy, with small deviations arising from loop fluctuation and slight changes in the relative helix positions. The sequence dependence of the fluctuation magnitudes is similar to the variation between the nmr-derived structure solutions. In both simulations, the N-terminal region of the protein forms a short, two-stranded beta-sheet, to which a third strand joins after approximately 100 ps. The additional strand may reflect nucleative properties of the beta-sheet required for disease-related prion conformational change.

Effects of divergent selection for body weight on three skeletal muscles characteristics in the chicken.

1. Histochemical (fibre type distribution and areas) and biochemical (myosin isoforms) characteristics of three muscles, M. anterior latissimus dorsi, M. pectoralis major and M. sartorius, were compared among male chickens of two lines at 11 and 55 weeks of age. 2. The lines were derived from a divergent selection based on growth rate. Cockerels from the Fast Growing Line (FGL) were 2.3 times heavier than those from the Slow Growing Line (SGL) when 11 weeks old and 1.7 times at 55 weeks of age. The latter age was chosen as representative of the adult stage and the 11-week age because, at this time, FGL cocks weighed as much as SGL cockerels at 55 weeks. 3. At both ages, the two lines showed similar fibre type distributions, but the total number in the ALD muscle, and the size (cross-sectional areas) of fibres in each muscle were higher in the FGL compared with the SGL (14.6% and 33% more at 11 and 55 weeks of age respectively in favour of the FGL birds). 4. The two lines displayed similar myosin isoform patterns when adult muscles were compared (55 weeks). They differed slightly at 11 weeks of age, muscle differentiation being completed only in the FGL. 5. Comparisons of the two lines at the same live weight (i.e. FGL cockerels at 11 weeks of age and SGL cockerels at 55 weeks) showed larger muscle fibres in the SGL and no difference in the isomyosin patterns.

Selection for rapid growth increases the number and the size of muscle fibres without changing their typing in chickens.

Quantitative (muscle fibre number and cross-sectional areas) and qualitative (myosin isoforms and metabolic enzyme activities) characteristics of two muscles, M. pectoralis major and M. anterior latissimus dorsi, were compared among male chickens of two lines during growth from hatching to adulthood. The lines were derived from a divergent selection based on growth rate. The two muscles were chosen on the basis of their histochemical profile. Pectoralis major muscle contains only fast contracting muscle fibres whereas anterior latissimus dorsi muscle is almost entirely made up with slow contracting fibres. At both ages, the two lines showed similar fibre type distributions. At hatching, fibre cross-sectional areas were equivalent in the two lines, but after the first week, animals from the fast growing line exhibited wider fibre areas, whatever the muscle, than animals from the slow growing line. The total number of fibres in a muscle was found greater in the fast growing line, irrespective of whether it was exactly determined (anterior latissimus dorsi muscle, + 20%) or only estimated (pectoralis major muscle). This number remains constant in the two lines throughout the growth. Myosin isoform profiles and metabolic enzyme activities were similar in the two lines, at both ages, and were in good agreement with the histochemical muscle fibre profiles.

Divergent selection for high or low growth rate modifies the response of muscle cells to serum or insulin-like growth factor-I in vitro.

Genetic differences in growth potential could result from changes in the levels of growth stimulatory factors or in the response of target tissues. The latter possibility was tested in adult myoblasts prepared from chickens selected for high (HG) or low growth rate (LG). Stimulation of [3H]-thymidine incorporation into DNA by serum was of higher amplitude in HG than LG muscle cells irrespective of whether the cell preparations were enriched in myoblasts or fibroblasts. HG myoblasts were also more responsive to insulin-like growth factor-I (IGF-I) in terms of [3H]-thymidine incorporation. IGF analogues with a reduced affinity for IGF binding proteins gave similar results suggesting that activity of binding proteins could not explain the difference between cells from the HG and LG lines. This difference was restricted to the proliferative stage because in myotubes, basal or IGF-I stimulated glucose and amino acid transports, tyrosine incorporation and protein degradation were not different.

Identification of 12 new yeast mitochondrial ribosomal proteins including 6 that have no prokaryotic homologues.

Mitochondrial ribosomal proteins were studied best in yeast, where the small subunit was shown to contain about 35 proteins. Yet, genetic and biochemical studies identified only 14 proteins, half of which were predictable by sequence homology with prokaryotic ribosomal components of the small subunit. Using a recently described affinity purification technique and tagged versions of yeast Ykl155c and Mrp1, we isolated this mitochondrial ribosomal subunit and identified a total of 20 proteins, of which 12 are new. For a subset of the newly described ribosomal proteins, we showed that they are localized in mitochondria and are required for the respiratory competency of the yeast cells. This brings to 26 the total number of proteins described as components of the mitochondrial small ribosomal subunit. Remarkably, almost half of the previously and newly identified mitochondrial ribosomal components showed no similarity to any known ribosomal protein. Homologues could be found, however, in predicted protein sequences from Schizosaccharomyces pombe. In more distant species, putative homologues were detected for Ykl155c, which shares conserved motifs with uncharacterized proteins of higher eukaryotes including humans. Another newly identified ribosomal protein, Ygl129c, was previously shown to be a member of the DAP-3 family of mitochondrial apoptosis mediators.

Requirement for nitric oxide in retinal neuronal cell death induced by activated Müller glial cells.

Retinal Müller glial cells express the inducible isoform (-2) of nitric oxide (NO) synthase (NOS) in vitro after stimulation by lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) or in vivo in some retinal pathologies. Because NO may have beneficial or detrimental effects in the retina, we have used cocultures of retinal neurons with retinal Müller glial (RMG) cells from mice disrupted for the gene of NOS-2 [NOS-2 (-/-)] to clarify the role of NO in retinal neurotoxicity. We first demonstrated that NO produced by activated RMG cells was not toxic for RMG cells themselves. Second, the NO released from LPS/IFN-gamma-stimulated RMG cells induced neuronal cell death, because no neuronal cell death has been observed in cocultures with RMG cells from NOS-2 (-/-) mice and because inhibition of NOS-2 induction by transforming growth factor-beta or blockade of NO release by different NOS inhibitors prevented neuronal cell death. Addition of urate, a peroxynitrite scavenger, or superoxide dismutase partially prevented neuronal cell death induced by NO, whereas the presence of a poly(ADP-ribose) synthetase inhibitor, caspase inhibitors, or a guanylate cyclase inhibitor had no significant effect on cell death. These results demonstrated that a large release of NO from RMG cells is responsible for retinal neuronal cell death in vitro, suggesting a neurotoxic role for NO and peroxynitrite during retinal inflammatory or degenerative diseases, where RMG cells were activated.

Role of nitric oxide in photoreceptor survival in embryonic chick retinal cell culture.

The presence of nitric oxide synthase (NOS) in chick retina during development has allowed us to study the role of nitric oxide (NO) during retinal differentiation in dissociated chick retinal cell culture from embryonic day 6. We have demonstrated the presence of nicotinamide adenine dinucleotide phosphate diaphorase staining in these cultures after 3 days in vitro (Div), with a maximal intensity after 8 Div, corresponding to embryonic day 14. Immunohistochemistry studies confirmed the presence of the two isoforms of NOS, NOS-I and -III, in dissociated retinal cell cultures at 8 Div. Addition of NG-monomethyl-L-arginine, a NOS inhibitor, to retinal cell cultures prevented NO production but did not modify the appearance and the survival of ganglion and amacrine cells. However, immunohistochemical analysis with distinct markers for photoreceptor cells (rods and cones) showed that inhibition of endogenous NOS in retinal cell cultures prevented the developmental decrease of rod number between 5 and 8 Div, thus supporting the hypothesis that NO may be involved in the cell death of rods during the development of the retina.