Influence of different heat stress models on nutrient digestibility and markers of stress, inflammation, lipid, and protein metabolism in broilers.

This experiment determined the effects of different HS models and pair-feeding (PF) on nutrient digestibility and markers of stress, inflammation, and metabolism in broilers. Birds (720 total) were allocated into 12 environmentally controlled chambers and reared under thermoneutral conditions until 20 d. Until 41 d birds were exposed to 4 treatments, including: thermoneutral at 24°C (TN-al), daily cyclic HS (12 h at 24 and 12 h at 35°C; cyHS), constant HS at 35°C (coHS), and PF birds maintained at 24°C and fed to equalize FI with coHS birds (TN-coPF). At d 41, ileal digesta were collected to determine nutrient apparent ileal digestibility (AID). Blood, liver, and breast tissues were collected from 8 birds per treatment to determine the mRNA expression of stress, inflammation, and metabolism markers. An additional 8 TN-al birds were sampled after acute HS exposure at 35°C for 4 h (aHS), and 8 cyHS birds were sampled either right before or 4 h after HS initiation. Data were analyzed by 1-way ANOVA and means were separated using Tukey's HSD test. Compared with TN-al birds, AID of nitrogen and ether extract were reduced in coHS birds, and both cyHS and coHS reduced (P < 0.05) AID of total essential amino acids. TNFα and SOD2 expression were increased (P < 0.05) under aHS, coHS, and TN-coPF conditions. IL6 and HSP70 were increased (P < 0.05) under coHS and aHS, respectively. Expression of lipogenic enzymes ACCα and FASN were reduced by coHS and TN-coPF, while coHS increased the lipolytic enzyme ATGL (P < 0.05). IGF1 was lowered in coHS birds, and p70S6K and MyoG were reduced under coHS and TN-coPF (P < 0.05). Interestingly, MuRF1 and MAFbx were increased (P < 0.05) under coHS only. Overall, these results indicate that coHS has a greater impact on nutrient digestibility and metabolism than aHS and cyHS. Interestingly, increased protein degradation during HS appears to be mostly driven by HS per se and not the reduced FI.

Flat Γ Moiré Bands in Twisted Bilayer WSe_{2}.

The recent observation of correlated phases in transition metal dichalcogenide moiré systems at integer and fractional filling promises new insight into metal-insulator transitions and the unusual states of matter that can emerge near such transitions. Here, we combine real- and momentum-space mapping techniques to study moiré superlattice effects in 57.4° twisted WSe_{2} (tWSe_{2}). Our data reveal a split-off flat band that derives from the monolayer Γ states. Using advanced data analysis, we directly quantify the moiré potential from our data. We further demonstrate that the global valence band maximum in tWSe_{2} is close in energy to this flat band but derives from the monolayer K states which show weaker superlattice effects. These results constrain theoretical models and open the perspective that Γ-valley flat bands might be involved in the correlated physics of twisted WSe_{2}.

Constant and cyclic chronic heat stress models differentially influence growth performance, carcass traits and meat quality of broilers.

This experiment compared the effects of 2 chronic heat stress (HS) models, constant (coHS), and cyclic (cyHS), on broiler performance, carcass characteristics, and meat quality. A total of 720 male chicks from a Cobb 500 line were placed in 12 environmentally controlled chambers divided into 2 pens of 30 birds. Before the experimental HS models were applied, chamber temperatures were gradually decreased from 32°C at placement to 24°C on d 20. From 20 to 41 d, 4 chambers were set to 35°C (coHS), and 4 chambers were set to 35°C for 12 h and 24°C for the next 12 h (cyHS). Four thermoneutral chambers were maintained at 24°C with half of the birds pair-fed to equalize feed intake (FI) with coHS birds (TN-coPF) and half fed ad-libitum (TN-al). From 20 to 41 d, FI and BW gain (BWG) of cyHS, coHS and TN-coPF birds were decreased (P < 0.001), whereas feed conversion ratio (FCR) was increased (P < 0.001) for coHS and TN-coPF birds compared with TN-al birds. The overall BWG and FCR of coHS birds were lower (P < 0.001) than TN-coPF birds. Both HS models reduced (P < 0.001) carcass weight, pectoralis major yield, total breast meat yield, and increased (P < 0.001) wing yield relative to TN-al birds, with each of these measurements more impacted by coHS than by cyHS. Pair-fed birds had lower (P < 0.001) fat pad and a higher total breast meat yield than coHS birds. They also had the lowest (P < 0.001) pectoralis major ultimate pH and yellowness, and these parameters were lower (P < 0.001) for coHS birds than for TN-al birds. Both HS models reduced (P < 0.001) the incidence of woody breast and white striping. Thus, these data indicate that the detrimental effects of HS cannot be entirely explained by reduced FI and that HS per se affects metabolic pathways associated with muscle and lipid accretion in broilers.

Mast cells' involvement in inflammation pathways linked to depression: evidence in mastocytosis.

Converging sources of evidence point to a role for inflammation in the development of depression, fatigue and cognitive dysfunction. More precisely, the tryptophan (TRP) catabolism is thought to play a major role in inflammation-induced depression. Mastocytosis is a rare disease in which chronic symptoms, including depression, are related to mast cell accumulation and activation. Our objectives were to study the correlations between neuropsychiatric features and the TRP catabolism pathway in mastocytosis in order to demonstrate mast cells' potential involvement in inflammation-induced depression. Fifty-four patients with mastocytosis and a mean age of 50.1 years were enrolled in the study and compared healthy age-matched controls. Depression and stress were evaluated with the Beck Depression Inventory revised and the Perceived Stress Scale. All patients had measurements of TRP, serotonin (5-HT), kynurenine (KYN), indoleamine 2,3-dioxygenase 1 (IDO1) activity (ratio KYN/TRP), kynurenic acid (KA) and quinolinic acid (QA). Patients displayed significantly lower levels of TRP and 5-HT without hypoalbuminemia or malabsorption, higher IDO1 activity, and higher levels of KA and QA, with an imbalance towards the latter. High perceived stress and high depression scores were associated with low TRP and high IDO1 activity. In conclusion, TRP metabolism is altered in mastocytosis and correlates with perceived stress and depression, demonstrating mast cells' involvement in inflammation pathways linked to depression.

Infrared- and Raman-spectroscopy measurements of a transition in the crystal structure and a closing of the energy gap of BiTeI under pressure.

BiTeI is a giant Rashba spin splitting system, in which a noncentrosymmetric topological phase has recently been suggested to appear under high pressure. We investigated the optical properties of this compound, reflectivity and transmission, under pressures up to 15 GPa. The gap feature in the optical conductivity vanishes above p∼9 GPa and does not reappear up to at least 15 GPa. The plasma edge, associated with intrinsically doped charge carriers, is smeared out through a phase transition at 9 GPa. Using high-pressure Raman spectroscopy, we follow the vibrational modes of BiTeI, providing additional clear evidence that the transition at 9 GPa involves a change of crystal structure. This change of crystal structure possibly inhibits the high-pressure topological phase from occurring.

[Prodromes of schizophrenia: consensus or confusion?]. / Prodromes de la schizophrénie: consensus ou confusion?

LITERATURE FINDINGS: Prospective studies of subjects at high genetic risk of psychosis (at least one first relative with schizophrenia) and retrospective studies of patients at the end of the first episode of delusion or hallucination have identified various subjective and objective symptoms which emerged months or years before the diagnostic of schizophrenia. The objective symptoms presently designed as prodromes are either transient or of infradiagnostic intensity. The objective signs have been used to define an ultrahigh risk (UHR) state, and have been operationalized by psychometric instruments, which also include criteria for genetic risk (schizotypal dimensions) and alteration of social functioning. The main instruments are the Comprehensive Assessment of At-risk Mental States (CAARMS) and the SIPS (Structured Interview for Prodromal Symptoms). The subjective symptoms, which consist exclusively in inner experiences, have been named basic symptoms, and are operationalized by the Bonn Scale for the Assessment of Basic Symptoms (BSABS) and the Schizophrenia Proneness Instrument (SPI-A, Adult version). Prospective studies of selected individuals with a psychiatric help demand have shown that signs of endogenicity (schizotypal traits), and severity (high symptomatic scores and poor functioning), are of major value to predict conversion. In contrast, the positive predictive value of isolated prodromal symptoms is rather poor (much less than the 80% required for clinical validation). DISCUSSION: This suggests that the population of subjects with prodromes is structured by two latent subgroups: those who express transient psychotic manifestations (which are quite frequent in the general population), and those with an active psychotic process, who are progressively evolving towards the categorical diagnostic of schizophrenia. However, results obtained by between groups comparison of mean psychometric variables are unable to distinguish between these two populations at baseline. Because of this, introduction of the risk of psychosis category in the DSM-V has been bitterly criticized. In accordance, therapeutic prevention assays using antipsychotics, antidepressants, or cognitive therapy have provided inconsistent results. Only the administration of ω-3 polyunsaturated fatty acids has produced a long term efficient effect.

Expression of seasonality in Merinos d'Arles ewes of different genotypes at the MT1 melatonin receptor gene.

Spontaneous ovulatory activity (SOA) in spring has been used to study the out-of-season breeding ability of Merinos d'Arles (MA) ewes. Within this breed, an association was found between more intense seasonality and genotype -/- at a MnlI restriction site (allele - for its absence v. + for its presence) in Exon II of the MT1 receptor gene. This study was designed to ascertain whether this association results in a direct effect of the MT1 genotype on the expression of seasonality in MA ewes. In the first year of the study, genotyping of 314 MA ewes at locus MnlI was carried out and resulted in frequencies of 43.0%, 44.9% and 12.1% for genotypes +/+, +/- and -/-, respectively. The SOA of these ewes was determined in early April of two consecutive years by assaying plasma progesterone concentrations in two blood samples taken 9 days apart. Groups of 30 ewes of each homozygous genotype (+/+ and -/-) were identified from this population and their SOA was followed by taking blood samples at regular intervals between January and mid-April of the second and third year of the study. In the second year, groups of ewes were managed together on rangelands, whereas in the third year each group was split into two subgroups given differential feed levels. The results clearly showed that genotype had no significant effect on SOA during the 2- to 3-month period preceding the introduction of rams for spring mating. In the second year of the study, in which the experimental procedure allowed a fair comparison of the fertility of ewes in spring mating, fertility was similar for both genotypes. The reciprocity of the association was not demonstrated and the MnlI polymorphic site could not be used as a genetic marker of selection for out-of-season breeding ability, at least not in the MA breed. The percentage of cycling ewes significantly decreased between January and April, and older ewes (5 or 6 years old depending on the year of the study) were more cyclic than younger ones (2 and 3 years old, respectively). The differential feeding level of ewes from early February did not significantly affect their SOA during the time period studied in the third year of the study.

[Telomeres in the brain cortex of depressive patients]. / Longueur des télomères dans le cortex des patients atteints de troubles dépressifs.

BACKGROUND: Telomeres are complex structures formed by the end of the DNA molecule at the tip of chromosomal arms. The telomeric sequence, which results from the repetition of the hexanucleotide TTAGGG, is partly single strand and is associated with more than ten proteins, including the enzyme telomerase. Because of the characteristics of the DNA replication process, only telomerase is able to elongate the telomeric sequence. Since the telomerase gene is repressed in virtually all the somatic cells, telomeres progressively shorten at each S phase of the cell cycle, and this shortening is accelerated by oxidative stress. A critically shortened telomere activates the genetic program of cell senescence and/or apoptosis. The telomere length measured in peripheral blood leucocytes is considered a reliable marker of biological age, mortality risk and exposure to various pathological conditions, including cardiovascular disease, dementia and metabolic syndrome. Telomere erosion has been observed in psychiatric disorders including schizophrenia and mood disorders, suggesting an accelerated aging of 10 to 20 years. Whether this peripheral dynamic is reflected by a similar pattern in the brain remains unknown. To address this issue, we have measured the telomere length in the occipital DNA cortex of 24 patients with major depressive disorder and 12 controls (donated by the Stanley Research Institute). METHODOLOGY: The mean telomere length has been evaluated by a real time quantitative PCR technique, which amplified the telomere sequence and a reference single copy sequence. Results have been expressed by the ratios of Ct obtained for the two amplification curves. RESULTS: The mean Ct values were strictly identical (0.79 ± 0.001) and the 36 PCR curves were coincident. DISCUSSION: This study demonstrates for the first time that there is no shortening of telomeres in the cortex of patients with depressive disorder. Previous results have shown that in normal tissues telomeres length is inversely correlated to age, even in non proliferating tissues, but that the change is minimal in the brain. Thus, although consistent evidence for the role of a systemic and brain inflammation associated oxidative stress in depression has been provided, it must be concluded that the cerebral state of telomeres is not affected by the mechanism operating in the leucocytes. This observation raises the issue of the relation between the psychiatric pathological process and the peripheral telomere marker. It suggests the existence of specific telomere stabilizing factors in the cortex cells.

Polymicrogyria in a child with inv dup del(9p) and 22q11.2 microduplication.

Polymicrogyria (PMG) is a relatively common malformation of the cortex for which the pathogenesis remains poorly understood. Both acquired and genetic causes are known, and to date more than 70 cases of PMG have been associated with chromosomal abnormalities. Here we report on a 12-year-old girl presenting with asymmetrical PMG predominantly affecting the right occipital lobe. She was the only child of consanguineous parents. At 7 years of age she was referred for mental retardation with speech delay and seizures. Cytogenetic studies of the patient revealed an inverted 9p duplication/deletion and bacterial artificial chromosomes (BACs)-array also showed a 22q11.2 microduplication confirmed by quantitative PCR. This case is of interest in the search for candidate genes and emphasizes the importance of the 22q11 region in PMG. It also highlights the efficiency of BACs-array in detecting complex rearrangements.

Study of the Fermi surface of ZrB12 using the de Haas-van Alphen effect.

The de Haas-van Alphen (dHvA) effect in the cluster superconductor ZrB12 was studied by magnetic torque measurements in magnetic fields up to 28 T at temperatures down to 0.07 K. The dHvA oscillations due to orbits from the neck sections and "cubic box" of the Fermi surface were detected. The dHvA frequencies as well as the cyclotron effective masses were calculated using the full-potential linear muffin-tin orbitals method within the generalized gradient approximation. A comparison of the experimental and calculated cyclotron mass shows unusually large electron-phonon interaction on the neck (lambdaep=0.95) and box (lambdaep=1.07) sections of the Fermi surface on the Brillouin zone boundaries.

Array-CGH in a series of 30 patients with mental retardation, dysmorphic features, and congenital malformations detected an interstitial 1p22.2-p31.1 deletion in a patient with features overlapping the Goldenhar syndrome.

Genosensor Array 300 (Abbott) is a multiplex platform for array-based comparative genomic hybridization that detects unbalanced genomic aberrations including whole chromosome gains/losses, microdeletions, duplications and unbalanced subtelomeric rearrangements. A series of 30 patients with unexplained mental retardation, dysmorphic features, congenital abnormalities and normal high resolution karyotype and FISH subtelomeric studies were analyzed using Genosensor Array 300 array-CGH. We identified a chromosomal aberration in one patient with an interstitial 1p31.1 deletion. FISH analysis with BACs specific probes of the 1p region confirmed the interstitial 1p22.2-p31.1 deletion. The patient was a 20-year-old man with short stature, facial dysmorphism including asymmetry, scoliosis, severe psychomotor delay and an epibulbar dermoid cyst. The phenotype was compatible with Goldenhar syndrome despite the absence of asymmetric ears. This observation is of interest since it could be a clue in the search for the genes responsible for Goldenhar syndrome. This study demonstrates the utility of the array-CGH technology in detecting interstitial deletions.

Clinical, molecular, and genotype-phenotype correlation studies from 25 cases of oral-facial-digital syndrome type 1: a French and Belgian collaborative study.

Oral-facial-digital syndrome type 1 (OFD1) is characterised by an X linked dominant mode of inheritance with lethality in males. Clinical features include facial dysmorphism with oral, tooth, and distal abnormalities, polycystic kidney disease, and central nervous system malformations. Large interfamilial and intrafamilial clinical variability has been widely reported, and 18 distinct mutations have been previously reported within OFD1. A French and Belgian collaborative study collected 25 cases from 16 families. OFD1 was analysed using direct sequencing and phenotype-genotype correlation was performed using chi2 test. X inactivation studies were performed on blood lymphocytes. In 11 families, 11 novel mutations, including nine frameshift, one nonsense, and one missense mutation were identified, which spanned nine different exons. A combination of our results with previously reported cases showed that the majority of mutations (65.5%) was located in exons 3, 8, 9, 13, and 16. There was phenotype-genotype correlation between (a) polycystic kidney disease and splice mutations; (b) mental retardation and mutations located in exons 3, 8, 9, 13, and 16; and (c) tooth abnormalities and mutations located in coiled coil domains. Comparing the phenotype of the families with a pathogenic mutation to families with absence of OFD1 mutation, polycystic kidneys and short stature were significantly more frequent in the group with no OFD1 mutation, whereas lingual hamartomas were significantly more frequent in the group with OFD1 mutation. Finally, an X inactivation study showed non-random X inactivation in a third of the samples. Differential X inactivation between mothers and daughters in two families with high intrafamilial variability was of particular interest. Slight phenotype-genotype correlations were established, and X inactivation study showed that skewed X inactivation could be partially involved in the pathogenesis of intrafamilial clinical variability.

Prolificacy genes in sheep: the French genetic programmes.

It has been demonstrated that variations in litter size or ovulation rate in different breeds of sheep can be associated with the segregation of several major genes. This set of natural mutants constitutes a valuable resource to determine key points in the biochemical pathways controlling the development of ovarian follicles. The French genetic programmes were devised to identify two of these genes: the Booroola (FecB) and Lacaune genes. The FecB prolific mutation corresponds to a non-conservative mutation (Q249R) in the intracellular kinase-signalling domain of the bone morphogenetic protein receptor type IB (BMPR-IB) gene. The Lacaune gene is situated on ovine chromosome 11. Positional cloning is currently in progress to identify the relevant gene and mutation. A similar approach, limited to linkage testing of candidate genes, is proposed to classify the different prolificacy genes in sheep.

Stage-dependent activation of cell cycle and apoptosis mechanisms in the right ventricle by pressure overload.

The molecular basis of the intrinsic vulnerability of the compliant right ventricle to chronic pressure overload is poorly understood. Extensive apoptosis, possibly coupled with aberrant cell cycle reentry, in response to unrestrained biomechanical stress may account for this phenotypic flaw. To address this issue we have studied changes in expression of the cell cycle and apoptosis regulators in the right ventricle following induction of pulmonary hypertension in the rat by injection of monocrotaline. Hypertrophy, apoptosis and cell cycle events, as well as expression of their regulator genes were documented during a period of 31 days. The hypertrophy index reached 127% at day 31. At the early stage both apoptosis and cell proliferation pathways were coincidentally activated. The level of cyclin A and E transcripts steadily increased, the labeling index was 4.8% at day 31, and expression of the caspase-3 gene peaked at day 14. Until day 21 execution of apoptosis was prevented, probably by a high level of Bcl-2. At this time point Bcl-2 collapsed, cyclin D1 was upregulated, the differentiation gatekeeper p27Kip1 was downregulated, pro-caspase-3 was activated and extensive apoptosis developed. These results indicate that the right ventricle is especially vulnerable to apoptotic pressure-dependent stimuli, and that the cell cycle and apoptosis pathways were co-activated in this experimental model.

Changes in HSP70 and P53 expression are related to the pattern of electromechanical alterations in rat cardiomyocytes during simulated ischemia.

The objective was to relate the response of the HSP70 and P53 genes to the cessation and the recovery of cardiac muscle cell functions when submitted to ischemia-reperfusion. We have measured the electromechanical activity, the released enzymes and HSP70 RNA and protein levels in cultured neonatal rat cardiomyocytes (CM) in a substrate-free, hypoxia-reoxygenation model of ischemia-reperfusion. In parallel the expression of the two genes P53 (the key apoptosis regulator gene) and P21/Waf1 (the P53 target gene) has been evaluated. The functional recovery during post-'ischemic' reoxygenation was associated with an overexpression of HSP70 and P53 lasting until the functional parameters reverted back to the normal, prehypoxic values. In contrast, extending the substrate-free hypoxic treatment worsens the dysfunction of the cardiac muscle cell and, in these conditions, reoxygenation failed to restore cell functions and to activate HSP70. Finally, in the conditions of reversible 'ischemic' cell injury, an early and transitory activation of P53 was associated with the functional recovering process of the CM submitted to simulated ischemia. These observations are suggestive of a contributive role of both HSP70 and P53 to a cytoprotective program activated by reoxygenation in post-'ischemic' CM.

Upregulation of the netrin receptor (DCC) gene during activation of b lymphocytes and modulation by interleukins.

The DCC (deleted in colon cancer) gene has a brain restricted high expression pattern. It encodes a transmembrane protein of the immunoglobulin superfamily identified as the netrin-1 receptor. It might be a member of the so called "brain-lymphoid" molecules, which control key cell surface events. To test this hypothesis we have assessed the DCC mRNA level in human normal and malignant myeloid and lymphoid cells. A high mRNA content has been observed only in mature B cells at the secreting or presecreting stage. Expression of DCC was also assessed in the anti-CD40 model of immunopoiesis. Activation of purified tonsillar B cells by anti-CD 40 antibody strongly increased the DCC mRNA level and this effect was dramatically enhanced by the association of IL-2 + IL-10, which is a potent and selective in vitro inducer of the B cell memory phenotype. In contrast no effect has been detected after activation of T cells by anti-CD3. These data suggest that the DCC encoded netrin receptor is involved in B cell immunopoiesis.

[Expression of p21 WAF1/CIP1 protein in colorectal cancers: study of its relation to p53 mutation and Ki67 antigen expression]. / Expression de la protéine p21WAF1/CIP1 dans les cancers colorectaux: étude de sa relation avec les mutations du gène p53 et l'expression de la protéine p53 et de l'antigène Ki67.

Mutations of the p53 gene are the most common genetic alteration in malignant human tumors. A cyclin-dependent kinase inhibitor, p21WAF1/CIP1, is thought to be an important mediator of p53-induced cell cycle arrest. Although numerous studies have reported p53 expression and mutation in colorectal cancer few of them have correlated p53 expression with that of its downstream effector p21 and with the proliferation index as measured by expression of the Ki67 nuclear antigen. We studied p53, p21 and Ki67 expression by immunohistochemistry and molecular biology in 35 colorectal carcinomas. We compared these findings with each other and with clinical factors. Sixty three percent of tumors expressed p53 whereas seventy one percent expressed p21WAF1/CIP1. In adenocarcinomas, p21 staining was heterogeneous: p21-reactive cells were seen in the most differentiated areas. There was no correlation between p21WAF1/CIP1 and p53 expression, p53 mutation, Ki67 expression or clinical factors such as sex or location of the tumor. On the other hand, there was a statistical relationship between p21 expression and survival: our results indicated an association between high p21 expression and lower stages p21WAF1/CIP1 appears to be induced independently of p53 in these tumors and may be associated with differentiation rather than proliferation.