Calcium and phosphorus digestibility in broilers as affected by varying phytate concentrations from corn.

Dietary phytate P (PP) concentration impacts Ca and P digestibility in broilers. Research was conducted to determine the impact of increasing concentration of dietary PP, with and without phytase, on broiler standardized ileal digestibility (SID) of Ca and P. Digestible (Dig) Ca and P were calculated by multiplying SID and the analyzed dietary Ca and P concentrations. The experiment was a factorial arrangement of 2 phytase (0 and 1,000 U/kg) and 4 PP (0.16, 0.23, 0.29, and 0.34%) concentrations. Treatments were fed for 36 h from 20 to 22 d of age (4 b/pen, n ≥ 7 replicate pens/treatment). Different ratios of corn and corn germ were used to achieve the desired PP concentrations. A limestone with 800 µm geometric mean diameter was used as the sole Ca source to achieve 0.7% Ca in the final diets (96% Ca from limestone). An additional diet was fed that was N, Ca- and P-free, for the determination of endogenous losses of each nutrient. Distal ileal digesta were pooled from all birds in a pen. There were no interactions between PP and phytase on SID Ca or Dig Ca from limestone. Irrespective of phytase inclusion, increasing PP from 0.16 to 0.34% decreased SID Ca from 53.8 to 38.1% (P < 0.05). The SID Ca averaged 41.5 and 51.4% in diets containing 0 and 1000 U phytase/kg, respectively, across all PP concentrations (P < 0.05). Interactions were seen between PP and phytase on SID and Dig P (P < 0.05) with SID P of 31.1, 24.0, 20.1, and 16.3% for broilers fed 0.16, 0.23, 0.29, and 0.34% PP diets without phytase, respectively. When phytase was included at 1000 U/kg, SID P was 89.9, 87.5, 73.9 and 60.4% for diets containing 0.16, 0.23, 0.29 and 0.34% PP, respectively (P < 0.05). Overall, phytase improved SID Ca and P independent of PP concentration. However, with increasing PP concentration, both SID Ca and P were negatively affected.

Expression of genes related to ileal barrier function in heritage and modern broiler chickens.

1. An experiment was conducted to determine differences in the expression of genes encoding intestinal barrier proteins between fast, medium and slow-growing chickens. Chicken breeds Athens Canadian Random Bred (ACRB), Longenecker's Heritage (LHR), RedBro, Hubbard H1 (HH1), Cobb500 and Ross708 were raised from hatch for 35 d.2. Ileal samples were collected at embryonic day E19 (-2 days post-hatch), hatch and d 7, 14, 21, 28 and 35 post-hatch to assess the expression of genes encoding tight junction proteins (claudins, CLDN; occludin, OCLN; zonula occludens, ZO; and junctional adhesion molecules, JAM), mucin (Muc2), immunoglobulin A (IgA), polymeric immunoglobulin receptor (pIgR) and fatty acid binding protein (FABP2).3. Expression of CLDN-1 was increased (p < 0.0001) in LHR compared to Cobb500 while CLDN-5 was increased (p < 0.0001) in ACRB, HH1, RedBro and Ross708 compared to LHR as well as in ACRB compared to Cob500. Occludin was upregulated (p = 0.01) in ACRB and LHR compared to Ross708 at d 14 post-hatch. Expression of ZO-1 was upregulated (p = 0.001) in LHR compared to Ross708, HH1 and Cobb500. Tight junction genes, except CLDN-4, JAM-2 and JAM-3 were downregulated (p < 0.0001) at hatch and d 7 post-hatch. Expression of Muc2 was increased (p < 0.0001) in LHR compared to RedBro and from -2 d to d 7 post-hatch.4. Immunoglobulin A was increased (p = 0.001) in LHR compared to Ross708 and HH1 at -2 d post-hatch and in LHR compared to ACRB, Cobb500 and Ross708 at hatch. In addition, IgA expression was increased in all breeds at d 14 post-hatch while pIgR was upregulated (p = 0.02) in Cobb500 and Ross708 compared to ACRB, HH1, LHR and RedBro at hatch.5. The gene expression patterns suggest that selection for growth may have not induced changes in junctional complexes and immune defence genes. However, the results confirmed that the expression of these genes is age dependent.

Growth and Cyclin-E Expression in the Stony Coral Species Orbicella faveolata Post-Microfragmentation.

AbstractCoral growth is critical to reef health, resilience under rapidly changing environmental conditions, and restoration efforts. Although fragmenting coral has been occurring for many years in an effort to restore reefs, recently it was discovered that microfragmenting, the process of cutting one piece of coral into many small pieces (about three to five polyps), induces exponential growth. Our study investigates the process by which microfragments of nine different genotypes from the stony coral species Orbicella faveolata grow and exhibit Cyclin-E expression. Microfragments were examined by using a high-powered dissecting microscope with a camera to document the precise areas of tissue exhibiting exponential growth. We found that new polyp formation occurs only on the microfragment edges and that edge polyp growth rates varied between different genotypes. We then extracted tissue from both the edge and the center of five genotypes for genetic analysis. We chose to analyze Cyclin-E expression because it is involved with stimulating mitotic division and is a conserved signaling pathway that is known to exist in Drosophila, mammals, and Cnidaria. Two primers for Cyclin-E were utilized to examine the level of expression for center and edge tissue. We found that Cyclin-E is expressed differentially between O. faveolata polyps, with a tendency for increased expression of the Cyclin-E in edge versus center tissue in each of five genotypes, although this result was not significant. Despite consistently higher levels of Cyclin-E expression within an organism's edge tissue, genotypes varied significantly in the degree of increased expression. This variation positively correlated with growth rate, suggesting the potential for molecular selection in aid of more rapid reef restoration. Future work will focus on deciphering the specific growth pathways involved in microfragmented coral growth and analyzing expression patterns in injured tissues.

Expression of genes associated with nutrient uptake in intestines of chickens with different growth potentials show temporal changes but are not correlated with growth.

1. The study was designed to compare the expression of genes that encode proteins located at either the brush border (BB) or basolateral (BL) of the gut epithelium among fast and slow-growing broilers.2. Six broiler breeds with different growth capacities were used: Ross 708, Hubbard H1 (HH1), Cobb 500, Longenecker's Heritage (LHR), Red-Bro, and the Athens Canadian Randombred Control (ACRB). Birds were sampled between embryonic day (ED) 19 and day 35 post-hatch (PH).3. Performance parameters indicated that Ross 708, HH1, and Cobb 500 had the highest body weights (BW) while ACRBs had the lowest.4. Quantitative RT-PCR was performed on 13 genes encoding proteins associated with nutrient processing and uptake. Statistical analysis was carried out (ANOVA) for eight BB genes: Aminopeptidase N (APN), four amino acid transporters, (ATBo,+, BoAT, bo,+AT, EAAT3) a di- and tri-peptide transporter (PepT1), and two sugar transporters (GLUT5 and SGLT1). Analysis of four amino acid transporters (CAT1, CAT2, LAT1, and γ+LAT1), and a single sugar transporter (GLUT2) associated with BL was carried out.5. Four BB associated genes (APN, EAAT3, BoAT, and b0,+AT) in the small intestine were negatively correlated with growth.6. In most cases, genes encoding BB proteins increased in expression over time (P < 0.05) in the small intestine, while, in the caeca, the expression decreased (P < 0.05). The mRNA of BL-associated proteins showed decreased (P < 0.05) expression over time in all gut segments, with exception of GLUT2, which increased in expression in the small intestine.7. The temporal changes in gene expression were consistent among bird lines and BB associated genes tended to increase over time, while BL associated genes tended to decrease over time. Correlation analysis indicated that mRNA expression of nutrient transporter genes may not be a good predictor of growth potential.

The effect of delayed feeding post-hatch on caeca development in broiler chickens.

1. Broiler chicks are frequently deprived of food up to 72 h due to uneven hatching rates, management procedures and transportation to farms. Little is known about the effect of delayed feeding due to extended hatching times on the early neonatal development of the caeca. Therefore, the objective of this study was to investigate the developmental changes and effects of a 48-h delay in feed access immediately post-hatch (PH) on the caeca.2. After hatch, birds (Ross 708) were randomly divided into two treatment groups (n = 6 battery pen/treatment). One group (early fed; EF) received feed and water immediately after hatch, while the second group (late fed; LF) had access to water but had delayed access to feed for 48 h. Contents averaging across all regions of the caeca were collected for mRNA expression as well as for histological analysis at -48, 0, 4 h PH and then at 1, 2, 3, 4, 6, 8, 10, 12 and 14 days PH.3. Expression of MCT-1 (a nutrient transporter), Cox7A2 (related to mitochondrial function) IgA, pIgR, and ChIL-8 (immune function) genes was affected by delayed access to feed that was dependent by the time PH. Expression of immune and gut barrier function-related genes (LEAP2 and MUC2, respectively) was increased in LF group. There was no effect of feed delay on expression of genes related to mitochondrial functions in the caeca, although developmental changes were observed (ATP5F1B, Cox4|1). Caecal mucus and muscle thickness were affected by delayed access to feed during caeca development.4. The data suggested a limited effect of delayed feed access PH on the developmental changes in caecal functions. However, the caeca seemed to be relatively resistant to delayed access to feed early PH, with only a few genes affected.

Involvement of serum anti-retinal antibodies in the pathophysiology of diabetic retinopathy: a pilot study.

The aim of this single-center cross-sectional study was to identify tissue targets for circulating anti-retinal antibodies (ARAs) in the serum of patients with diabetic retinopathy (DR). The study included 61 participants with DR (30 with nonproliferative diabetic retinopathy and 31 with proliferative diabetic retinopathy) and 30 healthy controls. An indirect immunofluorescence (IIF) test was used to detect serum ARAs and identify their targets in the tissue. Four types of ARAs were found in serum samples from DR patients: antibodies against the outer segments of the rods, antibodies against the outer segments of the cones, antibodies against the cytoplasmic components of retinal nuclear layer cells, and antibodies against retinal nerve fibers. A significant difference was noted between groups in the prevalence of antibodies against the outer segments of the rods (NPDR, 40%; PDR, 74.2%; and controls, 40%; P = 0.008) as well as antibodies against the outer segments of the cones (NPDR, 23.3%; PDR, 61.3%; and controls, 30%; P = 0.005). Interestingly, the distribution of immunofluorescence intensity for the outer segments of the rods and cones differed significantly between study groups (P ≢ 0.001 and P = 0.019, respectively). In conclusion, the results of our pilot study showed that in most patients with DR, the outer segments of photoreceptors tend to be the tissue target for serum ARAs. This may indicate their possible involvement in the pathogenesis of DR. However, further research is needed to fully elucidate whether these antibodies participate in photoreceptor damage in the course of DR.

Quantitative assessment of bacterial growth phase utilizing flow cytometry.

Flow cytometry is currently underutilized for bacterial phenotyping and standard microbiological techniques do not provide phenotypic information about the state of the bacterial disease. Pseudomonas aeruginosa is a human pathogen of increased importance in public health due to both the ability to cause chronic diseases and the prevalence of functionally different subsets that can be difficult to treat and diagnose. In the present study, we used flow cytometry to analyze the growth phase of P. aeruginosa. A simple method for single cell quantitative detection of bacterial biofilm and planktonic cells was established with a combination of membrane permeable (SYTO 60) and impermeable (TOTO-1) dyes plus the addition of polystyrene counting beads. The specificity of the dye combination for biofilm detection was determined by comparison with impaired biofilm forming strains of P. aeruginosa LasI/RhlI-/- and ∆PfPhage. Results suggest that flow cytometric bacterial phenotyping serves as an expandable platform that may be useful for enumeration of population level variation in P. aeruginosa studies.

Effects of limestone particle size and dietary Ca concentration on apparent P and Ca digestibility in the presence or absence of phytase.

The present study evaluated the effects of limestone particle size and Ca concentration on apparent ileal digestibility (AID) of P and Ca in the presence or absence of a 6-phytase derived from Buttiauxella sp., expressed in Trichoderma. Treatment diets were corn-soybean meal (SBM) based with no added inorganic Ca or P. The design consisted of a factorial arrangement of 2 particle sizes of limestone from the same source (mean particle size: pulverized, PUV < 75 µm; particulate, PAR = 402 µm); 3 Ca (0.6, 0.8, and 1.0%) and 2 phytase levels (0 and 1,000 (FTU)/kg) plus the corn-SBM basal diet with no added Ca (0.14% Ca), resulting a total of 13 treatments (Trts, n = 9, 3 birds/n). Starting at 27 d of age, broilers were fed the mash diets for 32 h, then sampled for gizzard pH and distal ileal digestibility. Gizzard pH was 1.94 in birds fed diet without added Ca and was similar to those fed diet with PAR limestone regardless of phytase. Gizzard pH was increased in birds fed PUV limestone diets irrespectively of phytase inclusion compared to birds fed 0.14% Ca (P < 0.05), except in birds fed 0.60% Ca diet. In the absence of phytase, AID P was reduced as a result of increases in limestone inclusion (P < 0.05), with a greater effect seen in PUV as compared to PAR limestone. The AID Ca in birds fed PUV limestone diets was lower than that of those fed PAR limestone diets (22.1% vs. 28.2%; P < 0.05). In the presence of phytase, the AID P was not affected by increasing Ca concentration when PAR limestone was used as the Ca source (average = 64.3%), whereas AID P decreased from 66.9% (0.6% Ca) to 51.0% (1.0% Ca) when PUV limestone was used as the Ca source (P < 0.05). In summary, impact of Ca concentration on AID Ca and P was dependent on limestone particle size and phytase inclusion.

Insulin immuno-neutralization decreases food intake in chickens without altering hypothalamic transcripts involved in food intake and metabolism.

In mammals, insulin regulates blood glucose levels and plays a key regulatory role in appetite via the hypothalamus. In contrast, chickens are characterized by atypical glucose homeostasis, with relatively high blood glucose levels, reduced glucose sensitivity of pancreatic beta cells, and large resistance to exogenous insulin. The aim of the present study was to investigate in chickens the effects of 5 h fasting and 5 h insulin immuno-neutralization on hypothalamic mRNA levels of 23 genes associated with food intake, energy balance, and glucose metabolism. We observed that insulin immune-neutralization by administration of anti-porcine insulin guinea pig serum (AI) significantly decreased food intake and increased plasma glucose levels in chickens, while 5 h fasting produced a limited and non-significant reduction in plasma glucose. In addition, 5 h fasting increased levels of NPY, TAS1R1, DIO2, LEPR, GLUT1, GLUT3, GLUT8, and GCK mRNA. In contrast, AI had no impact on the levels of any selected mRNA. Therefore, our results demonstrate that in chickens, food intake inhibition or satiety mechanisms induced by insulin immuno-neutralization do not rely on hypothalamic abundance of the 23 transcripts analyzed. The hypothalamic transcripts that were increased in the fasted group are likely components of a mechanism of adaptation to fasting in chickens.

Personality traits as an endophenotype in genetic studies on suicidality in bipolar disorder.

Introduction The influence of personality traits on suicidal behaviour risk has been well documented. Personality traits and suicidal behaviour are partially genetically determined and personality has been described as an endophenotype of suicidal behaviour. The aim of this study was to investigate a possible association between personality traits with suicidal behaviour and selected serotonergic gene polymorphisms. METHODS: In the study we included 156 patients meeting DSM-IV criteria for bipolar disorder (BP) and 93 healthy controls. The personality dimensions were assessed using the Temperament and Character Inventory (TCI). We genotyped two selected polymorphisms of the tryptophan hydroxylase 1 (TPH1) gene (rs1800532 218A>C and rs1799913 779A>C) and polymorphism in the promoter region of serotonin transporter gene (5-HTTLPR, rs25531) related to serotoninergic neurotransmission. Multiple poisson regression, logistic regression and Kruskal-Wallis tests were applied. RESULTS: We found numerous differences between the BP patients and the control group in terms of their TCI dimensions/subdimensions. Significant differences were found between patients with, and without, suicidal attempts in fatigability and asthenia (Ha4), as well as in harm avoidance (Ha). We also found that the interactions between TCI subdimensions (the interaction of disordiness (Ns4) and spiritual acceptance (St3), disordiness (Ns4) and integrated conscience (C5), extravagance (Ns3) and resourcefulness (Sd3)) were significantly contributing for suicidal behaviour risk. We found association between all studied genetic polymorphisms and several TCI dimensions and subdimensions. CONCLUSION: Our results confirm that personality traits are partially determined by genes. Both personality traits and the interactions between temperament and character traits, may be helpful in predicting suicidal behaviour.

Salivary alpha-amylase, secretory IgA and free cortisol as neurobiological components of the stress response in the acute phase of anorexia nervosa.

Objectives One novel hypothesis of the pathogenesis of anorexia nervosa (AN) is the possible role of mental stress in hyperactivity of the autonomic nervous system (ANS) and of the hypothalamic-pituitary-adrenal (HPA) axis. Two components of stress response - salivary alpha-amylase (sAA) and free cortisol - have been proposed. They can be determined in saliva, which closely reflects their concentrations in plasma. The purpose of this study was to measure salivary free cortisol, sAA and their correlation to secretory IgA (sIgA) of patients with AN in comparison to the average population. Methods A controlled clinical trial was designed for a matched group of 47 AN patients and 54 healthy individuals. After clinical examination, unstimulated salivary samples were taken during the acute stage of AN (BMI < 15 kg/m(2)) in the first week of hospitalisation. An enzyme-linked immunosorbent assay (ELISA) suitable for measuring sAA, sIgA and free cortisol were used. Results Anorexic patients exhibited disturbances in sAA secretion, and significantly increased cortisol and sIgA levels with a distinct correlation between these two parameters. Conclusions The behaviour of cortisol, sAA and sIgA levels can be assessed as an effect of stress reaction among AN patients with hyperactivity of the HPA axis and ANS dysregulation. The effect of stress response can be assessed reliably in saliva.

Age and adaptation to Ca and P deficiencies: 2. Impacts on amino acid digestibility and phytase efficacy in broilers.

A total of 1,152 straight-run hatchling Heritage 56M×fast feathering Cobb 500F broiler birds were used to determine Ca, age, and adaptation effects on apparent ileal digestibility of crude protein (AID of CP), amino acids (AID of AA) and phytase efficacy. Twelve treatments with 8 replicates, each were fed from 7 to 9 d (6 birds per replicate), 7 to 21 d (6 birds per replicate) and 19 to 21 d (3 birds per replicate) d of age. Diets were prepared with 3 Ca (0.65, 0.80, and 0.95%) and 2 non-phytate P, (0.20 and 0.40%) concentrations. A 6-phytase was added at 500 or 1,000 FTU/kg to the 0.20% nPP diet at each Ca concentration. The age and adaptation effects were determined by comparing the responses between birds fed from 7 to 9 and 19 to 21 d of age, 19 to 21, and 7 to 21 d of age, respectively. An age effect was observed regardless of Ca, nPP, or phytase concentration, with older birds (19 to 21 d) having greater apparent ileal digestibility (AID) of amino acids (AA) and CP than younger birds (7 to 9 d; P<0.05). Response to adaptation varied depending on Ca, nPP, and phytase concentrations. Constant lower AID of CP and AA was seen in adapted birds (7 to 21 d) compared to unadapted bird (19 to 21 d) when 0.20% nPP diets were fed at 0.95% Ca concentrations (P<0.05). At 0.40% nPP, there was no effect of adaptation on AID of CP and AA at any Ca concentration. Phytase efficacy was significantly lower in younger (7 to 9 d) compared to older birds (19 to 21 d; P<0.05), except at 0.65% Ca. Phytase inclusion increased AID of CP and AA regardless of Ca (P<0.05). In conclusion, the AID of CP and AA can be affected by diet, age, and adaptation.

Impact of response criteria (tibia ash weight vs. percent) on phytase relative non phytate phosphorus equivalance.

The current study was conducted to evaluate the impacts of using tibia ash percentage or ash weight as the response criteria on estimated phytase relative equivalence. Straight run broilers were fed treatment (Trt) diets from 7 to 21 d age (6 birds/pen, 8 pens/Trt). The corn-soy based Trt were formulated to contain 0.80% Ca and 4 non-phytate phosphorus (nPP) concentrations (0.20, 0.27, 0.34, and 0.40%). Monocalcium phosphate was the inorganic phosphate source added to achieve 4 different dietary nPP concentrations and against which the nPP relative equivalence of phytase was determined. A 6-phytase (Danisco Animal Nutrition, DuPont Industrial Biosciences, Marlborough, UK) was added at 500 or 1,000 phytase unit ( FTU: )/kg to the 0.20% nPP diet resulting 6 total Trts. Tibia ash was determined at 21 d age. Phytase fed at 500 or 1,000 FTU/kg increased tibia ash weight and ash percentage compared to that of birds fed 0.20% nPP diet without phytase (P<0.05). Graded nPP were log transformed and regressed against tibia ash (weight and percentage) to calculate phytase nPP relative equivalence. The R2 obtained from pen value regressions were 0.81 and 0.84, for tibia ash weight and percentage, respectively. Ash percentage from birds fed 500 and 1,000 FTU phytase/kg fell within the range obtained with the MCP additions. Ash weight (842 mg/tibia) from birds fed 1,000 FTU phytase/kg exceeded (P<0.05) maximum weight (773 mg/tibia) measured in birds fed the greatest nPP Trt (0.40%), thus the nPP relative equivalence was only calculated in birds fed 500 FTU phytase/kg Trt. The nPP relative equivalence in birds fed 500 FTU phytase/kg were 0.117 and 0.168% based on ash percentage and weight, respectively (P<0.05). The nPP relative equivalence in birds fed 1,000 FTU phytase/kg was 0.166% for ash percentage. Results suggested that ash weight better reflects the amount of bone mineralization as compared to ash percentage and using ash percentage may lead to an underestimation of phytase efficacy.

Assessment of postcrumble addition of limestone and calcium-specific appetite in broilers during the starter phase.

A study was done to determine whether broilers can regulate Ca intake when limestone is provided separately or mixed with a crumbled feed of variable Ca and P content, and the influence of this on performance and apparent ileal digestibility (AID) of Ca and P (AIDP). Twelve crumbled diets were fed from 10 to 20 d of age (8 replicates, 8 broilers/replicate). Diets A to D contained 0.28% nonphytate P (nPP) and 0.27, 0.51, 0.77, and 1.02% Ca, respectively. Diets E to H contained 0.48% nPP and 0.41, 0.51, 0.77, and 1.02% Ca, respectively. A large particle size limestone was mixed manually to the crumbled diet on a daily basis to achieve 1.02% total Ca in diets A to H. Diets I to L had the same Ca and nPP as diets A to D, but limestone was provided in a separate feeder to assess spatial importance of limestone supply. Limestone consumption, provided in a separate feeder, decreased as Ca concentration increased in the crumble diet (P < 0.05). Calcium intake increased as Ca concentration in crumbled diets increased (P < 0.05). Increased tibia ash and decreased AIDP were observed as Ca intake increased (P < 0.05). When limestone was added to diets containing 0.28% nPP postcrumble, Ca intake (6.38 g/bird), tibia ash (717 mg/bone), and AIDP (39.78%) were not affected by crumbled diet Ca concentration or consumed Ca. Broilers fed diets containing 0.48% nPP and limestone mixed with the crumble, Ca intake changed (5.96, 6.93, 6.59, and 6.04 g/bird for crumble diet with 0.41, 0.51, 0.77, and 1.02% Ca, respectively). Increasing Ca concentration in the crumble from 0.41 to 1.02% resulted in greater tibia ash (875 mg/bone) but lower AIDP (P < 0.05), although Ca intake was similar. In conclusion, when large particle size limestone was provided ad libitum, the ability of broilers to select for Ca was not sufficient to meet their requirement when crumble Ca was less than 0.77%. The AIDP was highest in birds fed the 0.27% Ca concentration diet.

A genome-wide association study of anorexia nervosa.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

The 3rd Schizophrenia International Research Society Conference, 14-18 April 2012, Florence, Italy: summaries of oral sessions.

The 3rd Schizophrenia International Research Society Conference was held in Florence, Italy, April 14-18, 2012 and this year had as its emphasis, "The Globalization of Research". Student travel awardees served as rapporteurs for each oral session and focused their summaries on the most significant findings that emerged and the discussions that followed. The following report is a composite of these summaries. We hope that it will provide an overview for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research.

Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project.

There is substantial inter-individual variation in response to antidepressants, and genetic variation may, in part, explain these differences. For example, there is evidence to suggest that variation in the serotonin transporter gene (SLC6A4) predicts response to selective serotonin reuptake inhibitors (SSRIs). Environmental factors such as the occurrence of stressful life events before treatment may also be important. One prior report suggests that both factors interact in predicting response to antidepressants. GENDEP, a prospective part-randomized pharmacogenomics trial, collected longitudinal data on the outcome of 811 patients with major depression undergoing treatment with either an SSRI (escitalopram) or a tricyclic antidepressant (nortriptyline). Life events experienced over 6 months preceding treatment were measured using a List of Threatening Experiences Questionnaire, and several polymorphisms in the serotonin transporter gene (SLC6A4) have been genotyped including the serotonin transporter-linked polymorphic region (5-HTTLPR). Stressful life events were shown to predict a significantly better response to escitalopram but had no effect on response to nortriptyline. Variation in the 5-HTTLPR and another polymorphism in the gene, STin4, significantly modified these effects. Gene-environment interactions including life events may therefore be important not only in the aetiology of depression, but also in predicting response to antidepressant medication.

Dopamine D1 receptor gene polymorphism is associated with prophylactic lithium response in bipolar disorder.

BACKGROUND: Previously, we have found an association between the -48 A/G polymorphism of the dopamine receptor D1 (DRD1) gene and bipolar disorder. The aim of the present study was to investigate a possible association of this polymorphism with the quality of the prophylactic lithium response in bipolar patients. METHODS: Ninety-two patients (39 male, 53 female), aged 30-77 (mean: 54 years) were studied. They have received lithium for prophylactic purposes for 5-27 years (mean: 15 years). Twenty-four patients were identified as excellent lithium responders (ER), 48 patients as partial responders (PR), and 20 patients were non-responders (NR). They all were genotyped for -48 A/G polymorphism of the DRD1 gene. RESULTS: The frequency of G/G genotype in ER, PR, and NR patients was 21%, 48%, and 60%, respectively, and the frequency of G allele was 58%, 76%, and 80%, respectively. DISCUSSION: The results obtained suggest that the higher frequency of G allele, and G/G genotype, which has been associated with a predisposition to bipolar illness, is also connected with a poorer prophylactic effect of lithium.

Expression and activity of the 5'-adenosine monophosphate-activated protein kinase pathway in selected tissues during chicken embryonic development.

The 5'-adenosine monophosphate-activated protein kinase (AMPK) is a highly conserved serine-threonine protein kinase and a key part of a kinase-signaling cascade that senses cellular energy status (adenosine monophosphate:adenosine triphosphate ratio) and acts to maintain energy homeostasis by coordinately regulating energy-consuming and energy-generating metabolic pathways. The objective of this study was to investigate aspects of the AMPK pathway in the liver, brain, breast muscle, and heart from d 12 of incubation through hatch in chickens. We first determined mRNA and protein expression profiles for a major upstream AMPK kinase, LKB1, which is known to activate (phosphorylate) AMPK in response to increases in the adenosine monophosphate:adenosine triphosphate ratio. Expression of LKB1 protein was greatest in the brain, which demonstrated tissue-specific patterns for phosphorylation. Next, AMPK subunit mRNA and protein expression profiles were determined. Significant changes in AMPK subunit mRNA expression occurred in all tissues from d 12 of incubation to hatch. Differences in the levels of active (phosphorylated) AMPK as well as alpha and beta subunit proteins were observed in all 4 tissues during embryonic development. Finally, we determined the protein level and phosphorylation status of an important downstream target for AMPK, acetyl-coenzyme A carboxylase. The expression of acetyl-co-enzyme A carboxylase and phosphorylated acetyl-coenzyme A was greater in the brain than the liver, but was undetectable by Western blotting in the breast muscle and heart throughout the period of study. Together, our results are the first to demonstrate the expression and activity of the AMPK pathway in key tissues during the transition from embryonic to posthatch development in chickens.

Mechanisms regulating feed intake, energy expenditure, and body weight in poultry.

To achieve energy balance and maintain a constant BW, changes in feed intake and energy expenditure must be coordinated and tightly regulated. This may not hold true for some poultry species intensively selected for such economically important traits as growth and meat production. For example, the modern commercial broiler breeder does not adequately control voluntary feed intake to meet its energy requirements and maintain energy balance. As a consequence, feeding must be limited in these birds to avoid overconsumption and excessive fattening during production. It is important to determine a genetic basis to help explain this situation and to offer potential strategies for producing more efficient poultry. This review summarizes what is currently known about the control of feed intake and energy expenditure at the gene level in birds. Highly integrated regulatory systems have been identified that link the control of feeding with the sensing of energy status. How such systems function in poultry is currently being explored. One example recently identified in chickens is the adenosine monophosphate-activated protein kinase pathway that links energy sensing with modulation of metabolic activity to maintain energy homeostasis at the cellular level. In the hypothalamus, this same pathway may also play an important role in regulating feed intake and energy expenditure commensurate with perceived whole body energy needs. Genes encoding key regulatory factors such as hormones, neuropeptides, receptors, enzymes, and transcription factors produce the molecular components that make up intricate and interconnected neural, endocrine, and metabolic pathway networks linking peripheral tissues with the central nervous system. Moreover, coordinate expression of specific gene groups can establish functional pathways that respond to and are regulated by such factors as hormones, nutrients, and metabolites. Thus, with a better understanding of the genetic and molecular basis for regulating feed intake and energy expenditure in birds important progress can be made in developing, evaluating, and managing more efficient commercial poultry lines.