Schizophrenia is a debilitating psychiatric disorder, leading to both physical and social morbidity. Worldwide 1% of the population is struggling with the disease, with 100,000 new cases annually ...only in the United States. Despite its importance, the goal of finding effective treatments for schizophrenia remains a challenging task, and previous work conducted expensive large-scale phenotypic screens. This work investigates the benefits of Machine Learning for graphs to optimize drug phenotypic screens and predict compounds that mitigate abnormal brain reduction induced by excessive glial phagocytic activity in schizophrenia subjects. Given a compound and its concentration as input, we propose a method that predicts a score associated with three possible compound effects, i.e., reduce, increase, or not influence phagocytosis. We leverage a high-throughput screening to prove experimentally that our method achieves good generalization capabilities. The screening involves 2218 compounds at five different concentrations. Then, we analyze the usability of our approach in a practical setting, i.e., prioritizing the selection of compounds in the SWEETLEAD library. We provide a list of 64 compounds from the library that have the most potential clinical utility for glial phagocytosis mitigation. Lastly, we propose a novel approach to computationally validate their utility as possible therapies for schizophrenia.
Hematologic parameters and the levels of certain plasma metabolites offer an objective measure, and real-time insight into the physiological status of an animal. We hypothesized that blood chemistry ...analysis in brooding poults varies with even minor differences of temperature and can affect poult performance. A total of 2,240 one-day-old turkey hens were assigned randomly to 1 of 4 treatments Control (C) = 32C and 60%RH; cold stress (CS) = 29C and 60%RH; heat stress (HS) = 35C and 60%RH; and heat stress plus humidity (HHS) = 35C and 75%RH. In all the treatments, the temperatures were lowered 2°C the first week, and 1.5°C each week thereafter. The relative humidity was maintained constant, as much as possible, throughout the 35 d duration of the experiment. Brooding treatment affected pH, partial carbon dioxide (pCO2), potassium (K), and sodium (Na). The treatments HS and HHS had higher pH and K, and lower pCO2 and K in the blood. These changes suggest an attempt by the poults to cool down by increased water intake and panting. Furthermore, by the end of the experiment more birds in these 2 treatment groups had distended crops, possible to increased water intake also. The increase of ketone in the plasma, at 3 d of age, of poults from the 2 warmest brooding conditions (HS and HHS) suggests that these birds were consuming less feed and using more fat as its main fuel source. Furthermore, at 28 d of age significantly more poults from HS and HHS had reduced ventricular contractility of their hearts. However, no significant differences in the concentration of creatinine kinase (CK) or cardiac troponin I (cTnI) were found between treatments. In conclusion, this research revealed that blood parameters were influenced by minor temperature and humidity changes. Warmer brooding temperatures resulted in a higher incidence of pendulous crop. Overall, there were no significant differences in the estimated BW between the treatments. Further research is needed to optimize the number of samples needed and the time of sampling to optimize brooding conditions. We also need to investigate blood parameters that can reveal reduced contractility of the heart and if the reduced myocardial contractility from birds kept at a higher temperature and relative humidity predisposes them to dilated cardiomyopathy or other metabolic diseases.
Feed costs represent a significant portion of the cost of poultry production. This study, in 3 experiments, was conducted to evaluate the effectiveness of a heat-stable xylanase (XYL) as a dietary ...supplement and its effect on digesta viscosity, nitrogen-corrected apparent metabolizable energy (AMEn), and live performance in broiler chicks. Experiment 1: the objective was to determine the effects of the amount and type of enzyme supplementation on digesta viscosity, AMEn, and bird performance using 7 diets. The dietary treatments were: no supplementation (C), 5 levels of XYL (1 to 16 ppm), or supplementation with a carbohydrase cocktail (CC). Experiment 2: the objective was to determine the interaction of the dietary XYL and the energy content of the feed. There were 2 levels of XYL (0 and 20 ppm) and 3 dietary energy levels (2,770, 2,920, and 3,070 kcal/kg ME). Experiment 3: the objective was to determine the interaction of the dietary XYL and feed form. The treatments were: 5 levels of XYL (0 to 40 ppm) and 2 feed forms (mash and crumble). Broiler chicks were reared in battery cages to 21 d. Statistical analysis of the data was completed using Proc GLM of SAS (9.2) (SAS Institute, Cary, NC).
In experiment 1, increasing XYL (0 to 16 ppm) resulted in a decrease in digesta viscosity and an increase in AMEn. The XYL included as low as 1 ppm resulted in a significant increase in AMEn which reached 5% with 16 ppm XYL. In contrast, increase in BWG (4%) above values with the basal diet was greatest with 1 ppm XYL. In experiment 2, the caloric content of the diet influenced the increase in AMEn with inclusion of XYL, 8% and 6% increases with 2,920 kcal/kg and 3,070 kcal/kg diets, respectively. Without addition of XYL, BWG was significantly lower when fed the diet with the highest energy content. In experiment 3, feed form x XYL influenced the effect of XYL on BWG. The BWG was greater when birds were fed the crumble diet with XYL vs when they were fed the mash feed with XYL. The xylanase proved effective for broilers to 21 d when fed the diets used herein with changes in digesta viscosity, increased dietary AMEn, and improved bird performance represented by either BW gain or FCR.
Large White male turkey genetic lines (GL) comparison in performance and processing yields under the same conditions are rare in the literature. Two rearing experiments (EXP) were conducted to ...accomplish 2 objectives. The first objective was to test the effects of poult source and genetic lines on performance and processing yields. The second objective was to extract season and growth patterns when comparing both EXP common treatments. In EXP 1, male poults from 5 different sources were randomly assigned to 48 concrete: litter-covered floor pens. In EXP 2, male poults from 7 different genetic lines were randomly assigned to 48 concrete: litter-covered floor pens. For both EXP, the experimental design was a completely randomized block design with a one-factor arrangement. Both EXP were placed in the same house with the same management and nutrition in two separate seasons of the same year. Bird performance and carcass processing yield were analyzed in SAS 9.4 or JMP 15.1 in a mixed model. In EXP 1 no significant difference in BW or processing yield was observed. However, a similar GL from a commercial hatchery had an improved feed conversion ratio (FCR) over the same GL sourced directly from the genetic company hatchery. In EXP 2, statistical differences were observed in performance and breast meat yield depending on the GL. A season effect was observed when comparing the two EXP. Birds raised in the fall season had a 2 kg BW increase, on average, over their spring counterparts. This difference in BW can also be observed in a statistically higher breast meat yield by the birds raised in the fall over the ones raised in the spring. In conclusion, a comparison between GL resulted in effects due to genetic line, poult source, and rearing season on bird performance and carcass yield.
Bedding (litter) is essential to poultry performance and health and can have an environmental impact after use in the poultry facility such as a soil amendment or as an alternative energy source. ...Pine shavings are the most common bedding used for turkey production. However, the increase in its price and its increasing scarcity in some areas have created new research opportunities for reusing litter as bedding. Improvement in feed pellet quality has been reported to improve poultry performance. However, the reports for turkeys are limited and dated. This study's objective was to determine how the improvement of feed pellet quality and the use of biochar added to a combination of used turkey brooder house litter and Miscanthus grass as bedding affects turkey performance, small intestine morphology, and ammonia production. Nicolas Select (Aviagen Turkeys, Lewisburg, WV) male poults (816) were randomly assigned to 48 concrete litter floor pens on the day of hatch. The experiment used a completely randomized block design with a 2 × 4 factorial arrangement of treatments: 2 levels of fines in the feed and 4 bedding treatments. The bedding treatments were a constant level of used turkey brooder house litter combined with a varying combination of biochar and Miscanthus grass. Turkey's body weight (BW), body weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR) were determined. Differences in treatment means were considered to be statistically significant at P ≤ 0.05 using a mixed model in SAS 9.4. Turkeys fed the feed with improved pellet quality had a higher BW from 3 to 17 wk (17.0 ± 0.1 kg) than turkeys fed an increased abundance of fines (16.72 ± 0.1 kg). Turkeys fed feed with increased pellet quality had a lower FI (45.6 vs. 48.1 ± 0.4 kg) and improved FCR (2.20 vs. 2.31 ± 0.01) from 0 to 20 wk. Litter treatment with 20% biochar resulted in higher BW at 20 wk (20.91 ± 0.16 kg) because of increased BWG at 11 wk over the rest of the biochar levels (3.7 ± 0.1 kg). Strategies to reduce the abundance of fines in feed through feed formulation, feed manufacturing, feed transport, and in-house feed management should be considered to increase male turkeys' performance. There may be opportunities to use biochar as a litter amendment to improve turkey health and performance.
High levels of polyunsaturated fatty acids in avian sperm cause more susceptibility to lipid peroxidation. Aging in roosters reduces the antioxidant capacity of sperm and thus fertility. The purpose ...of this study was to investigate the effects of different levels of alpha-lipoic acid (ALA) as a feed supplement to improve the semen quality and fertility parameters of aged broiler breeder roosters and identification of its most effective level. A total of forty-two roosters at 45 wk of age were randomly assigned to 7 treatments (0, 15, 40, 70, 95, 120, and 145 mg ALA/bird per day) for 8 wk. Semen parameters and body weight were assessed biweekly, and testosterone plasma levels were determined in the 8th wk of the experimental period. Artificial insemination was performed at the end of the experiment to evaluate the fertility potential. The dietary administration of ALA had no significant effects on body weight, semen volume, average path velocity, linearity, straightness, wobble, the amplitude of lateral head displacement, beat-cross frequency, sperm concentration, morphology, plasma testosterone level, fertility, or hatchability (P > 0.05). Alpha-lipoic acid supplementations resulted in a significant decrease in seminal malondialdehyde concentration and immotile (type D) sperms (P < 0.05). The total motility, progressive motility (types A + type B sperms), curvilinear velocity, straight-line velocity, viability, and membrane integrity of sperm improved with ALA dietary supplementations (P < 0.05). With increasing ALA levels, improvement in semen parameters had an incremental trend until the level of 95 mg ALA. Thus, 95 mg dietary ALA as an antioxidant supplement can improve semen quality of aging breeder roosters while higher doses resulted in no further improvement.
The objective of this study was to evaluate the effects of dietary chromium (Cr), as Cr propionate (Cr Prop), on measures of insulin sensitivity in turkeys. Plasma glucose and nonesterified fatty ...acid (NEFA), and liver glycogen concentrations were used as indicators of insulin sensitivity. One-day-old Nicholas Large White female poults (n = 336) were randomly assigned to dietary treatments consisting of 0 (control), 0.2, 0.4, or 0.6 mg supplemental Cr/kg diet. Each treatment consisted of 12 replicate cages with 7 turkeys per cage. Final BW were taken on d 34, and on d 35 two birds from each cage were sampled for plasma glucose and NEFA, and liver glycogen determination at the initiation (fed state) and termination (fasted state) of a 24-h fast. Following a 24-h fast, 2 turkeys per cage were refed (refed state) their treatment diet for 4 h, and then harvested. Feed/gain and ADG did not differ between control and Cr-supplemented turkeys over the 34-d study, but feed intake tended (P = 0.071) to be greater for controls than turkeys receiving 0.4 mg Cr/kg diet. Fed turkeys had greater plasma glucose (P = 0.002) and liver glycogen (P = 0.001) concentrations, and lower (P = 0.001) NEFA concentrations than fasted birds. Turkeys refed after fasting had greater (P = 0.001) plasma glucose and liver glycogen concentrations, and lower (P = 0.001) plasma NEFA levels than fed turkeys. Liver glycogen and plasma NEFA concentrations did not differ among control and Cr-supplemented birds in the fed, fasted, or refed state. Plasma glucose concentrations were not affected by treatment in fed or fasted turkeys. Turkeys supplemented with 0.2 or 0.4 mg Cr/kg and refed after fasting had lower (quadratic, P = 0.038) plasma glucose concentrations than controls. Plasma glucose concentrations in refed birds did not differ among Cr-supplemented turkeys. The lower plasma glucose concentration in Cr-supplemented turkeys following refeeding is consistent with Cr enhancing insulin sensitivity.
Sperm can be selected as a natural vector for the production of transgenic animals. Methyl-beta-cyclodextrin (MBCD) removes cholesterol from the phospholipid membrane of sperm and improves the ...efficiency of DNA uptake by sperm. In experiment 1, fresh sperm was treated with various concentrations of MBCD. The direct effects of MBCD on sperm parameters were monitored. In experiment 2, different concentrations of MBCD (0, 1, 2, and 4 mmol) were assessed for the transfection of genetically exogenous construction to rooster sperm. Washed semen was divided into 5 equal groups for the incubation and transfection with a pcDNA3.1+/hG-CSF vector (exogenous DNA) as follows; Treatment I—Control (washed semen without DNA); Treatment II—Control (washed semen with DNA); Treatment III—(washed semen incubated with DNA and 1 mmol MBCD); Treatment IV—(washed semen incubated with DNA and 2 mmol MBCD); and Treatment V—(washed semen incubated with DNA and 4 mmol MBCD). We demonstrated that rooster spermatozoa spontaneously can uptake exogenous DNA; this was assessed using exogenous DNA amplification (sperm genomic DNA used as a template for PCR reaction) after DNase I treatment. In addition, total motility (TM), progressive motility (PM), velocity parameters curvilinear velocity (VCL), straight linear velocity (VSL), sperm track straightness (STR), linearity (LIN), membrane integrity (MI), and membrane functionality were posttransfectionally evaluated. The concentrations of 1 and 2 mmol MBCD significantly (P < 0.05) improved the motion characteristics and membrane integrity of fresh sperm. The presence of hG-CSF in rooster sperm was detected by PCR and based on sperm analyses MBCD (1 mmol) improved the percentage of motility (98.9 ± 0.81), membrane functionality (64 ± 1.64), and MI (76.2 ± 1.65) after transfection when compared with the other groups (P < 0.05). For the production of transgenic chicken, hens were inseminated (AI) by transfected sperm treated with 1 and 0 mmol MBCD. A PCR analysis of the blood samples and dead embryo tissues of chicks did not reveal the transgene integration.
PDF
