Evaluating the potential role of tryptophan in calf milk replacers to facilitate weaning

Tryptophan is a precursor of serotonin, a neurotransmitter that participates in the control of the affective state of an animal. We hypothesized that Trp supplementation could help dairy calves to cope with weaning stress. Twenty-seven Holstein male calves (48 ± 0.8 d old; 82 ± 2.6 kg of body weight) were used to evaluate the effects of Trp supplementation at a rate of 4.5 g/d via milk replacer (MR) on performance and behavioral parameters around weaning. All calves received the same feeding program (6 L/d at 15% dry matter from d 1 to 7, 4 L/d at 15% dry matter from d 8 to 14, and 2 L/d at 15% dry matter in one feeding until d 21 of study) and were completely weaned 22 d after the beginning of the study (around 70 d of life). Calves were fed a starter feed (19.3% crude protein and 16.2% neutral detergent fiber, on a dry matter basis) and chopped straw ad libitum. Animals were weighed weekly, dry matter intakes were recorded daily, lying behavior was recorded using accelerometers throughout the study, and scan sampling was performed twice a week, 1 h after the morning feeding, to record behavioral activity (nonnutritive oral behaviors, suckling a neighbor calf, standing, resting, rumination, vocalizations, eating, and drinking). Tryptophan supplementation did not affect calf performance or concentrate and MR intake, but straw intake tended to be greater in nonsupplemented compared with Trp-supplemented calves (153 vs. 129 ± 9.0 g/d, respectively). Lying time, lying bouts, and lying duration decreased when changes in the MR feeding program occurred, independent of treatment. Similarly, differences in behavioral observations occurred along days of study, with no effect of Trp supplementation. The main changes observed in calf behavior were an increase in vocalizations and standing time 1 h after the morning feeding at weaning, but again these changes were independent of treatment. Parameters measured in serum and plasma indicated an increase in Trp, kynurenine, and the kynurenine/Trp ratio after feeding in the Trp calves. A tendency for lower plasma glucose concentration after feeding was observed in the Trp group. No changes in stress markers such as cortisol and haptoglobin in serum were detected. In conclusion, supplementing 4.5 g/d of Trp via MR between 48 and 62 d of life had no effect on performance or behavior in calves around weaning.info:eu-repo/semantics/publishedVersio

Spindle configuration of in vitro matured bovine oocytes vitrified and warmed in media supplemented with a biopolymer produced by an Antarctic bacterium

Biological molecules isolated from organisms that live under subfreezing conditions could be used to protect oocytes from cryoinjuries suffered during cryopreservation. Bacterial exopolysaccharides (EPS) constitute a common class of molecules that interact with ice in nature either by triggering ice nucleation or by inhibition of ice nucleation and growth. The aim of this work was to evaluate the spindle configuration of in vitro matured bovine oocytes vitrified/warmed in media supplemented with exopolysaccharide (M1) produced by Pseudomonas sp ID1 (Carrión et al., Carbohydr Polym 117:1028. 2015). After 22 h of in vitro maturation, a total of 546 oocytes form prepubertal (3 replicates) and 405 oocytes from adult cows (4 replicates) were vitrified/warmed in media supplemented with various concentrations of EPS M1 (0, 0.001, 0.01, 0.1 and 1 mg/ml). After warming, oocytes were allowed to recover for 2 additional hours in IVM medium. Fresh, non-vitrified oocytes were used as a control. At 24 h of IVM, oocytes from all treatments were fixed and immunostained with the Alexa-fluor 488 antibody and DAPI. Microtubule and chromosome distribution was analyzed by immunocytochemistry under a fluorescent microscope. ANOVA was performed to analyze differences in meiotic spindle configuration (P < 0.05). When cow oocytes were vitrified, similar percentages of normal spindle configuration were observed when compared to fresh control oocytes, except for the 0.1 mg/ml EPS M1 group that showed significantly lower rates compared to the fresh control group. Significantly higher rates of prepubertal oocytes exhibiting a normal spindle configuration were recorded in the non-vitrified group compared to all vitrified/warmed groups, regardless of the EPS M1 supplementation. However, the addition of EPS M1 to the vitrification/warming media decreased the ratio of decondensation or absence of chromosomes and microtubules in prepubertal oocytes. Although percentages of normal spindle configuration after vitrification were lower for prepubertal than for cow oocytes, no significant differences were observed when oocytes were vitrified with 0.001, 0.1 and 1 mg/ml EPS M1. In conclusion, supplementation with EPS M1 concentrations during vitrification and warming did not induce adverse changes in the spindle of bovine oocytes, regardless of the concentration used. Although a more severe damage on spindle configuration could be observed after vitrification of prepubertal oocytes, EPS supplementation during vitrification and warming seems to have a greater benefit during vitrification of prepubertal than adult bovine oocytes. Further experiments are required to investigate if in vitro-matured oocytes vitrified/warmed in presence EPS M1 can improve their development competence after being vitrified/warmed. This study was supported by the Spanish Ministry of Science and Innovation (Project AGL2016-79802-P and grant CTQ2014-59632-R)

Metabolome and proteome changes in skeletal muscle and blood of pre-weaning calves fed leucine and threonine supplemented diets

In pre-weaning calves, both leucine and threonine play important roles in growth and muscle metabolism. In this study, metabolomics, proteomics and clinical chemistry were used to assess the effects of leucine and threonine supplementation added to milk replacer on 14 newborn Holstein male calves: 7 were fed a control diet (Ctrl) and 7 were fed the Ctrl diet supplemented with 0.3% leucine and 0.3% threonine (LT) from 5.6 days of age to 53.6 days. At this time, blood and semitendinosus muscle biopsies were collected for analysis. Integrated metabolomics and proteomics showed that branched-chain amino acids (BCAA) degradation and mitochondrial oxidative metabolism (citrate cycle and respiratory chain) were the main activated pathways in muscle because of the supplementation. BCAA derivatives and metabolites related to lipid mobilization showed the major changes. The deleterious effects of activated oxidative phosphorylation were balanced by the upregulation of antioxidant proteins. An increase in protein synthesis was indicated by elevated aminoacyl-tRNA biosynthesis and increased S6 ribosomal protein phosphorylation in skeletal muscle. In conclusion, LT group showed greater BCAA availability and mitochondrial oxidative activity; as the muscle cells undergo greater aerobic metabolism, antioxidant defenses were activated to compensate for possible cell damage. Data are available via ProteomeXchange (PXD016098)info:eu-repo/semantics/acceptedVersio

Safety outcomes during pediatric GH therapy: final results from the prospective GeNeSIS observational program

CONTEXT: Safety concerns regarding premature mortality, diabetes, neoplasia and cerebrovascular disease in association with growth hormone (GH) therapy have been raised. OBJECTIVE: To assess incidence of key safety outcomes. DESIGN: Prospective, multinational, observational study (1999-2015). SETTING: 22,311 GH-treated children from 827 investigative sites in 30 countries. PATIENTS: Children with growth disorders. INTERVENTIONS: GH treatment. MAIN OUTCOME MEASURES: Standardized mortality (SMR) and incidence (SIR) ratios with 95% confidence intervals (CI) for mortality, diabetes, and primary cancer, using general population registries. RESULTS: Predominant short stature diagnoses were GH deficiency (63%), idiopathic short stature (13%), and Turner syndrome (8%), with mean±SD follow-up of 4.2±3.2 years (∼92,000 person-years [PY]). Forty-two deaths occurred in patients with follow-up, with SMR (95% CI) of 0.61 (0.44-0.82); the SMR was elevated for patients with cancer-related organic GH deficiency (5.87 [3.21-9.85]). Based on 18 cases, Type 2 diabetes (T2DM) risk was elevated (SIR 3.77 [2.24-5.96]), but 72% had risk factors. In patients without cancer history, 14 primary cancers were observed (SIR 0.71 [0.39-1.20]). Second neoplasms occurred in 31/622 (5.0%) cancer survivors (10.7 [7.5-15.2] cases/1000 PY), and intracranial tumor recurrences in 67/823 (8.1%) tumor survivors (16.9 [13.3-21.5] cases/1000 PY). All 3 hemorrhagic stroke cases had risk factors. CONCLUSIONS: GeNeSIS data support the favourable safety profile of pediatric GH treatment. Overall risk for death or primary cancer was not elevated in GH-treated children, and no hemorrhagic strokes occurred in patients without risk factors. T2DM incidence was elevated compared to the general population, but most cases had diabetes risk factors

ALADIN is Required for the Production of Fertile Mouse Oocytes

Asymmetric cell divisions depend on the precise placement of the spindle apparatus. In mammalian oocytes, spindles assemble close to the cell's center, but chromosome segregation takes place at the cell periphery where half of the chromosomes are expelled into small, nondeveloping polar bodies at anaphase. By dividing so asymmetrically, most of the cytoplasmic content within the oocyte is preserved, which is critical for successful fertilization and early development. Recently we determined that the nucleoporin ALADIN participates in spindle assembly in somatic cells, and we have also shown that female mice homozygously null for ALADIN are sterile. In this study we show that this protein is involved in specific meiotic stages, including meiotic resumption, spindle assembly, and spindle positioning. In the absence of ALADIN, polar body extrusion is compromised due to problems in spindle orientation and anchoring at the first meiotic anaphase. ALADIN null oocytes that mature far enough to be fertilized in vitro are unable to support embryonic development beyond the two-cell stage. Overall, we find that ALADIN is critical for oocyte maturation and appears to be far more essential for this process than for somatic cell divisions

ILC3 function as a double-edged sword in inflammatory bowel diseases

Inflammatory bowel diseases (IBD), composed mainly of Crohn’s disease (CD) and ulcerative colitis (UC), are strongly implicated in the development of intestinal inflammation lesions. Its exact etiology and pathogenesis are still undetermined. Recently accumulating evidence supports that group 3 innate lymphoid cells (ILC3) are responsible for gastrointestinal mucosal homeostasis through moderate generation of IL-22, IL-17, and GM-CSF in the physiological state. ILC3 contribute to the progression and aggravation of IBD while both IL-22 and IL-17, along with IFN-γ, are overexpressed by the dysregulation of NCR− ILC3 or NCR+ ILC3 function and the bias of NCR+ ILC3 towards ILC1 as well as regulatory ILC dysfunction in the pathological state. Herein, we feature the group 3 innate lymphoid cells’ development, biological function, maintenance of gut homeostasis, mediation of IBD occurrence, and potential application to IBD therapy

Synthetic Nanoparticles for Vaccines and Immunotherapy

The immune system plays a critical role in our health. No other component of human physiology plays a decisive role in as diverse an array of maladies, from deadly diseases with which we are all familiar to equally terrible esoteric conditions: HIV, malaria, pneumococcal and influenza infections; cancer; atherosclerosis; autoimmune diseases such as lupus, diabetes, and multiple sclerosis. The importance of understanding the function of the immune system and learning how to modulate immunity to protect against or treat disease thus cannot be overstated. Fortunately, we are entering an exciting era where the science of immunology is defining pathways for the rational manipulation of the immune system at the cellular and molecular level, and this understanding is leading to dramatic advances in the clinic that are transforming the future of medicine.1,2 These initial advances are being made primarily through biologic drugs– recombinant proteins (especially antibodies) or patient-derived cell therapies– but exciting data from preclinical studies suggest that a marriage of approaches based in biotechnology with the materials science and chemistry of nanomaterials, especially nanoparticles, could enable more effective and safer immune engineering strategies. This review will examine these nanoparticle-based strategies to immune modulation in detail, and discuss the promise and outstanding challenges facing the field of immune engineering from a chemical biology/materials engineering perspectiveNational Institutes of Health (U.S.) (Grants AI111860, CA174795, CA172164, AI091693, and AI095109)United States. Department of Defense (W911NF-13-D-0001 and Awards W911NF-07-D-0004

Abdominal obesity and low physical activity are associated with insulin resistance in overweight adolescents: a cross-sectional study

ABSTRACT: Background: Previous studies have assessed the metabolic changes and lifestyles associated with overweight adolescents. However, these associations are unclear amongst overweight adolescents who have already developed insulin resistance. This study assessed the associations between insulin resistance and anthropometric, metabolic, inflammatory, food consumption, and physical activity variables amongst overweight adolescents. Methods: This cross-sectional study divided adolescents (n = 120) between 10 and 18 years old into 3 groups: an overweight group with insulin resistance (O + IR), an overweight group without insulin resistance (O-IR), and a normal-weight control group (NW). Adolescents were matched across groups based on age, sex, pubertal maturation, and socioeconomic strata. Anthropometric, biochemical, physical activity, and food consumption variables were assessed. Insulin resistance was assessed using homeostatic model assessment (HOMA Calculator Version 2.2.2 from ©Diabetes Trials Unit, University of Oxford), and overweight status was assessed using body mass index according to World Health Organization (2007) references. A chi-square test was used to compare categorical variables. ANOVAs or Kruskal-Wallis tests were used for continuous variables. Multiple linear regression models were used to calculate the probability of the occurrence of insulin resistance based on the independent variables. Results: The risk of insulin resistance amongst overweight adolescents increases significantly when they reach a waist circumference > p95 (OR = 1.9, CIs = 1.3-2.7, p = 0.013) and watch 3 or more hours/day of television (OR = 1.7, CIs = 0.98-2.8, p = 0.033). Overweight status and insulin resistance were associated with higher levels of inflammation (hsCRP ≥1 mg/L) and cardiovascular risk according to arterial indices. With each cm increase in waist circumference, the HOMA index increased by 0.082; with each metabolic equivalent (MET) unit increase in physical activity, the HOMA index decreased by 0.026. Conclusions: Sedentary behaviour and a waist circumference > p90 amongst overweight adolescents were associated with insulin resistance, lipid profile alterations, and higher inflammatory states. A screening that includes body mass index, in waist circumference, and physical activity evaluations of adolescents might enable the early detection of these alterations