NR1 Splicing Variant NR1a in Cerebellar Granule Neurons Constitutes a Better Motor Learning in the Mouse.

As an excitatory neuron in the cerebellum, the granule cells play a crucial role in motor learning. The assembly of NMDAR in these neurons varies in developmental stages, while the significance of this variety is still not clear. In this study, we found that motor training could specially upregulate the expression level of NR1a, a splicing form of NR1 subunit. Interestingly, overexpression of this splicing variant in a cerebellar granule cell-specific manner dramatically elevated the NMDAR binding activity. Furthermore, the NR1a transgenic mice did not only show an enhanced motor learning, but also exhibit a higher efficacy for motor training in motor learning. Our results suggested that as a "junior" receptor, NR1a facilitates NMDAR activity as well as motor skill learning.

Comparison of genomic prediction methods for residual feed intake in broilers.

Residual feed intake (RFI) is a measure of the feed efficiency of animals. Previous studies have identified SNPs associated with RFI. The objective of this study was to compare the GBLUP model with the GA-BLUP model including previously identified associated SNPs. The nine associated SNPs were obtained from the genome-wide association study on a discovery population as preselection information. These models were analysed using ASREML software using a 5-fold cross-validation method on a validation population. With the genetic architecture (GA) matrix used, which was conducted with the nine RFI-associated SNPs, the prediction accuracy of RFI was improved compared with the original GBLUP model. The calculated optimal ω was 0.981 for RFI, which is in line with the optimal range from 0.9 to 1.0 in the gradient test. The prediction accuracy increased by 2% in the GA-BLUP model with ω being 0.981 compared with the GBLUP model. In conclusion, the GA-BLUP with the nine RFI-associated SNPs and an optimal ω can improve the prediction accuracy for a specific trait compared with GBLUP.

Continuous immunosuppression is required for suppressing immune responses to xenografts in non-human primate brains.

Continuous immunosuppression has been widely used in xenografts into non-human primate brains. However, how immune responses change after transplantation in host brains under continuous immunosuppressive administration and whether immunosuppression can be withdrawn to mitigate side effects remain unclear. Human induced neural stem/progenitor cells (iNPCs) have shown long-term survival and efficient neuronal differentiation in primate brains. Here, we evaluate the immune responses in primate brains triggered by human grafts. The results show that the immune responses, including the evident activation of microglia and the strong infiltration of lymphocytes (both T- and B-cells), are caused by xenografts at 4 months post transplantation (p.t.), but significantly reduced at 8 months p.t. under continuous administration of immunosuppressant Cyclosporin A. However, early immunosuppressant withdrawal at 5 months p.t. results in severe immune responses at 10 months p.t. These results suggest that continuous long-term immunosuppression is required for suppressing immune responses to xenografts in primate brains.

Large-scale genomic and transcriptomic analyses elucidate the genetic basis of high meat yield in chickens.

INTRODUCTION: Investigating the genetic markers and genomic signatures related to chicken meat production by combing multi-omics methods could provide new insights into modern chicken breeding technology systems. OBJECT: Chicken is one of the most efficient and environmentally friendly livestock, especially the fast-growing white-feathered chicken (broiler), which is well known for high meat yield, but the underlying genetic basis is poorly understood. METHOD: We generated whole-genome resequencing of three purebred broilers (n = 748) and six local breeds/lines (n = 114), and sequencing data of twelve chicken breeds (n = 199) were obtained from the NCBI database. Additionally, transcriptome sequencing of six tissues from two chicken breeds (n = 129) at two developmental stages was performed. A genome-wide association study combined with cis-eQTL mapping and the Mendelian randomization was applied. RESULT: We identified > 17 million high-quality SNPs, of which 21.74% were newly identified, based on 21 chicken breeds/lines. A total of 163 protein-coding genes underwent positive selection in purebred broilers, and 83 genes were differentially expressed between purebred broilers and local chickens. Notably, muscle development was proven to be the major difference between purebred broilers and local chickens, or ancestors, based on genomic and transcriptomic evidence from multiple tissues and stages. The MYH1 gene family showed the top selection signatures and muscle-specific expression in purebred broilers. Furthermore, we found that the causal gene SOX6 influenced breast muscle yield and also related to myopathy occurrences. A refined haplotype was provided, which had a significant effect on SOX6 expression and phenotypic changes. CONCLUSION: Our study provides a comprehensive atlas comprising the typical genomic variants and transcriptional characteristics for muscle development and suggests a new regulatory target (SOX6-MYH1s axis) for breast muscle yield and myopathy, which could aid in the development of genome-scale selective breeding aimed at high meat yield in broiler chickens.

Combined effect of microbially derived cecal SCFA and host genetics on feed efficiency in broiler chickens.

BACKGROUND: Improving feed efficiency is the most important goal for modern animal production. The regulatory mechanisms of controlling feed efficiency traits are extremely complex and include the functions related to host genetics and gut microbiota. Short-chain fatty acids (SCFAs), as significant metabolites of microbiota, could be used to refine the combined effect of host genetics and gut microbiota. However, the association of SCFAs with the gut microbiota and host genetics for regulating feed efficiency is far from understood. RESULTS: In this study, 464 broilers were housed for RFI measuring and examining the host genome sequence. And 300 broilers were examined for cecal microbial data and SCFA concentration. Genome-wide association studies (GWAS) showed that four out of seven SCFAs had significant associations with genome variants. One locus (chr4: 29414391-29417189), located near or inside the genes MAML3, SETD7, and MGST2, was significantly associated with propionate and had a modest effect on feed efficiency traits and the microbiota. The genetic effect of the top SNP explained 8.43% variance of propionate. Individuals with genotype AA had significantly different propionate concentrations (0.074 vs. 0.131 µg/mg), feed efficiency (FCR: 1.658 vs. 1.685), and relative abundance of 14 taxa compared to those with the GG genotype. Christensenellaceae and Christensenellaceae_R-7_group were associated with feed efficiency, propionate concentration, the top SNP genotypes, and lipid metabolism. Individuals with a higher cecal abundance of these taxa showed better feed efficiency and lower concentrations of caecal SCFAs. CONCLUSION: Our study provides strong evidence of the pathway that host genome variants affect the cecal SCFA by influencing caecal microbiota and then regulating feed efficiency. The cecal taxa Christensenellaceae and Christensenellaceae_R-7_group were identified as representative taxa contributing to the combined effect of host genetics and SCFAs on chicken feed efficiency. These findings provided strong evidence of the combined effect of host genetics and gut microbial SCFAs in regulating feed efficiency traits. Video Abstract.

Dominant changes in the breast muscle lipid profiles of broiler chickens with wooden breast syndrome revealed by lipidomics analyses.

BACKGROUND: Chicken is the most consumed meat worldwide and the industry has been facing challenging myopathies. Wooden breast (WB), which is often accompanied by white striping (WS), is a serious myopathy adversely affecting meat quality of breast muscles. The underlying lipid metabolic mechanism of WB affected broilers is not fully understood. RESULTS: A total of 150 chickens of a white-feathered, fast-growing pure line were raised and used for the selection of WB, WB + WS and control chickens. The lipids of the breast muscle, liver, and serum from different chickens were extracted and measured using ultra performance liquid chromatography (UPLC) plus Q-Exactive Orbitrap tandem mass spectrometry. In the breast, 560 lipid molecules were identified. Compared to controls, 225/225 of 560 lipid molecules (40.2%) were identified with differential abundance (DA), including 92/100 significantly increased neutral lipids and 107/98 decreased phospholipids in the WB/WB + WS groups, respectively. The content of monounsaturated fatty acids (MUFA) was significantly higher, and the polyunsaturated fatty acids (PUFA) and saturated fatty acids (SFA) were significantly lower in the affected breasts. In the liver, 434 lipid molecules were identified, and 39/61 DA lipid molecules (6.7%/14.1%) were detected in the WB and WB + WS groups, respectively. In the serum, a total of 529 lipid molecules were identified and 4/44 DA lipid molecules (0.8%/8.3%) were detected in WB and WB + WS group, respectively. Compared to controls, the content of MUFAs in the serum and breast of the WB + WS group were both significantly increased, and the content of SFAs in two tissues were both significantly decreased. Only five lipid molecules were consistently increased in both liver and serum in WB + WS group. CONCLUSIONS: We have found for the first time that the dominant lipid profile alterations occurred in the affected breast muscle. The relative abundance of 40.2% of lipid molecules were changed and is characteristic of increased neutral lipids and decreased phospholipids in the affected breasts. Minor changes of lipid profiles in the liver and serum of the affected groups were founded. Comprehensive analysis of body lipid metabolism indicated that the abnormal lipid profile of WB breast may be independent of the liver metabolism.

Integrated metabolomics and lipidomics evaluate the alterations of flavor precursors in chicken breast muscle with white striping symptom.

White striping (WS) is the most common myopathy in the broiler chicken industry. To reveal flavor changes of WS meat objectively, flavor precursors of WS breast muscle were evaluated systematically with integrated metabolomics and lipidomics. The results showed that WS could be distinguished from normal controls by E-nose, and four volatile compounds (o-xylene, benzene, 1,3-dimethyl, 2-heptanone and 6-methyl and Acetic acid and ethyl ester) were detected as decreased compounds by gas chromatography-mass spectrometry. Lipidomic analysis showed that WS breast fillets featured increased neutral lipid (83.8%) and decreased phospholipid molecules (33.2%). Targeted metabolomic analysis indicated that 16 hydrophilic metabolites were altered. Thereinto, some water-soluble flavor precursors, such as adenosine monophosphate, GDP-fucose and L-arginine increased significantly, but fructose 1,6-bisphosphate and L-histidine significantly decreased in the WS group. These results provided a systematic evaluation of the flavor precursors profile in the WS meat of broiler chickens.

Serum Creatine Kinase as a Biomarker to Predict Wooden Breast in vivo for Chicken Breeding.

The present study aimed to find a blood marker for the prediction of wooden breast (WB) in live broiler to assist the genetic selection of fast-growing chickens. The experiments were carried out with two chicken flocks: 250 male broilers in flock 1 and 100 male and female broilers in flock 2. Both flocks were slaughtered and measured. The breast filets were assessed by combining subjective scoring and compression force at 28 (flock 1 only) and 42 days of age. The enzyme activity in serum and breast tissue (flock 1 only) of normal and affected groups was tested. The results showed that the compression force was significantly different between the normal and affected groups at 28 and 42 days of age (P < 0.001), and it increased significantly with rising WB and WS scores. The serum creatine kinase (CK) value increased significantly with rising compression force at 42 days of age (P < 0.001). The serum CK positively correlated with compression force (r = 0.608; P < 0.001) and the linear regression equation (serum CK = 0.9960∗compression force + 1.884) was established for the line studied. The association between serum CK and compression force is consistent between flocks 1 and 2. In conclusion, our study confirmed that compression force could be the quantitative indicator to differentiate breast filets and found that serum CK could be a candidate biomarker to predict WB in live broilers and assist genetic selection in broiler breeding.

Micro-encapsulated essential oils and organic acids combination improves intestinal barrier function, inflammatory responses and microbiota of weaned piglets challenged with enterotoxigenic Escherichia coli F4 (K88+).

This study evaluated the effects of micro-encapsulated (protected) organic acids (OA) and essential oils (EO) combination, P(OA + EO), and effects of a regular blend of free acids (FA) on the growth, immune responses, intestinal barrier and microbiota of weaned piglets challenged with enterotoxigenic Escherichia coli (ETEC) F4 (K88+). A total of 30 crossbred (Duroc × Landrace × Large White) weaned barrows (7.41 ± 0.06 kg, 28 d old) were assigned randomly to 5 treatments: 1) non-challenged positive control (PC), 2) ETEC F4 (K88+)-challenged negative control (NC), 3) NC + kitasamycin at 50 mg/kg + olaquindox at 100 mg/kg + free acidifier (FA) at 5 g/kg, 4) NC + kitasamycin at 50 mg/kg + olaquindox at 100 mg/kg + P(OA + EO) at 1 g/kg (P1), 5) NC + kitasamycin at 50 mg/kg + olaquindox at 100 mg/kg + P(OA + EO) at 2 g/kg (P2). Each dietary treatment had 6 replicates of one piglet each and the study lasted for 3 wk. On d 7, pigs in NC, FA, P1 and P2 were orally dosed with 10 mL of ETEC F4 (K88+) culture (1 × 109 CFU/mL). From d 7 to 14 after the ETEC F4 (K88+) challenge, P1 increased gain-to-feed ratio (G:F) significantly (P < 0.05) compared with NC and FA groups. From d 14 to 21, P2 increased the average daily gain of pigs (P < 0.05) compared with NC and FA groups. Compared with NC, P2 reduced tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-10 concentrations (P < 0.05) in sera collected at 4 h later after ETEC F4 (K88+) challenge. On d 21, P1 increased occludin and zonula occludens-1 protein expression in ileum compared with NC (P < 0.05). After this 3-wk experiment, alpha diversity of gut microbiota was decreased by P2 compared with PC, and P1 increased the relative abundance of Lactobacillus in ileum, cecum and colon (P < 0.05). In conclusion, dietary P(OA + EO) additive at 2 g/kg combined with antibiotics could improve piglet performance and attenuate inflammation, and P(OA + EO) additive at 1 g/kg combined with antibiotics improved intestinal barrier and increased beneficial microbiota composition after an F4 (K88+) challenge.