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Feed consumption represents a major cost in poultry production and improving feed efficiency is one of the important goals in breeding strategies. The present study aimed to analyze the relationship between feed efficiency and relevant traits and find the proper selection method for improving feed efficiency by using the Northeast Agricultural University High and Low Fat broiler lines that were divergently selected for abdominal fat content. A total of 899 birds were used to measure the feed intake (FI), abdominal fat weight (AFW), and body weight traits. The abdominal fat percentage (AFP), feed conversion ratio (FCR), and the residual feed intake (RFI) were calculated for each individual broiler. The differences in the AFW, AFP, and in traits relevant to feed efficiency, such as FCR and RFI, between the fat line and the lean line were analyzed, and the genetic parameters were estimated for AFW, AFP, and feed efficiency relevant traits. The results showed that AFW, AFP, body weight gain (BWG), FI, FCR, and RFI were significantly higher in the fat line compared with the lean line. The heritability of FI, BWG, FCR, RFI, AFW, and AFP were 0.45, 0.28, 0.36, 0.38, 0.33, and 0.30, respectively. Both FCR and RFI showed high positive genetic correlations with FI, AFW, and AFP and relatively low, negative genetic correlations with BWG. The RFI showed much higher positive genetic correlation with the abdominal fat traits than FCR. In addition, the FCR showed negative genetic correlation with body weight of 4 wk (BW4) and 7 wk (BW7), whereas RFI showed positive genetic correlation with BW4 and BW7. The results showed that both RFI and FCR could be used for improving feed efficiency. When selecting against RFI, the AFP could be significantly reduced, and by selecting against FCR, the body weight could be improved simultaneously.

The present study aimed to search for chicken abdominal fat deposition-related polymorphisms within RB1 and to provide functional evidence for significantly associated genetic variants. Association analyses showed that 11 single nucleotide polymorphisms (SNPs) in intron 17 of RB1, were significantly associated with both abdominal fat weight (P G repressed the transcriptional efficiency of RB1 in vitro, through binding nuclear factor-kappa B (NF-KB) and SRY-related HMG box protein 2 (SOX2). Furthermore, RB1 mRNA expression levels in the abdominal fat tissue of individuals with the A/A genotype of g.32828A>G were lower than those of individuals with the G/G genotype. Collectively, we propose that the intronic SNP g.32828A>G of RB1 is an obesity-associated variant that directly affects binding with NF-KB and SOX2, leading to changes in RB1 expression which in turn may influence chicken abdominal fat deposition.

The generation of transgenic chickens is of both biomedical and agricultural significance, and recently chicken transgenesis technology has been greatly advanced. However, major issues still exist in the efficient production of transgenic chickens. This study was designed to optimize the production of enhanced green fluorescence protein (EGFP)-transgenic broilers, including egg windowing at the blunt end (air cell) of egg, and the direct transfection of circulating primordial germ cells by microinjection of the Tol2 plasmid-liposome complex into the early embryonic dorsal aorta. For egg windowing, we discovered that proper manipulation of the inner shell membrane at the blunt end could improve the rate of producing G0 transgenic roosters. From 27 G0 roosters, we successfully collected semen with EGFP-positive sperms from 16 and 19 roosters after direct fluorescence observation and fluorescence-activated cell sorting analyses (13 detected by both methods), respectively. After artificial insemination using the G0 rooster with the highest number of EGFP fluorescent sperm, one G1 EGFP transgenic broiler (1/81, 1.23%) was generated. Our results indicate that appropriate egg windowing and screening of potentially transgene-positive roosters can improve the production of germline-transmitted transgenic birds.

One of the main objectives of broiler breeding is to prevent excessive abdominal adipose deposition. The role of RNA modification in adipose deposition is not clear. This study was aimed to map m6A modification landscape in chicken adipose tissue. MeRIP-seq was performed to compare the differences in m6A methylation pattern between fat and lean broilers. We found that start codons, stop codons, coding regions, and 3′-untranslated regions were generally enriched for m6A peaks. The high m6A methylated genes (fat birds vs. lean birds) were primarily associated with fatty acid biosynthesis and fatty acid metabolism, while the low m6A methylated genes were mainly involved in processes associated with development. Furthermore, we found that the mRNA levels of many genes may be regulated by m6A modification. This is the first comprehensive characterization of m6A patterns in the chicken adipose transcriptome, and provides a basis for studying the role of m6A modification in fat deposition.

Summary Decades of artificial selection have significantly improved performance and efficiency of animal production systems. However, little is known about the microevolution of genomes due to intensive breeding. Using whole-genome sequencing, we document dynamic changes of chicken genomes under divergent selection on adiposity over 19 generations. Directional selection reduced within-line but increased between-line genomic differences. We observed that artificial selection tended to result in recruitment of preexisting variations of genes related to adipose tissue growth. In addition, novel mutations contributed to divergence of phenotypes under selection but contributed significantly less than preexisting genomic variants. Integration of 15 generations genome sequencing, genome-wide association study, and multi-omics data further identified that genes involved in signaling pathways important to adipogenesis, such as autophagy and lysosome (URI1, MBL2), neural system (CHAT), and endocrine (PCSK1) pathways, were under strong selection. Our study provides insights into the microevolutionary dynamics of domestic animal genomes under artificial selection., Graphical Abstract, Highlights • Directional selection reduces within-line but increases between-line genomic difference • Artificial selection tends to recruit preexisting variations of genes for fatness • Novel mutations contribute to the divergence of fatness under artificial selection • Genes involved in signaling pathways important to adipogenesis are under selection, Biological Sciences; Evolutionary Biology; Genetics; Genomics

1. During the long history of chicken domestication, eyelid colour, like skin colour and shank colour, has been one of the physical traits of Chinese indigenous chickens that influence consumer buying behaviour. In China, the Lindian chicken, which has coloured feathers, is renowned for the appetizing flavour of its meat and eggs, and its eyelid colours vary from deep (black) to light shades (light yellow). 2. To investigate genes involved in eyelid colour, the expression profiles of black and light-yellow eyelids of Lindian chickens were analysed with transcriptome sequencing. 3. A total of 13 466 genes were detected in the eyelids, among which 14 were differentially expressed. Among these differentially expressed genes (DEGs), three key genes, premelanosome protein (PMEL), dopachrome tautomerase (DCT), and tyrosinase (TYR), encoded proteins that positively regulate melanogenesis and melanin deposition. PMEL, DCT and TYR were expressed much more strongly in the black eyelids than in the light-yellow eyelids. A Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that tyrosine metabolism and melanogenesis genes were significantly enriched among these DEGs (corrected P 0.05). 4. In conclusion, melanin may be one of the main factors involved in Lindian chicken eyelid colour. Furthermore, these results provide a valuable resource for the future study of the physical traits of Lindian chicken.

Genetic selection for meat production performance of broilers concomitantly causes excessive abdominal fat deposition, accompanied by several adverse effects, such as the reduction of feed conversion efficiency and reproduction performance. Our previous studies have identified important genes regulating chicken fat deposition, using the Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF) as an animal model. However, the molecular mechanism underlying fat deposition differences between fat and lean broilers remains largely unknown. Here, we integrated the transcriptome (RNA-Seq) and quantitative proteome (isobaric tags for relative and absolute quantitation, iTRAQ) profiling analyses on abdominal fat tissues from NEAUHLF chicken lines. Differentially expressed genes (2167 DEGs, corrected p-value 0.01) and differentially abundant proteins (199 DAPs, corrected p-value 0.05) were identified in lean line compared to fat line. Down-regulated DEGs and DAPs mainly enriched in pathways related to fatty acid metabolism, fatty acid biosynthesis, and PPAR signaling, and interestingly, up-regulated DEGs and DAPs enriched both in lysosome pathway. Moreover, numerous key DEGs and DAPs involved in long-chain fatty acid uptake, in situ lipogenesis (fatty acid and cholesterol synthesis), and lipid droplet accumulation were discovered after integrated transcriptome and proteome analysis. SIGNIFICANCE: Excessive abdominal fat deposition critically affects the health of broilers and causes economic loss to broiler producers, but the molecular mechanism of abdominal fat deposition is still unclear in chicken. We identified key DEGs/DAPs and potential pathways through an integration of chicken abdominal fat tissues transcriptome and proteome analyses. Our findings will facilitate a better revealing the mechanism and provide a novel insight into abdominal fat content discrepancy between the fat and lean chicken lines.

Cisplatin resistance is still one of the main reasons for failure of clinical therapy for cervical cancer. But the underlying molecular mechanisms involved in cisplatin resistance of cervical cancer have still remained unclear. Recent studies reported that long noncoding RNAs (lncRNAs) are novel nonprotein-coding transcripts, which might play a key role in cancer biogenesis and prognosis. One of the lncRNAs, urothelial cancer associated 1 (UCA1), has been shown to promote different types of cancer cell proliferation, migration, and invasion. This study showed that overexpression of UCA1 confers cisplatin resistance by promoting cancer cell proliferation and inhibiting apoptosis. In addition, knockdown of UCA1 remarkably decreased cisplatin resistance in cervical cancer cells. Moreover, results also indicated that UCA1 was involved in signaling pathways modulating cell apoptosis and proliferation. UCA1 suppressed apoptosis by downregulating caspase 3 and upregulating CDK2, whereas enhanced cell proliferation by increased level of survivin and decreased level of p21. This study reports for the first time that UCA1 might play an important role in the cisplatin resistance in cervical cancer, and also explain partially how UCA1 promotes cisplatin resistance in cancer cells. These results provide evidence to support that UCA1 can be used as a potential target for a novel therapeutic strategy for cervical cancer.

A genome-wide association study has shown a number of chicken (Gallus gallus) single nucleotide polymorphism (SNP) markers to be significantly associated with abdominal fat content in Northeast Agricultural University (NEAU) broiler lines selected divergently for abdominal fat content (NEAUHLF). The six significant SNPs are located in the kinase insert domain receptor (KDR), tumor suppressor candidate 3 (TUSC3), phosphoribosyl pyrophosphate amidotransferase (PPAT), exocyst complex component 1 (EXOC1), v-myb myeloblastosis viral oncogene homolog (avian)-like 2 (MYBL2) and KIAA1211 (undefined) genes. In this study, the expression levels of these genes were investigated in both abdominal fat and liver tissues using 32 14th generation chickens from the NEAUHLF. The levels of expression of KDR in abdominal fat and KDR and TUSC3 in liver differed significantly between the two lines. The expression level of KDR in the abdominal fat was significantly correlated with the abdominal fat weight (AFW) and abdominal fat percentage (AFP). The expression levels of KDR, TUSC3 and PPAT in liver were significantly correlated with AFW and AFP, indicating that the six genes, especially KDR and TUSC3, could be associated with fat traits in domestic chickens. This study could provide insight into the mechanisms underlying the formation of abdominal fat in chickens.

Peroxisome proliferator-activated receptor gamma regulates adipogenesis. The genomic structure of the chicken peroxisome proliferator-activated receptor gamma (cPPARγ) gene has not been fully characterized, and only one cPPARγ gene mRNA sequence has been reported in genetic databases. Using 5' rapid amplification of cDNA ends, we identified five different cPPARγ mRNAs that are transcribed from three transcription initiation sites. The open reading frame analysis showed that these five cPPARγ transcript variants (cPPARγ1 to 5) could encode two cPPARγ protein isoforms (cPPARγ1 and cPPARγ2), which differ only in their N-terminal region. Quantitative real-time RT-PCR analysis showed that, of these five cPPARγ transcript variants, cPPARγ1 was ubiquitously highly expressed in various chicken tissues, including adipose tissue, liver, kidney, spleen and duodenal; cPPARγ2 was exclusively highly expressed in adipose tissue; cPPARγ3 was highly expressed in adipose tissue, kidney, spleen and liver; cPPARγ4 and cPPARγ5 were ubiquitously weakly expressed in all the tested tissues, and comparatively, cPPARγ5 was highly expressed in adipose tissue, heart, liver and kidney. The comparison of the expression of the five cPPARγ transcript variants showed that adipose tissue cPPARγ1 expression was significantly higher in the fat line than in the lean line from 2 to 7 wk of age (P

In humans, obesity is associated with increased or decreased levels of serum biochemical indicators. However, the relationship is not as well understood in chickens. Due to long-term intense selection for fast growth rate, modern broilers have the problem of excessive fat deposition, exhibiting biochemical or metabolic changes. In the current study, the Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF) were used to identify differences in serum biochemical parameters between the 2 lines. A total of 18 serum biochemical indicators were investigated in the 16th, 17th, and 18th generation populations of NEAUHLF, and the genetic parameters of these serum biochemical indicators were estimated. After analyzing the data from these 3 generations together, the results showed that the levels of 16 of the tested serum biochemical parameters were significantly different between the lean and fat birds. In the fat birds, serum concentrations of high-density lipoprotein cholesterol (HDL-C), HDL-C:low-density lipoprotein cholesterol (LDL-C), total bile acid, total protein, albumin, globulin, aspartate transaminase (AST):alanine transaminase (ALT), γ-glutamyl transpeptidase (GGT), uric acid, and creatinine were very significantly higher (P < 0.01), whereas LDL-C, albumin:globulin, glucose, AST, ALT, and free fatty acids concentrations in serum were very significantly lower than those in the lean birds (P < 0.01). Of these 16 serum biochemical parameters, 5 (LDL-C, HDL-C:LDL-C, total bile acid, albumin, and albumin:globulin) had high heritabilities (0.58 ≤ h2 ≤ 0.89), 6 (HDL-C, total protein, globulin, AST:ALT, GGT, and creatinine) had moderate heritabilities (0.29 ≤ h2 ≤ 0.48), and the remaining 5 had low heritabilities (h2 < 0.20). Serum HDL-C, HDL-C:LDL-C, and glucose had higher positive genetic correlation coefficients (rg) with abdominal fat traits (0.30 ≤ rg ≤ 0.80), whereas serum globulin, AST, and uric acid showed higher negative genetic correlations with abdominal fat traits (–0.62 ≤ rg ≤ –0.30). The remaining 10 serum biochemical parameters had lower genetic correlations with abdominal fat traits (–0.30 < rg < 0.30). In conclusion, we identified serum HDL-C and HDL-C:LDL-C levels as potential biomarkers for selection of lean birds. These findings will also be useful in future studies for investigating obesity and lipid metabolism in humans as well as in other animal species.

Herpes simplex virus 1 (HSV-1) is the most prevalent human virus and causes global morbidity because the virus is able to infect multiple cell types. Remarkably, HSV infection switches between lytic and latent cycles, where T cells play a critical role. However, the precise way of virus-host interactions is incompletely understood. Here we report that HSV-1 productively infected Jurkat T-cells and inhibited antigen-induced T cell receptor activation. We discovered that HSV-1-encoded Us3 protein interrupted TCR signaling and interleukin-2 production by inactivation of the linker for activation of T cells. This study unveils a mechanism by which HSV-1 intrudes into early events of TCR-mediated cell signaling and may provide novel insights into HSV infection, during which the virus escapes from host immune surveillance.

Chicken preadipocytes cultured in cocktail supplement with rosiglitazone resulted in a marked increase in lipid droplet accumulation, glycerol-3-phosphate dehydrogenase (GPDH) activity and mRNA expression of adipocyte fatty acid-binding protein (aP2), G0/G1 switch gene 2 (G0S2), peroxisome proliferator-activated receptor γ (PPARγ) and lipolysis. The present study provides a novel induction method for in vitro chicken preadipocyte differentiation., The preadipocyte differentiation biological process involves a cascade of transcriptional events that culminates in the expression of peroxisome proliferator-activated receptor (PPAR) γ. The differentiation cocktail [insulin (INS), dexamethasone (DEX) and isobutylmethylxanthine (IBMX)] can induce preadipocyte differentiation in mammals, but it is insufficient for chicken (Gallus gallus) adipogenesis. Oleate can induce chicken preadipocyte differentiation, but these differentiated preadipocytes may not be fully functional. The objective of the current study was to evaluate whether chicken preadipocytes can be induced to mature adipocytes by a novel induction method using differentiation cocktail supplemented with PPARγ agonist(s). Chicken preadipocytes cultured in cocktail supplemented with rosiglitazone or troglitazone resulted in a marked increase in lipid droplet accumulation (P

After 13 generations of divergent selection for abdominal fatness, 2 chicken lines (a fat line and a lean line) have been established. To clarify the cellular mechanism underlying the differences in fatness between the fat and lean lines, cellularity characteristics of the abdominal adipose tissues were analyzed during the first 7 wk of age by electron microscopy, proliferating cell nuclear antigen staining, and DNA content measurement. The abdominal fat percentage at 7 wk of age in the fat chicken line was 3.8 times that of the lean line, and was accompanied by a 1.3-fold increase in adipocyte diameter and a 2.4-fold increase in adipocyte number. The total cell number of the abdominal fat pad in the fat chicken line was 1.9 times that of the lean line at 7 wk of age. However, no significant difference was observed in the proliferation rate of stroma vascular fraction cells between the 2 chicken lines. These findings suggest that the divergently selected fat and lean chickens have different adipose tissue ontogeny.

Fatty acid-binding proteins (FABPs) may facilitate the diffusion of fatty acids within the cytoplasm. Adipocyte FABP (A-FABP) null mice exhibit altered rates of lipolysis, and reprogrammed expression of genes related to lipid metabolism. In the current study, chicken adipocytes with short hairpin RNA-mediated knockdown and cDNA overexpression of A-FABP were used to investigate the role of chicken A-FABP in lipid metabolism of adipocytes. The results showed that there was no significant change of lipid metabolism in the A-FABP interference adipocytes. However, in the A-FABP overexpression adipocytes, the lipolysis was increased significantly at 36 h (p

Insulin-like growth factor binding protein 2 (IGFBP2) is the predominant insulin-like growth factor binding protein in serum of different species. It binds insulin-like growth factors and plays an important role in growth and fat metabolism. The current study was designed to investigate the associations of IGFBP2 gene 3'-flanking region polymorphisms with chicken fatness traits. The random populations (5 distinct populations: Arbor Acres broiler, Hyline Brown layer, Shiqiza, BeijingYou, and Baier), the Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF), and the the Northeast Agricultural University F 2 (NEAU F 2 ) resource population were used in the current study. Body weight and body composition traits were measured in NEAUHLF and NEAU F 2 populations. A SNP of 1196C > A in the 3'-flanking region of the IGFBP2 gene was detected, and the PCR-single strand conformation polymorphism method was then used to genotype all of the individuals derived from the above populations. There was a highly significant difference (P < 0.01) in the allele frequency among the 5 distinct populations. The IG-FBP2 polymorphism was significantly associated with abdominal fat weight and percentage of abdominal fat (P < 0.05) in NEAUHLF and NEAU F 2 populations. The research suggests that the IGFBP2 gene could be a candidate locus or linked to a major gene that affects fatness traits in chickens.

Fatty acid-binding proteins (FABP) belong to a superfamily of lipid binding proteins that exhibit a high affinity for long chain fatty acids and appear to function in metabolism and intracellular transportation of lipids. The current study was designed to investigate the effects of heart (H)-FABP gene on chicken growth and body composition traits. The Northeast Agricultural University divergent broiler lines for abdominal fat and a broiler X silkie F2 population were used in this study. Body weight and body composition traits were measured in the populations. Primers were designed according to the chicken H-FABP gene sequence. Polymorphisms between parental lines were detected by DNA sequencing. PCR-RFLP and PCR-fragment length polymorphism methods were developed to genotype the populations. The results showed that the H-FABP gene polymorphisms in the two populations were associated with abdominal fat percentage. It implied that H-FABP gene can be a candidate locus or linked to a major gene(s) that affects abdominal fat content in the chicken.

Excessive abdominal fat content (AFC) has negative impacts on feed efficiency and carcass quality. Unlike AFC, intramuscular fat content (IMFC) could be a favourable trait, which has a positive impact on meat quality. To meet consumers' needs, a long-term goal of broiler breeders is to decrease AFC and improve the IMFC simultaneously. The current study was designed to investigate the relationship between AFC and IMFC and to compare IMFC, including the pectoral major muscle fat content (PIMFC) and intramuscular fat content of leg muscle (LIMFC), between two broiler lines divergently selected for abdominal fat percentage over 17 generations. The results showed that there was a significant difference in PIMFC and LIMFC between the two lines in all five generation populations used. The birds in the lean line had significantly lower AFC but higher PIMFC and LIMFC than the birds in the fat line. We also detected differences in the liver fat content (LFC) between the two lines and the results showed that birds in the fat line had significant higher LFC than birds in the lean line. Our results indicated that a desirable broiler line with higher IMFC but lower AFC could be obtained by genetic selection.

AIM: To investigate the expression of zinc finger protein 139 (ZNF139) in gastric cancer (GC), and to analyze its clinical significance. METHODS: A total of 108 patients who were diagnosed with GC and underwent surgery between January 2005 and March 2007 were enrolled in this study. Gastric tumor specimens and paired tumor-adjacent tissues were collected and paraffin-embedded, and the clinicopathologic characteristics and prognosis were recorded. The expression of ZNF139, Bcl-2, Bax, and caspase-3 were determined by immunohistochemistry, and apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling. SPSS 13.0 software was used for data processing and analyses, and significance was determined at P < 0.05. RESULTS: The expression of ZNF139 was stronger in tumors than in tumor-adjacent tissues (66.67% vs 44.44%; P < 0.01). Overexpression of ZNF139 correlated with tumor differentiation, invasion depth, clinical stage, lymphatic metastasis, and blood vessel invasion (all Ps < 0.05). Patients with overexpression of ZNF139 had a poorer prognosis (P < 0.01), and overexpression of ZNF139 was an independent factor for the prognosis of GC patients by a Cox survival analysis (P = 0.02). A negative relationship between ZNF139 and the apoptosis index was observed (r = -0.686; P < 0.01). The expression of Bcl-2 in GC was stronger than in tumor-adjacent tissues (66.67% vs 41.67%), whereas the expression levels of Bax and caspase-3 were lower in primary tumors (54.63% and 47.22%, respectively) than in tumor-adjacent tissues (73.15% and 73.15%, respectively) (all Ps < 0.05). The expression of ZNF139 negatively correlated with caspase-3 (r = -0.370; P < 0.01). The expressions of Bcl-2 and Bax were also negatively correlated (r = -0.231; P = 0.02). The expressions of caspase-3 and Bax protein were positively correlated (r = 0.217; P = 0.024). CONCLUSION: ZNF139 is related to clinicopathologic characteristics and prognosis of GC. Furthermore, it is overexpressed and involved in apoptosis in GC tissues by regulating caspase-3.

Parthenolide (PTL) is a sesquiterpene lactone isolated from feverfew and exhibits potent antitumor activity against various cancers. Many studies indicate that PTL treatment leads to apoptosis, however, the mechanism has not been defined. Here, we observed that cells underwent autophagy shortly after PTL treatment. Inhibition of autophagy by knocking out autophagy associated gene atg5 blocked PTL-induced apoptosis. Surprisingly, PTL decreased the level of translation initiation factor eIF4E binding protein 1 (4E-BP1) in correlation with autophagy. Ectopic expression or shRNA knockdown of 4E-BP1 further verified the effect of 4E-BP1 on PTL-induced autophagy. Meanwhile, PTL elevated the cellular reactive oxygen species (ROS) which located upstream of the depletion of 4E-BP1, and contributed to the consequent autophagy. This study revealed 4E-BP1 as a trigger for PTL-induced autophagy and may lead to therapeutic strategy to enhance the efficacy of anticancer drugs.

Vav proteins are guanine nucleotide exchange factors (GEFs) that activate a group of small G proteins (GTPases). Vav1 is predominantly expressed in hematopoietic cells, whereas Vav2 and Vav3 are ubiquitously distributed in almost all human tissues. All three Vav proteins contain conserved structural motifs and associate with a variety of cellular activities including proliferation, migration, and survival. Previous observation with Jurkat leukemia T cells showed that Vav1 possessed anti-apoptotic activity by enhancing Bcl-2 transcription. However the mechanism has not been unveiled. Here, we explored the effectors of Vav1 in promoting Bcl-2 expression in Jurkat cells and revealed that Rac2-Akt was specifically evoked by the expression of Vav1, but not Vav2 or Vav3. Although all three Vav isoforms existed in Jurkat cells, Rac2 was distinguishably activated by Vav1 and that led to enhanced Bcl-2 expression and cell survival. Akt was modulated downstream of Vav1-Rac2, and the activation of Akt was indispensable in the enhanced transcription of Bcl-2. Intriguingly, neither Vav2 nor Vav3 was able to activate Rac2-Akt pathway as determined by gene silencing approach. Our data illustrated a unique role of Vav1 in T leukemia survival by selectively triggering Rac2-Akt axis and elevating the expression of anti-apoptotic Bcl-2.

Fatty acid-binding proteins are considered to be the carriers for the transportation of intracellular fatty acids and play an important role in the development of fatness traits. Adipocyte fatty acid-binding protein (A-FABP) is one of the family members. The current study was designed to analyze the tissue expression characterization of chicken A-FABP and its expression difference between the fat and lean males in abdominal fat tissue to reveal the possible relationship between the expression of A-FABP and abdominal fat tissue development and growth in chicken. First, fusion protein glutathione S-transferase/A-FABP was induced and purified, and then the antiserum containing specific polyclonal antibodies was obtained by immunizing healthy female rabbits using the purified fusion protein. Second, tissue expression characterization of A-FABP was investigated by Western blot. Finally, A-FABP expression difference in abdominal fat tissue between the fat and lean males was investigated by real-time reverse transcription-PCR and Western blot methods. The results showed that A-FABP expressed specifically in abdominal fat tissue and the mRNA expression level of A-FABP in fat males was lower than that of lean males at 2, 3, 4, 6, 7, 9, and 10 wk of age (P < 0.05), and the protein expression level of fat males was lower than that of lean males at 6 and 10 wk of age (P < 0.05). These results suggested that chicken A-FABP might affect abdominal fat deposition through changing its expression level, and the possible mechanism may be that a high expression level of A-FABP induced the high lipolytic rate and led to the decreased abdominal fat mass accordingly.

Acetyl-CoA carboxylase alpha (ACCalpha) is a major rate-limiting enzyme in the biogenesis of long-chain fatty acids. It can catalyze the carboxylation of acetyl-CoA to form malonyl-CoA that plays a key role in the regulation of fatty acid metabolism. The objective of the present study was to investigate the associations of ACCalpha gene polymorphisms with chicken growth and body composition traits. The Northeast Agricultural University broiler lines divergently selected for abdominal fat content and the Northeast Agricultural University F(2) Resource Population were used in the current study. Body weight and body composition traits were measured in the aforementioned two populations. A synonymous mutation was detected in the exon 19 region of ACCalpha gene, then polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was developed to genotype all the individuals derived from the aforementioned populations. Association analysis revealed that the polymorphism was associated with abdominal fat weight and percentage of abdominal fat in the two populations. The results suggested that ACCalpha gene could be a candidate locus or linked to a major gene that affects abdominal fat content in the chicken.

Fatty acid-binding proteins belong to a superfamily of lipid-binding proteins that exhibit a high affinity for long-chain fatty acids and appear to function in metabolism and intracellular transportation of lipids. The current study was designed to investigate expression characterization and association with growth and composition traits of the liver fatty acid-binding protein (L-FABP) gene in the chicken. Northern blot analysis indicated that the gene, similar to the mammal L-FABP gene, was expressed only in liver and intestinal tissues. The mRNA levels of the chicken L-FABP gene in liver and intestine had significant differences between the broilers and Baier layers. The China Agricultural University F(2) population was used in the present study. Body weight and body composition traits were measured in the populations. Primers for the coding region and 5' upstream region of the L-FABP gene were designed according to chicken genomic and cDNA sequence. Polymorphisms were detected by DNA sequencing, and the PCR single-strand conformation polymorphisms method was developed to genotype the F(2) population. The results indicated that the L-FABP gene polymorphisms were associated with abdominal fat weight and percentage of abdominal fat, and the L-FABP gene could be a candidate locus or linked to a major gene(s) that affects fatness traits in the chicken. The results of the current study provided basic molecular information for studying the role of the L-FABP gene in the regulation of lipid metabolism in avian species.

Fatty acid-binding proteins (FABP) belong to a superfamily of lipid binding proteins that exhibit a high affinity for long chain fatty acids and appear to function in metabolism and intracellular transportation of lipids. The current study was designed to investigate the effects of the adipocyte (A)-FABP gene on chicken growth and body composition traits. Two F2 resource populations were used in the current study. Body weight and body composition traits were measured in the populations. Primers for the coding region of the A-FABP gene were designed from chicken genomic and cDNA sequences. Polymorphism between parental lines was detected by DNA sequencing, and the PCR-RFLP method was developed to genotype the F2 populations. The results indicated that an A-FABP gene polymorphism was associated with abdominal fat weight and percentage of abdominal fat, and the A-FABP gene could be a candidate locus or linked to a major gene(s) that affects abdominal fat content in the chicken.

The battery of genetic toxicity tests required by most regulatory authorities includes both bacterial and mammalian cell assays and identifies practically all genotoxic carcinogens. However, the relatively high specificity of the Salmonella mutagenicity assay (Ames test) is offset by the low specificity of the established mammalian cell assays, which leads to difficulties in the interpretation of the biological relevance of results. This paper describes a new high-throughput assay that links the regulation of the human GADD45a gene to the production of Green Fluorescent Protein (GFP). A study of 75 well-characterised genotoxic and non-genotoxic compounds with diverse mechanisms of DNA-damage induction (including aneugens) reveals that the assay responds positively to all classes of genotoxic damage with both high specificity and high sensitivity. The current micro-well assay format does not include metabolic activation, but a separate low-throughput protocol demonstrates a successful proof-of-principle for an S9 metabolic activation assay with the model pro-mutagen cyclophosphamide. The test should be of value both as a tool in the selection of candidate compounds for further development, where additional data may be required because of conflicting information from the in vitro test battery, or in product development areas where the use of animals is to be discontinued. As a microplate assay however, it has the qualities of high throughput and low compound use that will facilitate its application in early screening for genotoxic liability.

We conducted a selection signature analysis using the chicken 60k SNP chip in two chicken lines that had been divergently selected for abdominal fat content (AFC) for 11 generations. The selection signature analysis used multiple signals of selection, including long-range allele frequency differences between the lean and fat lines, long-range heterozygosity changes, linkage disequilibrium, haplotype frequencies, and extended haplotype homozygosity. Multiple signals of selection identified ten signatures on chromosomes 1, 2, 4, 5, 11, 15, 20, 26 and Z. The 0.73 Mb PC1/PCSK1 region of the Z chromosome at 55.43-56.16 Mb was the most heavily selected region. This region had 26 SNP markers and seven genes, Mar-03, SLC12A2, FBN2, ERAP1, CAST, PC1/PCSK1 and ELL2, where PC1/PCSK1 are the chicken/human names for the same gene. The lean and fat lines had two main haplotypes with completely opposite SNP alleles for the 26 SNP markers and were virtually line-specific, and had a recombinant haplotype with nearly equal frequency (0.193 and 0.196) in both lines. Other haplotypes in this region had negligible frequencies. Nine other regions with selection signatures were PAH-IGF1, TRPC4, GJD4-CCNY, NDST4, NOVA1, GALNT9, the ESRP2-GALR1 region with five genes, the SYCP2-CADH4 with six genes, and the TULP1-KIF21B with 14 genes. Genome-wide association analysis showed that nearly all regions with evidence of selection signature had SNP effects with genome-wide significance (P

The objectives of the present study were to characterize the tissue expression of chicken (Gallus gallus) bone morphogenetic protein 4 (BMP4) and compare differences in its expression in abdominal fat tissue and serum between fat and lean birds and to determine a potential relationship between the expression of BMP4 and abdominal fat tissue growth and development. The results showed that chicken BMP4 messenger RNA (mRNA) and protein were expressed in various tissues, and the expression levels of BMP4 transcript and protein were relatively higher in adipose tissues. In addition, the mRNA and protein expression levels of BMP4 in abdominal fat tissue of fat males were lower than those of lean males at 1, 2, 5, and 7 wk of age (P < 0.05). Furthermore, the serum BMP4 content of fat males was lower than that of lean males at 7 wk of age (P < 0.05). BMP4 mRNA expression levels were significantly higher in preadipocytes than those in mature adipocytes (P < 0.05), and the expression level decreased during differentiation in vitro (P < 0.05). These results suggested that chicken BMP4 might affect abdominal fat deposition through differences in its expression level. The results of this study will provide basic molecular information for studying the role of BMP4 in the regulation of adipogenesis in avian species.

Background The gastrointestinal tract is populated by a complex and vast microbial network, with a composition that reflects the relationships of the symbiosis, co-metabolism, and co-evolution of these microorganisms with their host. The mechanism that underlies such interactions between the genetics of the host and gut microbiota remains elusive. Results To understand how genetic variation of the host shapes the gut microbiota and interacts with it to affect the metabolic phenotype of the host, we compared the abundance of microbial taxa and their functional performance between two lines of chickens (fat and lean) that had undergone long-term divergent selection for abdominal fat pad weight, which resulted in a 4.5-fold increase in the fat line compared to the lean line. Our analysis revealed that the proportions of Fusobacteria and Proteobacteria differed significantly between the two lines (8 vs. 18% and 33 vs. 24%, respectively) at the phylum level. Eight bacterial genera and 11 species were also substantially influenced by the host genotype. Differences between the two lines in the frequency of host alleles at loci that influence accumulation of abdominal fat were associated with differences in the abundance and composition of the gut microbiota. Moreover, microbial genome functional analysis showed that the gut microbiota was involved in pathways that are associated with fat metabolism such as lipid and glycan biosynthesis, as well as amino acid and energy metabolism. Interestingly, citrate cycle and peroxisome proliferator activated receptor (PPAR) signaling pathways that play important roles in lipid storage and metabolism were more prevalent in the fat line than in the lean line. Conclusions Our study demonstrates that long-term divergent selection not only alters the composition of the gut microbiota, but also influences its functional performance by enriching its relative abundance in microbial taxa. These results support the hypothesis that the host and gut microbiota interact at the genetic level and that these interactions result in their co-evolution. Electronic supplementary material The online version of this article (doi:10.1186/s12711-016-0270-5) contains supplementary material, which is available to authorized users.

Background Genomic regions controlling abdominal fatness (AF) were studied in the Northeast Agricultural University broiler line divergently selected for AF. In this study, the chicken 60KSNP chip and extended haplotype homozygosity (EHH) test were used to detect genome-wide signatures of AF. Results A total of 5357 and 5593 core regions were detected in the lean and fat lines, and 51 and 57 reached a significant level (PRB1, BBS7, MAOA, MAOB, EHBP1, LRP2BP, LRP1B, MYO7A, MYO9A and PRPSAP1, were detected. These genes may be important for AF deposition in chickens. Conclusions We provide a genome-wide map of selection signatures in the chicken genome, and make a contribution to the better understanding the mechanisms of selection for AF content in chickens. The selection for low AF in commercial breeding using this information will accelerate the breeding progress.