Vertnin (VRTN) variants have been associated with the number of thoracic vertebrae in European pigs, but the association has not been evidenced in Chinese indigenous pigs. In this study, we first performed a genome-wide association study in Chinese Erhualian pigs using one VRTN candidate causative mutation and the Illumina Porcine 60K SNP Beadchips. The VRTN mutation is significantly associated with thoracic vertebral number in this population. We further show that the VRTN mutation has pleiotropic and desirable effects on teat number and carcass (body) length across four diverse populations, including Erhualian, White Duroc × Erhualian F2 population, Duroc and Landrace pigs. No association was observed between VRTN genotype and growth and fatness traits in these populations. Therefore, testing for the VRTN mutation in pig breeding schemes would not only increase the number of vertebrae and nipples, but also enlarge body size without undesirable effects on growth and fatness traits, consequently improving pork production. Further, by using whole-genome sequence data, we show that the VRTN mutation was possibly introgressed from Chinese pigs into European pigs. Our results provide another example showing that introgressed Chinese genes greatly contributed to the development and production of modern European pig breeds.

Fatty acid composition in muscle is an important factor that affects the nutritive value and taste of pork. To investigate the genetic architecture of fatty acid composition of pork, we measured fatty acid contents in longissimus dorsi muscle of 1244 pigs from three divergent populations and conducted genome-wide association studies (GWAS) for fatty acid contents.

The TAM kinase (Tyro3, Axl, Mer) and its two ligands (Gas6 and protein S) have been shown to play an important regulatory role in the innate immune response. The present study aimed to investigate whether the tag single-nucleotide polymorphisms (tag SNPs) of these 5 protein-coding genes are associated with Behçet's disease (BD). A two-stage association study was performed in a total of 907 BD patients and 1780 healthy controls. Altogether 32 polymorphisms were tested, using a Sequenom MassARRAY genotyping method in the first stage and a PCR-restriction fragment length polymorphism (PCR-RFLP) assay in the replication phase. Real-time PCR was performed to test the relative mRNA expression level of GAS6 and PROS1 from different SNP genotyped healthy individuals. The frequency of the C allele and CC genotype of rs9577873 in GAS6 (Pc = 4.92 × 10(-5), Pc = 1.91 × 10(-5), respectively) and A allele and AA genotype of rs4857037 in PROS1 (Pc = 1.85 × 10(-6), Pc = 4.52 × 10(-7), respectively) were significantly increased in BD. GAS6 expression in CC carriers of rs9577873 was significantly lower than that in CT/TT individuals (P = 0.001). Decreased expression of GAS6 and increased pro-inflammatory cytokines (IL-6 and IFN-γ: P = 4.23 × 10(-4), P = 0.011, respectively) in individuals carrying the CC genotype suggest that the TAM-GAS6/PROS1 signal pathway may be involved in the pathogenesis of BD.

LacI is commonly used as a model to study the protein-DNA interaction and gene regulation. The headpiece of the lac-repressor (LacI) protein is an ideal system for investigation of nonspecific binding of the whole LacI protein to DNA. The hinge region of the headpiece has been known to play a key role in the specific binding of LacI to DNA, whereas its role in nonspecific binding process has not been elucidated. Here, we report the results of explicit solvent molecular dynamics simulation and continuum electrostatic calculations suggesting that the hinge region strengthens the nonspecific interaction, accounting for up to 50% of the micro-dissociation free energy of LacI from DNA. Consequently, the rate of microscopic dissociation of LacI from DNA is reduced by 2~3 orders of magnitude in the absence of the hinge region. We find the hinge region makes an important contribution to the electrostatic energy, the salt dependence of electrostatic energy, and the number of salt ions excluded from binding of the LacI-DNA complex.

The aim of the present study was to investigate the effect and mechanism of different concentrations of aspirin in inhibiting the ovarian cancer of p53N236S gene knock-in mice. In total, 28 male p53S mice, with an age range of 4-6 weeks and weight of 20-25 g were selected. The animals were transplanted with SKOV3 cells to establish subdermal human ovarian cancer. The mice were randomly divided into different groups according to the aspirin concentrations (mmol/l) used, i.e., 0, 1, 2 and 3. Subsequently, intraperitoneal injection was performed once every two days for 3 weeks. The tumor volume, lifetime, tumor cell proliferation inhibition rates, caspase-3 protein and bcl-2 protein expression of the four groups were analyzed and compared. Following aspirin treatment for 1, 2 and 3 weeks, the tumor volume of the 3 mmol/l aspirin group was significantly smaller than the other groups (P<0.05). The higher concentration of aspirin led to a smaller tumor size (P<0.05). The cell proliferation inhibition rate of the 3 mmol/l aspirin group was significantly larger than that of other groups (P<0.05). The relative expression level of caspase-3, bcl-2 protein of the 3 mmol/l aspirin group was significantly improved and reduced, respectively. In conclusion, aspirin can inhibit the growth of ovarian cancer of p53S rats due to its upregulation of the expression of caspase-3 protein and downregulation of the expression of bcl-2 protein.

Hematopoietic stem cells (HSCs) serve as a life-long reservoir for all blood cell types and are clinically useful for a variety of HSC transplantation-based therapies. Understanding the role of chromatin organization and regulation in HSC homeostasis may provide important insights into HSC development. Bromodomain- and PHD finger-containing protein 1 (BRPF1) is a multivalent chromatin regulator that possesses 4 nucleosome-binding domains and activates 3 lysine acetyltransferases (KAT6A, KAT6B, and KAT7), suggesting that this protein has the potential to stimulate crosstalk between different chromatin modifications. Here, we investigated the function of BRPF1 in hematopoiesis by selectively deleting its gene in murine blood cells. Brpf1-deficient pups experienced early lethality due to acute bone marrow failure and aplastic anemia. The mutant bone marrow and fetal liver exhibited severe deficiency in HSCs and hematopoietic progenitors, along with elevated reactive oxygen species, senescence, and apoptosis. BRPF1 deficiency also reduced the expression of multipotency genes, including Slamf1, Mecom, Hoxa9, Hlf, Gfi1, Egr, and Gata3. Furthermore, BRPF1 was required for acetylation of histone H3 at lysine 23, a highly abundant but not well-characterized epigenetic mark. These results identify an essential role of the multivalent chromatin regulator BRPF1 in definitive hematopoiesis and illuminate a potentially new avenue for studying epigenetic networks that govern HSC ontogeny.

Cooperation is pervasive and constitutes the core behavioral principle of human social life. Previous studies have revealed that mutual cooperation was reliably correlated with two reward-related brain regions, the ventral striatum and the orbitofrontal cortex. Using functional magnetic resonance imaging (fMRI), this study sought to investigate how the loss and gain contexts modulated the neural responses to mutual cooperation. Twenty-five female participants were scanned when they played a series of one-shot prisoner's dilemma games in the loss and gain contexts. Specifically, participants and partners independently chose to either cooperate with each other or not, and each was awarded or deprived of (in the gain context or the loss context, respectively) a sum of money which depended upon the interaction of their choices. Behavioral results indicated that participants cooperated in nearly half of the experiment trials and reported higher level of positive emotions for mutual cooperation in both contexts, but they cooperated more in the gain than in the loss context. At the neural level, stronger activities in the orbitofrontal cortex were observed for mutual cooperation compared with the other three outcomes in both contexts, while stronger activation in ventral striatum associated with mutual cooperation was observed in the gain context only. Together, our data indicated that, even in the one-shot interaction under loss context, participants still exhibited preference for cooperation and the rewarding experience from a mutually cooperative social interaction activated the ventral striatum and the orbitofrontal cortex, but the loss context weakened the association between the ventral striatum activation and mutual cooperation.

In this study, the prevalence of HIV-1 CRF01_AE intrasubtype recombinants in China is estimated and their contributions to the epidemic are explored.

Semen is a major vehicle for HIV transmission. Prostatic acid phosphatase (PAP) fragments, such as PAP248-286, in human semen can form amyloid fibrils to enhance HIV infection. Other endogenous or exogenous factors present during sexual intercourse have also been reported to promote the formation of seminal amyloid fibrils.

Lung cancer is the most common cause of cancer death worldwide. The poor survival rate is largely due to the extensive local invasion and metastasis. However, the mechanisms underlying the invasion and metastasis of lung cancer cells remain largely elusive. In this study, we examined the role of preferentially expressed antigen of melanoma (PRAME) in lung cancer metastasis. Our results show that PRAME is downregulated in lung adenocarcinoma and lung bone metastasis compared with normal human lung. Knockdown of PRAME decreases the expression of E-Cadherin and promotes the proliferation, invasion, and metastasis of lung cancer cells by regulating multiple critical genes, most of which are related to cell migration, including MMP1, CCL2, CTGF, and PLAU. Clinical data analysis reveals that the expression of MMP1 correlates with the clinical features and outcome of lung adenocarcinoma. Taken together, our data demonstrate that PRAME plays a role in preventing the invasion and metastasis of lung adenocarcinoma and novel diagnostic or therapeutic strategies can be developed by targeting PRAME.

Vascular leakage frequently occurs in patients with severe Staphylococcus aureus infection. However, the mechanism underlying S. aureus infection-induced vascular leakage remains unclear. Here, we identified the S. aureus virulence factor phenol-soluble modulin (PSM)α4 from the culture supernatant of strain USA300 as a stimulator of heparin-binding protein (HBP) release from polymorphonuclear neutrophils (PMNs) and demonstrated that PSMα4-induced HBP release from PMNs leads to vascular leakage. PSMα4 appeared less cytolytic than PSMα1-3 and was insensitive to lipoproteins; it significantly increased myeloperoxidase and elastase release from PMNs and cell surface CD63 expression in PMNs. PSMα4-induced HBP release required formyl peptide receptor 2 (FPR2) and phosphoinositide 3-kinase (PI3K) and depended on Ca(2+) influx and cytoskeleton rearrangement. Thus, PSMα4 may stimulate HBP release by activating FPR2 and PI3K to initiate PMN degranulation. PSMα4-induced HBP release from PMNs increased endothelial cell monolayer permeability in vitro and induced vascular leakage in mice. This novel function of PSMα4 may contribute to the pathogenesis of S. aureus and may be a potential therapeutic target.

Transposable elements and other repetitive DNA sequences are usually subject to DNA methylation and transcriptional silencing. However, anti-silencing mechanisms that promote transcription in these regions are not well understood. Here, we describe an anti-silencing factor, Bromodomain and ATPase domain-containing protein 1 (BRAT1), which we identified by a genetic screen in Arabidopsis thaliana. BRAT1 interacts with an ATPase domain-containing protein, BRP1 (BRAT1 Partner 1), and both prevent transcriptional silencing at methylated genomic regions. Although BRAT1 mediates DNA demethylation at a small set of loci targeted by the 5-methylcytosine DNA glycosylase ROS1, the involvement of BRAT1 in anti-silencing is largely independent of DNA demethylation. We also demonstrate that the bromodomain of BRAT1 binds to acetylated histone, which may facilitate the prevention of transcriptional silencing. Thus, BRAT1 represents a potential link between histone acetylation and transcriptional anti-silencing at methylated genomic regions, which may be conserved in eukaryotes.

Foxtail millet (Setaria italica) is a diploid C4 panicoid species. Because of its prominent drought resistance, small genome size, self-pollination, and short life cycle, foxtail millet has become an ideal model system for studying drought tolerance of crops. MicroRNAs (miRNAs) are endogenous, small RNAs that play important regulatory roles in the development and stress response in plants.

Most cervical cancer patients worldwide receive surgical treatments, and yet the current International Federation of Gynecology and Obstetrics (FIGO) staging system do not consider surgical-pathologic data. We propose a more comprehensive and prognostically valuable surgical-pathologic staging and scoring system (SPSs).

The molecular mechanism between Helicobacter pylori (H. pylori) infection and gastric cancer remained largely unknown. In this study, we determined the role of miRNA in H. pylori induced gastric cancer.

We built a cohort study of HIV patients taking long-term first-line Antiretroviral Therapy in 2003. In this assay, we focused on the development of primary drug resistance mutations against Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), K103N, Y181C and G190A.

Rab GTPases control exocytic and endocytic membrane trafficking such as exosomes release. As a secretory small GTPase, Rab3D is a vital regulator for protein secretion. However, the role of Rab3D in cancer was never systematically studied. The aim of this study is to examine its function and mechanism in cancer, especially metastasis. We detected protein levels of Rab3D in nine cancer cell lines and twelve types of clinical cancer specimens. Subsequently, we established in vitro migration and in vivo orthotopic metastatic mouse models to study the role of Rab3D in tumor metastasis. Here, we reported that the expression levels of Rab3D were dysregulated in cancer cells and highly correlated with tumor malignancies in the clinical samples. Increased expressions of Rab3D led to tumor invasion in vitro and lung metastasis in vivo, whereas Rab3D knockdown suppressed the tumor cell motility. Mechanistic studies revealed that Rab3D activated intracellular the AKT/GSK3β signaling to induce the EMT process. In addition, it also regulated the extracellular secretion of Hsp90α to promote tumor cell migration and invasion. These results prove that Rab3D is a key molecule to regulate tumor metastasis, suggesting that blocking the Rab3D function can be a potential therapeutic approach for cancer metastasis.

The avian influenza (H5N1) viral RNA polymerase protein PA(C) was used as a target to screen nine chlorogenic acid derivatives for their polymerase inhibitor activity. Among them, seven compounds were PA(C) ligands, and four inhibited influenza RNA polymerase activity. These results aid in the design of anti-influenza agents based on caffeoylquinic acid.

Treg/Th17 balance plays a critical role in maintaining immune homeostasis of acute graft-versus-host disease (aGVHD) patients. STAT3 is an important factor involved in the instability of Treg and the promotion of Th17. HMGB1 is a cytokine mediator of inflammation and an important chromatin protein regulating gene transcription. In this study, we found that the expressions of HMGB1 and STAT3 were higher in CD4(+) T cells of patients with aGVHD compared with those without aGVHD, and the HMGB1 expression was positively correlated with the STAT3 expression. Simultaneously, their expressions were positively correlated with the severity of the aGVHD. We also demonstrated that HMGB1 could regulate the expression of STAT3 by modulation of its DNA methylation in CD4(+) T cells, moreover downregulated HMGB1 in aGVHD CD4(+) T cells could change the ratio of Treg/Th17. These data strongly suggest that HMGB1 plays a crucial role in the regulation of Treg/Th17 and progression of aGVHD.

The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors with neuroprotective properties. GLP-1 mimetics are on the market as treatments for type 2 diabetes and are well tolerated. Both GLP-1 and GIP mimetics have shown neuroprotective properties in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. Novel GLP-1/GIP dual-agonist peptides have been developed and are tested in diabetic patients. Here we demonstrate the neuroprotective effects of a novel dual agonist (DA-JC1) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once-daily (20 mg/kg i.p.) for 7 days, and the dual agonist was injected 30 min later i.p. (50 nmol/kg bw). The PI3k inhibitor LY294002 (0.6 mg/kg i.v.) was co-injected in one group. DA-JC1 reduced or reversed most of the MPTP induced motor impairments in the rotarod and in a muscle strength test. The number of tyrosine hydroxylase (TH) positive neurons in the substantia nigra (SN) was reduced by MPTP and increased by DA-JC1. The ratio of anti-inflammatory Bcl-2 to pro-inflammatory BAX as well as the activation of the growth factor kinase Akt was reduced by MPTP and reversed by DA-JC1. The PI3k inhibitor had only limited effect on the DA-JC1 drug effect. Importantly, levels of the neuroprotective brain derived neurotropic factor (BDNF) were reduced by MPTP and enhanced by DA-JC1. The results demonstrate that DA-JC1 shows promise as a novel treatment for PD.