The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression.

Molecular classification of cancers into subtypes has resulted in an advance in our understanding of tumour biology and treatment response across multiple tumour types. However, to date, cancer profiling has largely focused on protein-coding genes, which comprise <1% of the genome. Here we leverage a compendium of 58,648 long noncoding RNAs (lncRNAs) to subtype 947 breast cancer samples. We show that lncRNA-based profiling categorizes breast tumours by their known molecular subtypes in breast cancer. We identify a cohort of breast cancer-associated and oestrogen-regulated lncRNAs, and investigate the role of the top prioritized oestrogen receptor (ER)-regulated lncRNA, DSCAM-AS1. We demonstrate that DSCAM-AS1 mediates tumour progression and tamoxifen resistance and identify hnRNPL as an interacting protein involved in the mechanism of DSCAM-AS1 action. By highlighting the role of DSCAM-AS1 in breast cancer biology and treatment resistance, this study provides insight into the potential clinical implications of lncRNAs in breast cancer

PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 Are Associated with Type 2 Diabetes in a Chinese Population

Recent advance in genetic studies added the confirmed susceptible loci for type 2 diabetes to eighteen. In this study, we attempt to analyze the independent and joint effect of variants from these loci on type 2 diabetes and clinical phenotypes related to glucose metabolism.Twenty-one single nucleotide polymorphisms (SNPs) from fourteen loci were successfully genotyped in 1,849 subjects with type 2 diabetes and 1,785 subjects with normal glucose regulation. We analyzed the allele and genotype distribution between the cases and controls of these SNPs as well as the joint effects of the susceptible loci on type 2 diabetes risk. The associations between SNPs and type 2 diabetes were examined by logistic regression. The associations between SNPs and quantitative traits were examined by linear regression. The discriminative accuracy of the prediction models was assessed by area under the receiver operating characteristic curves. We confirmed the effects of SNPs from PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 on risk for type 2 diabetes, with odds ratios ranging from 1.114 to 1.406 (P value range from 0.0335 to 1.37E-12). But no significant association was detected between SNPs from WFS1, FTO, JAZF1, TSPAN8-LGR5, THADA, ADAMTS9, NOTCH2-ADAM30 and type 2 diabetes. Analyses on the quantitative traits in the control subjects showed that THADA SNP rs7578597 was association with 2-h insulin during oral glucose tolerance tests (P = 0.0005, empirical P = 0.0090). The joint effect analysis of SNPs from eleven loci showed the individual carrying more risk alleles had a significantly higher risk for type 2 diabetes. And the type 2 diabetes patients with more risk allele tended to have earlier diagnostic ages (P = 0.0006).The current study confirmed the association between PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 and type 2 diabetes. These type 2 diabetes risk loci contributed to the disease additively

Risk factors for overweight and obesity, and changes in body mass index of Chinese adults in Shanghai

<p>Abstract</p> <p>Background</p> <p>Over the past two decades, the prevalence of overweight or obesity has increased in China. The aims of this study were to firstly assess the baseline prevelences and the risk factors for overweight and obesity, and secondly to detect the changes of body mass index (BMI) over a follow-up period in Chinese adults in Shanghai.</p> <p>Methods</p> <p>The data set of a population-based longitudinal study was analyzed. Anthropometric and biochemical data were collected for 5364 subjects (aged 25–95 years) during a period of 1998–2001. Among those individuals, 3032 subjects were interviewed and reexamined at the second survey from 2003 to 2004. Then the standardized prevalences for overweight and obesity were calculated using baseline data; the possible contributing factors of overweight and obesity were detected using binary logistic regression analysis; and the changes of BMI were evaluated after an average of 3.6-year follow-up period.</p> <p>Results</p> <p>(1) According to the WHO standard and the Chinese standard, the sex- and age-standardized prevalences were 27.5% and 32.4% for overweight, and 3.7% and 9.1% for obesity, respectively. (2) The risks of overweight and obesity differed among different age groups. Family history of obesity increased the risk of overweight and obesity by about 1.2-fold for both genders. Current male smokers had a lower risk of overweight and obesity (OR = 0.76, <it>p </it>< 0.05) than nonsmokers. In contrast, current male drinkers had a higher risk of overweight and obesity (OR = 1.42, <it>p </it>< 0.05) than nondrinkers. Compared with low-educated women, medium- and high- educated women were at lower risk of overweight and obesity, and the corresponding ORs (95% CIs) were 0.64 (0.52–0.79) and 0.50(0.36–0.68), respectively. (3) The annual changes of BMI means ranged from an increase of 0.1 kg/m²to a decrease of 0.2 kg/m²(by genders and age groups). Meanwhile, the BMI increase was statistically significant in the 35–44 years age group, and the BMI decrease was significant above 65 years for both genders.</p> <p>Conclusion</p> <p>This study showed high prevalence of overweight and obesity in Shanghai metropolis populations. The risk factors of overweight and obesity were multifactorial and gender specific. After 3.6 years, BMI means changed slightly, BMI increased mainly in middle-aged individuals and decreased in old individuals.</p

Recruitment of a SAP18-HDAC1 Complex into HIV-1 Virions and Its Requirement for Viral Replication

HIV-1 integrase (IN) is a virally encoded protein required for integration of viral cDNA into host chromosomes. INI1/hSNF5 is a component of the SWI/SNF complex that interacts with HIV-1 IN, is selectively incorporated into HIV-1 (but not other retroviral) virions, and modulates multiple steps, including particle production and infectivity. To gain further insight into the role of INI1 in HIV-1 replication, we screened for INI1-interacting proteins using the yeast two-hybrid system. We found that SAP18 (Sin3a associated protein 18 kD), a component of the Sin3a-HDAC1 complex, directly binds to INI1 in yeast, in vitro and in vivo. Interestingly, we found that IN also binds to SAP18 in vitro and in vivo. SAP18 and components of a Sin3A-HDAC1 complex were specifically incorporated into HIV-1 (but not SIV and HTLV-1) virions in an HIV-1 IN–dependent manner. Using a fluorescence-based assay, we found that HIV-1 (but not SIV) virion preparations harbour significant deacetylase activity, indicating the specific recruitment of catalytically active HDAC into the virions. To determine the requirement of virion-associated HDAC1 to HIV-1 replication, an inactive, transdominant negative mutant of HDAC1 (HDAC1H141A) was utilized. Incorporation of HDAC1H141A decreased the virion-associated histone deacetylase activity. Furthermore, incorporation of HDAC1H141A decreased the infectivity of HIV-1 (but not SIV) virions. The block in infectivity due to virion-associated HDAC1H141A occurred specifically at the early reverse transcription stage, while entry of the virions was unaffected. RNA-interference mediated knock-down of HDAC1 in producer cells resulted in decreased virion-associated HDAC1 activity and a reduction in infectivity of these virions. These studies indicate that HIV-1 IN and INI1/hSNF5 bind SAP18 and selectively recruit components of Sin3a-HDAC1 complex into HIV-1 virions. Furthermore, HIV-1 virion-associated HDAC1 is required for efficient early post-entry events, indicating a novel role for HDAC1 during HIV-1 replication

Chitosan cross-linked poly(acrylic acid) hydrogels: drug release control and mechanism

<p>Chitosan has been used to cross-link poly(acrylic acid) to give three pH-sensitive hydrogels designed to control the release of the drugs amoxicillin and meloxicam. The extent of cross-linking and solution pH was found to dominate the swelling behavior of these hydrogels as shown by scanning electron microscopy and swelling time dependencies. The rates of release of amoxicillin and meloxicam from the loaded hydrogels increased with increase in pH consistent with the extent of hydrogen bonding between hydrogel components and between the hydrogel and the drugs being important determinants of release rate. Both the Korsemeyer-Peppas and Weibull models fitted release data consistent with drug release occurred through a combination of drug diffusion and hydrogel relaxation processes. These hydrogels appear to provide an ideal basis for controlled drug delivery systems.</p

Transient supramolecular hydrogels formed by catalytic control over molecular self-assembly

The present work shows how transient supramolecular hydrogels can be formed by catalytically controlled molecular self-assembly. Catalysis formation of molecular gelators leads the self-assembly along a kinetically favored pathway, resulting in transient hydrogels. This work demonstrates an effective approach towards pathway-dependent supramolecular materials.Accepted Author ManuscriptChemE/Advanced Soft Matte