Acetyl-CoA carboxylase beta, encoded by the ACAB gene, plays an important role in the oxidation of fatty acids. The aim of this study was to check the hypothesis that allelic variants of ACACB influence the risk of obesity and type 2 diabetes mellitus. Twenty five tagging single nucleotide polymorphisms (SNPs) capturing common variants of the ACACB gene were selected and analyzed in two cohorts including 1695 postmenopausal women of the general population and in 161 women with severe obesity (BMI>35). In vitro binding of transcription factors was explored by electrophoretic mobility shift assays (EMSA). T alleles at the rs2268388 locus were overrepresented in women with severe obesity (18% vs. 10% in controls; OR 1.74 [95% confidence interval 1.30-2.47]), which was statistically significant after multiple-test adjustment (p=0.0004). Likewise, T alleles at the rs2268388 locus and C alleles at the rs2239607 locus were associated with diabetes, in the discovery as well as in the replication cohorts, even after women with severe obesity were excluded (OR 3.6 and 2.8, for TT and CC homozygotes, respectively). Allelic differences in the binding affinity for nuclear proteins were revealed in vitro by EMSA and competition experiments were consistent with the binding of glucorticoid receptor and serum response factor. In conclusion, common polymorphisms of ACACB gene are associated with obesity and, independently, with type 2 diabetes in postmenopausal women, suggesting that the activity of acetyl-CoA carboxylase beta plays an important role in these disorders related to energy metabolism.

We present the case of a 57-year old female patient diagnosed with systemic lupus erythematosus (SLE) along with glomerulonephritis and chronic intestinal pseudo-obstruction (CIPO). Dilatation of bile and pancreatic ducts not associated with malignant or litiasic obstruction is reported. The combination of bile duct associated with CIPO in a patient with lupus has not been previously reported in the literature and it probably suggests a smooth muscle dysmotility.

A sandwich-like system, fabricated with electrospun, poly(lactic-co-glycolic-acid) (PLGA) membranes incorporating either human recombinant bone morphogenetic protein 2 (BMP-2) enriched microspheres, rat bone marrow mesenchymal stem cells (rMSC), or rMSC with their Smurf1 (SMAD ubiquitin regulatory factor-1) expression knocked down by means of siRNA (rMSC573) at varying densities was evaluated in a rat calvarial, critical-size defect. The behavior of four membrane varieties, fabricated with different PLGA copolymers, was initially studied in rMSC cultures to decide on optimal membrane degradation and cell proliferation and differentiation characteristics. PLGA75:25 provided the most stable structure, and favored the cell environment. Radiological and histological analyses indicated bone repair in animals treated with the PLGA75:25 bioactivated systems. We found no synergist interaction between BMP-2 and rMSC 8 to 12 weeks postimplantation. By contrast, synergistic defect repair of around 85% was detected after 8 weeks of combined BMP-2 and rMSC573 treatment.

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BackgroundAccumulation of galactosphingolipids is a general characteristic of Fabry disease, a lysosomal storage disorder caused by the deficient activity of α-galactosidase A encoded by the GLA gene. Although many polymorphic GLA haplotypes have been described, it is still unclear whether some of these variants are causative of disease symptoms. We report the study of an inheritance of a complex intronic haplotype (CIH) (c.-10C > T, c.369 + 990C > A, c.370-81_370-77delCAGCC, c.640-16A > G, c.1000-22C > T) within the GLA gene associated with Fabry-like symptoms and galactosphingolipid accumulation.We analysed α-Gal A activity in plasma, leukocytes and skin fibroblasts in patients, and measured accumulation of galactosphingolipids by enzymatic methods and immunofluorescence techniques. Additionally, we evaluated GLA expression using quantitative PCR, EMSA, and cDNA cloning.ResultsCIH carriers had an altered GLA expression pattern, although most of the carriers had high residual enzyme activity in plasma, leukocytes and in skin fibroblasts. Nonetheless, CIH carriers had significant galactosphingolipid accumulation in fibroblasts in comparison with controls, and also glycolipid deposits in renal tubules and glomeruli. EMSA assays indicated that the c.-10C > T variant in the promoter affected a nuclear protein binding site.ConclusionsThus, inheritance of the CIH caused an mRNA deregulation altering the GLA expression pattern, producing a tissue glycolipid storage.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-015-0267-z) contains supplementary material, which is available to authorized users.