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Diabetes is a disorder characterized by loss of β cell mass and/or β cell function, leading to deficiency of insulin relative to metabolic need. To determine whether stem cell-derived β [...]

Author(s): Ioanna Mosialou; Steven Shikhel; Jian-Min Liu; Antonio Maurizi; Na Luo; Zhenyan He; Yiru Huang; Haihong Zong; Richard A. Friedman; Jonathan Barasch; Patricia Lanzano; Liyong Deng; Rudolph L. Leibel; Mishaela [...]

The corresponding authors were made aware of karyotype abnormalities through a routine quality control test of pluripotent stem cells used in the studies reported in this paper. After extensive internal [...]

Weprepared a new class of functional solutions by dissolving CuClor CuBr into 1-butyl-3-methylimidazolium bromide ([BMIM][Br]) or 1-ethyl-3-methylimidazoliumbromide ([EMIM][Br]). We determined experimentally the solubilityof propylene and propane in such solutions respectively at 1–8bar and 298–313 K, and investigated the separation of propylenefrom propylene/propane mixture. The absorption capacity and selectivityfor propylene were enhanced with the addition of Cu(I) salt and wereaffected by cationic side chain and anionic species following thisorder [EMIM][Br]-CuCl < [EMIM][Br]-CuBr < [BMIM][Br]-CuCl <[BMIM][Br]-CuBr. It was observed that this absorption was a chemicalnature through π-interaction between Cu(I) cation and propylene.In a typical result, the absorption capacity for propylene of [BMIM][Br]-CuBr(Cu(I) cation, 1.5 M) is 0.13 mol/L at 298 K and 1 bar while it is0.01 mol/L for propane with a selectivity of 13, which is comparableto those absorption systems with more expensive silver salts; theselectivity is high, up to 64.6 for 80 mol % propylene mixture withpropane. The effects of temperature and pressure on absorption wereinvestigated. Such systems of Cu(I) salt and ionic liquids are potentialabsorption reagents for separation of propylene and propane with competitivecost to silver systems. [ABSTRACT FROM AUTHOR]

Objective To determine the frequency of Melanocortin 4 Receptor ( MC4R) mutations in morbidly obese adolescents undergoing bariatric surgery and compare weight loss outcomes in patients with and without mutations. Design and Methods In this prospective cohort study, 135 adolescent patients evaluated for bariatric surgery were screened for MC4R mutations; 56 had 12-month postoperative data available for analysis. Results MC4R mutations were detected in five of the 135 patients (3.7%); four underwent restrictive bariatric surgery. For the three patients with gastric banding, percent excess weight loss (%EWL) postoperatively was 36.0% at 5 years in one, 47% at 4 years in the second, and 85% at 1 year in the third. For the patient with gastric sleeve resection, %EWL of 96% was attained at 1 year postoperatively. The four MC4R cases had a higher, although nonsignificant, %EWL compared to 52 nonmatched controls at 12 months postoperatively (48.6% vs. 23.4%; P < 0.37). When matched by age, sex, and race to 14 controls, there was no significant difference in %EWL ( P < 0.31), BMI change ( P < 0.27), or absolute weight loss ( P < 0.20). Conclusion The frequency of MC4R mutations is similar to prior studies, with affected patients showing beneficial weight loss outcomes. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) have played an essential role in cancer development. This study aimed to illustrate the impact and potential mechanism of circRACGAP1 action in NSCLC development. The expression patterns of circRACGAP1, miR-1296, and CDK2 in NSCLC tissues and cell lines were analysed by RT-qPCR. The function of circRACGAP1 in NSCLC cell proliferation and apoptosis was investigated using the CCK-8 assay, flow cytometry, TUNEL staining, and Western blot. The interaction among circRACGAP1, miR-1296, and CDK2 was clarified by dual-luciferase reporter assay while the correlation was confirmed by the Pearson correlation coefficient. The expression of circRACGAP1 and CDK2 was up-regulated in NSCLC tissues, while the expression of miR-1296 was down-regulated. Cell function studies further revealed that circRACGAP1 could promote NSCLC cell proliferation, accelerate the cell cycle process, up-regulate B-cell lymphoma 2 (Bcl2) expression, and down-regulate Bcl2-associated X (Bax) expression. miR-1296 was identified as a downstream target to reverse circRACGAP1-mediated cell proliferation. miR-1296 directly targeted the 3'-UTR of CDK2 to regulate proliferation and apoptosis of NSCLC cells. Additionally, the dual-luciferase reporter assay and Pearson correlation coefficient analysis proved that circRACGAP1 acted in NSCLC cells by negatively regulating miR-1296 expression and positively regulating CDK2 expression. In summary, our study revealed that circRACGAP1 promoted NSCLC cell proliferation by regulating the miR-1296/CDK2 pathway, providing potential diagnostic and therapeutic targets for NSCLC.

Using clinical exome sequencing (ES), we identified an autosomal recessive missense variant, c.153C>A (p.F51L), in the peroxisome biogenesis factor 26 gene ( PEX26 ) in a 19-yr-old female of Ashkenazi Jewish descent who was referred for moderate to severe hearing loss. The proband and three affected siblings are all homozygous for the c.153C>A variant. Skin fibroblasts from this patient show normal morphology in immunostaining of matrix proteins, although the level of catalase was elevated. Import rate of matrix proteins was significantly decreased in the patient-derived fibroblasts. Binding of Pex26-F51L to the AAA ATPase peroxins, Pex1 and Pex6, is severely impaired and affects peroxisome assembly. Moreover, Pex26 in the patient's fibroblasts is reduced to ∼30% of the control, suggesting that Pex26-F51L is unstable in cells. In the patient's fibroblasts, peroxisome-targeting signal 1 (PTS1) proteins, PTS2 protein 3-ketoacyl-CoA thiolase, and catalase are present in a punctate staining pattern at 37°C and in a diffuse pattern at 42°C, suggesting that these matrix proteins are not imported to peroxisomes in a temperature-sensitive manner. Analysis of peroxisomal metabolism in the patient's fibroblasts showed that the level of docosahexaenoic acid (DHA) (C22:6n-3) in ether phospholipids is decreased, whereas other lipid metabolism, including peroxisomal fatty acid β-oxidation, is normal. Collectively, the functional data support the mild phenotype of nonsyndromic hearing loss in patients harboring the F51L variant in PEX26 ., (© 2019 Tanaka et al.; Published by Cold Spring Harbor Laboratory Press.)