IGF2BP2 Alternative Variants Associated with Glutamic Acid Decarboxylase Antibodies Negative Diabetes in Malaysian Subjects

Background

The association of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) common variants (rs4402960 and rs1470579) with type 2 diabetes (T2D) has been performed in different populations. The aim of this study was to evaluate the association of alternative variants of IGF2BP2; rs6777038, rs16860234 and rs7651090 with glutamic acid decarboxylase antibodies (GADA) negative diabetes in Malaysian Subjects.

Methods/Principal Findings

IGF2BP2; rs6777038, rs16860234 and rs7651090 single nucleotide polymorphisms (SNPs) were genotyped in 1107 GADA negative diabetic patients and 620 control subjects of Asian from Malaysia. The additive genetic model adjusted for age, race, gender and BMI showed that alternative variants; rs6777038, rs16860234 and rs7651090 of IGF2BP2 associated with GADA negative diabetes (OR = 1.21; 1.36; 1.35, P = 0.03; 0.0004; 0.0002, respectively). In addition, the CCG haplotype and diplotype CCG-TCG increased the risk of diabetes (OR = 1.51, P = 0.01; OR = 2.36, P = 0.009, respectively).

Conclusions/Significance

IGF2BP2 alternative variants were associated with GADA negative diabetes. The IGF2BP2 haplotypes and diplotypes increased the risk of diabetes in Malaysian subject.     

Pioneer marine biofilms on artificial surfaces including antifouling coatings immersed in two contrasting French Mediterranean coast sites

Marine biofilm communities that developed on artificial substrata were investigated using molecular and microscopic approaches. Polystyrene, Teflon? and four antifouling (AF) paints were immersed for 2 weeks at two contrasting sites near Toulon on the French Mediterranean coast (Toulon military harbour and the natural protected area of Porquerolles Island). Biofilms comprising bacteria and diatoms were detected on all the coatings. The population structure as well as the densities of the microorganisms differed in terms of both sites and coatings. Lower fouling densities were observed at Porquerolles Island compared to Toulon harbour. All bacterial communities (analysed by PCR-DGGE) showed related structure, controlled both by the sites and the type of substrata. Pioneer microalgal communities were dominated by the same two diatom species, viz. Licmophora gracilis and Cylindrotheca closterium, at both sites, irrespective of the substrata involved. However, the density of diatoms followed the same trend at both sites with a significant effect of all the AF coatings compared to Teflon and polystyrene.     

A case report: Giant cystic parathyroid adenoma presenting with parathyroid crisis after Vitamin D replacement

ABSTRACT: BACKGROUND: Parathyroid adenoma with cystic degeneration is a rare cause of primary hyperparathyroidism. The clinical and biochemical presentation may mimic parathyroid carcinoma. Case Presentation: We report the case of a 55 year old lady, who had longstanding history of depression and acid peptic disease. Serum calcium eight months prior to presentation was slightly high, but she was never worked up. She was found to be Vitamin D deficient while being investigated for generalized body aches. A month after she was replaced with Vitamin D, she presented to us with parathyroid crisis. Her corrected serum calcium was 23.0 mg/dL. She had severe gastrointestinal symptoms and acute kidney injury. She had unexplained consistent hypokalemia until surgery. Neck ultrasound and CT scan revealed giant parathyroid cyst extending into the mediastinum. After initial medical management for parathyroid crisis, parathyroid cystic adenoma was surgically excised. Her serum calcium, intact parathyroid hormone, creatinine and potassium levels normalized after surgery. CONCLUSION: This case of parathyroid crisis, with very high serum calcium and parathyroid hormone levels, is a rare presentation of parathyroid adenoma with cystic degeneration. This case also highlights that Vitamin D replacement may unmask subclinical hyperparathyroidism. Consistent hypokalemia until surgery merits research into its association with hypercalcemia.     

Enhanced production and characterization of a β-glucosidase from <Emphasis Type="Italic">Bacillus halodurans</Emphasis> expressed in <Emphasis Type="Italic">Escherichia coli</Emphasis>

A putative β-glucosidase gene from the genome of Bacillus halodurans C-125 was expressed in E. coli under the regulation of T7lac promoter. On induction with isopropyl-β-D-1-thiogalactopyranoside, the enzyme expressed at ∼40% of the cell protein producing 238 mg/liter culture. With increase in culture cell density to A ₆₀₀ 12 in auto-inducing M9NG medium, β-glucosidase production increased 3-fold. Approximately 70% of the expressed enzyme was in a soluble form, while the rest was in an insoluble fraction of the cell lysate. The soluble and active form of the expressed enzyme was purified by ammonium sulfate precipitation followed by ion-exchange chromatography to a purity >98%. The mass of the enzyme as determined by MALDI-TOF mass spectrometry was 51,601 Da, which is nearly the same as the calculated value. Phylogenetic analysis of the β-glucosidase of B. halodurans was found to cluster with members of the genus Bacillus. Temperature and pH optima of the enzyme were found to be 45°C and 8.0, respectively, under the assay conditions. K _m and k _cat against p-nitrophenyl-β-D-glucopyranoside were 4 mM and 0.75 sec⁻¹, respectively. To our knowledge, this is the first report of high-level expression and characterization of a β-glucosidase from B. halodurans.     

Proteomics of breast cancer: the quest for markers and therapeutic targets

Proteomics of breast cancer has already delivered significant data in terms of proteome profiling in addition to the identification of a few proteins of potential interest for diagnosis and treatment. With more pathological and experimental situations being studied, it now enters into a new phase dominated by the concepts of deep proteome analysis and the definition of protein-protein interaction networks leading to mammary cell deregulation and cancer progression. Together, what could be called "Systems Proteomics", integrating with information from the genomics and the physiopathology, is clearly emerging to become the frame for future investigations. However, difficulties ahead should not be underestimated. First, the proteome is complex, and current tools are still far from providing a definitive solution for its exploration. Second, breast cancer is a multifactorial disease which is so diverse that a great deal of time and efforts will be necessary to define its associated proteome modifications and translate it into practical applications for the clinic.     

Phenolic constituents from the wood of Morus australis with cytotoxic activity

A new methylated flavonol, 5,7,2',4'-tetrahydroxy-3-methoxyflavone (1), had been isolated from the methanol extract of the wood of Morus australis, along with nine known compounds, kuwanon C (2), morusin (3), morachalcone A (4), oxyresveratrol (5), 4'-(2-methyl-2-buten-4-yl)oxyresveratrol (6), moracins M (7) and C (8), alboctalol (9), and macrourin B (10). The structures of these compounds were determined based on spectral evidence, including UV, IR, NMR, and mass spectra. Cytotoxic properties of compounds 1-10 were evaluated against murine leukemia P-388 cells. The prenylated stilbene 6 and 2-arylbenzofuran 8, and morusin (3) were found to have strong cytotoxic effects with IC50 values of 6.9, 8.7, and 10.1 microM, respectively.     

Characterization of a Saccharomyces cerevisiae mutant with enhanced production of beta-D-fructofuranosidase

The present study focused on the improvement of Saccharomyces cerevisiae through random mutagenesis for enhanced production of beta-D-fructofuranosidase (FFase) using sucrose salt media. Sixty strains of S. cerevisiae were isolated from different fruits and soil samples and screened for FFase production. Enzyme productivity of different yeast isolates ranged from 0.03 to 1.10 U/ml. The isolate with the highest activity was subjected to ultraviolet (UV) radiation and mutagenesis using N-methyl N-nitro N-nitroso guanidine (MNNG). One mutant produced FFase at a level of 17.8+/-0.9 U/ml. The MNNG-treated isolate was exposed to ethyl methane sulphonate (EMS), and a mutant with an enzyme activity of 25.56+/-1.4 U/ml was obtained. Further exposure to UV radiation and chemicals yielded a mutant exhibiting an activity of 34.12+/-1.8 U/ml. After optimization of incubation time (48 h), sucrose concentration (5.0 g/L), initial pH (6.0) and inoculum size (2.0% v/v), enzyme production reached 45.65+/-4.6 U/ml with a noticeable greater than 40-fold increase compared to the wild-type culture. On the basis of kinetic variables, notably Q(p) (0.723+/-0.2U/g/h), Y(p/s) (2.036+/-0.05 U/g) and q(p) (0.091+/-0.02 U/g yeast cells/h), the mutant S. cerevisiae UME-2 was found to be a hyperproducer of FFase (LSD 0.054, p0.05).