A Novel Locus for Ectodermal Dysplasia of Hair,Nail and Skin Pigmentation Anomalies Maps to Chromosome 18p11.32-p11.31

Ectodermal dysplasias (EDs) are a large heterogeneous group of inherited disorders exhibiting abnormalities in ectodermally derived appendages such as hair, nails, teeth and sweat glands. EDs associated with reticulated pigmentation phenotype are rare entities for which the genetic basis and pathophysiology are not well characterized. The present study describes a five generation consanguineous Pakistani family segregating an autosomal recessive form of a novel type of ectodermal dysplasia. The affected members present with sparse and woolly hair, severe nail dystrophy and reticulate skin pigmentation. After exclusion of known gene loci related with other skin disorders, genome-wide linkage analysis was performed using Illumina HumanOmniExpress beadchip SNP arrays. We linked this form of ED to human chromosome 18p11.32-p11.31 flanked by the SNPs rs9284390 (0.113Mb) and rs4797100 (3.14 Mb). A maximum two-point LOD score of 3.3 was obtained with several markers along the disease interval. The linkage interval of 3.03 Mb encompassed seventeen functional genes. However, sequence analysis of all these genes did not discover any potentially disease causing-variants. The identification of this novel locus provides additional information regarding the mapping of a rare form of ED. Further research, such as the use of whole-genome sequencing, would be expected to reveal any pathogenic mutation within the disease locus.     

Identifying simultaneous matrix metalloproteinases/soluble epoxide hydrolase inhibitors

Molecular and Cellular Biochemistry - Matrix metalloproteinase (MMP) and soluble epoxide hydrolase (sEH) have completely unrelated biological functions; however, their dysregulation produce similar...     

Salivary Proteomic Analysis of Betel Nut (Areca catechu) Consumers by Mass Spectrometry Revealed Primary Indication of Oral Malignancies

Areca nut is the fourth most widely used addictive and psychoactive substance consumed by approximately 10% of the world’s population. The use of areca nut is estimated to account for up to 50% of oral cancer in the low-income, and middle-income countries. In the present study, the effect of betel nut chewing on saliva proteomics was investigated by using mass spectrometry. Matrix-assisted laser desorption ionization mass spectrometry was used to generate a profile of the peptides in betel nut consumers and control group. We found 13 peptide peaks which were significantly altered (p?<?0.05) in the betel nut addicts when compared with the control group. These significant peptides signals were corresponding to protein cystatin SN (CST1), cystatin S (CST4), alpha 2 macroglobulin (A2M), complement C3 (C3), apolipoprotein E (APOE), serum albumin (ALB), matrix metalloproteinase-9 (MMP-9), deleted in malignant brain tumor protein 1 (DMBT1), zinc-alpha-2-glycoprotein (ZAG), and protein S100A8. The correlation analysis of significant peptides intensities with the history of betel nut chewing was also performed. The peptides of CST1 and CST4 showed negative correlation, whereas the peptides of the MMP-9, DMBT1, APOE, and C3 showed positive correlation with significant differences. STRING analysis of these proteins revealed that most of these proteins are interacting with each other. The present study identifies a number of proteins in a significantly different abundance in the betel nut consumers group. Some of these proteins are the reported biomarkers of several oral malignancies, which implies that the usage of betel nut could lead to inflammation, and development of oral cancer.

     

Abundance of Lactobacillus plantarum Strains with Beneficial Attributes in Blackberries (Rubus sp.), Fresh Figs (Ficus carica), and Prickly Pears (Opuntia ficus-indica) Grown and Harvested in Algeria

This first study performed on traditional fruits consumed in North Africa reveals their richness in microorganisms with beneficial attributes like cholesterol lowering capabilities. Blackberries (Rubus sp.), fresh figs (Ficus carica), and prickly pears (Opuntia ficus-indica) are fruits largely and traditionally consumed in Kabylia, a beautiful northern Algerian region. Here, 85 lactic acid bacteria (LAB)-isolates were isolated and identified by MALDI-TOF mass spectrometry. The identified species belong to Lactobacillus and Leuconostoc genera. These 85 LAB-isolates were then assessed for their capabilities to grow under conditions mimicking the gastrointestinal tract, and the resulting data were statistically treated with principal component analysis (PCA). After which, only 26 LAB-isolates were selected and characterized for their genetic relatedness using random amplified polymorphic DNA (RAPD) method. Following the genetic relatedness assessment, only 10 LAB-strains, among which nine Lactobacillus plantarum and one Lactobacillus paracasei were studied for their pathoproperties and some probiotic features. Interestingly, all of these 10 LAB-strains were devoid of adverse effects, but capable to adhere to human epithelial colorectal adenocarcinoma Caco-2 cells. Of note, these 10 LAB-strains exhibited an important in vitro hypocholesteromia effect, in strain-dependent manner. Moreover, the Lactobacillus strains exhibited a high bile salt hydrolase (BSH) activity which was correlated with expression of bsh2, bsh3 and bsh4 genes.

     

The role of mitochondrial membrane potential in ischemic heart failure

The molecular events occurring during myocardial infarction and cardioprotection are described with an emphasis on the changes of the mitochondrial membrane potential (ΔΨ_m). The low ΔΨ_m values of the normal beating heart (100–140 mV) are explained by the allosteric ATP-inhibition of cytochrome c oxidase (CcO) through feedback inhibition by ATP at high [ATP]/[ADP] ratios. During ischemia the mechanism is reversibly switched off by signaling through reactive oxygen species (ROS). At reperfusion high ΔΨ_m values cause a burst of ROS production leading to apoptosis and/or necrosis. Ischemic preconditioning is suggested to cause additional phosphorylation of CcO, protecting the enzyme from immediate dephosphorylation via ROS signaling.     

Synthesis of alginate‐silica hybrid hydrogel for biocatalytic conversion by β‐glucosidase in microreactor

The organic–inorganic hybrid materials have been used in different fields to immobilize biomolecules since they offer many advantages. The aim of this study was to optimize and characterize the alginate‐silica hybrid hydrogel as a stable and injectable form for microfluidic systems using internal gelation method and increase the stability and activity of immobilized enzyme for biocatalytic conversions as well. Characterization was carried out by scanning electron microscopy, energy dispersive spectroscopy/mapping, Brunauer–Emmett–Teller, Barrett–Joyner–Halenda, and Fourier‐transform infrared spectroscopy analyses, and the shrinkages of monoliths were evaluated. Subsequent to optimizing the enzyme concentration (40 μg), hydrolytic conversion of 4‐nitrophenyl β‐d ‐glucopyranoside (pNPG) was performed to understand the behavior of the bioconversion in the microfluidic system. The yield was 94% which reached the equilibrium at 24 h indicating that the alginate‐silica gel derived microsystem overcome some drawbacks of monolithic systems. Additionally, bioconversion of Ruscus aculeatus saponins was carried out at the same setup in order to obtain aglycon part, which has pharmaceutical significance. Although pure aglycon could not be achieved, an intermediate compound was obtained based on the HPLC analysis. The developed formulation can be utilized for various life science applications.     

Dynamics of metabolism and regulation of epigenetics during cardiomyocytes maturation

Maturation is the last step of heart growth that prepares the organ over the lifetime of the mammal for powerful, effective, and sustained pumping. Structural, gene expression, physiological, and functional specialties of cardiomyocytes describe this mechanism as the heart transits from fetus to adult phases. The main cornerstones of maturation of cardiomyocytes are reviewed and primary regulatory mechanisms are summarized to facilitate and organize these cellular activities. During embryonic development, cardiomyocytes proliferate rigorously but leave the cell cycle permanently immediately after the parturition of the child and experience terminal differentiation. The activation of a host of genes specific for the mature heart is correlated with the exit from the cell cycle. Even when exposed to mitogenic stimuli, the bulk of mature cardiomyocytes do not re-join the cell cycle. The reason for this permanent exit from the cell cycle is shown to be linked with stable switching off of the genes of the cell cycle directly involved in the G2/M transition phase and cytokinesis development. Researchers also trying to explain the molecular mechanism involved in stable inhibition of the gene and described structural changes (epigenetic and chromatin) in this mechanism. Substantial developments in the future with advances in the scientific platforms used for cardiomyocyte maturation research will broaden our understanding of this mechanism and result in better maturation of cardiomyocyte-derived pluripotent stem cells and effective treatment approaches for cardiovascular diseases.     

Synthesis, characterization, cytotoxic activity and DNA binding properties of the novel dinuclear cobalt(III) complex with the condensation product of 2-acetylpyridine and malonic acid dihydrazide

A novel dinuclear cobalt(III) complex with the condensation product of 2-acetylpyridine and malonic acid dihydrazide, N′,N′²-bis[(1E)-1-(2-pyridyl)ethylidene]propanedihydrazide was synthesized and characterized by elemental analysis, spectroscopy (NMR and infrared), and X-ray crystal analysis. The complex showed a moderate activity towards Artemia salina. The highest cytotoxic potential of the complex was observed on the epithelial breast cancer (MDA-361) cell line. The investigated complex induced apoptosis, the early apoptotic cells comprising 28.18%, compared to 5.64% of control cells in the same phase. The interaction of the complex with calf thymus DNA (CT-DNA) was monitored by blue shift and hyperchromism in the UV-vis spectra. The observed intrinsic binding constant (K_b = 4.2 × 10⁵ M^− 1) together with structural analysis of the complex indicate the groove binding.     

The acute toxicity of fenitrothion on narrow-clawed crayfish (Astacus leptodactylus Eschscholtz, 1823) in association with biomarkers of lipid peroxidation

The aim of this research was to evaluate the acute toxicity of fenitrothion to the crayfish (Astacus leptodactylus Eschscholtz, 1823), which is chosen as an alternative aquatic organism to fish by using the static test system and evaluate the basic lipid peroxidation parameters for the first 24 h. Crayfish of 27.3 ± 0.56 g mean weight and 10.0 ± 0.72 cm mean length were selected for the bioassay experiments. The experiments were repeated three times in 20 liters of tap water. The temperature of water was 21 ± 1°C. The data obtained were statistically evaluated by using a computer program developed by the United States Environmental Protection Agency, based on Finney's probit analysis method and the 96-h LC(50) value for crayfish was calculated to be 15.75 μg/L. The 95% lower and upper confidence limits for the LC(50) were 9.45 to 25.01 μg/L. In addition to the acute toxicity bioassay experiments, 24-h oxidative stress parameters such as malondialdehyde (MDA) levels and ferrous oxidation assay (FOX HP [hydrogen peroxide] equivalents) were also determined. Only MDA levels of hepatopancreas decreased at 5, 10, and 20 μg/L of fenitrothion doses. We can conclude that fenitrothion is highly toxic to crayfish, a nontarget organism in the ecosystem, and the lipid peroxidation indicators can be easily used for monitoring environmental effects.