Whole exome sequencing,in silico and functional studies confirm the association of the GJB2 mutation p.Cys169Tyr with deafness and suggest a role for the TMEM59 gene in the hearing process

The development of next generation sequencing techniques has facilitated the detection of mutations at an unprecedented rate. These efficient tools have been particularly beneficial for extremely heterogeneous disorders such as autosomal recessive non-syndromic hearing loss, the most common form of genetic deafness. GJB2 mutations are the most common cause of hereditary hearing loss. Amongst them the NM_004004.5: c.506G > A (p.Cys169Tyr) mutation has been associated with varying severity of hearing loss with unclear segregation patterns. In this study, we report a large consanguineous Emirati family with severe to profound hearing loss fully segregating the GJB2 missense mutation p.Cys169Tyr. Whole exome sequencing (WES), in silico, splicing and expression analyses ruled out the implication of any other variants and confirmed the implication of the p.Cys169Tyr mutation in this deafness family. We also show preliminary murine expression analysis that suggests a link between the TMEM59 gene and the hearing process. The present study improves our understanding of the molecular pathogenesis of hearing loss. It also emphasizes the significance of combining next generation sequencing approaches and segregation analyses especially in the diagnosis of disorders characterized by complex genetic heterogeneity.     

Global dynamics of hematopoietic stem cells and differentiated cells in a chronic myeloid leukemia model

We consider a mathematical model describing evolution of normal and leukemic hematopoietic stem cells (HSC) and differentiated cells in bone marrow. We focus on chronic myeloid leukemia (CML), a cancer of blood cells resulting from a malignant transformation of hematopoietic stem cells. The dynamics are given by a system of ordinary differential equations for normal and leukemic cells. Homeostasis regulates the proliferation of normal HSC and leads the dynamics to an equilibrium. This mechanism is partially efficient for leukemic cells. We define homeostasis by a functional of either hematopoietic stem cells, differentiated cells or both cell lines. We determine the number of hematopoietic stem cells and differentiated cells at equilibrium. Conditions for regeneration of hematopoiesis and persistence of CML are obtained from the global asymptotic stability of equilibrium states. We prove that normal and leukemic cells can not coexist for a long time. Numerical simulations illustrate our analytical results. The study may be helpful in understanding the dynamics of normal and leukemic hematopoietic cells.     

Molecular phylogeny of <Emphasis Type="Italic">Pisolithus</Emphasis> species from Moroccan forest woodlands

The phylogenetic relationships among 200 Pisolithus basidiomata collected from pine, oak, and eucalypt forests and rockrose scrubs in Morocco were investigated. Using PCR-RFLP analysis of the internal transcribed spacer (ITS) of ribosomal DNA, this collection could be divided into 5 groups, by using PCR-RFLP analysis of the internal transcribed spacer (ITS) of ribosomal DNA. The ITS of a representative basidioma of each group was sequenced, and a phylogenetic analysis was performed. The dendrogram suggests that at least five Pisolithus species are present in Morocco. Pisolithus basidiomata collected in the Pinus and Quercus forests correspond to Pisolithus arrhizus and P. species 4 as previously described by Martin and colleagues in 2002. Those collected from the eucalyptus forests, under E. gomphocephala and E. camaldulensis, correspond to P. albus and P. microcarpus. Basidiomata collected from the rockrose scrubs, under Cistus crispus, C. monspeliensis or C. salviifolius, are all identified as Pisolithus species 3. Phylogenetic analyses showed that our different Pisolithus grouped well with Pisolithus specimens from other geographical origins.     

Antibacterial,Cytotoxic and Genotoxic Assessment of New Sulfonamide Derivatives

In the last few years, the interest in sulfonamides has expanded owing to their broad spectrum of biological activities. Their flexible structure turns them into amazing candidates to replace old drugs or develop modern multi-target agents. In this study, a series of new sulfonamides ( sul1-5 ) was evaluated, in vitro, for the antibacterial, cytotoxic and genotoxic effects. The antibacterial activity was investigated against 12 clinical and 4 reference strains. Cytotoxic activity was carried out by the brine shrimp bioassay and the genotoxicity was assessed in the Ames test. An interesting antibacterial activity was showed especially against Gram negative strains. The inhibition zones varied between 15 and 30 mm, and the Minimum Inhibitory Concentrations (MIC's) values between 0.5 and 256 μg/ml. No antibacterial activity was shown with S. aureus isolates. Only Sul1 and Sul4 were active against P. aeruginosa. Compounds Sul1 and Sul2 showed a significant cytotoxicity with LC₅₀ equal to 18.29 and 18 μg/ml respectively, and a genotoxic effect against TA100 and TA1535 Salmonella strains. Only compounds Sul3 , Sul4 and Sul5 with an interesting antibacterial activity, no cytotoxicity and no genotoxic effects, could be exploited against resistant pathogens as new drugs.     

Enzymatic androgen assay: some properties of human placental microsomal aromatase

The androgen content of biological fluids can be determined after their conversion into estrogens using human placental microsomal aromatase (HPMA). The purpose of this paper is to report some physico-chemical properties of HPMA. Using an accurate, specific and sensitive assay for HPMA, Km values for dehydroepiandrosterone (DHEA), androstenedione and testosterone were found to increase with increasing amount of the detergent (Triton X-100) added. Analysis at substrate concentrations 5-10 times above and below the Km values did not indicate any anomalous kinetic behaviour. Triton X-100, used for enzyme solubilization, significantly decreased the rate of aromatization of the three substrates by increasing their Km values. This effect was more important for testosterone than for androstenedione or DHEA. Using a new protocol for the determination of aromatase activity, kinetic properties of aromatase before and after solubilization are described.     

Chemical Composition and in Vitro Antioxidant,Anti-Alzheimer,Anti-Diabetic,Anti-Tyrosinase,and Antimicrobial Properties of Essential Oils and Extracts Derived from Various Parts of the Algerian Calendula Suffruticosa Vahlsubsp. boissieri Lanza

Calendula suffruticosa Vahl subsp. boissieri Lanza is well-known for its medicinal properties in northeastern Algeria. As far as literature has been able to prove, no study has attempted to make a phytochemical or biological activity evaluation (antioxidants, enzyme inhibitors and antimicrobial potential). This work intends to evaluate, for the first time, the chemical constituents and study the previously mentioned biological activities of C. suffruticosa boissieri essential oil and different sections (flowers, leaves, roots) as well as the effect of changing the solvent (ethanol 70 %) and (methanol 70 %) on these activities. The essential oil of aerial parts of this plant was investigated using GC/MS, and 45 compounds were discovered, accounting for 98.01 % of the essential oil, including 23 monoterpenes, 6 sesquiterpenes, 12 diterpenes, 1 coumarin, 3 alkanes, methyl-cyclohexane (23.73 %), limonene (25.02 %), and o-cymene (13.20 %). Five methods were used to study the antioxidant activity (ABTS, DPPH, CUPRAC, reducing power, and β-carotene bleaching assay), where the results were impressive, especially for the essential oil. In addition, the hydroethanolic solvent (70 %) was found to be the most effective solvent for extraction in general compared to the hydromethanolic solvent (70 %). The extracts and essential oils of C. suffruticosa boissieri also showed a strong inhibiting ability against cholinesterase, tyrosinase, anti-α-amylase, α-glucosidase, and antimicrobials, a very valuable antioxidant, which is a real discovery. Based on these results, it can be said that this plant has important biological activities, so it can be used in the phytotherapy, food, or pharmaceutical sectors.