Molecular mechanisms that regulate auditory hair-cell differentiation in the mammalian cochlea

Mechanosensory hair cells of the vertebrate cochlea offer an excellent developmental system to study cell-fate specification, and to gain insight into the many human neurological deficits which result in a hearing loss, by affecting primarily the hair cells. Therefore, there is great interest in studying the molecular mechanisms that regulate their specification and differentiation. Recent studies, based mostly on loss-of-function experiments that target the role of Notch signaling and basic helix-loop-helix genes in inner-ear development have indicated that they can regulate mechanosensory hair cell-fate specification and their initial differentiation.     

Notch signaling regulates the pattern of auditory hair cell differentiation in mammals

The development of the mammalian cochlea is an example of patterning in the peripheral nervous system. Sensory hair cells and supporting cells in the cochlea differentiate via regional and cell fate specification. The Notch signaling components shows both distinct and overlapping expression patterns of Notch1 receptor and its ligands Jagged1 (Jag1) and Jagged2 (Jag2) in the developing auditory epithelium of the rat. On embryonic day 16 (E16), many precursor cells within the K?lliker's organ immunostained for the presence of both Notch1 and Jag1, while the area of hair cell precursors did not express either Notch1 and Jag1. During initial events of hair cell differentiation between E18 and birth, Notch1 and Jag1 expression predominated in supporting cells and Jag2 in nascent hair cells. Early after birth, Jag2 expression decreased in hair cells while the pattern of Notch1 expression now included both supporting cells and hair cells. We show that the normal pattern of hair cell differentiation is disrupted by alteration of Notch signaling. A decrease of either Notch1 or Jag1 expression by antisense oligonucleotides in cultures of the developing sensory epithelium resulted in an increase in the number of hair cells. Our data suggest that the Notch1 signaling pathway is involved in a complex interplay between the consequences of different ligand-Notch1 combinations during cochlear morphogenesis and the phases of hair cell differentiation.     

Vitamin D Supplementation Modulates Blood and Tissue Zinc, Liver Glutathione and Blood Biochemical Parameters in Diabetic Rats on a Zinc-Deficient Diet

Previous studies suggest a protective effect of vitamin D3 on zinc deficiency-induced insulin secretion and on pancreas β-cell function. The aim of this study was to investigate the effect of vitamin D on blood biochemical parameters, tissue zinc and liver glutathione in diabetic rats fed a zinc-deficient diet. For that purpose, Alloxan-induced diabetic rats were divided into four groups. The first group was fed a zinc-sufficient diet while the second group was fed a zinc-deficient diet. The third and fourth groups received zinc-sufficient or zinc-deficient diets plus oral vitamin D3 for 27 days. At the end of the experiment, blood, femur, pancreas, kidney and liver samples were taken from all rats. The serum, femur, pancreas, kidney and liver zinc concentrations, liver glutathione, serum alkaline phosphatase activity, daily body weight gain and food intake were lower in the zinc-deficient rats in comparison with those receiving adequate amounts of zinc. These values were increased in the zinc-deficient group that was supplemented with vitamin D3. The serum total cholesterol, triglycerides, total protein, urea, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and blood glucose values were higher in rats fed a zinc adequate diet, but their concentrations were decreased by vitamin D3 supplementation. The serum total protein levels were not changed by zinc deficiency and vitamin D3 supplementation. These results suggest that vitamin D3 modulates tissue zinc, liver glutathione and blood biochemical values in diabetic rats fed a zinc-deficient diet.     

Spasmolytic and anti-inflammatory effects of constituents from Hertia cheirifolia

A sesquiterpenoid Bakkenolide (1), and two steroids, (3β, 22E)-Stigmasta-5, 22-diène-3-ol (Stigmasterol) (2) and stigmasterol 3β-glucoside (3), isolated from the Hertia cheirifolia (L.) chloroform extract, were evaluated respectively for their spasmolytic and anti-inflammatory activities. We note that these natural products were isolated and purified for the first time from the specie Hertia cheirifolia. Their structures have been established by spectroscopy (1 and 2D NMR experiences) and mass spectrometry. Chloroform-, ethyl acetate- and methanol-extracts were also tested for their spasmolytic and anti-inflammatory activities. Spasmolytic and anti-inflammatory screening were based respectively on the contractile response effects on rat isolated smooth muscles and on the dose-related carrageenan induced paw edema in rats. screening of the crude extracts showed spasmolytic and anti-inflammatory positive results. The antispasmodic effect of Bakkenolide was found in the same range as that of Alverine, a standard musculotropic spasmolytic agent.     

Phenolic constituents of Convolvulus dorycnium L. flowers

The new phenolic metabolites 3-(2-butoxy-3-caffeoyl-1-hydroxycyclobutyl)-3-hydroxypropanoic acid, named as dorycnic acid (1), and 4-O-(4′-carboxymethyl-2′,4′,6′-trihydroxycyclohexyl)-vanillic acid (2), together with scopolin (3), kaempferol 3-rutinoside (4), scopoletin (5), and methyl caffeate (6) were isolated from the flowers of Convolvulus dorycnium L. Their structures were elucidated on the basis of spectroscopic evidence, and comparison with authentic samples. Compounds 1–6 were evaluated for their antioxidative activity in the 1,1-diphenyl-2-picrylhydrazyl assay, where the caffeic acid derivative 1 proved to possess the most potent scavenging activity, with an IC₅₀ value of 31.5 μM.     

Natural Products among Brown Algae: The Case of Cystoseira schiffneri Hamel (Sargassaceae,Phaeophyceae)

A chemotaxonomic study on the marine brown alga Cystoseira schiffneri collected from the Tunisian marine coast allowed us to identify kjellmanianone ( 1 ) and a new isololiolide derivative named schiffnerilolide ( 2 ). The structure elucidation and the assignment of relative configurations of the isolated natural products were based on advanced mass spectrometric and nuclear magnetic resonance techniques. This outcome suggested a close phylogenetic relationship of C. schiffneri with brown algae belonging to genus Sargassum C. Agardh . Molecular characterization using the nuclear small subunit rRNA (SSU rRNA) gene (18S) sequence as genetic marker was made. Pigment analysis showed a significant seasonal change of carotenoids, in particular of fucoxanthin and fucoxanthinol. Also galactolipids, the main constituents of the thylakoid membranes, showed remarkable seasonal changes.     

Tyrosine-1 of RNA Polymerase II CTD Controls Global Termination of Gene Transcription in Mammals

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Muslim Youth in Canadian Schools: Education and the Politics of Religious Identity

This article provides an ethnographic analysis of the schooling experiences of Muslim youth in Canada who are committed to maintaining an Islamic lifestyle despite the pressures of conformity to the dominant culture. Little attention has been paid to how religious identity intersects with other forms of social difference, such as race and gender in the schooling experiences of minoritized youth. Using a case study often Muslim students and parents, this article demonstrates how Muslim students were able to negotiate and maintain their religious identities within secular public schools. The participants' narratives address the challenges of peer pressure, racism, and Islamophobia. Their stories reveal how Muslim students are located at the nexus of social difference based on their race, gender, and religious identity. The discussion further explores the dynamics through which these youth were able to negotiate the continuity of their Islamic identity and practices within schools despite the challenges that they faced. Building upon existing theories of identity maintenance and construction, this research demonstrates how the interplay of the core factors of ambivalence, role performance, and interaction and isolation are implicated in the way Muslim students negotiate the politics of religious identity in their schooling experiences.