Analysis of CLDN14 gene in deaf Moroccan patients with non-syndromic hearing loss

Mutations in the CLDN14 gene, encoding the tight junction claudin 14 protein has been reported to date in an autosomal recessive form of isolated hearing loss DFNB29. In order to identify the contribution of CLDN14 to inherited deafness in Moroccan population, we performed a genetic analysis of this gene in 80 Moroccan familial cases. Our results show the presence of 7 mutations: 6 being conservative and one leading to a missense mutation (C11T) which was found at heterozygous and homozygous states, with a general frequency of 6.87%. The pathogenicity of the resulting T4M substitution is under discussion.     

Silver Sorption to Myxococcus xanthus Biomass

This paper deals with silver sorption to Myxococcus xanthus biomass. The dry biomass of this microorganism is shown to be a good sorbent for the recovery of silver present at low solution concentrations. Between initial silver concentrations of 2 and 0.05 mM, the percentage of accumulation ranges from 8.12% to 75% of the total silver present in the solution. Transmission electron microscopy study of M. xanthus wet biomass after silver accumulation shows the sorption within the extracellular polysaccharide, on the cell wall, and in the cytoplasm. The presence of silver deposits in the cytoplasm indicates that at least two mechanisms are involved in silver sorption by this bacterium biomass. First, silver was bound to the cell surface and extracellular polysaccharide, and second, a silver intracellular deposition process took place. The higher amount of silver deposits in the extracellular polysaccharide, present abundantly in M. xanthus cells, explains the capacity of this bacterium to bind silver efficiently. The results obtained indicate that the removal of silver by M. xanthus from the diluted solutions could be used in recycling this valuable metal. One interesting observation of this investigation is the crystalline form, possibly as chlorargyrite, in which the silver deposits are found in the M. xanthus cells.     

Competitive Formation of Hydroxycarbonate Green Rust 1 versus Hydroxysulphate Green Rust 2 in Shewanella putrefaciens Cultures

The formation of hydroxysulphate green rust 2, a Fe(II-III) compound commonly found during corrosion processes of iron-based materials in seawater, has not yet been reported in bacterial cultures. Here we used Shewanella putrefaciens, a dissimilatory iron-reducing bacterium to anaerobically catalyze the transformation of a ferric oxyhydroxide, lepidocrocite (γ-FeOOH), into Fe(II) in the presence of various sulphate concentrations. Biotransformation assays of γ-FeOOH were performed with formate as the electron donor under a variety of concentrations. The results showed that the competitive formation of hydroxycarbonate green rust 1 (GR1(CO₃ ^2?)) and hydroxysulphate green rust 2 (GR2(SO₄ ^{2 ?})) depended upon the relative ratio (R) of bicarbonate and sulphate concentrations. When R ≥ 0.17, GR1(CO₃ ^{2 ?}) only was formed whereas when R < 0.17, a mixture of GR2(SO₄ ^{2 ?}) and GR1(CO₃ ^{2 ?}) was obtained. These results demonstrated that the hydroxysulphate GR2 can originate from the microbial reduction of γ-FeOOH and confirmed the preference for carbonate over sulphate during green rust precipitation. The solid phases were characterized by X-ray diffraction, transmission Mössbauer spectroscopy and scanning electron microscopy. Diffuse reflectance infrared Fourier transform spectroscopy confirmed the presence of intercalated carbonate and sulphate in green rust's structure. This study sheds light on the influence of dissimilatory iron-reducing bacteria on microbiologically influenced corrosion.     

Early Gag Immunodominance of the HIV-Specific T-Cell Response during Acute/Early Infection Is Associated with Higher CD8+ T-Cell Antiviral Activity and Correlates with Preservation of the CD4+ T-Cell Compartment

The important role of the CD8⁺ T-cell response on HIV control is well established. Moreover, the acute phase of infection represents a proper scenario to delineate the antiviral cellular functions that best correlate with control. Here, multiple functional aspects (specificity, ex vivo viral inhibitory activity [VIA] and polyfunctionality) of the HIV-specific CD8⁺ T-cell subset arising early after infection, and their association with disease progression markers, were examined. Blood samples from 44 subjects recruited within 6 months from infection (primary HIV infection [PHI] group), 16 chronically infected subjects, 11 elite controllers (EC), and 10 healthy donors were obtained. Results indicated that, although Nef dominated the anti-HIV response during acute/early infection, a higher proportion of early anti-Gag T cells correlated with delayed progression. Polyfunctional HIV-specific CD8⁺ T cells were detected at early time points but did not associate with virus control. Conversely, higher CD4⁺ T-cell set points were observed in PHI subjects with higher HIV-specific CD8⁺ T-cell VIA at baseline. Importantly, VIA levels correlated with the magnitude of the anti-Gag cellular response. The advantage of Gag-specific cells may result from their enhanced ability to mediate lysis of infected cells (evidenced by a higher capacity to degranulate and to mediate VIA) and to simultaneously produce IFN-γ. Finally, Gag immunodominance was associated with elevated plasma levels of interleukin 2 (IL-2) and macrophage inflammatory protein 1β (MIP-1β). All together, this study underscores the importance of CD8⁺ T-cell specificity in the improved control of disease progression, which was related to the capacity of Gag-specific cells to mediate both lytic and nonlytic antiviral mechanisms at early time points postinfection.     

The Snakelike Chain Character of Unstructured RNA

In the absence of base-pairing and tertiary structure, ribonucleic acid (RNA) assumes a random-walk conformation, modulated by the electrostatic self-repulsion of the charged, flexible backbone. This behavior is often modeled as a Kratky-Porod “wormlike chain” (WLC) with a Barrat-Joanny scale-dependent persistence length. In this study we report measurements of the end-to-end extension of poly(U) RNA under 0.1 to 10 pN applied force and observe two distinct elastic-response regimes: a low-force, power-law regime characteristic of a chain of swollen blobs on long length scales and a high-force, salt-valence-dependent regime consistent with ion-stabilized crumpling on short length scales. This short-scale structure is additionally supported by force- and salt-dependent quantification of the RNA ion atmosphere composition, which shows that ions are liberated under stretching; the number of ions liberated increases with increasing bulk salt concentration. Both this result and the observation of two elastic-response regimes directly contradict the WLC model, which predicts a single elastic regime across all forces and, when accounting for scale-dependent persistence length, the opposite trend in ion release with salt concentration. We conclude that RNA is better described as a “snakelike chain,” characterized by smooth bending on long length scales and ion-stabilized crumpling on short length scales. In monovalent salt, these two regimes are separated by a characteristic length that scales with the Debye screening length, highlighting the determining importance of electrostatics in RNA conformation.     

Integrating multiple lines of evidence to better understand the evolutionary divergence of humpback dolphins along their entire distribution range: a new dolphin species in Australian waters?

The conservation of humpback dolphins, distributed in coastal waters of the Indo‐West Pacific and eastern Atlantic Oceans, has been hindered by a lack of understanding about the number of species in the genus (Sousa) and their population structure. To address this issue, we present a combined analysis of genetic and morphologic data collected from beach‐cast, remote‐biopsied and museum specimens from throughout the known Sousa range. We extracted genetic sequence data from 235 samples from extant populations and explored the mitochondrial control region and four nuclear introns through phylogenetic, population‐level and population aggregation frameworks. In addition, 180 cranial specimens from the same geographical regions allowed comparisons of 24 morphological characters through multivariate analyses. The genetic and morphological data showed significant and concordant patterns of geographical segregation, which are typical for the kind of demographic isolation displayed by species units, across the Sousa genus distribution range. Based on our combined genetic and morphological analyses, there is convincing evidence for at least four species within the genus (S. teuszii in the Atlantic off West Africa, S. plumbea in the central and western Indian Ocean, S. chinensis in the eastern Indian and West Pacific Oceans, and a new as‐yet‐unnamed species off northern Australia).     

Effects of cytoprotective antioxidants on lymphocytes from representative mitochondrial neurodegenerative diseases

Two new aza analogues of the neuroprotective agent idebenone have been synthesized and characterized. Their antioxidant activity, and ability to augment ATP levels have been evaluated in several different cell lines having suboptimal mitochondrial function. Both compounds were found to be good ROS scavengers, and to protect the cells from oxidative stress induced by glutathione depletion. The compounds were more effective than idebenone in neurodegenerative disease cells. These novel pyrimidinol derivatives were also shown to augment ATP levels in coenzyme Q₁₀-deficient human lymphocytes. The more lipophilic side chains attached to the pyrimidinol redox core in these compounds resulted in less inhibition of the electron transport chain and improved antioxidant activity.     

Synthesis and evaluation of the antimalarial,anticancer, and caspase 3 activities of tetraoxane dimers

The synthesis of a range of mono spiro and dispiro 1,2,4,5-tetraoxane dimers is described. Selected molecules were examined in in vitro assays to determine their antimalarial and anticancer potential. Our studies reveal that several molecules possess potent nanomolar antimalarial and single digit micromolar antiproliferative IC₅₀s versus colon (HT29-AK and leukemia (HL60) cell lines.