Point Mutations in the Monocarboxylate Transporter SLC16A12 Lead to Juvenile and Age-Related Cataract

Purpose: Previously we reported on a premature termination mutation in SLC16A12 that leads to dominant juvenile cataract and renal glucosuria. To assess the mutation rate and genotype-phenotype correlations of SLC16A12 in juvenile or age-related forms of cataract, we performed a mutation screen in cataract patients. Methods: Clinical data of approximately 660 patients were collected, genomic DNA was isolated and analyzed. Exons 3 to 8 including flanking intron sequences of SLC16A12 were PCR amplified and DNA sequence was determined. Selected mutations were tested by cell culture assays, in silico analysis and RT-PCR. Results: We found sequence alterations at a rate of approximately 1/75 patients. None of them was found in 360 control alleles. Alterations affect splice site and regulatory region but most mutations caused an amino acid substitution. The majority of the coding region mutations maps to trans-membrane domains. One mutation located to the 5'UTR. It affects translational efficiency of SLC16A12. In addition, we identified a cataract-predisposing SNP in the non-coding region that causes allele-specific splicing of the 5'UTR region. Conclusions: Altered translational efficiency of the solute carrier SLC16A12 and its allele-specific splicing strongly support a model of challenged homeostasis to cause various forms of cataract. In addition, the pathogenic property of the here reported sequence alterations is supported by the lack of known sequence variations within the coding region of SLC16A12. Due to the relatively high mutation rate, we suggest to include SLC16A12 in diagnostic cataract screening. Generally, our data recommend the assessment of regulatory sequences for diagnostic purposes.

City of Strawberry Point, June 30, 2003

City Audit Report

[Flot d'automobiles et foule importante, rond-point des Champs-Elysées, pylônes dédiés aux batailles de l'Ourcq et de la Marne, allégorie de la victoire, autour du 13 juillet 1919] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54836

[Passants au pied des pylônes dédiés à la bataille de l'Yser, allégorie de la victoire, rond-point des Champs-Elysées, près du Grand Palais, autour du 13 juillet 1919] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54839

[Foule importante au rond-point des Champs-Elysées, pylônes dédiés aux batailles de l'Ourcq, de la Marne et de l'Argonne, allégorie de la victoire, autels des cités martyres Arras et Soissons, autour du 13 juillet 1919] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54842

[Foule au rond-point des Champs-Elysées, au pied des pylônes dédiés à la bataille de l'Ourcq, allégorie de la victoire, et autel de la cité martyre Arras, autour du 13 juillet 1919] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54841

[Foule importante au rond-point des Champs-Elysées, pylônes dédiés aux batailles de l'Argonne et de l'Aisne, allégorie de la victoire, pyramide de canons pris à l'ennemi, autel de la cité martyre Verdun, autour du 13 juillet 1919] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54843

Report on Special Investigation of the Central Point Coordination for Calhoun and Pocahontas Counties for the Period July 1, 1998 through May 31, 2004

Report on a Special Investigation of the Central Point Coordination for Calhoun and Pocahontas Counties.

The effect of atmospheric absorption of sunlight on the runaway greenhouse point

The longwave emission of planetary atmospheres that contain a condensable absorbing gas in the infrared (i.e., longwave), which is in equilibrium with its liquid phase at the surface, may exhibit an upper bound. Here we analyze the effect of the atmospheric absorption of sunlight on this radiation limit. We assume that the atmospheric absorption of infrared radiation is independent of wavelength except within the spectral width of the atmospheric window, where it is zero. The temperature profile in radiative equilibrium is obtained analytically as a function of the longwave optical thickness. For illustrative purposes, numerical values for the infrared atmospheric absorption (i.e., greenhouse effect) and the liquid vapor equilibrium curve of the condensable absorbing gas refer to water. Values for the atmospheric absorption of sunlight (i.e., antigreenhouse effect) take a wide range since our aim is to provide a qualitative view of their effects. We find that atmospheres with a transparent region in the infrared spectrum do not present an absolute upper bound on the infrared emission. This result may be also found in atmospheres opaque at all infrared wavelengths if the fraction of absorbed sunlight in the atmosphere increases with the longwave opacity

City of Center Point, Independent Auditor's Reports, Financial Statements and Supplemental Information, Schedule of Findings, June 30, 2003

City Audit Report

Selective neurodegeneration induced in rotation-mediated aggregate cell cultures by a transient switch to stationary culture conditions: a potential model to study ischemia-related pathogenic mechanisms.

Aggregating brain cell cultures at an advanced maturational stage (20-21 days in vitro) were subjected for 1-3 h to anaerobic (hypoxic) and/or stationary (ischemic) conditions. After restoration of the normal culture conditions, cell loss was estimated by measuring the release of lactate dehydrogenase as well as the irreversible decrease of cell type-specific enzyme activities, total protein and DNA content. Ischemia for 2 h induced significant neuronal cell death. Hypoxia combined with ischemia affected both neuronal and glial cells to different degrees (GABAergic neurons>cholinergic neurons>astrocytes). Hypoxic and ischemic conditions greatly stimulated the uptake of 2-deoxy-D-glucose, indicating increased glucose consumption. Furthermore, glucose restriction (5.5 mM instead of 25 mM) dramatically increased the susceptibility of neuronal and glial cells to hypoxic and ischemic conditions. Glucose media concentrations below 2 mM caused selective neuronal cell death in otherwise normal culture conditions. GABAergic neurons showed a particularly high sensitivity to glucose restriction, hypoxia, and ischemia. The pattern of ischemia-induced changes in vitro showed many similarities to in vivo findings, suggesting that aggregating brain cell cultures provide a useful in vitro model to study pathogenic mechanisms related to brain ischemia.

[Foule importante au rond-point des Champs-Elysées, pylônes dédiés aux batailles de Verdun et Grand-Couronné, allégorie de la victoire, autels des cités martyres, autour du 13 juillet 1919] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54855

[Foule importante au rond-point des Champs-Elysées, pylônes dédiés aux batailles d'Alsace et de la Somme, allégorie de la victoire, pyramide de canons pris à l'ennemi, autels des cités martyres, autour du 13 juillet 1919] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54852

[Foule importante au rond-point des Champs-Elysées, pylônes dédiés à la bataille du Grand Couronné, allégorie de la victoire, pyramide de canons pris à l'ennemi, autel de la cité martyre Verdun, autour du 13 juillet 1919] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 54844