RESUMEN
To improve estimates of the long-term response of the marine carbon system to climate change a better understanding of the seasonal and interannual variability is needed. We use high-frequency multi-year data at three locations identified as climate change hotspots: two sites located close to South Pacific boundary currents and one in the Subantarctic Zone (SAZ). We investigate and identify the main drivers involved in the seasonal an interannual (2012-2016) variability of the carbon system. The seasonal variability at boundary current sites is temporally different and highly controlled by sea surface temperature. Advection processes also play a significant role on the monthly changes of the carbon system at the western boundary current site. The interannual variability at these sites most likely responds to long-term variability in oceanic circulation ultimately related to climatic indices such as the El Niño Southern Oscillation, the Pacific Decadal Oscillation and the Southern Annular Mode (SAM). In the SAZ, advection and entrainment processes drive most of the seasonality, augmented by the action of biological processes in spring. Given the relevance of advection and entrainment processes at SAZ, the interannual variability is most probably modulated by changes in the regional winds linked to the variability of the SAM.
RESUMEN
BACKGROUND: To examine the contribution of mutations within the Norrie disease (NDP) gene to the clinically similar retinal diseases Norrie disease, X-linked familial exudative vitreoretinopathy (FEVR), Coat's disease and retinopathy of prematurity (ROP). METHODS: A dataset comprising 13 Norrie-FEVR, one Coat's disease, 31 ROP patients and 90 ex-premature babies of <32 weeks' gestation underwent an ophthalmologic examination and were screened for mutations within the NDP gene by direct DNA sequencing, denaturing high-performance liquid chromatography or gel electrophoresis. Controls were only screened using denaturing high-performance liquid chromatography and gel electrophoresis. Confirmation of mutations identified was obtained by DNA sequencing. RESULTS: Evidence for two novel mutations in the NDP gene was presented: Leu103Val in one FEVR patient and His43Arg in monozygotic twin Norrie disease patients. Furthermore, a previously described 14-bp deletion located in the 5' unstranslated region of the NDP gene was detected in three cases of regressed ROP. A second heterozygotic 14-bp deletion was detected in an unaffected ex-premature girl. Only two of the 13 Norrie-FEVR index cases had the full features of Norrie disease with deafness and mental retardation. CONCLUSION: Two novel mutations within the coding region of the NDP gene were found, one associated with a severe disease phenotypes of Norrie disease and the other with FEVR. A deletion within the non-coding region was associated with only mild-regressed ROP, despite the presence of low birthweight, prematurity and exposure to oxygen. In full-term children with retinal detachment only 15% appear to have the full features of Norrie disease and this is important for counselling parents on the possible long-term outcome.
Asunto(s)
Proteínas del Ojo/genética , Mutación Missense , Proteínas del Tejido Nervioso/genética , Enfermedades de la Retina/genética , Retinopatía de la Prematuridad/genética , Vitreorretinopatía Proliferativa/genética , Regiones no Traducidas 5'/genética , Adolescente , Adulto , Niño , Cromatografía Líquida de Alta Presión , Sordera/genética , Femenino , Edad Gestacional , Humanos , Recién Nacido , Discapacidad Intelectual/genética , Masculino , Persona de Mediana Edad , Análisis de Secuencia de ADNRESUMEN
Mutations in the human homolog of the patched gene are associated with the developmental (and cancer predisposition) condition Nevoid Basal Cell Carcinoma Syndrome (NBCCS), as well as with sporadic basal cell carcinomas. Most mutations that have been identified in the germline of NBCCS patients are truncating or frameshift mutations, with amino acid substitutions rarely found. We show that a missense mutation in the sterol-sensing domain G509V acts as a dominant negative when assayed in vivo in Drosophila. Ectopic expression of a Drosophila patched transgene, carrying the analogous mutation to G509V, causes ectopic activation of Hedgehog target genes and ectopic membrane stabilisation of Smoothened. The G509V transgene behaves in a manner similar, except in its subcellular distribution, to a C-terminal truncation that has been characterised previously as a dominant-negative protein. G509V exhibits vesicular localisation identical to the wild-type protein, but the C-terminal truncated Patched molecule is localised predominantly to the plasma membrane. This finding suggests that dominant-negative function can be conferred by interruption of different aspects of Patched protein behaviour. Another mutation at the same residue, G509R, did not exhibit dominant-negative activity, suggesting that simple removal of the glycine at 509 is not sufficient to impart dominant-negative function.