ALBERT

Description: Background: Splenic epidermoid cyst is a benign tumor-like lesion affecting the spleen and sometimes occurs in familial form. The causality of such rare diseases remain challenging, however recently, with the emergence of exome re-sequencing, the genetics of many diseases have been unveiled. In the present study, we performed a combinatorial approach of genome-wide parametric linkage and exome analyses for a moderate-sized Japanese family with frequent occurrence of splenic epidermoid cyst to identify the genetic causality of the disease. Methods: Twelve individuals from the family were subject to SNP typing and exome re-sequencing was done for 8 family members and 4 unrelated patients from Kosovo. Linkage was estimated using multi-point parametric linkage analysis assuming a dominant mode of inheritance. All of the candidate variants from exome analysis were confirmed by direct sequencing. Results: The parametric linkage analysis suggested two loci on 1q and 14q with a maximal LOD score of 2.5 . Exome generated variants were prioritized based on; impact on the protein coding sequence, novelty or rareness in public databases, and position within the linkage loci. This approach identified three variants; variants of HMCN1 and CNTN2 on 1q and a variant of DDHD1 on 14q. The variant of HMCN1 (p.R5205H) showed the best co-segregation in the family after validation with Sanger sequencing. Additionally, rare missense variants (p.A4704V, p.T5004I, and p.H5244Q) were detected in three unrelated Kosovo patients. The identified variants of HMCN1 are on conserved domains, particularly the two variants on calcium-binding epidermal growth factor domain. Conclusions: The present study, by combining linkage and exome analyses, identified HMCN1 as a genetic causality of splenic epidermoid cyst. Understanding the biology of the disease is a key step toward developing innovative approaches of intervention.

Description: The CO2 increase in the ocean due to the uptake of anthropogenic CO2 is of major concern, due to potential changes in future ocean CO2 uptake that might be driven in a direction of relative less CO2 uptake in the future then today and the companying lowering of ocean pH. In this study we investigated the variability of CO2 system parameters, focusing particularly on the pH and how it changes with changes in other parameters like: temperature (T), salinity (S), total dissolved inorganic carbon (CT ), and total alkalinity (AT ). For Arabian Sea the data from the United States Joint Global Ocean Flux Study (US{JGOFS) in 1995 were used. For the Red Sea data from the Geochemical Ocean Section Study (GEOSECS) in 1977 and the Mer Rouge (MEROU) cruises in June and October 1982 were used. One of the major outcome of this research is: The seasonal and spatial variations in pH and therefore also for calcium carbonate saturation ( Ar for Aragonite and Ca for Calcite) is controlled by biological and physical processes that in turn is driven by the in uence of monsoonal seasons. In winter season the surface average pH, Ar, and Ca in the Arabian Sea were 8.07 0.01, 3.9 0.1 and 5.9 0.2, respectively. A relatively high biological production, due to the winter cooling and mixing caused by the northeast monsoonal winds increase the pH. During summer season Southwestern monsoonal winds caused upwelling along the coast of Oman, resulting in extremely low pH ( 7.9) values causing lower saturation for aragonite (Ar 2.36) and for calcite (Ca 3.62). Because of the strong change in pH, this area might serve as a natural laboratory for studies of ocean acidi fication.For comparison, in the Red Sea, the surface average pH was 8.1 0.02 during winter with higher values in the north due to lower temperatures and high AT and CT . The Ar and Ca were around 4.12 0.02 and 6.2 0.15, respectively, with highest values in the central part of the basin caused by higher temperatures. Summer surface pH was 8.07 0.03, with higher values in the north and the south due to the temperature. In the central of the Red Sea, pH was low due to the convergence (high temperature). The Ar and Ca were averaged to 4.6 0.3 and 6.95 0.35,respectively, with higher values in the south and north. This is attributed to the high biological productivity in the south and the high temperature in the center of the Red Sea. The vertical distributions of Ar, and Ca showed that the Arabian Sea is under-saturated with respect of aragonite below 600 meters and calcite below 3500 m, whereas the Red Sea is supersaturated throughout the water column. In both seas pH was higher in the surface layers due to the consumption of CO2 by photosynthesis, but decreased rapidly in subsurface waters due to the release of the CO2 by respiration processes. Between about 100 and 1500 m in the Arabian Sea pH is nearly constant because decreasing temperatures and decreased oxidation of the organic matter. The temperature e ect on pH is about 0.015 units per 1 C and anticorrelated both in the Arabian Sea and Red Sea. Thus, the 0.5 C warming reported for the Arabian Sea between 1904 and 1994 (Kumar et al., 2009a) theoretically results in a pH reduction of about 0.007. The temporal coverage of the available data is unfortunately too short to verify this assumption.

Description: Unpublished

Description: Ocean acidification

Description: pH

Description: CO2