Biliary atresia

Biliary atresia (BA) is a rare disease characterised by a biliary obstruction of unknown origin that presents in the neonatal period. It is the most frequent surgical cause of cholestatic jaundice in this age group. BA occurs in approximately 1/18,000 live births in Western Europe. In the world, the reported incidence varies from 5/100,000 to 32/100,000 live births, and is highest in Asia and the Pacific region. Females are affected slightly more often than males. The common histopathological picture is one of inflammatory damage to the intra- and extrahepatic bile ducts with sclerosis and narrowing or even obliteration of the biliary tree. Untreated, this condition leads to cirrhosis and death within the first years of life. BA is not known to be a hereditary condition. No primary medical treatment is relevant for the management of BA. Once BA suspected, surgical intervention (Kasai portoenterostomy) should be performed as soon as possible as operations performed early in life is more likely to be successful. Liver transplantation may be needed later if the Kasai operation fails to restore the biliary flow or if cirrhotic complications occur. At present, approximately 90% of BA patients survive and the majority have normal quality of life

Identification and characterization of DGA2, an acyltransferase of the DGAT1 acyl-CoA:diacylglycerol acyltransferase family in the oleaginous yeast Yarrowia lipolytica. New insights into the storage lipid metabolism of oleaginous yeasts

Triacylglycerols (TAG) and steryl esters (SE) are the principal storage lipids in all eukaryotic cells. In yeasts, these storage lipids accumulate within special organelles known as lipid bodies (LB). In the lipid accumulation-oriented metabolism of the oleaginous yeast Yarrowia lipolytica, storage lipids are mostly found in the form of TAG, and only small amounts of SE accumulate. We report here the identification of a new DAG acyltransferase gene, DGA2, homologous to the ARE genes of Saccharomyces cerevisiae. This gene encodes a member of the type 1 acyl-CoA:diacylglycerol acyltransferase family (DGAT1), which has not previously been identified in yeasts, but is commonly found in mammals and plants. Unlike the Are proteins in S. cerevisiae, Dga2p makes a major contribution to TAG synthesis via an acyl-CoA-dependent mechanism and is not involved in SE synthesis. This enzyme appears to affect the size and morphology of LB, suggesting a direct role of storage lipid proteins in LB formation. We report that the Are1p of Y. lipolytica was essential for sterol esterification, as deletion of the encoding gene (ARE1) completely abolished SE synthesis. Unlike its homologs in yeasts, YlARE1 has no DAG acyltransferase activity. We also reconsider the role and function of all four acyltransferase enzymes involved in the final step of neutral lipid synthesis in this oleaginous yeast

An integrated bioinformatics analysis reveals divergent evolutionary pattern of oil biosynthesis in high- and low-oil plants

Seed oils provide a renewable source of food, biofuel and industrial raw materials that is important for humans. Although many genes and pathways for acyl-lipid metabolism have been identified, little is known about whether there is a specific mechanism for high-oil content in high-oil plants. Based on the distinct differences in seed oil content between four high-oil dicots (20~50%) and three low-oil grasses (<3%), comparative genome, transcriptome and differential expression analyses were used to investigate this mechanism. Among 4,051 dicot-specific soybean genes identified from 252,443 genes in the seven species, 54 genes were shown to directly participate in acyl-lipid metabolism, and 93 genes were found to be associated with acyl-lipid metabolism. Among the 93 dicot-specific genes, 42 and 27 genes, including CBM20-like SBDs and GPT2, participate in carbohydrate degradation and transport, respectively. 40 genes highly up-regulated during seed oil rapid accumulation period are mainly involved in initial fatty acid synthesis, triacylglyceride assembly and oil-body formation, for example, ACCase, PP, DGAT1, PDAT1, OLEs and STEROs, which were also found to be differentially expressed between high- and low-oil soybean accessions. Phylogenetic analysis revealed distinct differences of oleosin in patterns of gene duplication and loss between high-oil dicots and low-oil grasses. In addition, seed-specific GmGRF5, ABI5 and GmTZF4 were predicted to be candidate regulators in seed oil accumulation. This study facilitates future research on lipid biosynthesis and potential genetic improvement of seed oil content

Ion homeostasis in the Chloroplast

peer reviewedThe chloroplast is an organelle of high demand for macro- and micro-nutrient ions, which are required for the maintenance of the photosynthetic process. To avoid deficiency while preventing excess, homeostasis mechanisms must be tightly regulated. Here, we describe the needs for nutrient ions in the chloroplast and briefly highlight their functions in the chloroplastidial metabolism. We further discuss the impact of nutrient deficiency on chloroplasts and the acclimation mechanisms that evolved to preserve the photosynthetic apparatus. We finally present what is known about import and export mechanisms for these ions. Whenever possible, a comparison between cyanobacteria, algae and plants is provided to add an evolutionary perspective to the description of ion homeostasis mechanisms in photosynthesis

Insights into fluid transport mechanisms at White Island from analysis of coupled very long-period (VLP), long-period (LP) and high-frequency (HF) earthquakes

The August 2012 to October 2013 White Island unrest sequence included 5 explosive volcanic eruptions and emplacement of a small dome. These events were linked to an overall increase in SO2 and H2S gas flux and RSAM seismic tremor which began in late 2011. Prior to this unrest, a small swarm of 25 events was observed on 19–21 August 2011 and captured on a temporary seismic array including 14 broadband sensors. Each event comprised coupled pulses having distinct high frequency (HF = 2–5 Hz), long-period (LP = 0.5–1.1 Hz) and very long period (VLP = 0.03–0.125 Hz or 8–30 s) earthquakes. For each coupled event, we compute the source locations, origin times and related uncertainties by application of standard arrival time locations for the HF earthquakes and waveform semblance for the LP and VLP earthquakes. Results suggest that the events are centred beneath the active vent at depths generally < 1.5 km. The HF and LP earthquakes have shallow depths (< 1 km), while VLP have slightly deeper source locations (0.8–1.5 km). Emergent onsets for LP and VLP sources make an analysis of the absolute origin times problematic but waveform matching of VLP to LP and HF components suggests that the main VLP pulse precedes the HF and LP source processes. Waveform inversion for the VLP source is consistent with the rupture of a high angle East-West oriented crack opening either in a purely tensile or shear-tensile manner. The moment of the isotropic component is estimated at 1.2 × 1012 Nm and the corresponding volumetric change is in the range 145–450 m3. Results are interpreted as an upward migration of fluids which first excite the VLP from a high angle crack in the magma carapace followed by the excitation of LP and HF source processes in the overlying hydrothermal systemEuropean Commission - Seventh Framework Programme (FP7)Ministry of Business, Innovation and Employment (MBIE)Earthquake Commission (EQC

Analysis and forward modeling of seismic anisotropy during the ongoing eruption of the Soufriere Hills Volcano, Montserrat, 1996-2007

Volcanic stress field analysis has been lauded as a potentially powerful tool for midterm to long-term eruption forecasting. However, because tectonic processes can also produce localized stress field reorientations, evidence for a direct causal link between observed stress field reorientations and magmatic activity is of critical importance. In this study, we show that local stress field reorientations preceding changes in volcanic activity at the Soufrière Hills Volcano, Montserrat, are observable using two independent measures of crustal stress (local (volcano-tectonic) earthquake fault plane solutions and measurements of shear wave splitting in regional earthquakes). We further demonstrate that the local stress field orientation during a 6 month period preceding the onset of eruptive activity at Soufrière Hills in 1999 is highly localized and spatiotemporally variable and that the spatial pattern of precursory local stress orientations is consistent with numerically modeled patterns of stress resulting from pressurization of a vertical dike. These observations provide compelling evidence for a direct causal link between pressurization of midlevel volcanic conduit systems by ascending magma and precursory local stress field reorientations and demonstrate that seismological analysis can be used to detect subtle local changes in stress that herald eruptive activity