Plasma FA composition in familial LCAT deficiency indicates SOAT2-derived cholesteryl ester formation in humans

Mutations in the LCAT gene cause familial LCAT deficiency (Online Mendelian Inheritance in Man ID: #245900), a very rare metabolic disorder. LCAT is the only enzyme able to esterify cholesterol in plasma, whereas sterol O-acyltransferases 1 and 2 are the enzymes esterifying cellular cholesterol in cells. Despite the complete lack of LCAT activity, patients with familial LCAT deficiency exhibit circulating cholesteryl esters (CEs) in apoB-containing lipoproteins. To analyze the origin of these CEs, we investigated 24 carriers of LCAT deficiency in this observational study. We found that CE plasma levels were significantly reduced and highly variable among carriers of two mutant LCAT alleles (22.5 [4.0–37.8] mg/dl) and slightly reduced in heterozygotes (218 [153–234] mg/dl). FA distribution in CE (CEFA) was evaluated in whole plasma and VLDL in a subgroup of the enrolled subjects. We found enrichment of C16:0, C18:0, and C18:1 species and a depletion in C18:2 and C20:4 species in the plasma of carriers of two mutant LCAT alleles. No changes were observed in heterozygotes. Furthermore, plasma triglyceride-FA distribution was remarkably similar between carriers of LCAT deficiency and controls. CEFA distribution in VLDL essentially recapitulated that of plasma, being mainly enriched in C16:0 and C18:1, while depleted in C18:2 and C20:4. Finally, after fat loading, chylomicrons of carriers of two mutant LCAT alleles showed CEs containing mainly saturated FAs. This study of CEFA composition in a large cohort of carriers of LCAT deficiency shows that in the absence of LCAT-derived CEs, CEs present in apoB-containing lipoproteins are derived from hepatic and intestinal sterol O-acyltransferase 2.     

Stable Associations Masked by Temporal Variability in the Marine Copepod Microbiome

Copepod-bacteria interactions include permanent and transient epi- and endobiotic associations that may play roles in copepod health, transfer of elements in the food web, and biogeochemical cycling. Microbiomes of three temperate copepod species (Acartia longiremis, Centropages hamatus, and Calanus finmarchicus) from the Gulf of Maine were investigated during the early summer season using high throughput amplicon sequencing. The most prominent stable component of the microbiome included several taxa within Gammaproteobacteria, with Pseudoalteromonas spp. especially abundant across copepod species. These Gammaproteobacteria appear to be promoted by the copepod association, likely benefitting from nutrient enriched microenvironments on copepods, and forming a more important part of the copepod-associated community than Vibrio spp. during the cold-water season in this temperate system. Taxon-specific associations included an elevated relative abundance of Piscirickettsiaceae and Colwelliaceae on Calanus, and Marinomonas sp. in Centropages. The communities in full and voided gut copepods had distinct characteristics, thus the presence of a food-associated microbiome was evident, including higher abundance of Rhodobacteraceae and chloroplast sequences in the transient communities. The observed variability was partially explained by collection date that may be linked to factors such as variable time since molting, gender differences, and changes in food availability and type over the study period. While some taxon-specific and stable associations were identified, temporal changes in environmental conditions, including food type, appear to be key in controlling the composition of bacterial communities associated with copepods in this temperate coastal system during the early summer.     

Phospholipid composition of plasma and erythrocytes in the neonate

The total phospholipids and their various classes in erythrocytes and blood plasma were determined quantitatively by means of two-dimensional thin-layer chromatography. The total amount of phospholipids in neonate plasma was approximately half of that found in adult plasma, however, the amount of phospholipids in erythrocytes of the neonate was significantly higher. The differences were observed in some classes of phospholipids in the plasma and erythrocytes of neonates as well as adult human beings.     

Genetic determinants of glutamine synthetase inDrosophila melanogaster: A gene for glutamine synthetase I resides in the 21B3-6 region

Recombinational and deletion mapping of electrophoretic variants of the glutamine synthetase I isozyme (GSI) in Drosophila melanogaster locates the gene in the 21B region on the second chromosome. We have conducted a genetic analysis of the region extending cytologically from 21A to 21B4-6. Recessive lethal mutations were generated by ethyl methanesulfonate (EMS) and ethyl nitrosourea (ENU) mutagenesis and by hybrid dysgenesis (HD). These lethals fall into seven functional groups, which were partially ordered by complementation with cytologically defined deficiencies of this region generated by hybrid dysgenesis. Two of the EMS- and two of the ENU-induced lethals fulfill biochemical criteria expected for null alleles of the GSI gene.     

Metabolic and energetic aspects of the growth of Clostridium butyricum on glucose in chemostat culture

The influence of a number of environmental parameters on the fermentation of glucose, and on the energetics of growth of Clostridium butyricum in chemostat culture, have been studied. With cultures that were continuously sparged with nitrogen gas, glucose was fermented primarily to acetate and butyrate with a fixed stoichiometry. Thus, irrespective of the growth rate, input glucose concentration specific nutrient limitation and, within limits, the culture pH value, the acetate/butyrate molar ratio in the culture extracellular fluids was uniformly 0.74±0.07. Thus, the efficiency with which ATP was generated from glucose catabolism also was constant at 3.27±0.02 mol ATP/mol glucose fermented. However, the rate of glucose fermentation at a fixed growth rate, and hence the rate of ATP generation, varied markedly under some conditions leading to changes in the Y _glucose and Y _ATP values. In general, glucose-sufficient cultures expressed lower yield values than a correponding glucose-limited culture, and this was particularly marked with a potassium-limited culture. However, with a glucose-limited culture increasing the input glucose concentration above 40g glucose·l^-1 also led to a significant decrease in the yield values that could be partially reversed by increasing the sparging rate of the nitrogen gas. Finally glucose-limited cultures immediately expressed an increased rate of glucose fermentation when relieved of their growth limitation. Since the rate of cell synthesis did not increase instantaneously, again the yield values with respect to glucose consumed and ATP generated transiently decreased.Two conditions were found to effect a change in the fermentation pattern with a lowering of the acetate/butyrate molar ratio. First, a significant decrease in this ratio was observed when a glucose-limited culture was not sparged with nitrogen gas; and second, a substantial (and progressive) decrease was observed to follow addition of increasing amounts of mannitol to a glucose-limited culture. In both cases, however, there was no apparent change in the Y _ATP value.These results are discussed with respect to two imponder-ables, namely the mechanism(s) by which C. butyricum might partially or totally dissociate catabolism from anabolism, and how it might dispose of the excess reductant [as NAD(P)H] that attends both the formation of acetate from glucose and the fermentation of mannitol. With regards to the latter, evidence is presented that supports the conclusion that the ferredoxin-mediated oxidation of NAD(P)H, generating H₂, is neither coupled to, nor driven by, an energy-yielding reaction.     

The proα2 (V) collagen gene (COL5A2) maps to 2q14→2q32, syntenic to the proα1 (III) collagen locus (COL3A1)

Summary A recombinant probe specific for the pro2 chain of human Type V collagen has been used for the localization of the corresponding gene (COL5A2) to chromosome 2. Regional mapping by in situ hybridization and analysis of DNA from humanxrodent cell lines indicated that COL5A2 is confined within the segment 2q142q32, thus syntenic to the pro1 (III) collagen gene (COL3A1).