The Accumulation of Tissue Cholesterol and Its Relationship to Bile Acid and Sterol Turnover

Normal and hypophysectomized rats were divided into equal homogeneous groups to determine the effect of cholestyramine, corn oil and cholesterol on the excretion of fecal bile acids and sterols. Bile acid turnover rates, pool sizes, and spectrums were studied and compared

A Rapid Flexible Method for Determining Bile Lipids

A rapid flexible method has been developed for the quantitative determination of bile lipids In gallbladder and hepatic bile and duodenal aspirates. Quantification of bile salts involves separation of bile salt conjugates from one another and other bile lipids by thin layer chromatography. The separated salts are determined using 3-hydroxysteroid dehydrogenase and gas liquid chromatography. Cholesterol is determined in petroleum ether extracts of saponified bile by application of the Lieberman-Burchard reaction. Phospholipid phosphorus is determined in purified bile lipid extracts by oxidation followed by application of Bartlett\u27s modification of the Fiske- SubbaRow method

The Effect of Psyllium Hydrocolloid and Cholestyramine on Hepatic Bile Lipid Composition in Man

The effects of a mucoid - psyllium hydrocolloid - and an anion exchange polymercholestryamine - on the total cholesterol, total phospholipid, total bile salt, cholate, chenodeoxycholate, and deoxycholate concentrations of hepatic bile were determined in six post-cholecystectomy patients. Bile was obtained by drainage through an indwelling T-tube, which was clamped except during bile collection. Psyllium hydrocolloid treatment (12 gm/day) for 6 to 29 days had little or no effect on the cholesterol or phospholipid concentration of hepatic bile, but increased the total bile salt pool by gradually increasing the concentration of deoxycholate. Cholestyramine treatment (12 gm/day) for 8 to 12 days had no significant effect on cholesterol, phospholipid or total bile salt concentrations. There was a significant increase in the tri- to di-hydroxy bile salt ratio due to decreases in chenodeoxycholate and deoxycholate concentrations. The ratio of taurine to glycine conjugates decreased because of reductions in concentrations of taurine conjugates and compensating increases in glycine conjugates. The influence of these changes on bile micelle stability and cholesterol solubility is discussed. It is concluded that the changes effected by psyllium hydrocolloid may result in more stable bile micelles and greater cholesterol solubility. No definite conclusions can be reached with respect to cholestyramine\u27s effects

Designing a resilient and coherent Trans-European conservation Network for Nature and People

To stop biodiversity decline in Europe, new policies have been introduced to protect 30% of EU terrestrial area by 2030 including 10% under strict protection. This network of conserved areas will expand on existing Natura 2000 sites and other conservation areas, as well as blue and green infrastructure. This Trans-European Nature Network (TEN-N) will be the main EU conservation instrument to afford sufficient protection to species and ecosystems of conservation concern. This project has been funded by the EU Horizon Program (~10 M €) to support Member States in their planning and implementation of TEN-N

An experiment of the combined treatment of traditional Lei-huo-jiu therapy with Chinese medicine for the lacrimal gland of Sjögren’s syndrome

This experiment chooses nonobese diabetic (NOD) mouse as the animal model of Sjögren’s syndrome and investigates the morphologic changes, the expression of inflammatory factors and growth factors of this mouse’s lacrimal gland in response to a combined treatment of traditional Lei-huo-jiu therapy alone and in combination with Chinese medicine. The methods were to (1) use a morphological approach to directly observe pathological changes of the lacrimal gland in response to combined treatment and (2) to detect the level of tumor necrosis factor (TNF)-α, interleukin (IL)-1, and nuclear factor kappa B (NF-κB) in lacrimal gland tissue caused by the combined treatments using a immunohistochemical approach. There is a reduction of the mast cell’s degranulation and modulation of the level of cytokines in TNF-α, IL-1, and NF-κB in the combined therapy group. The combined treatment of traditional Lei-huo-jiu therapy with Chinese medicine can improve the pathological changes of the lacrimal gland tissue of the NOD mouse through modulating the level of TNF-α, IL-1, and NF-κB which results in improved tear secretion and function of the lacrimal gland

A Novel Motif Identified in Dependence Receptors

Programmed cell death signaling is a critical feature of development, cellular turnover, oncogenesis, and neurodegeneration, among other processes. Such signaling may be transduced via specific receptors, either following ligand binding—to death receptors—or following the withdrawal of trophic ligands—from dependence receptors. Although dependence receptors display functional similarities, no common structural domains have been identified. Therefore, we employed the Multiple Expectation Maximization for Motif Elicitation and the Motif Alignment and Search Tool software programs to identify a novel transmembrane motif, dubbed dependence-associated receptor transmembrane (DART) motif, that is common to all described dependence receptors. Of 3,465 human transmembrane proteins, 25 (0.7%) display the DART motif. The predicted secondary structure features an alpha helical structure, with an unusually high percentage of valine residues. At least four of the proteins undergo regulated intramembrane proteolysis. To date, we have not identified a function for this putative domain. We speculate that the DART motif may be involved in protein processing, interaction with other proteins or lipids, or homomultimerization

Alzheimer's disease mutations in APP but not γ-secretase modulators affect epsilon-cleavage-dependent AICD production

Pathological amino-acid substitutions in the amyloid precursor protein (APP) and chemical gamma-secretase modulators affect the processing of APP by the gamma-secretase complex and the production of the amyloid-beta peptide A beta 42, the accumulation of which is considered causative of Alzheimer's disease. Here we demonstrate that mutations in the transmembrane domain of APP causing aggressive early-onset familial Alzheimer's disease affect both gamma- and epsilon-cleavage sites, by raising the A beta 42/40 ratio and inhibiting the production of AICD50-99, one of the two physiological APP intracellular domains (ICDs). This is in sharp contrast to gamma- secretase modulators, which shift A beta 42 production towards the shorter A beta 38, but unequivocally spare the epsilon-site and APP- and Notch-ICDs production. Molecular simulations suggest that familial Alzheimer's disease mutations modulate the flexibility of the APP transmembrane domain and the presentation of its gamma- site, modifying at the same time, the solvation of the epsilon-site

Simple rules can guide whether land or ocean based conservation will best benefit marine ecosystems

Coastal marine ecosystems can be managed by actions undertaken both on the land and in the ocean. Quantifying and comparing the costs and benefits of actions in both realms is therefore necessary for efficient management. Here, we quantify the link between terrestrial sediment run-off and a downstream coastal marine ecosystem, and contrast the cost-effectiveness of marine and land-based conservation actions. We use a dynamic land- and sea-scape model to determine whether limited funds should be directed to one of four alternative conservation actions – protection on land, protection in the ocean, restoration on land, or restoration in the ocean – to maximise the extent of light-dependent marine benthic habitats, across decadal time-scales. We apply the model to a case study seagrass meadow in Australia. We find that marine restoration is the most cost-effective action over decadal time-scales in this system, based on a conservative estimate of the rate at which seagrass can expand into new habitat. The optimal decision will vary in different social-ecological contexts, but some basic information can guide optimal investments to counteract land and ocean based stressors: (1) marine restoration should be prioritised if the rates of marine ecosystem decline and expansion are similar and low; (2) marine protection should take precedence if the rate of marine ecosystem decline is high, or if the adjacent catchment is relatively intact and has a low rate of vegetation decline; (3) land-based actions are optimal when the ratio of marine ecosystem expansion to decline is >1.4, with terrestrial restoration typically the most cost effective; and (4) land protection should be prioritised if the catchment is relatively intact, but the rate of vegetation decline is high. These rules-of-thumb illustrate how cost-effective conservation outcomes for connected land-ocean systems can proceed without complex modelling

Advances of the FRIB project

The Facility for Rare Isotope Beams (FRIB) Project has entered the phase of beam commissioning starting from the room-temperature front end and the superconducting linac segment of first 15 cryomodules. With the newly commissioned helium refrigeration system supplying 4.5K liquid helium to the quarter-wave resonators and solenoids, the FRIB accelerator team achieved the sectional key performance parameters as designed ahead of schedule accelerating heavy ion beams above 20MeV/u energy. Thus, FRIB accelerator becomes world's highest-energy heavy ion linear accelerator. We also validated machine protection and personnel protection systems that will be crucial to the next phase of commissioning. FRIB is on track towards a national user facility at the power frontier with a beam power two orders of magnitude higher than operating heavy-ion facilities. This paper summarizes the status of accelerator design, technology development, construction, commissioning as well as path to operations and upgrades