Role of extracellular retention of low density lipoproteins in atherosclerosis

The pathogenesis for atherosclerosis is still unclear, and several hypotheses have been articulated to explain the initiating events in atherogenesis. Although these hypotheses are by no means mutually exclusive, there is a growing body of recent evidence that has led to the concept that subendothelial retention of apolipoprotein B100-containing lipoproteins is the initiating event in atherogenesis. Subsequently, a series of biological responses to this retained material leads to specific molecular and cellular processes that promote lesion formation. The present review assesses some of the studies that support this concept.     

Trace mineral and vitamin concentrations in the liver and serum of wild muskoxen from Victoria Island

Selected trace minerals and vitamins were assayed in the liver and serum of 25 wild muskoxen (Ovibos moschatus) from Victoria Island, (Nunavut, Canada) in November, 1995. Mean +/- SE liver concentrations in micromol/kg wet weight were 260+/-16 for copper; 1.04+/-0.06 for selenium; 11.5+/-0.7 for molybdenum and 62.8+/-3.3 for vitamin E. Mean +/- SE serum concentrations in micromol/L were 14.2+/-0.3 for copper; 0.75+/-0.04 for selenium, 1.53+/-0.07 for vitamin A and 5.80+/-0.55 for vitamin E. Comparison of liver and serum concentrations of copper, selenium and vitamin E showed that the concentration in one tissue was a relatively poor indicator of the concentration in the other. The copper-molybdenum interaction often seen in domestic species was not observed. In general, the concentrations of metals and vitamins found in muskoxen were comparable to those in other ungulates although serum vitamin E concentrations were about one-fourth of those expected.     

How consistent are trends in arrival (and departure) dates of migrant birds in the UK?

We examine the first arrival and last departure dates of migrant bird species from, respectively, six and three English area bird reports. Of all 145 bird series, 50% demonstrated significantly earlier arrival in recent years, with the average advance over all species being 0.25 days/year or 12 days earlier over 50 years. Thirty percent of 67 series demonstrated significantly later departure, with the average species delay being 0.16 days/year or eight days later over 50 years. There was greater consistency between species in trends in first arrival than in last departure, with species such as sand martin Riparia riparia significantly earlier at all six sites while, for example, spotted flycatcher Muscicapa striata showed no significant change in arrival at all sites. Significant negative correlations between arrival dates and English temperatures were found for 26% of all series, but temperature effects on departures were less clear. We provide some evidence that trends in arrival dates may be masked by population declines in birds. Since migrant bird populations are in decline generally, this may suggest that the real advance in arrival dates may be greater than that reported here.     

Effect of gastrointestinal peptides on ingestion in old and young mice

Early satiety may play a role in the anorexia of aging. The effects of the peripheral satiety agents cholecystokinin (CCK), bombesin, glucagon, and calcitonin were studied in 8 and 25 month old mice. During normal feeding behavior, the older mice consumed more than their younger counterparts, however, when food deprived, the younger consumed more. All peptides inhibited food intake over the first hour after administration in young and old mice. CCK, bombesin, and calcitonin suppressed feeding in 25 month old mice to a greater extent than in 8 month old mice. However, CCK demonstrated the greatest age-related suppression of food intake. CCK has a potential role to play in the pathogenesis of the anorexia of aging.     

Evaluation of AFLP, a high-resolution DNA fingerprinting method, as a tool for molecular subtyping of enterohemorrhagic Escherichia coli O157:H7 isolates.

The amplified fragment-length polymorphism (AFLPTM) technique is based on the selective PCR amplification of restriction fragments. We investigated the utility of AFLP in the molecular subtyping of enterohemorrhagic Escherichia coli serotype O157:H7 isolates. We analyzed a total of 46 isolates of E. coli O157:H7 along with other serotypes, O26:H11, 0114:H19 and 0119:NT. Isolates of E. coli O157:H7 derived from the same outbreak showed an identical AFLP-banding pattern and were subtyped into the same group, giving results almost consistent with those of a pulsed-field gel electrophoresis (PFGE) study, while other serotypes showed clearly different patterns from those of E. coli O157:H7. These results suggest that the AFLP technique has potential as an alternative tool for the molecular epidemiology of E. coli O157:H7.     

Three-dimensional tissue cultures: current trends and beyond

Life science research focuses on deciphering the biochemical mechanisms that regulate cell proliferation and function and largely depends on the use of tissue culture methods in which cells are grown on two-dimensional hard plastic or glass surfaces. However, the flat surface of the tissue culture plate represents a poor topological approximation of the complex three-dimensional (3D) architecture of a tissue or organ composed of various cell types, extracellular matrix (ECM) and interstitial fluids. Moreover, if we consider a cell as a perfectly defined volume, flattened cells have full access to the environment and limited cell-to-cell contact. However if the cell is a cube in a simple cuboidal epithelium, then its access to the lumen is limited to one face, with the opposite face facing the basal membrane and the remaining four faces lying in close contact with neighbouring cells. This is of great importance when considering the access of viruses and bacteria to the cell surface, the excretion of soluble factors or proteins or the signalling within or between cells. This short review discusses various cell culture approaches to improve the simulation of the 3D environment of cells.     

Yeast lipin 1 orthologue pah1p regulates vacuole homeostasis and membrane fusion

Vacuole homotypic fusion requires a group of regulatory lipids that includes diacylglycerol, a fusogenic lipid that is produced through multiple metabolic pathways including the dephosphorylation of phosphatidic acid (PA). Here we examined the relationship between membrane fusion and PA phosphatase activity. Pah1p is the single yeast homologue of the Lipin family of PA phosphatases. Deletion of PAH1 was sufficient to cause marked vacuole fragmentation and abolish vacuole fusion. The function of Pah1p solely depended on its phosphatase activity as complementation studies showed that wild type Pah1p restored fusion, whereas the phosphatase dead mutant Pah1p(D398E) had no effect. We discovered that the lack of PA phosphatase activity blocked fusion by inhibiting the binding of SNAREs to Sec18p, an N-ethylmaleimide-sensitive factor homologue responsible for priming inactive cis-SNARE complexes. In addition, pah1Δ vacuoles were devoid of the late endosome/vacuolar Rab Ypt7p, the phosphatidylinositol 3-kinase Vps34p, and Vps39p, a subunit of the HOPS (homotypic fusion and vacuole protein sorting) tethering complex, all of which are required for vacuole fusion. The lack of Vps34p resulted in the absence of phosphatidylinositol 3-phosphate, a lipid required for SNARE activity and vacuole fusion. These findings demonstrate that Pah1p and PA phosphatase activity are critical for vacuole homeostasis and fusion.     

Progesterone, oestradiol-17 beta and LH during the oestrous cycle of muskoxen (Ovibos moschatus)

Progesterone, oestradiol-17 beta and LH were measured in plasma from 6 non-pregnant, captive, female muskoxen during the 1984 and 1985 breeding seasons. Jugular blood samples were taken on an alternating 3/4-day schedule in 1984 and daily or at 4-h intervals over oestrus, via indwelling jugular cannulae, for 6 weeks in 1985. Oestrous cycle length was 19.6 +/- 0.96 (s.d.) days (n = 19) and did not vary between the first and subsequent cycles of the season. Progesterone was lowest at oestrus (less than or equal to 0.1 ng/ml), began to rise on Days 4-5, peaked on Days 10-12 (mean = 2.6 ng/ml) and returned to baseline 2-5 days before the next oestrus. A small rise in progesterone before the first cycle of the breeding season was observed on 7 of 12 occasions. Oestradiol-17 beta was significantly higher (P less than 0.001) 1-4 days before, or coincident with, oestrus. The average duration of the LH peak was 24.6 h (n = 7) and coincided with observations of behavioural oestrus. In one animal behavioural oestrus and an LH peak preceded a small progesterone rise at the beginning of the breeding season. The temporal relationship of these three hormones during the muskox oestrous cycle is very similar to that seen in domestic ruminants.