New class I and II HLA alleles strongly associated with opposite patterns of progression to AIDS.

The genetics of resistance to infection by HIV-1 cohort consists of 200 slow and 75 rapid progressors to AIDS corresponding to the extremes of HIV disease outcome of 20,000 Caucasians of European descent. A comprehensive analysis of HLA class I and class II genes in this highly informative cohort has identified HLA alleles associated with fast or slow progression, including several not described previously. A quantitative analysis shows an overall HLA influence independent of and equal in magnitude (for the protective effect) to the effect of the CCR5-Delta32 mutation. Among HLA class I genes, A29 (p = 0.001) and B22 (p < 0.0001) are significantly associated with rapid progression, whereas B14 (p = 0.001) and C8 (p = 0.004) are significantly associated with nonprogression. The class I alleles B27, B57, C14 (protective), and C16, as well as B35 (susceptible), are also influential, but their effects are less robust. Influence of class II alleles was only observed for DR11. These results confirm the influence of the immune system on disease progression and may have implications on peptide-based vaccine development.     

Chromatid damage induced by fluorescent light during G2 phase in normal and Gardner syndrome fibroblasts. Interpretation in terms of deficient DNA repair

Skin fibroblasts from Gardner syndrome (GS) compared with those from normal donors showed a significantly higher incidence of chromatid gaps and breaks following exposure to low-intensity, cool-white fluorescent light during G2 phase of the cell cycle. Considerable evidence supports the concept that chromatid gaps and breaks seen directly after exposure to DNA-damaging agents represent unrepaired DNA single- and double-strand breaks respectively. The changes in incidence of chromatid aberrations with time after light exposure are consistent with the sequence of events known to follow DNA damage and repair. Initially, the incidence of light-induced chromatid gaps was equivalent in GS and normal fibroblasts. In the normal cells, the chromatid gaps disappeared by 1 h post-exposure, presumably as a result of efficient repair of DNA single-strand breaks. In contrast, the incidence of gaps increased in GS cells by 0.5 h followed by a decrease at 1 h and concomitant increase in chromatid breaks. It appears from these findings that the increased incidence of chromatid damage in GS fibroblasts results from deficient repair of DNA single-strand breaks which arise from incomplete nucleotide excision of DNA damage during G2 phase.     

The use of stable isotopes to trace small-scale movements by small fish species

Valuable biological information can be obtained by monitoring the movement of organisms. However, the choice of monitoring method becomes highly restricted when following small organisms (<100 mm), especially in aquatic ecosystems. Stable isotopes are being increasingly used in this respect but rarely at the local spatial scale, i.e. 10–1000 s of metres. We sought to identify movement of small fishes between a main river channel and its tributary. Little overlap in isotope baseline was detected between the two channels despite some temporal variability in δ¹⁵N of baseline indicator organisms in the main river. The individuals of two small cyprinid fish species (Leuciscus souffia and Alburnoides bipunctatus) of all the size classes (40–100 mm) caught within the tributary showed considerable heterogeneity in δ¹⁵N values. Classification and discriminant analysis on isotope-derived data distinguished two significantly different groups. Moreover, this result was supported by further sampling of fish caught in the main river (in May and December 2006). Alternative hypotheses, such as dietary differences, biological factors, temporal shifts and spatial differences in diet, did not explain δ¹⁵N variability. This application of stable isotopes at a relatively small spatial and temporal scales further demonstrates its potential as a tool for ecologists.     

Phosphatidylinositol inhibits microtubule assembly by binding to microtubule-associated protein 2 at a single, specific, high-affinity site.

The effects of various anionic phospholipids on the in vitro assembly of MAP2/tubulin microtubules has been examined. We show that the potency to inhibit is related to the polarity of the phospholipids and that this is consistent with a mode of action involving the sequencing of microtubule-associated proteins (MAPs) by nonspecific electrostatic interactions. The inhibitory potency of phosphatidylinositol (PI) is, however, considerably larger than predicted by this model. The effects of PI on MAP2/tubulin microtubule assembly have therefore been examined in greater detail by preparing phosphatidylcholine (PC) liposomes doped with increasing amounts of PI. We show that when the PI is sufficiently dispersed by dilution with PC, it inhibits microtubule assembly by binding to MAP2 with an apparent stoichiometry, after correction for the bilamellar nature of the liposomes, of 1:1 mol.mol-1 PI:MAP2. Furthermore, we show that the Kd of this interaction is in the submicromolar range.     

Effects of water flow on transmembrane ionic currents in neurons of Helix pomatia and in squid giant axons

1. The effects of water flow through the membrane produced by an osmotic gradient on the ionic currents in Helix neurons and in squid giant axons were studied. 2. Outward water flow had a marked effect on the ionic currents. 3. Cell volume diminution in hypertonic solution was accompanied by a decrease in the number of functioning ionic channels in the neurons. 4. Decrease of the tonicity of the external 10(-8) M TTX-containing solution leads to a transient recovery of the action potentials of the squid.     

Aneurysms after microvascular anastomoses. Incidence and pathogenesis in experimental animals.

This study has demonstrated that aneurysms occur in about 50 percent of the rat femoral arteries subjected to microvascular anastomosis. These aneurysms are consistent histologically--being characterized by medial necrosis, loss of elastic lamellae, and subintimal hyperplasia. Mechanical trauma is implicated as a factor in their pathogenesis, though further study in necessary to define the exact etiology.     

Feeding trials ofAphelenchus avenae on soil bacteria and actinomycetes

Summary Aphelenchus avenae and various unidentified bacteria and actinomycetes were cultured from soil samples taken from a pine-forest and a wheat-field. The nematode failed to reproduce in significant numbers on cultures of these micro-organisms and was apparently unable to utilize them as food sources.     

Cytoskeletal control of calcium absorption across the rat small intestine

1. The effect of colchicine, cytochalasin-B and procaine on calcium transport across the rat small intestine was investigated. The results obtained show the following: 2. Colchicine and cytochalasin-B at different concentrations inhibited significantly (P less than 0.001) calcium accumulation in rat intestinal cells, whereas procaine at different concentrations increased significantly (P less than 0.001) calcium accumulation in the rat small intestine. 3. Unidirectional influx of calcium across the rat small intestine was significantly inhibited (P less than 0.01) in the presence of colchicine and cytochalasin-B in the preincubation medium. Procaine, on the other hand, caused a significant increase (P less than 0.01) in the unidirectional influx of calcium across the rat intestinal cells. 4. The cell water content was not altered in the presence of the different drugs indicating that the changes in calcium transport across the rat intestinal cells are not due to alterations in the structure of the cell membrane.