Cellular immune responses in Huntington's disease (H.D.). Detection of H.D. and multiple sclerosis (M.S.) brain antigenicity by H.D. but not M.S. lymphocytes.

Lymphocytes from patients with Huntington's disease (H.D.) exhibit a cellular immune response which consists of two components: a minor component directed against antigen common to all human brains, and a major component directed against antigen found thus far only in H.D. and multiple sclerosis (M.S.) gray matter. M.S. lymphocytes exhibit a response to antigen common to all human brains, but fail to show any H.D. or M.S. brain-specific response.     

The effects of gravity on delayed and transplanted delayed tubed flaps.

Altering the position (elevated or dependent) had no immediate effect on the blood supply of delayed or transplanted delayed tubed flaps. However, after 72 hours the mean survival length in the dependent tubes was less than that in the elevated tubes. (This difference was only significant in the delayed untransplanted flaps, and not so in the delayed transplanted flaps). All of the dependent tubes had a significant increase in water content (compared to the elevated tubes). This increase was greater in the transplanted delayed tubed flaps. The tissue pCO2 levels were significantly increased after 24 hours in the dependent transplanted tubes, reflecting poor circulation and ischemia in them. The rate of clearance of subcutaneously injected technetium-99m was significantly increased in the dependent transplanted tubes after 72 hours, while in the elevated tubes the clearance rate was similar to that in normal skin. The morphological appearance of the vessels in these flaps complemented the results of the functional study.     

Kinetics of Na(+) transport in necturus proximal tubule

The dependence of proximal tubular sodium and fluid readsorption on the Na(+) concentration of the luminal and peritubular fluid was studied in the perfused necturus kidney. Fluid droplets, separated by oil from the tubular contents and identical in composition to the vascular perfusate, were introduced into proximal tubules, reaspirated, and analyzed for Na(+) and [(14)C]mannitol. In addition, fluid transport was measured in short-circuited fluid samples by observing the rate of change in length of the split droplets in the tubular lumen. Both reabsorptive fluid and calculated Na fluxes were simple, storable functions of the perfusate Na(+) concentration (K(m) = 35-39 mM/liter, V(max) = 1.37 control value). Intracellular Na(+), determined by tissue analysis, and open-circuit transepithelial electrical potential differences were also saturable functions of extracellular Na(+). In contrast, net reabsorptive fluid and Na(+) fluxes were linearly dependent on intracellular Na(+) and showed no saturation, even at sharply elevated cellular sodium concentrations. These concentrations were achieved by addition of amphotericin B to the luminal perfusate, a maneuver which increased the rate of Na(+) entry into the tubule cells and caused a proportionate rise in net Na(+) flux. It is concluded that active peritubular sodium transport in proximal tubule cells of necturus is normally unsaturated and remains so even after amphotericin-induced enhancement of luminal Na(+) entry. Transepithelial movement of NaCl may be described by a model with a saturable luminal entry step of Na(+) or NaCl into the cell and a second, unsaturated active transport step of Na(+) across the peritubular cell boundary.     

Cold Shock Syndrome in Anacystis nidulans

The phenomenon of cold shock in Anacystis nidulans has been explored further in terms of loss of viability and immediate and subsequent metabolic effects. Cold shock was observed also in two closely related strains in which unsaturated fatty acid contents are also known to be low and temperature-dependent. Loss of viability was maximum for cells grown at temperatures above 40 C (<10⁻⁴ survivors after 5 min at 0 C) but became negligibly small for cells grown below 34 C. Development of the cold-sensitive condition after transfer 25 → 39 C was slow and comparable to rate of growth; development of the insensitive condition after transfer 39 → 25 C was rapid, implying rapid in situ alteration. An immediate metabolic effect, observed as a decrease in rate of photosynthetic O₂ evolution measured at growth temperature, was less severe than loss of viability. Continued light incubation under growth conditions led to slow decay in rate of O₂ evolution accompanied by loss of membrane chlorophyll. The multiple effects which comprise the cold shock syndrome appear to be membrane-related phenomena and thereby provide an experimental probe of normal membrane function.     

Complete genome sequence of the plant commensal Pseudomonas fluorescens Pf-5

Pseudomonas fluorescens Pf-5 is a plant commensal bacterium that inhabits the rhizosphere and produces secondary metabolites that suppress soilborne plant pathogens. The complete sequence of the 7.1-Mb Pf-5 genome was determined. We analyzed repeat sequences to identify genomic islands that, together with other approaches, suggested P. fluorescens Pf-5's recent lateral acquisitions include six secondary metabolite gene clusters, seven phage regions and a mobile genomic island. We identified various features that contribute to its commensal lifestyle on plants, including broad catabolic and transport capabilities for utilizing plant-derived compounds, the apparent ability to use a diversity of iron siderophores, detoxification systems to protect from oxidative stress, and the lack of a type III secretion system and toxins found in related pathogens. In addition to six known secondary metabolites produced by P. fluorescens Pf-5, three novel secondary metabolite biosynthesis gene clusters were also identified that may contribute to the biocontrol properties of P. fluorescens Pf-5.     

PILER: identification and classification of genomic repeats

SUMMARY: Repeated elements such as satellites and transposons are ubiquitous in eukaryotic genomes. De novo computational identification and classification of such elements is a challenging problem. Therefore, repeat annotation of sequenced genomes has historically largely relied on sequence similarity to hand-curated libraries of known repeat families. We present a new approach to de novo repeat annotation that exploits characteristic patterns of local alignments induced by certain classes of repeats. We describe PILER, a package of efficient search algorithms for identifying such patterns. Novel repeats found using PILER are reported for Homo sapiens, Arabidopsis thalania and Drosophila melanogaster. AVAILABILITY: The PILER software is freely available at http://www.drive5.com/piler.     

Accumulation and clearance of orally administered erythromycin and its derivative, azithromycin, in juvenile fall chinook salmon Oncorhynchus tshawytscha

Fall Chinook salmon Oncorhynchus tshawytscha were fed practical diets medicated with azithromycin (30 mg kg(-1) fish for 14 d) or erythromycin (100 mg kg(-1) fish for 28 d) either 1, 2, or 3 times beginning 14 d after initiation of exogenous feeding (February) and ending at smoltification (June). Average tissue concentrations of azithromycin increased from 19.0 microg g(-1) in fry to 44.9 microg g(-1) in smolts, and persisted in the tissues > 76 d after treatment ceased. Tissue concentrations of erythromycin were comparatively low, ranging from 0.2 microg g(-1) in fry to 10.4 microg g(-1) in smolts. Erythromycin was not detectable 21 d post-treatment. Neither antibiotic caused histopathologically significant lesions in the trunk kidney or other organ tissues. The high tissue concentrations and prolonged retention of azithromycin in Chinook may be factors that increase the efficacy of the antibiotic against Renibacterium salmoninarum, compared with erythromycin, particularly in early life history stages before covertly infected fish show clinical signs of disease.     

Role of the fungal Ras-protein kinase A pathway in governing epithelial cell interactions during oropharyngeal candidiasis

Tpk1p, Tpk2p and Efg1p are members of the Ras-protein kinase A pathway that governs the yeast-to-hyphal transition in Candida albicans. We used tpk1Delta/tpk1Delta, tpk2Delta/tpk2Delta and efg1Delta/efg1Delta mutants to investigate the role of these proteins in regulating the interactions of C. albicans with oral epithelial cell lines in vitro and virulence in murine models of oropharyngeal candidiasis (OPC) and haematogenously disseminated candidiasis (HDC). The tpk1Delta/tpk1Delta strain adhered to, invaded and damaged oral epithelial cells in vitro similarly to the wild-type strain. In contrast, both the tpk2Delta/tpk2Delta and efg1Delta/efg1Delta strains had reduced capacity to invade and damage oral epithelial cells, and the efg1Delta/efg1Delta strain also exhibited decreased adherence to these cells. Consistent with these in vitro findings, the tpk2Delta/tpk2Delta and efg1Delta/efg1Delta strains also had significantly attenuated virulence during OPC. Therefore, Tpk2p and Efg1p both govern factors that enable C. albicans to invade and damage oral epithelial cells in vitro and cause OPC. These results also suggest that hyphal formation mediated by the Ras-protein kinase A pathway is a key virulence mechanism during OPC. Interestingly, the efg1Delta/efg1Delta strain, but not the tpk2Delta/tpk2Delta had reduced virulence during HDC. Thus, Tpk2p may be more important for governing virulence during OPC than HDC.