Neurite outgrowth is enhanced by laminin-mediated down-regulation of the low affinity neurotrophin receptor, p75NTR

Laminin (LN), an extracellular matrix component, is a key factor in promoting axonal regeneration, coordinately regulating growth in conjunction with trophic signals provided by the neurotrophins, including nerve growth factor (NGF). This study investigated potential interactions between the LN and NGF-mediated signaling pathways in PC12 cells and primary neurons. Neurite outgrowth stimulated by NGF was enhanced on a LN substrate. Western blot analysis of pertinent signal transduction components revealed both enhanced phosphorylation of early signaling intermediates upon co-stimulation, and a LN-induced down-regulation of p75NTR which could be prevented by the addition of integrin inhibitory arginine-glycine-aspartate (RGD) peptides. This p75NTR down-regulation was associated with a LN-mediated up-regulation of PTEN and resulted in a decrease in Rho activity. Studies using over-expression or siRNA-mediated knock-down of PTEN demonstrate a consistent inverse relationship with p75NTR, and the over-expression of p75NTR impaired neurite outgrowth on a LN substrate, as well as resulting in sustained activation of Rho which is inhibitory to neurite outgrowth. p75NTR is documented for its role in the transduction of inhibitory myelin-derived signals, and our results point to extracellular matrix regulation of p75NTR as a potential mechanism to ameliorate inhibitory signaling leading to optimized neurite outgrowth.     

Genetic Evidence that the uvsE Gene Product of Deinococcus radiodurans R1 Is a UV Damage Endonuclease

An in vitro transposition system, developed to facilitate gene disruption in Deinococcus radiodurans R1, has been used to inactivate the gene designated dr1819 in uvrA-1(+) and uvrA-1 backgrounds. dr1819 encodes a protein with homology to a UV DNA damage endonuclease expressed by Schizosaccharomyces pombe. Interruption of dr1819 greatly sensitizes the uvrA-1 strain but not the uvrA-1(+) strain to UV light, indicating that the dr1819 gene product is a component in a DNA repair pathway that can compensate for the loss of nucleotide excision repair in this species. Clones of dr1819 will restore UV resistance to UVS78, a uvrA-1 uvsE strain, indicating that dr1819 and uvsE are the same locus.     

Holding effects on coliform enumeration in drinking water samples

Standard procedures for analyzing drinking water stress the need to adhere to the time and temperature conditions recommended for holding samples collected for microbiological testing. The National Drinking Water Laboratory Certification Program requires compliance with these holding limits, but some investigators have reported difficulties in meeting them. Research was conducted by standard analytical methods to determine if changes occurred when samples were held at 5 and 22 degrees C and analyzed at 0, 24, 30, and 48 h. Samples were analyzed for coliforms by the membrane filter and fermentation-tube procedures and for heterotrophs by the pour plate method. A total of 17 treated water samples were collected from a large municipal distribution system from August to December 1981, and 12 samples were collected from January to May 1983. The samples were dosed with coliforms previously isolated from the water system, Enterobacter cloacae in 1981 and Citrobacter freundii in 1983. The coliform counts declined linearly over time, and the rates of decline were significant at both 5 and 22 degrees C. Within 24 h at 22 degrees C, levels of E. cloacae and C. freundii decreased by 47 and 26%, respectively, and at 5 degrees C, E. cloacae numbers declined by 23%. Results from these representative laboratory-grown coliforms reinforced those previously obtained with naturally occurring coliforms under the same experimental conditions. Significantly, some samples with initially unacceptable counts (greater than 4/100 ml) met the safe drinking water limits after storage at 24 h at 5 and 22 degrees C and would have been classified as satisfactory.(ABSTRACT TRUNCATED AT 250 WORDS)     

Macrophage proteases can modify low density lipoproteins to increase their uptake by macrophages

When low density lipoprotein (LDL) was incubated with sonicated macrophages at acidic pH, its protein moiety was partially degraded by cathepsins B and D. The reisolated LDL was taken up by intact macrophages up to about 20 times as fast as control LDL. LDL proteolysis and its enhanced uptake could be inhibited almost entirely by the selective protease inhibitors leupeptin and pepstatin. If macrophages in atherosclerotic lesions were to release acidic proteases (either by exocytosis or following cell death) and these were to modify LDL, this may help to explain why so much cholesteryl ester accumulates in these cells.     

Neuromechanistic Model of Auditory Bistability

Sequences of higher frequency A and lower frequency B tones repeating in an ABA- triplet pattern are widely used to study auditory streaming. One may experience either an integrated percept, a single ABA-ABA- stream, or a segregated percept, separate but simultaneous streams A-A-A-A- and -B---B--. During minutes-long presentations, subjects may report irregular alternations between these interpretations. We combine neuromechanistic modeling and psychoacoustic experiments to study these persistent alternations and to characterize the effects of manipulating stimulus parameters. Unlike many phenomenological models with abstract, percept-specific competition and fixed inputs, our network model comprises neuronal units with sensory feature dependent inputs that mimic the pulsatile-like A1 responses to tones in the ABA- triplets. It embodies a neuronal computation for percept competition thought to occur beyond primary auditory cortex (A1). Mutual inhibition, adaptation and noise are implemented. We include slow NDMA recurrent excitation for local temporal memory that enables linkage across sound gaps from one triplet to the next. Percepts in our model are identified in the firing patterns of the neuronal units. We predict with the model that manipulations of the frequency difference between tones A and B should affect the dominance durations of the stronger percept, the one dominant a larger fraction of time, more than those of the weaker percept—a property that has been previously established and generalized across several visual bistable paradigms. We confirm the qualitative prediction with our psychoacoustic experiments and use the behavioral data to further constrain and improve the model, achieving quantitative agreement between experimental and modeling results. Our work and model provide a platform that can be extended to consider other stimulus conditions, including the effects of context and volition.     

National plastic surgery survey: brow lifting techniques and complications.

The purpose of this survey was to assess trends in brow lifting philosophy, techniques, and complications. This is the second of a three-part survey; the first part reported on complications with face lift techniques, and the final report will address practice management issues, including facility and ancillary procedures. Surveys were sent to 3800 members of the American Society of Plastic Surgeons; the response rate was 15 percent. This survey represents data on 6951 brow lifts, of which approximately 50 percent were performed endoscopically and 50 percent with a coronal incision. Several conclusions about the practice of the respondents were reached: (1) Both brow lift techniques were considered to be effective. (2) Surgeons considered coronal brow lifting to be more effective for the three basic goals of brow lifting: brow elevation, reduction of transverse lines, and reduction of glabellar lines. (3) Reported complication rates for both techniques were low, and the most frequent complication was alopecia (varying from 2.9 percent to 4 percent). (4) Patient satisfaction varied from 98.2 percent to 99.2 percent. (5) Major complications were rarely reported.