Both Pre- and Postsynaptic Activity of Nsf Prevents Degeneration of Hair-Cell Synapses

Vesicle fusion contributes to the maintenance of synapses in the nervous system by mediating synaptic transmission, release of neurotrophic factors, and trafficking of membrane receptors. N-ethylmaleimide-sensitive factor (NSF) is indispensible for dissociation of the SNARE-complex following vesicle fusion. Although NSF function has been characterized extensively in vitro, the in vivo role of NSF in vertebrate synaptogenesis is relatively unexplored. Zebrafish possess two nsf genes, nsf and nsfb. Here, we examine the function of either Nsf or Nsfb in the pre- and postsynaptic cells of the zebrafish lateral line organ and demonstrate that Nsf, but not Nsfb, is required for maintenance of afferent synapses in hair cells. In addition to peripheral defects in nsf mutants, neurodegeneration of glutamatergic synapses in the central nervous system also occurs in the absence of Nsf function. Expression of an nsf transgene in a null background indicates that stabilization of synapses requires Nsf function in both hair cells and afferent neurons. To identify potential targets of Nsf-mediated fusion, we examined the expression of genes implicated in stabilizing synapses and found that transcripts for multiple genes including brain-derived neurotrophic factor (bdnf) were significantly reduced in nsf mutants. With regard to trafficking of BDNF, we observed a striking accumulation of BDNF in the neurites of nsf mutant afferent neurons. In addition, injection of recombinant BDNF protein partially rescued the degeneration of afferent synapses in nsf mutants. These results establish a role for Nsf in the maintenance of synaptic contacts between hair cells and afferent neurons, mediated in part via the secretion of trophic signaling factors

Factors contributing to the time taken to consult with symptoms of lung cancer: a cross-sectional study

<b>Objectives</b>: To determine what factors are associated with the time people take to consult with symptoms of lung cancer, with a focus on those from rural and socially deprived areas. <b>Methods</b>: A cross-sectional quantitative interview survey was performed of 360 patients with newly diagnosed primary lung cancer in three Scottish hospitals (two in Glasgow, one in NE Scotland). Supplementary data were obtained from medical case notes. The main outcome measures were the number of days from (1) the date participant defined first symptom until date of presentation to a medical practitioner; and (2) the date of earliest symptom from a symptom checklist (derived from clinical guidelines) until date of presentation to a medical practitioner. <b>Results</b>: 179 participants (50%) had symptoms for more than 14 weeks before presenting to a medical practitioner (median 99 days; interquartile range 31–381). 270 participants (75%) had unrecognised symptoms of lung cancer. There were no significant differences in time taken to consult with symptoms of lung cancer between rural and/or deprived participants compared with urban and/or affluent participants. Factors independently associated with increased time before consulting about symptoms were living alone, a history of chronic obstructive pulmonary disease (COPD) and longer pack years of smoking. Haemoptysis, new onset of shortness of breath, cough and loss of appetite were significantly associated with earlier consulting, as were a history of chest infection and renal failure. <b>Conclusion</b>: For many people with lung cancer, regardless of location and socioeconomic status, the time between symptom onset and consultation was long enough to plausibly affect prognosis. Long-term smokers, those with COPD and/or those living alone are at particular risk of taking longer to consult with symptoms of lung cancer and practitioners should be alert to this

A relativistic helical jet in the gamma-ray AGN 1156+295

We present the results of a number of high resolution radio observations of the AGN 1156+295. These include multi-epoch and multi-frequency VLBI, VSOP, MERLIN and VLA observations made over a period of 50 months. The 5 GHz MERLIN images trace a straight jet extending to 2 arcsec at P.A. -18 degrees. Extended low brightness emission was detected in the MERLIN observation at 1.6 GHz and the VLA observation at 8.5 GHz with a bend of about 90 degrees at the end of the 2 arcsecond jet. A region of similar diffuse emission is also seen about 2 arcseconds south of the radio core. The VLBI images of the blazar reveal a core-jet structure with an oscillating jet on a milli-arcsecond (mas) scale which aligns with the arcsecond jet at a distance of several tens of milli-arcseconds from the core. This probably indicates that the orientation of the jet structure is close to the line of sight, with the northern jet being relativistically beamed toward us. In this scenario the diffuse emission to the north and south is not beamed and appears symmetrical. For the northern jet at the mas scale, proper motions of 13.7 +/-3.5, 10.6 +/- 2.8, and 11.8 +/- 2.8 c are measured in three distinct components of the jet (q_0=0.5, H_0=65 km /s /Mpc are used through out this paper). Highly polarised emission is detected on VLBI scales in the region in which the jet bends sharply to the north-west. The spectral index distribution of the source shows that the strongest compact component has a flat spectrum, and the extended jet has a steep spectrum. A helical trajectory along the surface of a cone was proposed based on the conservation laws for kinetic energy and momentum to explain the observed phenomena, which is in a good agreement with the observed results on scales of 1 mas to 1 arcsec.Comment: 19 pages with 18 figures. Accepted for publication in the A&