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

Porosity control of in situ forming tungsten carbide in laser additive manufacturing (LAM)

© 2020 Old City Publishing, Inc. Published by license under the OCP Science imprint, a member of the Old City Publishing Group.The effect of powder compression on the formation of porosity when heating with a laser beam has been investigated. The starting materials were elemental powders of Fe, W and C which were locally melted to form WC in Fe matrix by an in situ laser additive manufacturing (LAM) process. The resulting microstructures have been studied and chemical analysis has been performed. The main application for the process is for the production of WC based or carbide cutting tooling by very accurate deposition of hard-facing materials onto a steel substrate. Fe is used as the matrix material since ferrous alloys are employed as the substrate for these applications.Peer reviewe

e-VLBI observations of Circinus X-1: monitoring of the quiescent and flaring radio emission on AU scales

A recent detection of the peculiar neutron star X-ray binary Circinus X-1 with electronic very long baseline interferometry (e-VLBI) prompted the suggestion that compact, non-variable radio emission persists through the entire 16.6-day orbit of the binary system. We present the results of a high angular resolution monitoring campaign conducted with the Australian Long Baseline Array in real-time e-VLBI mode. e-VLBI observations of Circinus X-1 were made on alternate days over a period of 20 days covering the full binary orbit. A compact radio source associated with Circinus X-1 was clearly detected at orbital phases following periastron passage but no compact radio emission was detected at any other orbital phase, ruling out the presence of a persistent, compact emitting region at our sensitivity levels. The jet was not resolved at any epoch of our 1.4-GHz monitoring campaign, suggesting that the ultrarelativistic flow previously inferred to exist in this source is likely to be dark. We discuss these findings within the context of previous radio monitoring of Circinus X-1.Comment: Accepted for publication in MNRAS. 7 pages, 5 figure