25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Vaccine against peanut allergy based on engineered Virus-Like-Particles displaying single major peanut allergens

Background Peanut allergy is a severe and increasingly frequent disease with high medical, psychosocial and economical burden for affected patients. A causal, safe and effective therapy is not available. Objective We aimed to develop an immunogenic, protective and non-reactogenic vaccine candidate against peanut allergy based on Virus-like Particles (VLPs) coupled to single peanut allergens. Methods To generate vaccine candidates, extracts of roasted peanut (Ara R) or the single allergens Ara h 1 or Ara h 2 were coupled to immunologically optimized Cucumber Mosaic Virus-derived VLPs (CuMVtt). BALB/c mice were sensitized intraperitoneally with peanut extract absorbed to Alum. Immunotherapy consisted of one single subcutaneous injection of CuMVtt coupled to Ara R, Ara h 1 or Ara h 2. Results The vaccines CuMVtt-Ara R, CuMVtt-Ara h 1 and CuMVtt-Ara h 2 protected peanut sensitized mice against anaphylaxis after i.v. challenge with the whole peanut extract. Vaccines did not cause allergic reactions in sensitized mice. CuMVtt-Ara h 1 was able to induce specific IgG antibodies, diminished local reactions after skin-prick-tests and reduced the infiltration of the gastrointestinal tract by eosinophils and mast cells after oral challenge with peanut. The ability of CuMVtt-Ara h 1 to protect against challenge with the whole extract was mediated by IgG, as shown via passive IgG transfer. FcγRIIb was required for protection, indicating that immune-complexes with single allergens were able to block the allergic response against the whole extract, consisting of a complex allergen mixture. Conclusion Our data suggest that vaccination using single peanut allergens displayed on CuMVtt may represent a novel and safe therapy against peanut allergy

Changes in Work Practices for Safe Use of Formaldehyde in a University-Based Anatomy Teaching and Research Facility

Anatomy teaching and research relies on the use of formaldehyde (FA) as a preservation agent for human and animal tissues. Due to the recent classification of FA as a carcinogen, university hospitals are facing a challenge to (further) reduce exposure to FA. The aim of this study was to reduce exposure to FA in the anatomy teaching and research facility. Workers participated in the development of improved work practices, both technical and organizational solutions. Over a period of 6 years mitigating measures were introduced, including improvement of a down-flow ventilation system, introduction of local exhaust ventilation, collection of drain liquid from displayed specimens in closed containers and leak prevention. Furthermore, some organizational changes were made to reduce the number of FA peak exposures. Stationary and personal air sampling was performed in three different campaigns to assess the effect of these new work practices on inhalation exposure to FA. Samples were collected over 8 h (full shift) and 15 min (task-based) to support mitigation of exposure and improvement of work practices. Air was collected on an adsorbent coated with 2,4-dinitrophenylhydrazine (DNPH) and analyzed by HPLC-UV. Geometric mean (GM) concentrations of FA in the breathing zone over a work-shift were 123 µg/m³ in 2012 and 114 µg/m³ in 2014, exceeding the workplace standard of 150 µg/m³ (8 h time-weighted average, TWA) on 46% of the workdays in 2012 and 38% of the workdays in 2014. This exposure was reduced to an average of 28.8 µg/m³ in 2017 with an estimated probability of exceeding the OEL of 0.6%. Task-based measurements resulted in a mean peak exposures of 291 µg/m³ in 2012 (n = 19) and a mean of 272 µg/m³ in 2014 (n = 21), occasionally exceeding the standard of 500 µg/m³ (15 min TWA), and were reduced to a mean of 88.7 µg/m³ in 2017 (n = 12) with an estimated probability of exceeding the OEL of 1.6%