The chemosensory ecology of a foraging hawkmoth

While foraging, all animals need to balance their energetic cost and gains. The sensory systems provide the information, which form the bases for these energy-economic decisions and thus, link the sensory input directly to the fitness of the animal. Night-active hawkmoth species particularly rely on their olfactory system which detects the volatiles emitted by those plants visited by the moth. This dissertation examined the olfactory system and the foraging decisions of the hawkmoth Manduca sexta to gain further insights into the ecological pressures which might have directed the evolution of the olfactory system in hawkmoths and their coevolution with the flowers they visit. In order to address these questions we first studied the odour guided flight of M. sexta to flowers of different Nicotiana species, which matched the length of the moth proboscis to different degrees. It was found that the moth already selected the best matching flower at the first encounter with the odour plume emitted by this flower and that foraging on these matching flowers did result in the highest energy gain for the moth. We could further show that M. sexta recognise a plant headspace based on the composition of this blend rather than on its concentration. However, flower odours are readily intermixed with other volatiles and their detection is hence most reliable close to the flower. Here, we show that the moth uses specific olfactory neurons on the tip of its proboscis to evaluate flowers, and that this close range detection is crucial both for foraging as well as pollination. Finally, the effect of flower orientation on the foraging of M. sexta was analysed, finding that the synchronisation of floral volatiles and orientation is crucial for this moth-plant interaction. Taken together our studies on the foraging of hawkmoth might not only help to gain new insights into the evolution of sensory systems, but also on how these systems shapes the interaction between different species

A Challenge for a Male Noctuid Moth? Discerning the Female Sex Pheromone against the Background of Plant Volatiles

Finding a partner is an essential task for members of all species. Like many insects, females of the noctuid moth Heliothis virescens release chemical cues consisting of a species-specific pheromone blend to attract conspecific males. While tracking these blends, male moths are also continuously confronted with a wide range of other odor molecules, many of which are plant volatiles. Therefore, we analyzed how background plant odors influence the degree of male moth attraction to pheromones. In order to mimic a natural situation, we tracked pheromone-guided behavior when males were presented with the headspaces of each of two host plants in addition to the female pheromone blend. Since volatile emissions are also dependent on the physiological state of the plant, we compared pheromone attraction in the background of both damaged and intact plants. Surprisingly, our results show that a natural odor bouquet does not influence flight behavior at all, although previous studies had shown a suppressive effect at the sensory level. We also chose different concentrations of single plant-emitted volatiles, which have previously been shown to be neurophysiologically relevant, and compared their influence on pheromone attraction. We observed that pheromone attraction in male moths was significantly impaired in a concentration-dependent manner when single plant volatiles were added. Finally, we quantified the amounts of volatile emission in our experiments using gas chromatography. Notably, when the natural emissions of host plants were compared with those of the tested single plant compounds, we found that host plants do not release volatiles at concentrations that impact pheromone-guided flight behavior of the moth. Hence, our results lead to the conclusion that pheromone-plant interactions in Heliothis virescens might be an effect of stimulation with supra-natural plant odor concentrations, whereas under more natural conditions the olfactory system of the male moth appears to be well adapted to follow the female pheromone plume without interference from plant-emitted odors

Ventricular tachycardia (VT) storm after cryoballoon-based pulmonary vein isolation

Objective: Unusual clinical course. Background: Following catheter ablation of atrial fibrillation, increased incidence of ventricular arrhythmia has been observed. We report a case of sustained ventricular arrhythmia in a patient who underwent cryoballoon-based pulmonary vein isolation for symptomatic persistent atrial fibrillation. Case Report: A 57-year-old patient with dilated cardiomyopathy underwent CB-based pulmonary vein isolation for symptomatic persistent AF. On the day following an uneventful procedure, the patient for the first time experienced a sustained ventricular tachycardia that exacerbated into VT storm. Each arrhythmia was terminated by the ICD that had been implanted for primary prevention. Antiarrhythmic treatment with amiodarone was initiated immediately. The patient remained free from sustained ventricular arrhythmia during follow-up. Conclusions: After pulmonary vein isolation, physicians should be vigilant for ventricular arrhythmia. The influence of atrial autonomic innervation on ventricular electrophysiology is largely unknown

Implantable loop recorders in patients with unexplained syncope: Clinical predictors of pacemaker implantation

Background: Implantable loop recorders (ILR) are a valuable tool for the investigation of unexplained syncopal episodes. The aim of this retrospective single center study was to identify predictive factors for pacemaker implantation in patients with unexplained syncope who underwent ILR insertion. Methods: One hundred six patients were retrospectively analyzed (mean age 59.1 years; 47.2% male) with unexplained syncope and negative conventional testing who underwent ILR implantation. The pri- mary study endpoint was detection of symptomatic or asymptomatic bradycardia requiring pacemaker implantation.  Results: The average follow-up period after ILR implantation was 20 ± 15 months. Pacemaker im- plantation according to current guidelines was necessary in 22 (20.8%) patients, mean duration until index bradycardia was 81 ± 88 (2–350) days. Ten (45.5%) patients received a pacemaker due to sinus arrest, 7 (31.8%) patients due to third-degree atrioventricular block, 2 (9.1%) patients due to second- degree atrioventricular block and 1 (4.5%) patient due to atrial fibrillation with a slow ventricular rate. Three factors remained significant in multivariate analysis: obesity, which defined by a body mass index above 30 kg/m2 (OR: 7.39, p = 0.014), a right bundle branch block (OR: 9.40, p = 0.023) and chronic renal failure as defined by a glomerular filtration rate of less than 60 mL/min (OR: 6.42, p = 0.035). Conclusions: Bradycardia is a frequent finding in patients undergoing ILR implantation due to un- explained syncope. Obesity, right bundle branch block and chronic renal failure are independent clinical predictors of pacemaker implantation

results of the prospective observational Berlin Beat of Running study

Objectives: While regular physical exercise has many health benefits, strenuous physical exercise may have a negative impact on cardiac function. The ‘Berlin Beat of Running’ study focused on feasibility and diagnostic value of continuous ECG monitoring in recreational endurance athletes during a marathon race. We hypothesised that cardiac arrhythmias and especially atrial fibrillation are frequently found in a cohort of recreational endurance athletes. The main secondary hypothesis was that pathological laboratory findings in these athletes are (in part) associated with cardiac arrhythmias. Design: Prospective observational cohort study including healthy volunteers. Setting and participants: One hundred and nine experienced marathon runners wore a portable ECG recorder during a marathon race in Berlin, Germany. Athletes underwent blood tests 2–3 days prior, directly after and 1–2 days after the race. Results: Overall, 108 athletes (median 48 years (IQR 45–53), 24% women) completed the marathon in 249±43 min. Blinded ECG analysis revealed abnormal findings during the marathon in 18 (16.8%) athletes. Ten (9.3%) athletes had at least one episode of non-sustained ventricular tachycardia, one of whom had atrial fibrillation; eight (7.5%) individuals showed transient ST-T-segment deviations. Abnormal ECG findings were associated with advanced age (OR 1.11 per year, 95% CI 1.01 to 1.23), while sex and cardiovascular risk profile had no impact. Directly after the race, high-sensitive troponin T was elevated in 18 (16.7%) athletes and associated with ST-T-segment deviation (OR 9.9, 95% CI 1.9 to 51.5), while age, sex and cardiovascular risk profile had no impact. Conclusions: ECG monitoring during a marathon is feasible. Abnormal ECG findings were present in every sixth athlete. Exercise-induced transient ST-T-segment deviations were associated with elevated high-sensitive troponin T (hsTnT) values. Trial registration: ClinicalTrials.gov NCT01428778; Results

A hall plate based instrument to measure the snapback in the Large Hadron Collider superconducting dipole magnets

The decay and snapback of the magnetic field multipoles in superconducting particle accelerators like the Large Hadron Collider (LHC) could result in a significant particle beam loss unless adequately compensated. Whilst standard instrumentation used to measure the field quality of the superconducting magnets is good enough to measure the harmonic decay, it is not fast enough to measure the snapback. Therefore, a state of the art instrument was recently developed at CERN to measure the most important harmonics with a high measurement frequency and hence improve the understanding of the snapback phenomenon. In this paper we describe the instrument's principle of operation, its mechanical arrangement, its compensation system and its digital acquisition system. We also compare the performance of two different techniques implemented to achieve the necessary measurement resolution of 6 orders of magnitude lower than the main superimposed dipole field.peer-reviewe

Nonclinical cardiovascular safety of pitolisant: comparing International Conference on Harmonization S7B and Comprehensive in vitro Pro-arrhythmia Assay initiative studies

Background and purpose: We evaluated the concordance of results from two sets of nonclinical cardiovascular safety studies on pitolisant. Experimental approach: Nonclinical studies envisaged both in the ICH S7B guideline and Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative were undertaken. CiPA-initiative studies included in vitro ion channels and stem cell-derived human ventricular myocyte studies as well as in silico modelling of results to simulate human ventricular electrophysiology. ICH S7B-recommended studies included in vitro hERG studies, in vivo dog study with follow-up investigations in rabbit Purkinje fibres and in vivo studies in the Carlsson rabbit proarrhythmia model. Key results: Both sets of nonclinical studies consistently excluded pitolisant from having clinically relevant QT-liability or proarrhythmic potential. CiPA studies revealed pitolisant to have modest calcium channel blocking and late I Na reducing activities at high concentrations, which resulted in reduction of dofetilide-induced early after-depolarisations (EADs) by pitolisantin ICH S7B studies. Studies in stem cell-derived human cardiomyocytes with dofetilide or E-4031 given alone and in combination with pitolisant confirmed these properties. In silico modelling confirmed that the measured ion channel effects are consistent with results from both the stem cell-derived cardiomyocyte and rabbit Purkinje fibre studies and categorised pitolisant as a drug with low torsadogenic potential. The results from the two sets of nonclinical studies correlated well with two clinical QT studies. Conclusions and implications: Our experience supports the CiPA initiative but suggests that sponsors should consider investigating drug effects on EADs and the use of proarrhythmia models when the results from CiPA studies are ambiguous

Comparison of different in situ hybridization techniques for the detection of various RNA and DNA viruses

In situ hybridization (ISH) is a technique to determine potential correlations between viruses and lesions. The aim of the study was to compare ISH techniques for the detection of various viruses in different tissues. Tested RNA viruses include atypical porcine pestivirus (APPV) in the cerebellum of pigs, equine and bovine hepacivirus (EqHV, BovHepV) in the liver of horses and cattle, respectively, and Schmallenberg virus (SBV) in the cerebrum of goats. Examined DNA viruses comprise canine bocavirus 2 (CBoV-2) in the intestine of dogs, porcine bocavirus (PBoV) in the spinal cord of pigs and porcine circovirus 2 (PCV-2) in cerebrum, lymph node, and lung of pigs. ISH with self-designed digoxigenin-labelled RNA probe

Expression Pattern of Kv11 (Ether à-go-go-Related Gene; erg) K+ Channels in the Mouse Retina

In response to light, most retinal neurons exhibit gradual changes in membrane potential. Therefore K+ channels that mediate threshold currents are well-suited for the fine-tuning of signal transduction. In the present study we demonstrate the expression of the different Kv11 (ether-à-go-go related gene; erg) channel subunits in the human and mouse retina by RT PCR and quantitative PCR, respectively. Immunofluorescence analysis with cryosections of mouse retinae revealed the following local distribution of the three Kv11 subunits: Kv11.1 (m-erg1) displayed the most abundant expression with the strongest immunoreactivity in rod bipolar cells. In addition, immunoreactivity was found in the inner part of the outer plexiform layer (OPL), in the inner plexiform layer (IPL) and in the inner segments of photoreceptors. Immunoreactivity for Kv11.2 (m-erg2) was observed in the outer part of the OPL and throughout the IPL. Double-labeling for vGluT1 or synaptophysin indicated a mainly presynaptic localization of Kv11.2. While no significant staining for Kv11.3 (m-erg3) was detected in the neuronal retina, strong Kv11.3 immunoreactivity was present in the apical membrane of the retinal pigment epithelium. The different expression levels were confirmed by real-time PCR showing almost equal levels of Kv11.1 and Kv11.2, while Kv11.3 mRNA expression was significantly lower. The two main splice variants of Kv11.1, isoforms a and b were detected in comparable levels suggesting a possible formation of cGMP/cGK-sensitive Kv11.1 channels in photoreceptors and rod bipolar cells. Taken together, the immunohistological results revealed different expression patterns of the three Kv11 channels in the mouse retina supposing distinct physiological roles