The neuronal and molecular basis of quinine-dependent bitter taste signaling in Drosophila larvae.

The sensation of bitter substances can alert an animal that a specific type of food is harmful and should not be consumed. However, not all bitter compounds are equally toxic and some may even be beneficial in certain contexts. Thus, taste systems in general may have a broader range of functions than just in alerting the animal. In this study we investigate bitter sensing and processing in Drosophila larvae using quinine, a substance perceived by humans as bitter. We show that behavioral choice, feeding, survival, and associative olfactory learning are all directly affected by quinine. On the cellular level, we show that 12 gustatory sensory receptor neurons that express both GR66a and GR33a are required for quinine-dependent choice and feeding behavior. Interestingly, these neurons are not necessary for quinine-dependent survival or associative learning. On the molecular receptor gene level, the GR33a receptor, but not GR66a, is required for quinine-dependent choice behavior. A screen for gustatory sensory receptor neurons that trigger quinine-dependent choice behavior revealed that a single GR97a receptor gene expressing neuron located in the peripheral terminal sense organ is partially necessary and sufficient. For the first time, we show that the elementary chemosensory system of the Drosophila larva can serve as a simple model to understand the neuronal basis of taste information processing on the single cell level with respect to different behavioral outputs

Queries on medication use during pregnancy: characterisation of the Swiss Teratogen Information Service database.

Limited information on medication safety may result in concerns on how to treat pregnant and breast-feeding patients. The Swiss Teratogen Information Service (STIS) provides information to healthcare professionals about medications during pregnancy and breast feeding. Our objective was to describe the queries addressed to the STIS over the past two decades. The STIS maintains a database of queries on pregnancy outcomes after exposure to various substances, which may be a valuable source of information. We initially analysed the general characteristics of all queries. Thereafter, we focused on exposure to medications during singleton pregnancies and associated health-related aspects. From 2000 to 2019, 7148 queries were entered into the database. An increasing number of queries was recorded over the study period, with an average of 357 queries entered into the database per year. Most of the enquirers were physicians; more specifically, gynaecologists/obstetricians (2389/7148; 33.4%) and psychiatrists (1007/7148; 14.1%). Two thirds (4747/7148; 66.4%) of the queries addressed medication intake during pregnancy; the next most frequent queries concerned planned medication in the context of pregnancy (928/7148; 13.0%) or medication use during breast-feeding (873/7148; 12.2%). In more than 50% (3611/7148) of cases, women were treated with more than one drug; altogether, 15193 medications (taken alone or in combination) were identified. The most frequent queries concerned medicines for the nervous system (ATC group N, n = 7042), with selective serotonin reuptake inhibitors (n = 1271) in the leading position, followed by benzodiazepine derivatives (n = 1102) and other antidepressants (n = 780). The next most frequently mentioned drug classes were anti-infectives for systemic use (J, n = 1586) and drugs for the alimentary tract and metabolism (A, n = 1205). Analysis of follow-up information on cases of medication exposure during singleton pregnancies (n = 2672) revealed an offspring malformation rate of 4.2%. The organ system most often affected was the musculoskeletal system, followed by the circulatory system; congenital malformations of the nervous system and chromosomal abnormalities were also seen. The three most frequently documented congenital diagnoses were malformations of cardiac septa, the brain and major arteries. Healthcare professionals often have concerns regarding the treatment of pregnant women with medication, and require professional counselling in this area. A variety of drugs are mentioned in queries addressed to the STIS, of which psycholeptics and psychoanaleptics are the most frequent. Proper guidelines on their use during pregnancy appear particularly urgent

Quantum dot opto-mechanics in a fully self-assembled nanowire

We show that fully self-assembled optically-active quantum dots (QDs) embedded in MBE-grown GaAs/AlGaAs core-shell nanowires (NWs) are coupled to the NW mechanical motion. Oscillations of the NW modulate the QD emission energy in a broad range exceeding 14 meV. Furthermore, this opto-mechanical interaction enables the dynamical tuning of two neighboring QDs into resonance, possibly allowing for emitter-emitter coupling. Both the QDs and the coupling mechanism -- material strain -- are intrinsic to the NW structure and do not depend on any functionalization or external field. Such systems open up the prospect of using QDs to probe and control the mechanical state of a NW, or conversely of making a quantum non-demolition readout of a QD state through a position measurement.Comment: 20 pages, 6 figure

Composition of agarose substrate affects behavioral output of Drosophila larvae.

In the last decade the Drosophila larva has evolved into a simple model organism offering the opportunity to integrate molecular genetics with systems neuroscience. This led to a detailed understanding of the neuronal networks for a number of sensory functions and behaviors including olfaction, vision, gustation and learning and memory. Typically, behavioral assays in use exploit simple Petri dish setups with either agarose or agar as a substrate. However, neither the quality nor the concentration of the substrate is generally standardized across these experiments and there is no data available on how larval behavior is affected by such different substrates. Here, we have investigated the effects of different agarose concentrations on several larval behaviors. We demonstrate that agarose concentration is an important parameter, which affects all behaviors tested: preference, feeding, learning and locomotion. Larvae can discriminate between different agarose concentrations, they feed differently on them, they can learn to associate an agarose concentration with an odor stimulus and change locomotion on a substrate of higher agarose concentration. Additionally, we have investigated the effect of agarose concentration on three quinine based behaviors: preference, feeding and learning. We show that in all cases examined the behavioral output changes in an agarose concentration-dependent manner. Our results suggest that comparisons between experiments performed on substrates differing in agarose concentration should be done with caution. It should be taken into consideration that the agarose concentration can affect the behavioral output and thereby the experimental outcomes per se potentially due to the initiation of an escape response or changes in foraging behavior on more rigid substrates

The Effect of Two Sock Fabrics on Physiological Parameters Associated with Blister Incidence: A Laboratory Study

The goal of the present study was to investigate physiological effects, mainly at the level of the foot, of two sock fabrics with distinct moisture properties. Twelve participants wore two different socks, one on each foot. The following two sock types were used: PP: 99.6% polypropylene and 0.4% elastane and BLEND: 50% Merino wool, 33% polypropylene, and 17% polyamide. The participants walked three times on a treadmill at 5 km h−1, with no gradient for the first and third phase and a 10% upward inclination for the second walking phase. The microclimate temperature between the boot and foot was measured during walking. Preceding and following the walking phases, additional measurements were carried out at the level of the foot, i.e. skin temperature and skin hydration on three locations and skin friction between the posterior surface of the calcaneus and a glass plate. In addition, the moisture absorption of boots and socks was determined. Differences between the sock fabrics were found for weight gain and microclimate temperature: (i) PP tended to hold less water compared to BLEND, (ii) the boot's microclimate temperature resulted in larger values for BLEND measured at the dorsal surface at the level of the third metatarsal, and (iii) warmer microclimates of the boot were measured for PP compared to BLEND at the distal anterior end of the tibia. The established differences in moisture behavior of both socks did not result in detectable differences in parameters measured on the skin of the foo

A parameterization of Greenland's tip jets suitable for ocean or coupled climate models

Greenland's tip jets are low-level, high wind speed jets forced by an interaction of the synoptic-scale atmospheric flow and the steep, high orography of Greenland. These jets are thought to play an important role in both preconditioning for, and triggering of, open-ocean convection in the Irminger Sea. However, the relatively small spatial scale of the jets prevents their accurate representation in the relatively low resolution (~1 degree) atmospheric (re-)analyses which are typically used to force ocean general circulation models (e.g. ECMWF ERA-40 and NCEP reanalyses, or products based on these). Here we present a method of ‘bogussing’ Greenland's tip jets into such surface wind fields and thus, via bulk flux formulae, into the air-sea turbulent flux fields. In this way the full impact of these mesoscale tip jets can be incorporated in any ocean general circulation model of sufficient resolution. The tip jet parameterization is relatively simple, making use of observed linear gradients in wind speed along and across the jet, but is shown to be accurate to a few m s-1 on average. The inclusion of tip jets results in a large local increase in both the heat and momentum fluxes. When applied to a 1-dimensional mixed-layer model this results in a deepening of the winter mixed-layer of over 300 m. The parameterization scheme only requires 10 meter wind speed and mean sea level pressure as input fields; thus it is also suitable for incorporation into a coupled atmosphere-ocean climate model at the coupling stage

Investigation of gravity wave activity based on NDMC, NDACC and CTBTO measurements

GRIPS (Ground based Infrared P-branch Spectrometer) airglow measurements allow the derivation of kinetic temperature in the mesopause region during night with a temporal resolution of 10s to 15s. Amongst others, these time series can be used for the investigation of atmospheric dynamics like gravity wave activity. GRIPS measurements are performed in the framework of NDMC – the international Network for the Detection of Mesospheric Change. The project ARISE combines NDMC, NDACC (Network for the Detection of Atmospheric Composition Change) and CTBTO (Comprehensive Nuclear-Test-Ban Treaty Organization)measurements to infer a new 3D image of atmospheric dynamics from ground to mesopause. In this context, GRIPS data of about two to three years collected at the Observatory Haute-Provence, France and Catania, Italy are utilized to derive an index for shortand long-period gravity wave activity on daily and seasonal base. This time period includes also a stratospheric warming event. Potential energy density is calculated and compared with NDACC measurements at Haute-Provence; differences are discussed. For the measurements at the Italian station, comparisons of gravity wave and volcanic activity relying on infrasound array and seismic measurements are performed. First hints for volcanic induced mesopause gravity wave activity are presented

Activity of a Novel bcl-2/bcl-xL-Bispecific Antisense Oligonucleotide Against Tumors of Diverse Histologic Origins

Background: Increased expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL is involved in the development and progression of many tumors. We recently reported that the bcl-2/bcl-xL-bispecific antisense oligonucleotide 4625 induces apoptosis in lung carcinoma cells. To further assess the therapeutic potential of oligonucleotide 4625, we investigated its effect on a series of human tumor cell lines of diverse histologic origins in vitro and in vivo. Methods: Oligonucleotide 4625-mediated inhibition of bcl-2 and bcl-xL expression in vitro was measured in breast carcinoma cells with the use of reverse transcription-polymerase chain reaction (PCR), real-time PCR, and western blotting. Cytotoxicity was assessed in several different cell lines by measurement of tumor cell growth, propidium iodide uptake, and nuclear apoptosis. The in vivo activity of oligonucleotide 4625 was determined by the inhibition of growth of established tumor xenografts in nude mice, immunohistochemical staining of Bcl-2 and Bcl-x proteins in the tumors, and western blotting of tumor lysates. Apoptosis in tumor xenografts was detected with the use of in situ TUNEL (i.e., terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labeling) staining. All statistical tests are two-sided. Results: In breast carcinoma cells, oligonucleotide 4625 treatment reduced bcl-2 and bcl-xL messenger RNA levels in a dose-dependent manner. At 600 nM, oligonucleotide 4625 reduced Bcl-2 and Bcl-xL protein levels to 25% (95% confidence interval [CI] = 16% to 34%) and 20% (95% CI = 14% to 26%), respectively, of the levels in untreated cells and it decreased viability in all cell lines mainly by inducing apoptosis. In vivo, oligonucleotide 4625 statistically significantly inhibited the growth of breast and colorectal carcinoma xenografts by 51% (95% CI = 28% to 74%) and 59% (95% CI = 44% to 74%), respectively, relative to those treated with control oligonucleotide 4626; it also reduced Bcl-2 and Bcl-xL protein levels and induced tumor cell apoptosis. Conclusion: The bcl-2/bcl-xL-bispecific antisense oligonucleotide 4625 merits further study as a novel compound for cancer therap