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

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

ΔNp73 antisense activates PUMA and induces apoptosis in neuroblastoma cells

The p73 gene codes for various different protein isoforms. They include proteins expressed under the control of the P1 promoter that contain a transactivation domain and are similar in function to p53 (TAp73 isoforms), as well as proteins regulated by the P2 promoter that lack this domain and function as dominant negative inhibitors of TAp73 and p53 (ΔNp73 isoforms). Whereas TAp73 functions as a tumor suppressor with pro-apoptotic function, ΔNp73 is likely to prevent the induction of apoptosis in tumor cells and to participate in oncogenesis. Here we used a loss-of-function strategy to assess the role of ΔNp73 in SH-SY5Y neuroblastoma cells. An antisense oligonucleotide designed to target ΔNp73 mRNA, but not TAp73, was used to effectively downregulate this transcript. ΔNp73 downregulation was accompanied by increased levels of the pro-apoptotic BH3 family member PUMA at the mRNA and protein level, and by conformational activation of BAX which translocated to mitochondria. These ΔNp73 antisense-mediated alterations led to the induction of apoptosis as detected by decreased cell viability, augmented DNA fragmentation and increased caspase-3 activity in cell lysates. Our results demonstrate the cytoprotective role of ΔNp73 in neuroblastoma and suggest its use as a target for molecular intervention therap

Assessment of the cortisol awakening response: expert consensus guidelines

The cortisol awakening response (CAR), the marked increase in cortisol secretion over the first 30–45 min after morning awakening, has been related to a wide range of psychosocial, physical and mental health parameters, making it a key variable for psychoneuroendocrinological research. The CAR is typically assessed from self-collection of saliva samples within the domestic setting. While this confers ecological validity, it lacks direct researcher oversight which can be problematic as the validity of CAR measurement critically relies on participants closely following a timed sampling schedule, beginning with the moment of awakening. Researchers assessing the CAR thus need to take important steps to maximize and monitor saliva sampling accuracy as well as consider a range of other relevant methodological factors. To promote best practice of future research in this field, the International Society of Psychoneuroendocrinology initiated an expert panel charged with (i) summarizing relevant evidence and collective experience on methodological factors affecting CAR assessment and (ii) formulating clear consensus guidelines for future research. The present report summarizes the results of this undertaking. Consensus guidelines are presented on central aspects of CAR assessment, including objective control of sampling accuracy/adherence, participant instructions, covariate accounting, sampling protocols, quantification strategies as well as reporting and interpreting of CAR data. Meeting these methodological standards in future research will create more powerful research designs, thus yielding more reliable and reproducible results and helping to further advance understanding in this evolving field of research

OH airglow observations with two identical spectrometers: benefits of increased data homogeneity in the identification of variations induced by the 11-year solar cycle, the QBO, and other factors

Hydroxyl (OH) radical airglow observations have been performed at the environmental research station “Schneefernerhaus” (UFS; 47.42∘ N, 10.98∘ E) since October 2008, with continuous operation since July 2009. The instrumental setup relies on the parallel operation of two identical instruments, each a GRIPS (GRound-based Infrared P-branch Spectrometer), in order to achieve maximum completeness and homogeneity. After the first decade of observations the acquired time series are evaluated with respect to the main influences on data quality and comparability to those at other sites. Data quality is essentially limited by gaps impacting the completeness. While technical failures are largely excluded by the setup, gaps caused by adverse meteorological conditions can systematically influence estimates of the annual mean. The overall sampling density is high, with nightly mean temperatures obtained for 3382 of 4018 nights of observation (84 %), but the average coverage changes throughout the year. This can bias the annual mean up to 0.8 K if not properly accounted for. Sensitivity studies performed with the two identical instruments and their retrievals show that the comparability between the observations is influenced by the annual and semiannual cycle as well as the choice of Einstein-A coefficients, which influence the estimate of the annual cycle's amplitude. A strong 11-year solar signal of 5.9±0.6 K per 100 sfu is identified in the data. The OH temperatures follow the F10.7 cm value with a time lag of 90±65 d. However, the precise value depends on details of the analysis. The highest correlation (R2=0.91) is achieved for yearly mean OH temperatures averaged around 4 February and the F10.7 cm solar flux leading ahead with 110 d. A prominent 2-year oscillation is identified between 2011 and 2015. This signal is linked to the quasi-biennial oscillation (QBO), leading to a temperature reduction of approximately 1 K during QBO westward phases in 2011, 2013, and 2015 and a respective 1 K increase in 2012 and 2014 during QBO eastward phases. The amplitude of the semiannual cycle shows a similar behavior with the decade's minimum amplitudes (∼ 2.5–3 K) retrieved for 2011, 2013, and 2015 and maximum amplitudes observed in 2012 and 2014 (∼4 K). The signal appears to disappear after 2016 when the solar flux approaches its next minimum. Although it appears as a rather strict 24-month periodicity between 2011 and 2015, spectral analyses show a more or less continuous oscillation with a period of approximately 21 months over the entire time span, which can be interpreted as the result of a nonlinear interaction of the QBO (28 months) with the annual cycle (12 months).</p

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

Seasonal and intra-diurnal variability of small-scale gravity waves in OH airglow at two Alpine stations

Between December 2013 and August 2017 the instrument FAIM (Fast Airglow IMager) observed the OH airglow emission at two Alpine stations. A year of measurements was performed at Oberpfaffenhofen, Germany (48.09∘&thinsp;N, 11.28∘&thinsp;E) and 2 years at Sonnblick, Austria (47.05∘&thinsp;N, 12.96∘&thinsp;E). Both stations are part of the network for the detection of mesospheric change (NDMC). The temporal resolution is two frames per second and the field-of-view is 55&thinsp;km&thinsp;×&thinsp;60&thinsp;km and 75&thinsp;km&thinsp;×&thinsp;90&thinsp;km at the OH layer altitude of 87&thinsp;km with a spatial resolution of 200 and 280&thinsp;m per pixel, respectively. This resulted in two dense data sets allowing precise derivation of horizontal gravity wave parameters. The analysis is based on a two-dimensional fast Fourier transform with fully automatic peak extraction. By combining the information of consecutive images, time-dependent parameters such as the horizontal phase speed are extracted. The instrument is mainly sensitive to high-frequency small- and medium-scale gravity waves. A clear seasonal dependency concerning the meridional propagation direction is found for these waves in summer in the direction to the summer pole. The zonal direction of propagation is eastwards in summer and westwards in winter. Investigations of the data set revealed an intra-diurnal variability, which may be related to tides. The observed horizontal phase speed and the number of wave events per observation hour are higher in summer than in winter.</p

A comparative study of the use of organic carbon and loss on ignition in defining tropical organic soil materials

Organic soils or Histosols or peats as they are commonly referred to, are characterized by the presence of large amounts of organic soil materials (OSM), which is commonly quantified by the Walkley and Black (1934) (WB) method to determine the soil organic matter (SOM) using a correction factor of 1.724. SOM of Histosols is also identified through a combustion (loss on ignition, LOI) or elemental C-analysis (with a carbon-nitrogen-sulfur (CNS) analyzer with combustion and gas density detector). These methods were established using temperate and boreal peat deposits and here we demonstrate that tropical peat deposits require a modified approach. Typical SE-Asian tropical lowland peat pedons from rain forest and oil palm settings were sampled and the material analysed using a CNS analyzer, WB-C and LOI. The ratios for LOI:CNS-C for the 20 samples yielded values between 2.00-3.09 with a mean of 2.50 while the LOI:WB-C ratio yielded values from 1.75 to 2.58 with a mean of 1.94. A comparison of these values for topsoils and subsoils showed mean ratios (LOI:WB-C) of 1.94 and 1.89 for topsoils and subsoils, respectively. The forest samples had higher LOI:WB-C ratios than the subsoils from oil palm settings (1.94 vs 1.84). These values suggest that the standard factor of 1.724 to correct OSM to SOM for tropical soils is untenable. The values to convert CNS and WB-C values of tropical topsoils/subsoils to SOM or LOI should be 2.5 or 1.9, respectively. Our results indicate a significant difference in the soil organic carbon (SOC) of tropical lowland peats depending on the method used

Bryophyllum pinnatum enhances the inhibitory effect of atosiban and nifedipine on human myometrial contractility: an in vitro study

BACKGROUND The herbal medicine Bryophyllum pinnatum has been used as a tocolytic agent in anthroposophic medicine and, recently, in conventional settings alone or as an add-on medication with tocolytic agents such as atosiban or nifedipine. We wanted to compare the inhibitory effect of atosiban and nifedipine on human myometrial contractility in vitro in the absence and in the presence of B. pinnatum press juice (BPJ). METHODS Myometrium biopsies were collected during elective Caesarean sections. Myometrial strips were placed under tension into an organ bath and allowed to contract spontaneously. Test substances alone and at concentrations known to moderately affect contractility in this setup, or in combination, were added to the organ bath, and contractility was recorded throughout the experiments. Changes in the strength (measured as area under the curve (AUC) and amplitude) and frequency of contractions after the addition of all test substances were determined. Cell viability assays were performed with the human myometrium hTERT-C3 and PHM1-41 cell lines. RESULTS BPJ (2.5 μg/mL), atosiban (0.27 μg/mL), and nifedipine (3 ng/mL), moderately reduced the strength of spontaneous myometrium contractions. When BPJ was added together with atosiban or nifedipine, inhibition of contraction strength was significantly higher than with the tocolytics alone (p = 0.03 and p < 0.001, respectively). In the case of AUC, BPJ plus atosiban promoted a decrease to 48.8 ± 6.3% of initial, whereas BPJ and atosiban alone lowered it to 70.9 ± 4.7% and to 80.9 ± 4.1% of initial, respectively. Also in the case of AUC, BPJ plus nifedipine promoted a decrease to 39.9 ± 4.6% of initial, at the same time that BPJ and nifedipine alone lowered it to 78.9 ± 3.8% and 71.0 ± 3.4% of initial. Amplitude data supported those AUC data. The inhibitory effects of BPJ plus atosiban and of BPJ plus nifedipine on contractions strength were concentration-dependent. None of the test substances, alone or in combination, decreased myometrial cell viability. CONCLUSIONS BPJ enhances the inhibitory effect of atosiban and nifedipine on the strength of myometrial contractions, without affecting myometrium tissue or cell viability. The combination treatment of BPJ with atosiban or nifedipine has therapeutic potential

Smoothing data series by means of cubic splines: quality of approximation and introduction of a repeating spline approach

Cubic splines with equidistant spline sampling points are a common method in atmospheric science, used for the approximation of background conditions by means of filtering superimposed fluctuations from a data series. What is defined as background or superimposed fluctuation depends on the specific research question. The latter also determines whether the spline or the residuals – the subtraction of the spline from the original time series – are further analysed.Based on test data sets, we show that the quality of approximation of the background state does not increase continuously with an increasing number of spline sampling points and/or decreasing distance between two spline sampling points. Splines can generate considerable artificial oscillations in the background and the residuals.We introduce a repeating spline approach which is able to significantly reduce this phenomenon. We apply it not only to the test data but also to TIMED-SABER temperature data and choose the distance between two spline sampling points in a way that is sensitive for a large spectrum of gravity waves