All animals must detect noxious stimuli to initiate protective behavior, but the evolutionary origin of nociceptive systems is not well understood. Here we show that noxious heat and irritant ...chemicals elicit robust escape behaviors in the planarian Schmidtea mediterranea and that the conserved ion channel TRPA1 is required for these responses. TRPA1-mutant Drosophila flies are also defective in noxious-heat responses. We find that either planarian or human TRPA1 can restore noxious-heat avoidance to TRPA1-mutant Drosophila, although neither is directly activated by heat. Instead, our data suggest that TRPA1 activation is mediated by H
O
and reactive oxygen species, early markers of tissue damage rapidly produced as a result of heat exposure. Together, our data reveal a core function for TRPA1 in noxious heat transduction, demonstrate its conservation from planarians to humans, and imply that animal nociceptive systems may share a common ancestry, tracing back to a progenitor that lived more than 500 million years ago.
The Drosophila antenna contains receptor neurons for mechanical, olfactory, thermal, and humidity stimuli. Neurons expressing the ionotropic receptor IR40a have been implicated in the selection of an ...appropriate humidity range 1, 2, but although previous work indicates that insect hygroreceptors may be made up by a “triad” of neurons (with a dry-, a cold-, and a humid-air-responding cell 3), IR40a expression included only cold- and dry-air cells. Here, we report the identification of the humid-responding neuron that completes the hygrosensory triad in the Drosophila antenna. This cell type expresses the Ir68a gene, and Ir68a mutation perturbs humidity preference. Next, we follow the projections of Ir68a neurons to the brain and show that they form a distinct glomerulus in the posterior antennal lobe (PAL). In the PAL, a simple sensory map represents related features of the external environment with adjacent “hot,” “cold,” “dry,” and “humid” glomeruli—an organization that allows for both unique and combinatorial sampling by central relay neurons. Indeed, flies avoided dry heat more robustly than humid heat, and this modulation was abolished by silencing of dry-air receptors. Consistently, at least one projection neuron type received direct synaptic input from both temperature and dry-air glomeruli. Our results further our understanding of humidity sensing in the Drosophila antenna, uncover a neuronal substrate for early sensory integration of temperature and humidity in the brain, and illustrate the logic of how ethologically relevant combinations of sensory cues can be processed together to produce adaptive behavioral responses.
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•Fly hygroreceptors are composed of a “triad,” with a dry, a cold, and a humid cell•Humid-sensing neurons require the ionotropic receptor IR68a•Axons of dry and humid receptors and of thermoreceptors form a combined sensory map•Second-order projection neurons include mono- and multi-modal cell types
Frank et al. describe humid-air receptors in the fly antenna. Previous work identified dry-air receptors, and they now show that humid and dry cells converge with thermosensory neurons in the brain, creating a sensory map for environmental parameters. They also describe second-order neurons that sample multiple modalities for early integration
Abstract
Cancer-associated fibroblast (CAF), an activated type of fibroblast, is a major stromal cell that contributes to tumor initiation and development in the tumor microenvironment (TME). We ...previously reported that fractionated radiation rather than acute radiation causes progressive damage to mitochondria and increases the generation of reactive oxygen species, playing an important role in the fibroblast activation in normal tissue injury. Activated fibroblasts then become CAF by interacting with tumor cells, promoting tumor growth in vivo. We here examined the chronic radiation effect on fibroblast activation. Acute radiation (<2.5 Gy) did not increase alpha-Smooth muscle actin, a CAF marker expression in healthy human cells, whereas chronic radiation (2.5 Gy) did. It can be concluded that the induction of fibroblast activation changes across acute radiation, fractionated radiation, and chronic radiation depending on the irradiation technique. This study highlights that radiation activates fibroblasts, playing a role in radiation-related tumor development via TME formation.
Simple innate behavior is often described as hard-wired and largely inflexible. Here, we show that the avoidance of hot temperature, a simple innate behavior, contains unexpected plasticity in ...Drosophila. First, we demonstrate that hot receptor neurons of the antenna and their molecular heat sensor, Gr28B.d, are essential for flies to produce escape turns away from heat. High-resolution fly tracking combined with a 3D simulation of the thermal environment shows that, in steep thermal gradients, the direction of escape turns is determined by minute temperature differences between the antennae (0.1°-1 °C). In parallel, live calcium imaging confirms that such small stimuli reliably activate both peripheral thermosensory neurons and central circuits. Next, based on our measurements, we evolve a fly/vehicle model with two symmetrical sensors and motors (a "Braitenberg vehicle") which closely approximates basic fly thermotaxis. Critical differences between real flies and the hard-wired vehicle reveal that fly heat avoidance involves decision-making, relies on rapid learning, and is robust to new conditions, features generally associated with more complex behavior.
ABSTRACT
In 2021 BL Lacertae underwent an extraordinary activity phase, which was intensively followed by the Whole Earth Blazar Telescope (WEBT) Collaboration. We present the WEBT optical data in ...the BVRI bands acquired at 36 observatories around the world. In mid-2021 the source showed its historical maximum, with R = 11.14. The light curves display many episodes of intraday variability, whose amplitude increases with source brightness, in agreement with a geometrical interpretation of the long-term flux behaviour. This is also supported by the long-term spectral variability, with an almost achromatic trend with brightness. In contrast, short-term variations are found to be strongly chromatic and are ascribed to energetic processes in the jet. We also analyse the optical polarimetric behaviour, finding evidence of a strong correlation between the intrinsic fast variations in flux density and those in polarization degree, with a time delay of about 13 h. This suggests a common physical origin. The overall behaviour of the source can be interpreted as the result of two mechanisms: variability on time-scales greater than several days is likely produced by orientation effects, while either shock waves propagating in the jet, or magnetic reconnection, possibly induced by kink instabilities in the jet, can explain variability on shorter time-scales. The latter scenario could also account for the appearance of quasi-periodic oscillations, with periods from a few days to a few hours, during outbursts, when the jet is more closely aligned with our line of sight and the time-scales are shortened by relativistic effects.
Context. The BL Lac object 3C 371 was observed by the Transiting Exoplanet Survey Satellite (TESS) for approximately a year, between July 2019 and July 2020, with an unmatched two-minute imaging ...cadence. In parallel, the Whole Earth Blazar Telescope (WEBT) Collaboration organized an extensive observing campaign, providing three years of continuous optical monitoring between 2018 and 2020. These datasets allow for a thorough investigation of the variability of the source. Aims. The goal of this study is to evaluate the optical variability of 3C 371. Taking advantage of the remarkable cadence of TESS data, we aim to characterize the intra-day variability (IDV) displayed by the source and identify its shortest variability timescale. With this estimate, constraints on the size of the emitting region and black hole mass can be calculated. Moreover, WEBT data are used to investigate long-term variability (LTV), including in terms of the spectral behavior of the source and the polarization variability. Based on the derived characteristics, we aim to extract information on the origin of the variability on different timescales. Methods. We evaluated the variability of 3C 371 by applying the variability amplitude tool, which quantifies variability of the emission. Moreover, we employed common tools, such as ANOVA (ANalysis Of VAariance) tests, wavelet and power spectral density (PSD) analyses to characterize the shortest variability timescales present in the emission and the underlying noise affecting the data. We evaluated the short- and long-term color behavior to understand its spectral behavior. The polarized emission was analyzed, studying its variability and possible rotation patterns of the electric vector position angle (EVPA). Flux distributions of the IDV and LTV were also studied with the aim being to link the flux variations to turbulent and/or accretion-disk-related processes. Results. Our ANOVA and wavelet analyses reveal several entangled variability timescales. We observe a clear increase in the variability amplitude with increasing width of the time intervals evaluated. We are also able to resolve significant variations on timescales of as little as ∼0.5 h. The PSD analysis reveals a red-noise spectrum with a break at IDV timescales. The spectral analysis shows a mild bluer-when-brighter (BWB) trend on long timescales. On short timescales, mixed BWB, achromatic and redder-when-brighter signatures can be observed. The polarized emission shows an interesting slow EVPA rotation during the flaring period, where a simple stochastic model can be excluded as the origin with a 3 σ significance. The flux distributions show a preference for a Gaussian model for the IDV, and suggest it may be linked to turbulent processes, while the LTV is better represented by a log-normal distribution and may have a disk-related origin.
Humidity Sensing in Drosophila Enjin, Anders; Zaharieva, Emanuela E.; Frank, Dominic D. ...
Current biology,
05/2016, Letnik:
26, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Environmental humidity influences the fitness and geographic distribution of all animals 1. Insects in particular use humidity cues to navigate the environment, and previous work suggests the ...existence of specific sensory mechanisms to detect favorable humidity ranges 2–5. Yet, the molecular and cellular basis of humidity sensing (hygrosensation) remains poorly understood. Here we describe genes and neurons necessary for hygrosensation in the vinegar fly Drosophila melanogaster. We find that members of the Drosophila genus display species-specific humidity preferences related to conditions in their native habitats. Using a simple behavioral assay, we find that the ionotropic receptors IR40a, IR93a, and IR25a are all required for humidity preference in D. melanogaster. Yet, whereas IR40a is selectively required for hygrosensory responses, IR93a and IR25a mediate both humidity and temperature preference. Consistent with this, the expression of IR93a and IR25a includes thermosensory neurons of the arista. In contrast, IR40a is excluded from the arista but is expressed (and required) in specialized neurons innervating pore-less sensilla of the sacculus, a unique invagination of the third antennal segment. Indeed, calcium imaging showed that IR40a neurons directly respond to changes in humidity, and IR40a knockdown or IR93a mutation reduced their responses to stimuli. Taken together, our results suggest that the preference for a specific humidity range depends on specialized sacculus neurons, and that the processing of environmental humidity can happen largely in parallel to that of temperature.
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•Drosophila species prefer distinct humidity ranges, related to their native habitat•The ionotropic receptors IR25a, IR93a, and IR40a are all required for RH preference•RH changes are sensed by IR40a neurons in the sacculus, an antennal substructure•RH and temperature are processed by different cells in the Drosophila antenna
Enjin et al. describe genes and neurons necessary for humidity responses in Drosophila. Humidity responses require the ionotropic receptors IR25a, IR93a, and IR40a, expressed in specialized neurons of the antennal sacculus. Humidity preference is innate and species specific: “desert” flies prefer a drier environment, while “rainforest” flies prefer a humid one.
Compared to type 1 diabetes, the role of the immune and autoimmune pathogenetic mechanisms is much less studied in the type 2 diabetes. Toll-like receptors 4 (TLR4) have a leading role in ...inflammation, insulin resistance, and vascular damage. This study aimed to analyze the relationship between the polymorphisms in
gene and different stages in the glucose continuum from prediabetes to the type 2 diabetes and chronic microvascular complications.
The study included 113 patients with the type 2 diabetes, 29 participants with prediabetes, and 28 controls. Polymerase chain reaction (PCR) was used for genotyping Asp299Gly and Thr399Ile polymorphism, followed by restriction analysis.
The difference in the genotype frequency for both polymorphisms in patients with the type 2 diabetes or prediabetes compared to that in controls was not significant. Patients with heterozygous genotype of Asp299Gly polymorphism had a higher prevalence of diabetic retinopathy (42.9%) than participants with homozygous genotype (9.0%) (OR 95%CI=7.61 1.41–41.08; p=0.018). No association was established for diabetic polyneuropathy and nephropathy. Prevalence of chronic diabetes complications was not related to Thr399Ile polymorphism.
Our study demonstrates that Asp299Gly and Thr399Ile polymorphisms seem not to be associated with the type 2 diabetes and prediabetes but Asp299Gly may contribute to diabetic retinopathy predisposition.
Determining the pattern of activity of individual connections within a neural circuit could provide insights into the computational processes that underlie brain function. Here, we develop new ...strategies to label active synapses by trans-synaptic fluorescence complementation in Drosophila. First, we demonstrate that a synaptobrevin-GRASP chimera functions as a powerful activity-dependent marker for synapses in vivo. Next, we create cyan and yellow variants, achieving activity-dependent, multi-colour fluorescence reconstitution across synapses (X-RASP). Our system allows for the first time retrospective labelling of synapses (rather than whole neurons) based on their activity, in multiple colours, in the same animal. As individual synapses often act as computational units in the brain, our method will promote the design of experiments that are not possible using existing techniques. Moreover, our strategies are easily adaptable to circuit mapping in any genetic system.
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