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Water sensation is a specific taste modality in the fruit fly. Water-induced hypoosmolarity activates specific gustatory receptor neurons; however, the molecular identity of the putative osmolarity sensor in these neurons remains unknown. We found that amiloride and its analogs specificallyantagonizedtheresponseofwatergustatoryreceptorneuronsandthebehavioroffliestowardwaterstimulation.Deletionofthegene that encodes the amiloride-sensitive PPK28 channel, a DEG/eNaC (degenerin/epithelial sodium channel) family member, abolished the waterinduced activity of water gustatory receptor neurons and greatly diminished the behavioral response of flies to water. Ectopic expression of the PPK28 channel in the bitter cells within the intermediate-type sensilla renders these sensilla responsive to water stimuli. Thus, the amiloridesensitive PPK28 channel may serve as the osmolarity sensor for gustatory water reception in the fruit fly.

Drosophila larval locomotion, which entails rhythmic body contractions, is controlled by sensory feedback from proprioceptors. The molecular mechanisms mediating this feedback are little understood. By using genetic knock-in and immunostaining, we found that the Drosophila melanogaster transmembrane channel-like (tmc) gene is expressed in the larval class I and class II dendritic arborization (da) neurons and bipolar dendrite (bd) neurons, both of which are known to provide sensory feedback for larval locomotion. Larvae with knockdown or loss of tmc function displayed reduced crawling speeds, increased head cast frequencies, and enhanced backward locomotion. Expressing Drosophila TMC or mammalian TMC1 and/or TMC2 in the tmc-positive neurons rescued these mutant phenotypes. Bending of the larval body activated the tmc-positive neurons, and in tmc mutants this bending response was impaired. This implicates TMC's roles in Drosophila proprioception and the sensory control of larval locomotion. It also provides evidence for a functional conservation between Drosophila and mammalian TMCs.proprioception | locomotion | mechanosensation

In Drosophila larvae, the class IV dendritic arborization (da) neurons are polymodal nociceptors. Here, we show that ppk26 (CG8546) plays an important role in mechanical nociception in class IV da neurons. Our immunohistochemical and functional results demonstrate that ppk26 is specifically expressed in class IV da neurons. Larvae with mutant ppk26 showed severe behavioral defects in a mechanical nociception behavioral test but responded to noxious heat stimuli comparably to wild-type larvae. In addition, functional studies suggest that ppk26 and ppk (also called ppk1) function in the same pathway, whereas piezo functions in a parallel pathway. Consistent with these functional results, we found that PPK and PPK26 are interdependent on each other for their cell surface localization. Our work indicates that PPK26 and PPK might form heteromeric DEG/ENaC channels that are essential for mechanotransduction in class IV da neurons.

BackgroundItch, chronic itch in particular, can have a significant negative impact on an individual’s quality of life. However, the molecular mechanisms underlying itch processing in the central nervous system remain largely unknown.ResultsWe report here that activation of ERK signaling in the spinal cord is required for itch sensation. ERK activation, as revealed by anti-phosphorylated ERK1/2 immunostaining, is observed in the spinal dorsal horn of mice treated with intradermal injections of histamine and compound 48/80 but not chloroquine or SLIGRL-NH2, indicating that ERK activation only occurs in histamine-dependent acute itch. In addition, ERK activation is also observed in 2, 4-dinitrofluorobenzene (DNFB)-induced itch. Consistently, intrathecal administration of the ERK phosphorylation inhibitor U0126 dramatically reduces the scratching behaviors induced by histamine and DNFB, but not by chloroquine. Furthermore, administration of the histamine receptor H1 antagonist chlorpheniramine decreases the scratching behaviors and ERK activation induced by histamine, but has no effect on DNFB-induced itch responses. Finally, the patch-clamp recording shows that in histamine-, chloroquine- and DNFB-treated mice the spontaneous excitatory postsynaptic current (sEPSC) of dorsal horn neurons is increased, and the decrease of action potential threshold is largely prevented by bathing of U0126 in histamine- and DNFB-treated mice but not those treated with chloroquine.ConclusionOur results demonstrate a critical role for ERK activation in itch sensation at the spinal level.

Patients with rheumatic diseases are often more susceptible to different bacteria and viruses because of immune impairment, but it is not clear whether there is a higher risk of infection and a more serious course of disease for novel coronavirus (SARS-CoV-2). We performed this systematic review and meta analysis to assess the risk and clinical outcomes of COVID-19 in patients with rheumatic diseases compared with the general population. We searched PubMed, EMBASE, Scopus and Web of Science databases from January 1, 2020 to October 20, 2020 to determine epidemiological information related to patients with rheumatic diseases and COVID-19, including clear risk estimate or data that could be converted and extracted. We included 26 observational studies, totaling about 2000 patients with rheumatic diseases of whom were infected with COVID-19. Meta-analysis showed that the risk of COVID-19 infection in rheumatic patients was significantly higher than that in the general population (OR = 1.53, 95% CI 1.24–1.88, P = 0.000). In terms of hospitalization and severe clinical outcomes associated with COVID-19, we found that rheumatic patients showed similar results to the reference population (hospitalization OR = 1.36, 95% CI 0.81–2.29, P = 0.247; admitted to ICU OR = 1.94, 95% CI 0.88–4.27, P = 0.098; death OR = 1.29, 95% CI 0.84–1.97, P = 0.248). The presence of comorbidities, hypertension, lung diseases were significantly associated with the increased risk of COVID-19-related hospitalization in rheumatic patients and anti-TNF drugs were associated with lower hospitalization risk. Older age was related to severe COVID-19. Our meta-analysis indicated that rheumatic patients were at a higher risk of COVID-19 infection but might not lead to a more serious disease process. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-04803-9.

In insects, olfactory information received by peripheral olfactory receptor neurons (ORNs) is conveyed from the antennal lobes (ALs) to higher brain regions by olfactory projection neurons (PNs). Despite the knowledge that multiple types of PNs exist, little is known about how these different neuronal pathways work cooperatively. Here we studied the Drosophila GABAergic mediolateral antennocerebral tract PNs (mlPNs), which link ipsilateral AL and lateral horn (LH), in comparison with the cholinergic medial tract PNs (mPNs). We examined the connectivity of mlPNs in ALs and found that most mlPNs received inputs from both ORNs and mPNs and participated in AL network function by forming gap junctions with other AL neurons. Meanwhile, mlPNs might innervate LH neurons downstream of mPNs, exerting a feedforward inhibition. Using dual-color calcium imaging, which enables a simultaneous monitoring of neural activities in two groups of PNs, we found that mlPNs exhibited robust odor responses overlapping with, but broader than, those of mPNs. Moreover, preferentially down-regulation of GABA in most mlPNs caused abnormal courtship and aggressive behaviors in male flies. These findings demonstrate that in Drosophila, olfactory information in opposite polarities are carried coordinately by two parallel and interacted pathways, which could be essential for appropriate behaviors.circuit | electrical coupling | electrophysiology | multicolor calcium imaging | multiglomerular I n insects, the detection of olfactory cues begins at the peripheral olfactory receptor neurons (ORNs), which transfer the chemical information into neural signals and convey them to the first central relay station-the antennal lobes (ALs) (1-3). After AL local processing, olfactory information is relayed to higher brain regions via different groups of projection neurons (PNs) (4-6). Except some pioneering studies in Hymenopterans (7-11) and Lepidopterans (12), little is known about how these different PNs connect in the olfactory circuit and work physiologically. As the most studied PN type in Drosophila, the cholinergic PNs (mPNs) form the medial antennocerebral tract and convey excitatory signals encoding odor identity and intensity (13-15) that are necessary for the fly to perform appropriate behaviors (16,17). However, how olfactory information is delivered via pathways mediated by PNs other than mPNs remains to be elucidated. In this study, we focused on the mediolateral antennocerebral tract PNs (mlPNs), which are the second largest PN subset (∼50 mlPNs in each hemisphere) and reported to be largely GABAergic with axons terminating mainly in the lateral horn (LH) (18,19). Based on the extent of their dendritic arborization, mlPNs can be further categorized into three subtypes: the uniglomerular mlPNs (type 1 mlPNs, mlPN1s); the multiglomerular mlPNs (mlPN2s), which comprise the great majority (>80%) of mlPNs; and the panglomerular mlPNs (mlPN3s) (19). Here we focused on mlPN1s and mlPN2s, which exclusively link ALs with the ipsilateral LH and were la...

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