Mapping the Contact Sites of the Escherichia coli Division-Initiating Proteins FtsZ and ZapA by BAMG Cross-Linking and Site-Directed Mutagenesis.

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Mapping the Contact Sites of the Escherichia coli Division-Initiating Proteins FtsZ and ZapA by BAMG Cross-Linking and Site-Directed Mutagenesis.

Int J Mol Sci. 2018 Sep 26;19(10):

Authors: Roseboom W, Nazir MG, Meiresonne NY, Mohammadi T, Verheul J, Buncherd H, Bonvin AMJJ, de Koning LJ, de Koster CG, de Jong L, den Blaauwen T

Abstract
Cell division in bacteria is initiated by the polymerization of FtsZ at midcell in a ring-like structure called the Z-ring. ZapA and other proteins assist Z-ring formation and ZapA binds ZapB, which senses the presence of the nucleoids. The FtsZ⁻ZapA binding interface was analyzed by chemical cross-linking mass spectrometry (CXMS) under in vitro FtsZ-polymerizing conditions in the presence of GTP. Amino acids residue K42 from ZapA was cross-linked to amino acid residues K51 and K66 from FtsZ, close to the interphase between FtsZ molecules in protofilaments. Five different cross-links confirmed the tetrameric structure of ZapA. A number of FtsZ cross-links suggests that its C-terminal domain of 55 residues, thought to be largely disordered, has a limited freedom to move in space. Site-directed mutagenesis of ZapA reveals an interaction site in the globular head of the protein close to K42. Using the information on the cross-links and the mutants that lost the ability to interact with FtsZ, a model of the FtsZ protofilament⁻ZapA tetramer complex was obtained by information-driven docking with the HADDOCK2.2 webserver.

PMID: 30261644 [PubMed - in process]

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Sentinels at the wall: epithelial-derived cytokines serve as triggers of upper airway type 2 inflammation.

Sentinels at the wall: epithelial-derived cytokines serve as triggers of upper airway type 2 inflammation.

Int Forum Allergy Rhinol. 2018 Sep 10;:

Authors: Patel NN, Kohanski MA, Maina IW, Workman AD, Herbert DR, Cohen NA

Abstract
Recent evidence has demonstrated an expanding role of respiratory epithelial cells in immune surveillance and modulation. Studies have been focusing on the earliest events that link epithelial injury to downstream inflammatory responses. Cytokines produced by and released from respiratory epithelial cells are among these early trigger signals. Epithelial-derived cytokines, namely thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33, have come to the forefront of recent investigations. Each of these 3 cytokines has been implicated in chronic rhinosinusitis (CRS), asthma, and atopy. Herein we review studies elucidating the roles of epithelial-derived cytokines in the pathobiology of upper airway disease, with particular emphasis on type 2 inflammatory conditions.

PMID: 30260580 [PubMed - as supplied by publisher]

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Can the Identification of Odorants Within a Mixture Be Trained?

Can the Identification of Odorants Within a Mixture Be Trained?

Chem Senses. 2018 Sep 27;:

Authors: Poupon D, Fernandez P, Boisvert SA, Migneault-Bouchard C, Frasnelli J

Abstract
Identifying odors within mixtures is a difficult task: humans are able to recognize only up to 4 odors within a mixture. We wanted to test the effects of olfactory training on this ability. We used 7 odorants to create 35 olfactory stimuli of 1, 2, 3, 4, or 5 odorants. The task consisted of identifying the odorants present within the mixture. We trained novices on this task for 5 days: they came to the laboratory to perform the task once a day before coming back for the final testing. Then, we compared them to sommeliers, thus olfaction experts, and untrained novices. Results showed that sommeliers outperformed the other groups with mixtures of up to 4 odorants but not with mixtures of 5 odorants. The short olfactory training allowed trained participants to perform as well as sommeliers when it came to identifying single odorants but was not enough to improve their performance when stimuli were mixtures of 2 or more odorants. This study supports the idea that the number of odors we can recognize within a mixture is limited but suggests training can improve the performance: a short olfactory training is enough to enhance the ability to identify single odorants, whereas expertise refines identification ability of mixtures of up to 4 odorants.

PMID: 30260369 [PubMed - as supplied by publisher]

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Signal detection and coding in the accessory olfactory system.

Signal detection and coding in the accessory olfactory system.

Chem Senses. 2018 Sep 25;:

Authors: Mohrhardt J, Nagel M, Fleck D, Ben-Shaul Y, Spehr M

Abstract
In many mammalian species, the accessory olfactory system (AOS) plays a central role in guiding behavioral and physiological responses to social and reproductive interactions. Because of its relatively compact structure and its direct access to amygdalar and hypothalamic nuclei, the accessory olfactory pathway provides an ideal system to study sensory control of complex mammalian behavior. During the last several years, many studies employing molecular, behavioral, and physiological approaches have significantly expanded and enhanced our understanding of this system. The purpose of the current review is to integrate older and newer studies to present an updated and comprehensive picture of vomeronasal signaling and coding with an emphasis on early AOS processing stages. These include vomeronasal sensory neurons (VSNs) in the vomeronasal organ (VNO), and the circuitry of the accessory olfactory bulb (AOB). Because the overwhelming majority of studies on AOS function employ rodents, this review is largely focused on this phylogenetic order, and on mice in particular. Taken together, the emerging view from both older literature and more recent studies is that the molecular, cellular and circuit properties of chemosensory signaling along the accessory olfactory pathway are in many ways unique. Yet, it has also become evident that, like the main olfactory system (MOS), the AOS also has the capacity for adaptive learning, experience, and state-dependent plasticity. In addition to describing what is currently known about AOS function and physiology, we highlight what we believe are important gaps in our knowledge, which thus define exciting directions for future investigation.

PMID: 30256909 [PubMed - as supplied by publisher]

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Sharing an environment with sick conspecifics alters odors of healthy animals.

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Sharing an environment with sick conspecifics alters odors of healthy animals.

Sci Rep. 2018 Sep 24;8(1):14255

Authors: Gervasi SS, Opiekun M, Martin T, Beauchamp GK, Kimball BA

Abstract
Body odors change with health status and the odors of sick animals can induce avoidance behaviors in healthy conspecifics. Exposure to sickness odors might also alter the physiology of healthy conspecifics and modify the odors they produce. We hypothesized that exposure to odors of sick (but non-infectious) animals would alter the odors of healthy cagemates. To induce sickness, we injected mice with a bacterial endotoxin, lipopolysaccharide. We used behavioral odor discrimination assays and analytical chemistry techniques followed by predictive classification modeling to ask about differences in volatile odorants produced by two types of healthy mice: those cohoused with healthy conspecifics and those cohoused with sick conspecifics. Mice trained in Y-maze behavioral assays to discriminate between the odors of healthy versus sick mice also discriminated between the odors of healthy mice cohoused with sick conspecifics and odors of healthy mice cohoused with healthy conspecifics. Chemical analyses paired with statistical modeling revealed a parallel phenomenon. Urine volatiles of healthy mice cohoused with sick partners were more likely to be classified as those of sick rather than healthy mice based on discriminant model predictions. Sickness-related odors could have cascading effects on neuroendocrine or immune responses of healthy conspecifics, and could affect individual behaviors, social dynamics, and pathogen spread.

PMID: 30250285 [PubMed - in process]

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Anxiety Body Odors as Context for Dynamic Faces: Categorization and Psychophysiological Biases.

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Anxiety Body Odors as Context for Dynamic Faces: Categorization and Psychophysiological Biases.

Perception. 2018 Sep 19;:301006618797227

Authors: Rocha M, Parma V, Lundström JN, Soares SC

Abstract
Body odors (BOs) can convey social information. In particular, their effects are maximal when their presence is paired with meaningful social contexts. Static faces have been widely used as social stimuli. However, they miss a key feature of our phenomenological experience, characterized by multisensory dynamic stimulations. Here, we investigate how BO sampled from individuals experiencing a transitory anxiety state, (a) induce a stress response and (b) bias the recognition of dynamic facial expressions, compared with BO of relaxed individuals. Participants ( n=46) categorized the emotion of a face, morphing from a neutral expression to either an angry or happy expression, during exposure to either BO condition. In addition, their cardiac activity was measured. Exposure to anxiety BO increased the accuracy of dynamic facial recognition and reduced cardiac parasympathetic activity. These results suggest that in social situations that simulate part of the multisensory and dynamic features of real-life social contexts, anxiety BOs will induce a stress response in recipients, modulating both arousal and cognitive-emotional skills but facilitating emotional facial processing.

PMID: 30231844 [PubMed - as supplied by publisher]

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Individual Differences in the Perception of Color Solutions.

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Individual Differences in the Perception of Color Solutions.

Foods. 2018 Sep 18;7(9):

Authors: Hoppu U, Puputti S, Aisala H, Laaksonen O, Sandell M

Abstract
The color of food is important for flavor perception and food selection. The aim of the present study was to evaluate the visual color perception of liquid samples among Finnish adult consumers by their background variables. Participants (n = 205) ranked six different colored solutions just by looking according to four attributes: from most to least pleasant, healthy, sweet and sour. The color sample rated most frequently as the most pleasant was red (37%), the most healthy white (57%), the most sweet red and orange (34% both) and the most sour yellow (54%). Ratings of certain colors differed between gender, age, body mass index (BMI) and education groups. Females regarded the red color as the sweetest more often than males (p = 0.013) while overweight subjects rated the orange as the sweetest more often than normal weight subjects (p = 0.029). Personal characteristics may be associated with some differences in color associations.

PMID: 30231463 [PubMed]

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Calmodulin regulates MGRN1-GP78 interaction mediated ubiquitin proteasomal degradation system.

Calmodulin regulates MGRN1-GP78 interaction mediated ubiquitin proteasomal degradation system.

FASEB J. 2018 Sep 19;:fj201701413RRR

Authors: Mukherjee R, Bhattacharya A, Sau A, Basu S, Chakrabarti S, Chakrabarti O

Abstract
The mechanism by which the endoplasmic reticulum (ER) ubiquitin ligases sense stress to potentiate their activity is poorly understood. GP78, an ER E3 ligase, is best known for its role in ER-associated protein degradation, although its activity is also linked to mitophagy, ER-mitochondria junctions, and MAPK signaling, thus highlighting the importance of understanding its regulation. In healthy cells, Mahogunin really interesting new gene (RING) finger 1 (MGRN1) interacts with GP78 and proteasomally degrades it to alleviate mitophagy. Here, we identify calmodulin (CaM) as the adapter protein that senses fluctuating cytosolic Ca2+ levels and modulates the Ca2+-dependent MGRN1-GP78 interactions. When stress elevates cytosolic Ca2+ levels in cultured and primary neuronal cells, CaM binds to both E3 ligases and inhibits their interaction. Molecular docking, simulation, and biophysical studies show that CaM interacts with both proteins with different affinities and binding modes. The physiological impact of this interaction switch manifests in the regulation of ER-associated protein degradation, ER-mitochondria junctions, and relative distribution of smooth ER and rough ER.-Mukherjee, R., Bhattacharya, A., Sau, A., Basu, S., Chakrabarti, S., Chakrabarti, O. Calmodulin regulates MGRN1-GP78 interaction mediated ubiquitin proteasomal degradation system.

PMID: 30230921 [PubMed - as supplied by publisher]

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Lineage-specific duplication and adaptive evolution of bitter taste receptor genes in bats.

Lineage-specific duplication and adaptive evolution of bitter taste receptor genes in bats.

Mol Ecol. 2018 Sep 19;:

Authors: Jiao H, Wang Y, Zhang L, Jiang P, Zhao H

Abstract
By generating raw genetic material and diverse biological functions, gene duplication represents a major evolutionary mechanism that is of fundamental importance in ecological adaptation. The lineage-specific duplication events of bitter taste receptor genes (Tas2rs) have been identified in a number of vertebrates, but functional evolution of new Tas2r copies after duplication remains largely unknown. Here we present the largest data set of bat Tas2rs to date, identified from existing genome sequences of 15 bat species and newly sequenced from 17 bat species, and demonstrate lineage-specific duplications of Tas2r16, Tas2r18 and Tas2r41 that only occurred in Myotis bats. Myotis bats are highly speciose and represent the only mammalian genus that is naturally distributed on every continent except Antarctica. The occupation of such diverse habitats might have driven the Tas2r gene expansion. New copies of Tas2rs in Myotis bats have shown molecular adaptation and functional divergence. For example, three copies of Tas2r16 in Myotis davidii showed differential sensitivities to arbutin and salicin that may occur in their insect prey, as suggested by cell-based functional assays. We hypothesize that functional differences among Tas2r copies in Myotis bats would increase their survival rate through preventing the ingestion of an elevated number of bitter-tasting dietary toxins from their insect prey, which may have facilitated their adaptation to diverse habitats. Our study demonstrates functional changes of new Tas2r copies after lineage-specific duplications in Myotis bats and highlights the potential role of taste perception in exploiting new environments. This article is protected by copyright. All rights reserved.

PMID: 30230081 [PubMed - as supplied by publisher]

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To flourish or perish: evolutionary TRiPs into the sensory biology of plant-herbivore interactions.

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To flourish or perish: evolutionary TRiPs into the sensory biology of plant-herbivore interactions.

Pflugers Arch. 2018 Sep 18;:

Authors: Startek JB, Voets T, Talavera K

Abstract
The interactions between plants and their herbivores are highly complex systems generating on one side an extraordinary diversity of plant protection mechanisms and on the other side sophisticated consumer feeding strategies. Herbivores have evolved complex, integrative sensory systems that allow them to distinguish between food sources having mere bad flavors from the actually toxic ones. These systems are based on the senses of taste, olfaction and somatosensation in the oral and nasal cavities, and on post-ingestive chemosensory mechanisms. The potential ability of plant defensive chemical traits to induce tissue damage in foragers is mainly encoded in the latter through chemesthetic sensations such as burning, pain, itch, irritation, tingling, and numbness, all of which induce innate aversive behavioral responses. Here, we discuss the involvement of transient receptor potential (TRP) channels in the chemosensory mechanisms that are at the core of complex and fascinating plant-herbivore ecological networks. We review how "sensory" TRPs are activated by a myriad of plant-derived compounds, leading to cation influx, membrane depolarization, and excitation of sensory nerve fibers of the oronasal cavities in mammals and bitter-sensing cells in insects. We also illustrate how TRP channel expression patterns and functionalities vary between species, leading to intriguing evolutionary adaptations to the specific habitats and life cycles of individual organisms.

PMID: 30229297 [PubMed - as supplied by publisher]

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Bivariate genome-wide association analysis strengthens the role of bitter receptor clusters on chromosomes 7 and 12 in human bitter taste.

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Bivariate genome-wide association analysis strengthens the role of bitter receptor clusters on chromosomes 7 and 12 in human bitter taste.

BMC Genomics. 2018 Sep 17;19(1):678

Authors: Hwang LD, Gharahkhani P, Breslin PAS, Gordon SD, Zhu G, Martin NG, Reed DR, Wright MJ

Abstract
BACKGROUND: Human perception of bitter substances is partially genetically determined. Previously we discovered a single nucleotide polymorphism (SNP) within the cluster of bitter taste receptor genes on chromosome 12 that accounts for 5.8% of the variance in the perceived intensity rating of quinine, and we strengthened the classic association between TAS2R38 genotype and the bitterness of propylthiouracil (PROP). Here we performed a genome-wide association study (GWAS) using a 40% larger sample (n = 1999) together with a bivariate approach to detect previously unidentified common variants with small effects on bitter perception.
RESULTS: We identified two signals, both with small effects (< 2%), within the bitter taste receptor clusters on chromosomes 7 and 12, which influence the perceived bitterness of denatonium benzoate and sucrose octaacetate respectively. We also provided the first independent replication for an association of caffeine bitterness on chromosome 12. Furthermore, we provided evidence for pleiotropic effects on quinine, caffeine, sucrose octaacetate and denatonium benzoate for the three SNPs on chromosome 12 and the functional importance of the SNPs for denatonium benzoate bitterness.
CONCLUSIONS: These findings provide new insights into the genetic architecture of bitter taste and offer a useful starting point for determining the biological pathways linking perception of bitter substances.

PMID: 30223776 [PubMed - in process]

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Impaired Odor Perception in Autism Spectrum Disorder Is Associated with Decreased Activity in Olfactory Cortex.

Impaired Odor Perception in Autism Spectrum Disorder Is Associated with Decreased Activity in Olfactory Cortex.

Chem Senses. 2018 Sep 14;:

Authors: Koehler L, Fournel A, Albertowski K, Roessner V, Gerber J, Hummel C, Hummel T, Bensafi M

Abstract
Autism Spectrum Disorders (ASDs) are characterized by atypical sensory functioning in the visual, tactile, and auditory systems. Although less explored, olfactory changes have been reported in ASD patients. To explore these changes on a neural level, 18 adults with ASD and 18 healthy neurotypical controls were examined in a 2-phase study. Participants were first tested for odor threshold and odor identification. Then, (i) structural magnetic resonance (MR) images of the olfactory bulb were acquired, and (ii) a functional MR imaging olfaction study was conducted. ASD patients exhibited decreased function for odor thresholds and odor identification; this was accompanied by a relatively decreased activation in the piriform cortex. In conclusion, these findings suggest, that the known alterations in olfaction in ASD are rooted in the primary olfactory cortex.

PMID: 30219913 [PubMed - as supplied by publisher]

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Microvillous cells in the olfactory epithelium express elements of the solitary chemosensory cell transduction signaling cascade.

Microvillous cells in the olfactory epithelium express elements of the solitary chemosensory cell transduction signaling cascade.

PLoS One. 2018;13(9):e0202754

Authors: Genovese F, Tizzano M

Abstract
The nasal cavity hosts an array of chemoresponsive cells, including the extended olfactory system and several other cells involved in detection of and responses to irritants. Solitary chemosensory cells (SCCs), which respond to irritants and bacteria, express the transient receptor potential channel TRPM5 an essential element of the taste transduction-signaling cascade. Microvillous cells (MVCs), non-neuronal cells situated in the apical layer of the main olfactory epithelium, also express TRPM5, but their function has not yet been clarified. TRPM5-positive MVCs, like SCCs, show a cholinergic phenotype expressing choline acetyl transferase (ChAT), but none of the other elements of the bitter taste transduction cascade could be detected. We reexamined TRPM5-positive MVCs with more sensitive gene expression and staining techniques to clarify whether they rely only on TRPM5 and ChAT or express other elements of the taste/SCC transduction cascade. Analyzing existing RNA sequencing data from whole olfactory mucosa and isolated olfactory sensory neurons, we determined that several elements of the taste/SCC transduction cascade, including taste receptors, are expressed in the olfactory mucosa in cells other than olfactory sensory neurons. Immunostaining confirmed the presence TRPM5 and ChAT in a subset of cells of the olfactory mucosa, which also showed the expression of PLCB2, gustducin, and T1R3. Specifically, these cells were identified as TRPM5-positive MVCs. Furthermore, we examined whether MVCs are innervated by trigeminal fibers, similarly to SCCs. Using antibodies against trigeminal nerve markers calcitonin gene-related peptide and substance P, we determined that, despite the cholinergic phenotype, most MVCs in the olfactory mucosa lacked consistent trigeminal innervation. Our findings indicate that MVCs, like SCCs, express all the elements of the bitter taste transduction cascade but that, unlike SCCs, they possess only sparse trigeminal innervation. The cholinergic phenotype of MVCs suggests a modulatory function of the surrounding olfactory epithelium, through the release of acetylcholine.

PMID: 30212469 [PubMed - in process]

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Individual variation in PROP status, fungiform papillae density and responsiveness to taste stimuli in a large population sample.

Individual variation in PROP status, fungiform papillae density and responsiveness to taste stimuli in a large population sample.

Chem Senses. 2018 Sep 10;:

Authors: Dinnella C, Monteleone E, Piochi M, Spinelli S, Prescott J, Pierguidi L, Gasperi F, Laureati M, Pagliarini E, Predieri S, Torri L, Barbieri S, Valli E, Bianchi P, Braghieri A, Del Caro A, Di Monaco R, Favotto S, Moneta E

Abstract
Despite considerable research investigating the role of PROP bitterness perception and variation of fungiform papillae density (FPD) in food perception, this relationship remains controversial as well as the association between the two phenotypes. Data from 1119 subjects (38.6% male; 18-60 years) enrolled in the Italian Taste project were analysed. Responsiveness to the bitterness of PROP was assessed on the general Labelled Magnitude Scale. FPD was determined from manual counting on digital images of the tongue. Solutions of tastes, astringent and pungent sensations were prepared to be moderate/strong on a gLMS. Four foods had tastants added to produce four variations in target sensations from weak to strong (pear juice: citric acid, sourness, chocolate pudding: sucrose, sweetness; bean purée: sodium chloride, saltiness and tomato juice: capsaicin, pungency). Females gave ratings to PROP and showed FPD that were significantly higher than males. Both phenotype markers significantly decreased with age. No significant correlations were found between PROP ratings and FPD. FPD variation doesn't affect perceived intensity of solutions. Responsiveness to PROP positively correlated to perceived intensity of most stimuli in solution. A significant effect of FPD on perceived intensity of target sensation in foods was found in a few cases. Responsiveness to PROP positively affected all taste intensities in subjects with low FPD while there were no significant effects of PROP in high FPD subjects. These data highlight a complex interplay between PROP status and FPD and the need of a critical reconsideration of their role in food perception and acceptability.

PMID: 30204849 [PubMed - as supplied by publisher]

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The scent of security: Odor of romantic partner alters subjective discomfort and autonomic stress responses in an adult attachment-dependent manner.

The scent of security: Odor of romantic partner alters subjective discomfort and autonomic stress responses in an adult attachment-dependent manner.

Physiol Behav. 2018 Sep 06;:

Authors: Granqvist P, Vestbrant K, Döllinger L, Liuzza MT, Olsson MJ, Blomkvist A, Lundström JN

Abstract
When in a stressful situation, access to adult attachment figures (e.g., romantic partners) is an important means by which adults regulate stress responses. The practice of smelling a partner's worn garment is reported as a self-treatment against stress. Here, we experimentally determined whether exposure to a partner's body odor attenuates adults' subjective discomfort and psychophysiological responses, and whether such effects are qualified by adult attachment security. In a blocked design, participants (N = 34) were presented with their partner's body odor, their own body odor, the odor of a clean t-shirt and rose odor, while exposed to weak electric shocks to induce discomfort and stress responses. Results showed that partner body odor reduces subjective discomfort during a stressful event, as compared with the odor of oneself. Also, highly secure participants had attenuated skin conductance when exposed to partner odor. We conclude that partner odor is a scent of security, especially for attachment-secure adults.

PMID: 30196084 [PubMed - as supplied by publisher]

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Sulphur dioxide and arsenic affect male reproduction via interfering with spermatogenesis in mice.

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Sulphur dioxide and arsenic affect male reproduction via interfering with spermatogenesis in mice.

Ecotoxicol Environ Saf. 2018 Sep 05;165:164-173

Authors: Li X, Yi H, Wang H

Abstract
As two potential environmental hazards, sulphur dioxide (SO2) and arsenic have adverse effects on male reproduction, but the mechanism of which and their combined toxicity are not clear. In this study, we investigate male reproductive toxicity with a focus on spermatogenesis by treating mice with 5 mg/m3 SO2 and/or 5 mg/L arsenic. Our results showed that arsenic exposure caused significant decreases in water and food consumption and body weight in mice, whereas these changes were not observed in the SO2-only group. Both SO2 and arsenic reduced sperm counts, increased the percentage of sperm malformation, and induced abnormal testicular pathological changes. Elevated H2O2 and MDA contents, declined T-SOD activity, decreased spermatogenic cell counts, enhanced caspase-3 activity, and increased TUNEL-positive cells were also observed in mice exposed to SO2 and/or arsenic. Moreover, SO2 and arsenic co-exposure changed the mRNA levels of Bax and Bcl-2, decreased serum testosterone levels, and downregulated the expression of steroidogenic-related genes (LHR, StAR, and ABP) in mice. These findings provide a new theoretical basis for understanding how SO2 and arsenic interfere with spermatogenesis leading to infertility. These results also suggest that SO2 and arsenic co-exposure likely result in an additive effect on male reproductive toxicity in mice.

PMID: 30195209 [PubMed - as supplied by publisher]

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A plant-responsive bacterial-signaling system senses an ethanolamine derivative.

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A plant-responsive bacterial-signaling system senses an ethanolamine derivative.

Proc Natl Acad Sci U S A. 2018 Sep 06;:

Authors: Coutinho BG, Mevers E, Schaefer AL, Pelletier DA, Harwood CS, Clardy J, Greenberg EP

Abstract
Certain plant-associated Proteobacteria sense their host environment by detecting an unknown plant signal recognized by a member of a LuxR subfamily of transcription factors. This interkingdom communication is important for both mutualistic and pathogenic interactions. The Populus root endophyte Pseudomonas sp. GM79 possesses such a regulator, named PipR. In a previous study we reported that PipR activates an adjacent gene (pipA) coding for a proline iminopeptidase in response to Populus leaf macerates and peptides and that this activation is dependent on a putative ABC-type transporter [Schaefer AL, et al. (2016) mBio 7:e01101-16]. In this study we identify a chemical derived from ethanolamine that induces PipR activity at picomolar concentrations, and we present evidence that this is the active inducer present in plant leaf macerates. First, a screen of more than 750 compounds indicated ethanolamine was a potent inducer for the PipR-sensing system; however, ethanolamine failed to bind to the periplasmic-binding protein (PBP) required for the signal response. This led us to discover that a specific ethanolamine derivative, N-(2-hydroxyethyl)-2-(2-hydroxyethylamino) acetamide (HEHEAA), binds to the PBP and serves as a potent PipR-dependent inducer. We also show that a compound, which coelutes with HEHEAA in HPLC and induces pipA gene expression in a PipR-dependent manner, can be found in Populus leaf macerates. This work sheds light on how plant-associated bacteria can sense their environment and on the nature of inducers for a family of plant-responsive LuxR-like transcription factors found in plant-associated bacteria.

PMID: 30190434 [PubMed - as supplied by publisher]

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Taste Exam: A Brief and Validated Test.

Taste Exam: A Brief and Validated Test.

J Vis Exp. 2018 Aug 17;(138):

Authors: Douglas JE, Mansfield CJ, Arayata CJ, Cowart BJ, Colquitt LR, Maina IW, Blasetti MT, Cohen NA, Reed DR

Abstract
The emerging importance of taste in medicine and biomedical research, and new knowledge about its genetic underpinnings, has motivated us to supplement classic taste-testing methods in two ways. First, we explain how to do a brief assessment of the mouth, including the tongue, to ensure that taste papillae are present and to note evidence of relevant disease. Second, we draw on genetics to validate taste test data by comparing reports of perceived bitterness intensity and inborn receptor genotypes. Discordance between objective measures of genotype and subjective reports of taste experience can identify data collection errors, distracted subjects or those who have not understood or followed instructions. Our expectation is that fast and valid taste tests may persuade researchers and clinicians to assess taste regularly, making taste testing as common as testing for hearing and vision. Finally, because many tissues of the body express taste receptors, taste responses may provide a proxy for tissue sensitivity elsewhere in the body and, thereby, serve as a rapid, point-of-care test to guide diagnosis and a research tool to evaluate taste receptor protein function.

PMID: 30176005 [PubMed - in process]

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PKR Senses Nuclear and Mitochondrial Signals by Interacting with Endogenous Double-Stranded RNAs.

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PKR Senses Nuclear and Mitochondrial Signals by Interacting with Endogenous Double-Stranded RNAs.

Mol Cell. 2018 Aug 28;:

Authors: Kim Y, Park J, Kim S, Kim M, Kang MG, Kwak C, Kang M, Kim B, Rhee HW, Kim VN

Abstract
Protein kinase RNA-activated (PKR) induces immune response by sensing viral double-stranded RNAs (dsRNAs). However, growing evidence suggests that PKR can also be activated by endogenously expressed dsRNAs. Here, we capture these dsRNAs by formaldehyde-mediated crosslinking and immunoprecipitation sequencing and find that various noncoding RNAs interact with PKR. Surprisingly, the majority of the PKR-interacting RNA repertoire is occupied by mitochondrial RNAs (mtRNAs). MtRNAs can form intermolecular dsRNAs owing to bidirectional transcription of the mitochondrial genome and regulate PKR and eIF2α phosphorylation to control cell signaling and translation. Moreover, PKR activation by mtRNAs is counteracted by PKR phosphatases, disruption of which causes apoptosis from PKR overactivation even in uninfected cells. Our work unveils dynamic regulation of PKR even without infection and establishes PKR as a sensor for nuclear and mitochondrial signaling cues in regulating cellular metabolism.

PMID: 30174290 [PubMed - as supplied by publisher]

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Postnatal exposure to ethanol increases its oral acceptability to adolescent rats.

Postnatal exposure to ethanol increases its oral acceptability to adolescent rats.

Chem Senses. 2018 Aug 29;:

Authors: Tang J, Youngentob SL, Glendinning JI

Abstract
The aversive flavor of ethanol limits intake by many consumers. We asked whether intermittent consumption of ethanol increases its oral acceptability, using rats as a model system. We focused on adolescent rats because they (like their human counterparts) have a higher risk for alcohol overconsumption than do adult rats following experience with the drug. We measured the impact of ethanol exposure on (i) the oral acceptability of ethanol and surrogates for its bitter (quinine) and sweet (sucrose) flavor components in brief-access lick tests; and (ii) responses of the glossopharyngeal (GL) taste nerve to oral stimulation with the same chemical stimuli. During the exposure period, the experimental rats had access to chow, water and 10% ethanol every other day for 16 days; the control rats had access to chow and water over the same time period. The experimental rats consumed 7-14 g/day of 10% ethanol across the exposure period. This ethanol consumption significantly increased the oral acceptability of 3, 6 and 10% ethanol, but had no impact on the oral acceptability of quinine, sucrose or NaCl. The ethanol exposure also diminished responses of the GL nerve to oral stimulation with ethanol, but not quinine, sucrose or NaCl. Taken together, these findings indicate that ethanol consumption increases the oral acceptability of ethanol in adolescent rats, and that this increased oral acceptability is mediated, at least in part, by an exposure-induced reduction in responsiveness of the peripheral taste system to ethanol per se, rather than its bitter and sweet flavor components.

PMID: 30169758 [PubMed - as supplied by publisher]

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