Cyclophosphamide Induced Disruptions to Appetitive Qualities and Detection Thresholds of NaCl: Comparison of single dose and dose fractionation effects.

Cyclophosphamide Induced Disruptions to Appetitive Qualities and Detection Thresholds of NaCl: Comparison of single dose and dose fractionation effects.

Chem Senses. 2018 May 19;:

Authors: Jewkes BC, Gomella MG, Lowry ET, Benner JA, Delay ER

Abstract
Chemotherapy is one of the most common treatments for cancer, however a side effect is often altered taste. This study examined how cyclophosphamide, a chemotherapy drug, affects salt taste in mice. Based on previous findings, it was predicted that cyclophosphamide-induced disruptions in salt taste would be observed near days 2-4, 8-12, and 22-24 days post treatment, and that multiple, smaller doses would cause more severe disruptions to taste. To test these predictions, two experiments were performed, one using brief access testing to measure appetitive qualities, and another using operant conditioning to measure detection thresholds. After a single 100 mg/kg cyclophosphamide injection, peak alterations in brief access lick rates were seen near days 5-8 and 15 post treatment, whereas peak alterations in detection thresholds were seen 6, 14 and 20 days post treatment. After five 20 mg/kg injections of cyclophosphamide, brief access lick rates revealed disruptions only on post injection day 8 whereas thresholds appeared to cycle, gradually increased to and decreased from peak elevations on post treatment days 4, 10, 15, 20, and 23. While salt taste functions were disrupted by cyclophosphamide, the patterns of these disruptions were less severe and shorter than expected from cell morphology studies, suggesting a functional adjustment to maintain behavioral accuracy. Fractionation of cyclophosphamide dosing had minimum effect on brief access responses but caused longer, cyclic-like disruptions of detection thresholds compared to single dose administration.

PMID: 29788185 [PubMed - as supplied by publisher]

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Identification and characterization of chemosensory genes in the antennal transcriptome of Spodoptera exigua.

Identification and characterization of chemosensory genes in the antennal transcriptome of Spodoptera exigua.

Comp Biochem Physiol Part D Genomics Proteomics. 2018 May 07;27:54-65

Authors: Du LX, Liu Y, Zhang J, Gao XW, Wang B, Wang GR

Abstract
Chemical senses are crucial for insect behaviors such as host preference, mate choice and oviposition site selection. Various protein families are involved in these processes, including odorant receptors (ORs), ionotropic receptors (IRs), gustatory receptors (GRs), chemosensory proteins (CSPs), odorant binding proteins (OBPs) and sensory neuron membrane proteins (SNMPs). To better understand the olfactory mechanism in Spodoptera exigua, we conducted transcriptome analysis of adult antennae and identified a total of 157 candidate chemosensory genes encoding 51 ORs, 20 IRs, 7 GRs, 32 CSPs, 45 OBPs and 2 SNMPs. Quantitative real time PCR (qPCR) analysis of the tissue- and sex-specific expression profiles of ORs, GRs and IRs revealed that these genes could be detected in at least one tissue tested. SexiOR6, 11, 13 and 16, which were predicted to be pheromone receptors based on phylogenetic analysis, exhibited male-specific antennae expression. SexiOR18, 26, 28, 30, 34, 39, and 40 exhibited female-biased expression. SexiGR1, SexiGR2 and SexiGR3, are predicted carbon dioxide receptors, and the former was expressed specifically in antennae, and the latter two were expressed both in antennae and labial palps. SexiIRs had diverse expression profiles. SexiIR8a and SexiIR25a were quite conserved and expressed at high levels. This work will greatly facilitate the understanding of olfactory system in S. exigua and provides valuable information for further functional studies of the chemoreception mechanism in Lepidopteran moths.

PMID: 29787920 [PubMed - as supplied by publisher]

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Total Synthesis of the Marine Phosphomacrolide, (-)-Enigmazole A, Exploiting Multicomponent Type I Anion Relay Chemistry (ARC) in Conjunction with a Late-Stage Petasis-Ferrier Union/Rearrangement.

Total Synthesis of the Marine Phosphomacrolide, (-)-Enigmazole A, Exploiting Multicomponent Type I Anion Relay Chemistry (ARC) in Conjunction with a Late-Stage Petasis-Ferrier Union/Rearrangement.

J Org Chem. 2018 May 22;:

Authors: Ai Y, Kozytska MV, Zou Y, Khartulyari AS, Maio WA, Smith AB

Abstract
An effective late-stage large-fragment union/rearrangement exploiting the Petasis-Ferrier protocol, in conjunction with multicomponent Type I Anion Relay Chemistry (ARC) to access advanced intermediates, permits completion of a convergent, stereocontrolled total synthesis of the architecturally complex phosphomacrolide (-)-enigmazole A (1).

PMID: 29786446 [PubMed - as supplied by publisher]

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Solitary Chemosensory Cells are a Primary Epithelial Source of Interleukin-25 in Chronic Rhinosinusitis with Nasal Polyps.

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Solitary Chemosensory Cells are a Primary Epithelial Source of Interleukin-25 in Chronic Rhinosinusitis with Nasal Polyps.

J Allergy Clin Immunol. 2018 May 17;:

Authors: Kohanski MA, Workman AD, Patel NN, Hung LY, Shtraks JP, Chen B, Blasetti M, Doghramji L, Kennedy DW, Adappa ND, Palmer JN, Herbert DR, Cohen NA

Abstract
BACKGROUND: IL-25 can function as an early signal for the respiratory Type 2 response characteristic of allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). In the mouse gut, tuft cells are the epithelial source of IL-25. However, the source of human airway epithelial IL-25 has remained elusive.
OBJECTIVE: In this study, we sought to determine if the solitary chemosensory cell (SCC) is the predominant source of IL-25 in the sinonasal epithelium.
METHOD: Flow cytometry and immunofluorescence for SCCs and IL-25 were used to interrogate polyp and turbinate tissue from patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Mucus was collected during acute inflammatory exacerbations from patients with CRSwNP or CRS without nasal polyps and IL-25 levels determined by Enzyme Linked Immuno-Sorbent Assay (ELISA). Lastly, sinonasal epithelial cultures derived from polyp and turbinate tissue were stimulated with IL-13 and analyzed for SCC proliferation and IL-25 production.
RESULTS: This study demonstrates that a discrete cell type, likely a solitary chemosensory cell (SCC), characterized by expression of the taste-associated G-protein, gustducin, and the intestinal tuft cell marker, doublecortin-like kinase 1, DCAMKL1, is the predominant source of IL-25 in the human upper airway. Additionally, we show that patients with CRSwNP have increased numbers of SCCs in nasal polyp tissue and in-vitro IL-13 exposure both increased proliferation and induced apical secretion of IL-25 into the mucus layer.
CONCLUSIONS: Inflammatory sinus polyps but not adjacent turbinate tissue have an expansion of a solitary chemosensory cell population that is the source of epithelial IL-25.

PMID: 29778504 [PubMed - as supplied by publisher]

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Smelling Anxiety Chemosignals Impairs Clinical Performance of Dental Students.

Smelling Anxiety Chemosignals Impairs Clinical Performance of Dental Students.

Chem Senses. 2018 May 15;:

Authors: Singh PB, Young A, Lind S, Leegaard MC, Capuozzo A, Parma V

Abstract
Despite the fact that human body odors can transfer anxiety-related signals, the impact of such signals in real-life situations is scant. In this study, the effects of anxiety chemosignals on the performance of dental students operating on simulation units, wearing t-shirts imbued with human sweat and masked with eugenol were tested. Twenty-four 4th year dental students (17F) donated their body odors in two sessions (Anxiety and Rest). Twenty-four normosmic, sex- and age-matched test subjects who were3rd year dental students performed three dental procedures while smelling masked anxiety body odors, masked rest body odors or masker alone. The intensity and pleasantness ratings showed that the test subjects could not report perceptual differences between the odor conditions. When exposed to masked anxiety body odors the test subject's dental performance was significantly worse than when they were exposed to masked rest body odors and masker alone, indicating that their performance was modulated by exposure to the emotional tone of the odor. These findings call for a careful evaluation of the anxiety-inducing effects of body odors in performance-related tasks and provide the first ecological evaluation of human anxiety chemosignal communication.

PMID: 29767685 [PubMed - as supplied by publisher]

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Lack of respiratory and ocular effects following acute propylene glycol exposure in healthy humans.

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Lack of respiratory and ocular effects following acute propylene glycol exposure in healthy humans.

Inhal Toxicol. 2018 May 15;:1-9

Authors: Dalton P, Soreth B, Maute C, Novaleski C, Banton M

Abstract
OBJECTIVE: Propylene glycol (PG) is a widely used solvent, chemical intermediate and carrier substance for foods, pharmaceutical and cosmetic products. Professional and occupational exposure to PG aerosol and vapor may occur from theatrical smoke generators and during application of deicing products to airplanes. While PG is considered to have low toxicity, the results of one study suggested that brief (1-min) exposure to PG mist elicited ocular and respiratory effects in humans. Because the high concentrations and brief exposure duration in that study were not representative of most occupational exposures, a controlled experimental exposure study was conducted to clarify or confirm the earlier findings.
MATERIALS AND METHODS: Ten males and 10 females were exposed to PG aerosol for 4 hrs at 20 and 100 mg/m3 and 30 min at 200 mg/m3. Total PG exposure concentrations (droplets plus gas phase) were 95.6, 442.4 and 871 mg/m3 for the three conditions, respectively. Participants rode a stationary bicycle to simulate physical effort at regular intervals during exposure. Objective measures evaluated in this study included ocular irritation via eye blink task and eye photography and pulmonary function via spirometry, while subjective measures included health symptoms ratings, irritation and dryness ratings of eyes, nose, throat and mouth.
RESULTS: Objective measures of pulmonary function and ocular irritation did not reveal any exposure-related changes. Exposure-related changes in symptom reporting were observed; however, the highest symptom ratings did not exceed "slight" on the scale.
CONCLUSIONS: The results indicate at the concentrations and acute durations tested, PG does not affect human respiratory function or produce ocular irritation.

PMID: 29764241 [PubMed - as supplied by publisher]

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Pilot Experiment: The Effect of Added Flavorants on the Taste and Pleasantness of Mixtures of Glycerol and Propylene Glycol.

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Pilot Experiment: The Effect of Added Flavorants on the Taste and Pleasantness of Mixtures of Glycerol and Propylene Glycol.

Chemosens Percept. 2018 Apr;11(1):1-9

Authors: Rao PD, Nanding H, Strasser AA, Wise PM

Abstract
Introduction: The US Food and Drug Administration banned most "sweet" flavorants for use in cigarettes due to the concern that sweet flavors appeal to young, beginning smokers. However, many of the same flavors, including fruity and confection-associated aromas (e.g. vanilla) are still used in e-cigarettes. Sweet flavors may have a number of effects, including enhancement of the taste of other ingredients. The current work focused on the impact of model flavorants on the taste of a mixture of propylene glycol and vegetable glycerine, solvents used in most e-cigarettes and related products.
Methods: A device delivered mixtures of propylene glycol and vegetable glycerine into the mouth in parallel with puffs of clean air (control) or odorized air. Aromas included two "fruity" esters ("pineapple" and "banana"), two confection-associated aromas ("vanilla" and "caramel/malty"), menthol (not a "sweet" aroma, but commonly used in e-cigarettes), and a "burnt" aroma not expected enhance flavor. Twenty young adults, aged 18-25, rated the sweetness, bitterness, and pleasantness of all stimuli (within-subjects design).
Results: Both fruity aromas significantly enhanced sweetness, both confection-associated aromas significantly enhanced pleasantness, and the caramel/malty aroma significantly reduced bitterness. Menthol and the "burnt" aroma had no measurable effects on the taste of solvent mixtures.
Conclusion: Some flavorants modulated the taste of solvents commonly used in e-cigarettes in ways consistent with an enhanced sensory profile.
Implications: If similar effects occur in actual products, improved flavor profiles could facilitate continued use, particularly in non-smokers experimenting with e-cigarettes and related products.

PMID: 29755639 [PubMed]

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If technological intelligent extraterrestrials exist, what biological traits are de rigueur.

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If technological intelligent extraterrestrials exist, what biological traits are de rigueur.

Life Sci Space Res (Amst). 2018 May;17:15-22

Authors: Taylor ER

Abstract
If extraterrestrials exist in the depths of cosmic space, and are capable of interstellar communications, even space flight, there is no requirement that they be humanoid in form. However, certain humanoid capabilities would be advantageous for tool fashioning and critical to operating space craft as well as functioning under the disparate extreme conditions under which they may be forced to operate. They would have to be "gas breathing". The reasonable assumption that life based upon the same elements as Earth life requiring water stems from the unique properties of water that no other similar low molecular weight nonmetal hydride offers. Only water offers the diversity of chemical properties and reactivity, including the existence of the three common physical states within a limited temperature range of service to life, avoiding the issues presented by any alternatives. They must, like us, possess a large, abstract-thinking brain, and probably possess at least all the fundamental senses that humankind possess. They would also be carbon-based life, using oxygen as the electron sink of their biochemistry for the reasons considered. They most likely are homeothermic as us, though they may not necessarily be mammalian as we are. Their biochemistry could differ some from ours, perhaps presenting contact hazards for both species as discussed.

PMID: 29753409 [PubMed - in process]

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Activation of airway epithelial bitter taste receptors by Pseudomonas aeruginosa quinolones modulates calcium, cyclic-AMP, and nitric oxide signaling.

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Activation of airway epithelial bitter taste receptors by Pseudomonas aeruginosa quinolones modulates calcium, cyclic-AMP, and nitric oxide signaling.

J Biol Chem. 2018 May 10;:

Authors: Freund JR, Mansfield CJ, Doghramji LJ, Adappa ND, Palmer JN, Kennedy DW, Reed DR, Jiang P, Lee RJ

Abstract
Bitter taste receptors (T2Rs), discovered in many tissues outside the tongue, have recently become potential therapeutic targets. We showed previously that airway epithelial cells express several T2Rs that activate innate immune responses that may be important for treatment of airway diseases such as chronic rhinosinusitis. It is imperative to more clearly understand what compounds activate airway T2Rs as well as their full range of functions. T2R isoforms in airway motile cilia (T2Rs 4, 14, 16, and 38) produce bactericidal levels of nitric oxide (NO) that also increase ciliary beating, promoting clearance of mucus and trapped pathogens. Bacterial quorum-sensing acyl-homoserine lactones (AHLs) activate T2Rs and stimulate these responses in primary airway cells.  Quinolones are another type of quorum sensing molecule used by Pseudomonas aeruginosa.  To elucidate if bacterial quinolones activate airway T2Rs, we analyzed calcium, cAMP, and NO dynamics using a combination of fluorescent indicator dyes and FRET-based protein biosensors.  T2R-transfected HEK293T cells, several lung epithelial cell lines, and primary sinonasal cells grown and differentiated at air-liquid interface were tested with 2-heptyl-3-hydroxy-4-quinolone (known as Pseudomonas quinolone signal; PQS), 2,4-dihydroxyquinolone (DHQ), and 4-hydroxy-2-heptylquinolone (HHQ). In HEK293T cells, PQS activated T2R4, 16, and 38 while HHQ activated T2R14.  DHQ had no effect.  PQS and HHQ increased calcium and decreased both baseline and stimulated cAMP levels in cultured and primary airway cells.  In primary cells, PQS and HHQ activated levels of NO synthesis previously shown to be bactericidal. This study suggests airway T2R-mediated immune responses are activated by bacterial quinolones as well as AHLs.

PMID: 29748385 [PubMed - as supplied by publisher]

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Solitary chemosensory cells producing interleukin-25 and group-2 innate lymphoid cells are enriched in chronic rhinosinusitis with nasal polyps.

Solitary chemosensory cells producing interleukin-25 and group-2 innate lymphoid cells are enriched in chronic rhinosinusitis with nasal polyps.

Int Forum Allergy Rhinol. 2018 May 09;:

Authors: Patel NN, Kohanski MA, Maina IW, Triantafillou V, Workman AD, Tong CCL, Kuan EC, Bosso JV, Adappa ND, Palmer JN, Herbert DR, Cohen NA

Abstract
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is commonly characterized by type-2 inflammation. It is established that group-2 innate lymphoid cells (ILC2s) are a subset of immune cells important in orchestrating mucosal type-2 response. IL-25 is an epithelial-derived cytokine that is a critical activator of ILC2s. Recent evidence demonstrates that specialized taster epithelial cells, such as solitary chemosensory cells (SCCs), may be producers of IL-25. To elucidate the relationship between SCCs and ILC2s in CRSwNP, we sought to quantify ILC2s and SCCs to determine if these cell types are enriched in nasal polyps compared to healthy sinonasal mucosa.
METHODS: We quantified SCCs and ILC2s using multicolor flow cytometry in nasal polyps and non-inflamed turbinate mucosa from seven patients and investigated the role of IL-13 and dexamethasone on SCC frequency using tissue explants of nasal polyps and turbinate mucosa.
RESULTS: SCCs were found to be the primary source of IL-25. Nasal polyps demonstrated higher populations of SCCs (33.0% vs 5.6%, p < 0.001) and ILC2s (2.40% vs 0.19%, p = 0.008) compared to patient-matched nonpolypoid turbinates. In cultured polyp explants, exogenous IL-13 increased the proportion of epithelial SCCs (40.2% IL-13 condition vs 28.9% untreated, p = 0.012), and this effect was reversed by addition of dexamethasone (40.2% vs 8.9%, p < 0.0005).
CONCLUSION: These data support SCC and ILC2 expansion as well as increased IL-25 production in nasal polyps and may represent early events in the pathogenesis of CRSwNP. IL-13 stimulates proliferation of SCC in a feed-forward loop, a process that is steroid-sensitive.

PMID: 29742315 [PubMed - as supplied by publisher]

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Burly1 is a mouse QTL for lean body mass that maps to a 0.8-Mb region of chromosome 2.

Burly1 is a mouse QTL for lean body mass that maps to a 0.8-Mb region of chromosome 2.

Mamm Genome. 2018 May 08;:

Authors: Lin C, Fesi BD, Marquis M, Bosak NP, Lysenko A, Koshnevisan MA, Duke FF, Theodorides ML, Nelson TM, McDaniel AH, Avigdor M, Arayata CJ, Shaw L, Bachmanov AA, Reed DR

Abstract
To fine map a mouse QTL for lean body mass (Burly1), we used information from intercross, backcross, consomic, and congenic mice derived from the C57BL/6ByJ (host) and 129P3/J (donor) strains. The results from these mapping populations were concordant and showed that Burly1 is located between 151.9 and 152.7 Mb (rs33197365 to rs3700604) on mouse chromosome 2. The congenic region harboring Burly1 contains 26 protein-coding genes, 11 noncoding RNA elements (e.g., lncRNA), and 4 pseudogenes, with 1949 predicted functional variants. Of the protein-coding genes, 7 have missense variants, including genes that may contribute to lean body weight, such as Angpt41, Slc52c3, and Rem1. Lean body mass was increased by the B6-derived variant relative to the 129-derived allele. Burly1 influenced lean body weight at all ages but not food intake or locomotor activity. However, congenic mice with the B6 allele produced more heat per kilogram of lean body weight than did controls, pointing to a genotype effect on lean mass metabolism. These results show the value of integrating information from several mapping populations to refine the map location of body composition QTLs and to identify a short list of candidate genes.

PMID: 29737391 [PubMed - as supplied by publisher]

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Multisensory integration processing during olfactory-visual stimulation-An fMRI graph theoretical network analysis.

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Multisensory integration processing during olfactory-visual stimulation-An fMRI graph theoretical network analysis.

Hum Brain Mapp. 2018 May 07;:

Authors: Ripp I, Zur Nieden AN, Blankenagel S, Franzmeier N, Lundström JN, Freiherr J

Abstract
In this study, we aimed to understand how whole-brain neural networks compute sensory information integration based on the olfactory and visual system. Task-related functional magnetic resonance imaging (fMRI) data was obtained during unimodal and bimodal sensory stimulation. Based on the identification of multisensory integration processing (MIP) specific hub-like network nodes analyzed with network-based statistics using region-of-interest based connectivity matrices, we conclude the following brain areas to be important for processing the presented bimodal sensory information: right precuneus connected contralaterally to the supramarginal gyrus for memory-related imagery and phonology retrieval, and the left middle occipital gyrus connected ipsilaterally to the inferior frontal gyrus via the inferior fronto-occipital fasciculus including functional aspects of working memory. Applied graph theory for quantification of the resulting complex network topologies indicates a significantly increased global efficiency and clustering coefficient in networks including aspects of MIP reflecting a simultaneous better integration and segregation. Graph theoretical analysis of positive and negative network correlations allowing for inferences about excitatory and inhibitory network architectures revealed-not significant, but very consistent-that MIP-specific neural networks are dominated by inhibitory relationships between brain regions involved in stimulus processing.

PMID: 29736907 [PubMed - as supplied by publisher]

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Activation of intestinal tuft cell-expressed Sucnr1 triggers type 2 immunity in the mouse small intestine.

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Activation of intestinal tuft cell-expressed Sucnr1 triggers type 2 immunity in the mouse small intestine.

Proc Natl Acad Sci U S A. 2018 May 07;:

Authors: Lei W, Ren W, Ohmoto M, Urban JF, Matsumoto I, Margolskee RF, Jiang P

Abstract
The hallmark features of type 2 mucosal immunity include intestinal tuft and goblet cell expansion initiated by tuft cell activation. How infectious agents that induce type 2 mucosal immunity are detected by tuft cells is unknown. Published microarray analysis suggested that succinate receptor 1 (Sucnr1) is specifically expressed in tuft cells. Thus, we hypothesized that the succinate-Sucnr1 axis may be utilized by tuft cells to detect certain infectious agents. Here we confirmed that Sucnr1 is specifically expressed in intestinal tuft cells but not in other types of intestinal epithelial cells, and demonstrated that dietary succinate induces tuft and goblet cell hyperplasia via Sucnr1 and the tuft cell-expressed chemosensory signaling elements gustducin and Trpm5. Conventional mice with a genetic Sucnr1 deficiency (Sucnr1-/-) showed diminished immune responses to treatment with polyethylene glycol and streptomycin, which are known to enhance microbiota-derived succinate, but responded normally to inoculation with the parasitic worm Nippostrongylus brasiliensis that also produces succinate. Thus, Sucnr1 is required for microbiota-induced but not for a generalized worm-induced type 2 immunity.

PMID: 29735652 [PubMed - as supplied by publisher]

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Development of an International Odor Identification Test for Children: The Universal Sniff Test.

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Development of an International Odor Identification Test for Children: The Universal Sniff Test.

J Pediatr. 2018 May 02;:

Authors: Schriever VA, Agosin E, Altundag A, Avni H, Cao Van H, Cornejo C, de Los Santos G, Fishman G, Fragola C, Guarneros M, Gupta N, Hudson R, Kamel R, Knaapila A, Konstantinidis I, Landis BN, Larsson M, Lundström JN, Macchi A, Mariño-Sánchez F, Martinec Nováková L, Mori E, Mullol J, Nord M, Parma V, Philpott C, Propst EJ, Rawan A, Sandell M, Sorokowska A, Sorokowski P, Sparing-Paschke LM, Stetzler C, Valder C, Vodicka J, Hummel T

Abstract
OBJECTIVE: To assess olfactory function in children and to create and validate an odor identification test to diagnose olfactory dysfunction in children, which we called the Universal Sniff (U-Sniff) test.
STUDY DESIGN: This is a multicenter study involving 19 countries. The U-Sniff test was developed in 3 phases including 1760 children age 5-7 years. Phase 1: identification of potentially recognizable odors; phase 2: selection of odorants for the odor identification test; and phase 3: evaluation of the test and acquisition of normative data. Test-retest reliability was evaluated in a subgroup of children (n = 27), and the test was validated using children with congenital anosmia (n = 14).
RESULTS: Twelve odors were familiar to children and, therefore, included in the U-Sniff test. Children scored a mean ± SD of 9.88 ± 1.80 points out of 12. Normative data was obtained and reported for each country. The U-Sniff test demonstrated a high test-retest reliability (r27 = 0.83, P < .001) and enabled discrimination between normosmia and children with congenital anosmia with a sensitivity of 100% and specificity of 86%.
CONCLUSIONS: The U-Sniff is a valid and reliable method of testing olfaction in children and can be used internationally.

PMID: 29730147 [PubMed - as supplied by publisher]

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Olfactory fMRI: implications of stimulation length and repetition time.

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Olfactory fMRI: implications of stimulation length and repetition time.

Chem Senses. 2018 May 03;:

Authors: Georgiopoulos C, Witt ST, Haller S, Dizdar N, Zachrisson H, Engström M, Larsson EM

Abstract
Studying olfaction with functional Magnetic Resonance imaging (fMRI) poses various methodological challenges. This study aimed to investigate the effects of stimulation length and repetition time (TR) on the activation pattern of four olfactory brain regions: the anterior and the posterior piriform cortex, the orbitofrontal cortex and the insula. 22 healthy participants with normal olfaction were examined with fMRI, with two stimulation lengths (6 seconds and 15 seconds) and two TRs (0.901 seconds and 1.34 seconds). Data were analyzed using General Linear Model (GLM), Tensorial Independent Component Analysis (TICA) and by plotting the event related time course of brain activation in the four olfactory regions of interest. The statistical analysis of the time courses revealed that short TR was associated with more pronounced signal increase and short stimulation was associated with shorter time to peak signal. Additionally, both long stimulation and short TR were associated with oscillatory time courses, whereas both short stimulation and short TR resulted in more typical time courses. GLM analysis showed that the combination of short stimulation and short TR could result in visually larger activation within these olfactory areas. TICA validated that the tested paradigm was spatially and temporally associated with a functionally connected network that included all four olfactory regions. In conclusion, the combination of short stimulation and short TR is associated with higher signal increase and shorter time to peak, making it more amenable to standard GLM-type analyses than long stimulation and long TR, and it should, thus, be preferable for olfactory fMRI.

PMID: 29726890 [PubMed - as supplied by publisher]

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Distinct gating mechanism of SOC channel involving STIM-Orai coupling and an intramolecular interaction of Orai in Caenorhabditis elegans.

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Distinct gating mechanism of SOC channel involving STIM-Orai coupling and an intramolecular interaction of Orai in Caenorhabditis elegans.

Proc Natl Acad Sci U S A. 2018 Apr 30;:

Authors: Kim KM, Wijerathne T, Hur JH, Kang UJ, Kim IH, Kweon YC, Lee AR, Jeong SJ, Lee SK, Lee YY, Sim BW, Lee JH, Baig C, Kim SU, Chang KT, Lee KP, Park CY

Abstract
Store-operated calcium entry (SOCE), an important mechanism of Ca2+ signaling in a wide range of cell types, is mediated by stromal interaction molecule (STIM), which senses the depletion of endoplasmic reticulum Ca2+ stores and binds and activates Orai channels in the plasma membrane. This inside-out mechanism of Ca2+ signaling raises an interesting question about the evolution of SOCE: How did these two proteins existing in different cellular compartments evolve to interact with each other? We investigated the gating mechanism of Caenorhabditis elegans Orai channels. Our analysis revealed a mechanism of Orai gating by STIM binding to the intracellular 2-3 loop of Orai in C. elegans that is radically different from Orai gating by STIM binding to the N and C termini of Orai in mammals. In addition, we found that the conserved hydrophobic amino acids in the 2-3 loop of Orai1 are important for the oligomerization and gating of channels and are regulated via an intramolecular interaction mechanism mediated by the N and C termini of Orai1. This study identifies a previously unknown SOCE mechanism in C. elegans and suggests that, while the STIM-Orai interaction is conserved between invertebrates and mammals, the gating mechanism for Orai channels differs considerably.

PMID: 29712850 [PubMed - as supplied by publisher]

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Normal feline behaviour: … and why problem behaviours develop.

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Normal feline behaviour: … and why problem behaviours develop.

J Feline Med Surg. 2018 May;20(5):411-421

Authors: Bradshaw J

Abstract
Practical relevance: Cats are descended from a solitary, territorial ancestor, and while domestication has reduced their inherited tendency to be antagonistic towards all animals larger than their typical prey, they still place more reliance on the security of their territory than on psychological attachments to people or other cats, the exact opposite to dogs. Many feline problem behaviours stem from perceived threats to this security, often due to conflicts with other cats. Others are more developmental in origin, often caused by inadequate exposure to crucial stimuli, especially people, during the socialisation period. Strongly aversive events experienced at any age can also contribute. A third category comprises normal behaviour that owners deem unacceptable, such as scratching of furniture. Evidence base: This review identifies three areas in which basic research is inadequate to support widely employed concepts and practices in feline behavioural medicine. First, classification of cats' problem behaviours relies heavily on approaches derived from studies of their behavioural ecology and, to some extent, extrapolation from canine studies. Few studies have focused on cats in the home, the environment in which most behavioural disorders are expressed. Secondly, cats' chemical senses (olfactory and vomeronasal) are far more sensitive than our own, making it difficult for owners or clinicians to fully comprehend the sensory information upon which they base their behaviour. Thirdly, although the concept of psychological distress is widely invoked as an intervening variable in behavioural disorders, there are still no reliable measures of distress for pet cats in the home. Global importance: Psychological distress of some kind is the primary cause of many of the behavioural problems presented to clinicians, but surveys indicate that many more cats display the same clinical signs without their owners ever seeking help. The welfare of this 'invisible' group could be improved by veterinarians taking a more proactive approach to educating their clients about the behavioural needs of pet cats.

PMID: 29706092 [PubMed - in process]

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