Τρίτη 31 Ιουλίου 2018

Prefrontal Control Over Occipital Responses to Crossmodal Overlap Varies Across the Congruency Spectrum.

Prefrontal Control Over Occipital Responses to Crossmodal Overlap Varies Across the Congruency Spectrum.

Cereb Cortex. 2018 Jul 27;:

Authors: Lundström JN, Regenbogen C, Ohla K, Seubert J

Abstract
While matched crossmodal information is known to facilitate object recognition, it is unclear how our perceptual systems encode the more gradual congruency variations that occur in our natural environment. Combining visual objects with odor mixtures to create a gradual increase in semantic object overlap, we demonstrate high behavioral acuity to linear variations of olfactory-visual overlap in a healthy adult population. This effect was paralleled by a linear increase in cortical activation at the intersection of occipital fusiform and lingual gyri, indicating linear encoding of crossmodal semantic overlap in visual object recognition networks. Effective connectivity analyses revealed that this integration of olfactory and visual information was achieved by direct information exchange between olfactory and visual areas. In addition, a parallel pathway through the superior frontal gyrus was increasingly recruited towards the most ambiguous stimuli. These findings demonstrate that cortical structures involved in object formation are inherently crossmodal and encode sensory overlap in a linear manner. The results further demonstrate that prefrontal control of these processes is likely required for ambiguous stimulus combinations, a fact of high ecological relevance that may be inappropriately captured by common task designs juxtaposing congruency and incongruency.

PMID: 30060139 [PubMed - as supplied by publisher]



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Σάββατο 28 Ιουλίου 2018

Olfactory and trigeminal systems interact in the periphery.

Olfactory and trigeminal systems interact in the periphery.

Chem Senses. 2018 Jul 25;:

Authors: Tremblay C, Frasnelli J

Abstract
The olfactory and trigeminal systems are intimately connected as most odorants stimulate both sensory systems. They interact by mutually suppressing and enhancing each other. However, the location and the degree of their interaction remain unclear. One method to test sensitivity in the trigeminal system is the odor localization task: when an odorant is presented to one nostril, we are able to localize the stimulated nostril only if the odorant stimulates the trigeminal nerve. Our objective was to evaluate the interaction between olfactory and trigeminal system by measuring the effect of an olfactory co-stimulation on the ability to localize a trigeminal stimulus. More specifically, we evaluated the influence of an olfactory co-stimulation with pure odors (phenyl ethanol, vanillin), presented either ipsilaterally or contralaterally, on the localization of predominantly trigeminal stimuli (mustard oil, eucalyptol). The ipsilateral, but not the contralateral, olfactory co-stimulation with a pure odorant increased the capacity to localize a trigeminal stimulus. These results suggest an interaction between the olfactory and trigeminal systems at peripheral, i.e., mucosal, levels.

PMID: 30052799 [PubMed - as supplied by publisher]



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[Olfactory receptors expressed in various non-olfactory tissues.]

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[Olfactory receptors expressed in various non-olfactory tissues.]

Clin Calcium. 2018;28(8):1124-1129

Authors: Ihara S, Touhara K

Abstract
Olfactory receptor(OR)genes constitute the largest gene family in mammals. Some of them have been shown to be expressed not only in the olfactory system, but also in various non-olfactory tissues. So far, the roles of such ectopically expressed ORs have been suggested mainly by in vitro experiments using cultured cells or tissues. Recently, analyses using OR knockout mice have revealed a few examples of important physiological functions outside the olfactory epithelium. An OR expressed in the carotid body senses the hypoxia and regulates breathing. An OR expressed in enterochromaffin(EC)cells in the gut senses microbial metabolites and induces a serotonin release to modulate serotonin-sensitive primary afferent neurons. These results suggest that ectopically expressed ORs sense an internal environmental change through chemical cues and modulate physiologically significant functions specific to each tissue where an OR is expressed. Further work will be required to understand their roles in other tissues.

PMID: 30049923 [PubMed - in process]



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Παρασκευή 27 Ιουλίου 2018

Exploring potentially alternative non-canonical DNA duplex structures through simulation.

Exploring potentially alternative non-canonical DNA duplex structures through simulation.

J Biomol Struct Dyn. 2018 Jul 26;:1-15

Authors: Galindo-Murillo R, Cheatham TE, Hopkins RC

Abstract
Hopkins proposed an alternative and chirally distinct family of double stranded DNA models that have antiparallel chains with 5' → 3' senses opposite to those of the right-handed Watson-Crick (WC) family. Termed configuration II, this family of double stranded DNA models contains both right-handed, II-R, and left-handed, II-L, forms, with Z-DNA as an example of the latter. Relative interstrand binding energies for six DNA duplex models, two each of configuration I-R (standard Watson-Crick canonical B-DNA), II-R and II-L for the duplex d(CGCGAATTCGCG), have been estimated under identical conditions using MM-PBSA analysis from molecular dynamics (MD) trajectories using three different AMBER force fields. These simulations support the stereo chemical soundness of configuration II dsDNA forms. Recent force fields (bsc1 and OL15) successfully render stable II-L structures, whereas the previous force field, bsc0, generated stable II-R structures although with an energy difference between II-R and II-L of ∼30 kcal/mol.

PMID: 30047316 [PubMed - as supplied by publisher]



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Τρίτη 24 Ιουλίου 2018

Tracking traumatic head injuries with the chemical senses.

Tracking traumatic head injuries with the chemical senses.

World J Otorhinolaryngol Head Neck Surg. 2018 Mar;4(1):46-49

Authors: Frank ME, Hettinger TP

Abstract
Chemosensory disorders, primarily olfactory, have diagnostic significance for prevalent human illnesses, but the multitude of smells makes measuring function appear daunting. The olfactory system operates under dynamic natural sensing conditions in which many individual odor chemicals are waxing and waning. Yet, in experimentally controlled simulations, mixture-component selective adaptation shows individual or shared prominent characteristic odors are detected but molecular stimulus features are not. As in other biological chemical signaling systems, including taste, odors activate dedicated receptors (OR). Given rapid OR adaptation with the passage of time, individual odor recognition is momentary. Receptive dendrites of the nearly 400 genetically variable human-OR in the olfactory epithelium critically project axons to the olfactory bulb through perforations in the cribriform plate of the skull. Analytic chemical-quality codes detect single odor-mixture components. However, identities of no more than 3 or 4 most salient odors are perceived due to central mixture-suppression, the mutual inhibition among diverse olfactory-bulb or cortical neurons. The componental codes allow olfaction to readily discern odor quality and valence of a wide range of unrelated chemicals, a few at a time. Head trauma may result in a partial or complete loss of smell and facial trauma a loss of taste-nerve function. Testing smell could plot the course of recovery from chronic traumatic encephalopathies that prevail in contact sports. Measuring brain function with olfaction would provide simpler and more direct monitoring of prognosis than biochemical sensors.

PMID: 30035261 [PubMed]



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Κυριακή 22 Ιουλίου 2018

Total Synthesis of (-)-Nodulisporic Acids D, C, and B: Evolution of a Unified Synthetic Strategy.

Related Articles

Total Synthesis of (-)-Nodulisporic Acids D, C, and B: Evolution of a Unified Synthetic Strategy.

J Am Chem Soc. 2018 Jul 20;:

Authors: Zou Y, Li X, Yang Y, Berritt S, Melvin J, Gonzales S, Spafford M, Smith AB

Abstract
A unified synthetic strategy leading to the total synthesis of (-)-nodulisporic acids D, C, and B is described. Key synthetic transformations include a nickel-chromium-mediated cyclization, an aromatic ring functionalization employing a novel copper-promoted alkylation, a palladium-catalyzed cross-coupling cascade/indole ring construction, and a palladium-mediated regio- and diastereoselective allylic substitution/cyclization reaction, the latter to construct ring D.

PMID: 30028603 [PubMed - as supplied by publisher]



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Πέμπτη 19 Ιουλίου 2018

Acquired olfactory dysfunction in children and adolescents - a systematic review of the literature.

Acquired olfactory dysfunction in children and adolescents - a systematic review of the literature.

Chem Senses. 2018 Jul 18;:

Authors: Schriever VA, Gellrich J, von der Hagen M, Hummel T

Abstract
Olfactory function can be influenced by many factors and olfactory dysfunction is associated with several diseases. But even considering this, the causes of acquired olfactory dysfunction in children are not well understood. This review was conducted to gain an overview of the etiologies of acquired olfactory dysfunction in a pediatric population. Studies were identified using a predefined literature search including studies if patients were ≤18 years of age and results of psychophysical olfactory testing were reported. A total of 44 articles met the inclusion criteria for this review and were included in the qualitative analysis. The influence of six disease groups on olfactory function in children was observed (Otorhinolaryngology; Traumatic brain injury; Oncology; Psychiatric diseases; Environmental factors and other diseases). The current literature is convincing that diseases in the otorhinolaryngology group as well as traumatic brain injury can lead to acquired olfactory dysfunction, whereas according to the current literature the role of other influencing factors such as most psychiatric disorders remain uncertain. A number of diseases and circumstances affect olfactory function in children and may cause acquired olfactory dysfunction in this age group. Nevertheless more research is needed to better understand the causes of acquired olfactory dysfunction in children. Future research should have the goal of early diagnosis and, if possible, early treatment of the condition to prevent a negative impact of olfactory dysfunction on children and adolescents.

PMID: 30020456 [PubMed - as supplied by publisher]



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Gli3 is a negative regulator of Tas1r3-expressing taste cells.

http:--journals.plos.org-plosgenetics-re https:--www.ncbi.nlm.nih.gov-corehtml-pm Related Articles

Gli3 is a negative regulator of Tas1r3-expressing taste cells.

PLoS Genet. 2018 02;14(2):e1007058

Authors: Qin Y, Sukumaran SK, Jyotaki M, Redding K, Jiang P, Margolskee RF

Abstract
Mouse taste receptor cells survive from 3-24 days, necessitating their regeneration throughout adulthood. In anterior tongue, sonic hedgehog (SHH), released by a subpopulation of basal taste cells, regulates transcription factors Gli2 and Gli3 in stem cells to control taste cell regeneration. Using single-cell RNA-Seq we found that Gli3 is highly expressed in Tas1r3-expressing taste receptor cells and Lgr5+ taste stem cells in posterior tongue. By PCR and immunohistochemistry we found that Gli3 was expressed in taste buds in all taste fields. Conditional knockout mice lacking Gli3 in the posterior tongue (Gli3CKO) had larger taste buds containing more taste cells than did control wild-type (Gli3WT) mice. In comparison to wild-type mice, Gli3CKO mice had more Lgr5+ and Tas1r3+ cells, but fewer type III cells. Similar changes were observed ex vivo in Gli3CKO taste organoids cultured from Lgr5+ taste stem cells. Further, the expression of several taste marker and Gli3 target genes was altered in Gli3CKO mice and/or organoids. Mirroring these changes, Gli3CKO mice had increased lick responses to sweet and umami stimuli, decreased lick responses to bitter and sour taste stimuli, and increased glossopharyngeal taste nerve responses to sweet and bitter compounds. Our results indicate that Gli3 is a suppressor of stem cell proliferation that affects the number and function of mature taste cells, especially Tas1r3+ cells, in adult posterior tongue. Our findings shed light on the role of the Shh pathway in adult taste cell regeneration and may help devise strategies for treating taste distortions from chemotherapy and aging.

PMID: 29415007 [PubMed - indexed for MEDLINE]



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Τρίτη 17 Ιουλίου 2018

Semantic congruence alters functional connectivity during olfactory-visual perception.

Semantic congruence alters functional connectivity during olfactory-visual perception.

Chem Senses. 2018 Jul 14;:

Authors: Sijben R, Hoffmann-Hensel SM, Rodriguez-Raecke R, Haarmeier T, Freiherr J

Abstract
Previous research has shown that humans struggle to interpret multiple perceptual signals when the information provided by these signals is incongruent. In the context of olfactory-visual integration, behavioral and neuronal differences in response to congruent and incongruent stimulus pairs have been established. Here, we explored functional connectivity of the human brain with regards to the perception of congruent and incongruent food stimuli. Participants were simultaneously presented olfactory and visual stimuli of four different food objects, two healthy and two unhealthy objects. Stimulus pairs were grouped into "Congruent" (olfactory and visual presentation of the same object), "Semi-Congruent" (stimuli of similar "healthiness") and "Incongruent" (healthy-unhealthy stimulus combination). Using functional magnetic resonance imaging and psychophysiological interaction analyses, we revealed part of a neural network, the nodes of which show differential connectivity depending on the level of congruency of the presented stimulus combinations. This network relies strongly on, mostly left, inferior frontal gyrus. The analysis of such network transcends standard subtractive designs and indicates the need for more detailed formulations of neuronal models and increased specificity in functional imaging.

PMID: 30010874 [PubMed - as supplied by publisher]



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On the meaning(s) of perceived complexity in the chemical senses.

On the meaning(s) of perceived complexity in the chemical senses.

Chem Senses. 2018 Jul 16;:

Authors: Spence C, Wang QJ

Abstract
Complexity is a term that is often invoked by those writing appreciatively about the taste, aroma/bouquet, and/or flavour of food and drink. Typically, the term is used as though everyone knows what is being talked about. Rarely is any explanation given, and the discussion soon moves on to other topics. However, oftentimes it is not at all clear what, exactly, is being referred to. A number of possibilities are outlined here, including physical complexity at the level of individual molecules, at the level of combinations of molecules giving rise to a specific flavour profile (e.g., as in a glass of quality wine or a cup of specialty coffee), at the level of combinations of distinct ingredients/elements (e.g., as when composing a particularly intricate dish in a high-end restaurant, say, or when pairing food with wine), and/or the number of stimuli/steps involved in the process of creation. Of course, people might also be referring to some aspect of their perceptual experience, and one of the intriguing questions in this space concerns the nature of the relationship(s) between these different ways of conceptualizing complexity in the chemical senses. However, given that physical/chemical and perceived complexity so often diverge, we argue that it is the latter notion, or rather inferred complexity, that is the most relevant when it comes to the chemical senses. Finally, we look at the role of expertise and review the evidence suggesting that inferred complexity can emerge either from a unitary taste experience that is judged to be complex, or from a tasting experience having multiple individuable elements.

PMID: 30010729 [PubMed - as supplied by publisher]



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Τρίτη 10 Ιουλίου 2018

Automated analysis of breathing waveforms using BreathMetrics: a respiratory signal processing toolbox.

Automated analysis of breathing waveforms using BreathMetrics: a respiratory signal processing toolbox.

Chem Senses. 2018 Jul 07;:

Authors: Noto T, Zhou G, Schuele S, Templer J, Zelano C

Abstract
Nasal inhalation is the basis of olfactory perception and drives neural activity in olfactory and limbic brain regions. Therefore, our ability to investigate the neural underpinnings of olfaction and respiration can only be as good as our ability to characterize features of respiratory behavior. However, recordings of natural breathing are inherently non-stationary, non-sinusoidal, and idiosyncratic making feature extraction difficult to automate. The absence of a freely-available computational tool for characterizing respiratory behavior is a hindrance to many facets of olfactory and respiratory neuroscience. To solve this problem, we developed BreathMetrics, an open-source tool that automatically extracts the full set of features embedded in human nasal airflow recordings. Here we rigorously validate BreathMetrics' feature estimation accuracy on multiple nasal airflow datasets, intracranial electrophysiological recordings of human olfactory cortex, and computational simulations of breathing signals. We hope this tool will allow researchers to ask new questions about how respiration relates to body, brain, and behavior.

PMID: 29985980 [PubMed - as supplied by publisher]



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Different olfactory percepts evoked by orthonasal and retronasal odorant delivery.

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Different olfactory percepts evoked by orthonasal and retronasal odorant delivery.

Chem Senses. 2018 Jul 02;:

Authors: Hannum M, Stegman MA, Fryer JA, Simons CT

Abstract
The Duality of Smell hypothesis suggests odorants delivered orthonasally elicit different sensations compared to those delivered retronasally despite activating the same receptors in the olfactory epithelium. Presently, we investigated this further using a matching paradigm free from odorant or semantic memory bias. Subjects were asked to evaluate an aroma delivered in one condition (orthonasal or retronasal delivery) and match the same aroma from four unknowns evaluated in the same or different delivery condition. Panelists matched flavors in four delivery conditions: orthonasal-orthonasal, retronasal-retronasal, retronasal-orthonasal, and orthonasal-retronasal. For orthonasal presentation, panelists smelled samples using their nostrils, and for retronasal presentation, panelists swallowed aqueous flavors. In experiment 1, panelists were instructed to match familiar flavors (banana, grape, orange, raspberry). In experiments 2 and 3, panelists used the same experimental design with either four unfamiliar flavors (kinnow, longan, pawpaw, prunus) or four distinct subtypes of a strawberry flavor (woody, green, ripe, candy). In experiment 1, the number of correct matches in each condition did not significantly differ suggesting stability in the perceptual construct across delivery routes. However, in experiments 2 and 3, significantly more samples were correctly matched in the orthonasal-orthonasal and retronasal-retronasal conditions compared to the retronasal-orthonasal or orthonasal-retronasal conditions suggesting aroma perception is dependent on delivery route. Additionally, across the four delivery methods, the ability to correctly match flavors decreased as flavor familiarity decreased or similarity increased and may reflect the different cognitive strategies employed by subjects when matching these stimuli. Our results suggest odorant percepts are route-dependent and consistent with the Duality of Smell phenomenon.

PMID: 29982522 [PubMed - as supplied by publisher]



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Fear Odor Facilitates the Detection of Fear Expressions Over Other Negative Expressions.

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Fear Odor Facilitates the Detection of Fear Expressions Over Other Negative Expressions.

Chem Senses. 2018 Jul 05;43(6):443

Authors: Kamiloglu RG, Smeets MAM, de Groot JHB, Semin GR

PMID: 29982461 [PubMed - in process]



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Bitter fruit: Inverse associations between PTC and Antidesma bunius perception.

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Bitter fruit: Inverse associations between PTC and Antidesma bunius perception.

Chem Senses. 2018 Jul 05;:

Authors: Wooding SP

Abstract
Ability to perceive the bitter compound phenylthiocarbamide (PTC) is inherited via a dominant "taster" allele of the TAS2R38 gene, while inability is inherited via a recessive "non-taster" allele. This raises a question: Is the non-taster allele functionless, or does it mediate perception of compounds other than PTC? New evidence supports speculation that it is indeed functional. Associations between TAS2R38 mutations and bitter sensitivity to the tropical berry Antidesma bunius are the inverse of those PTC, suggesting that the non-taster allele enables perception to compounds in the fruit.

PMID: 29982450 [PubMed - as supplied by publisher]



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Imprinting of a Non-pheromonal Cue and Its Protective Effect on Alien Male-Induced Implantation Failure in Mice.

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Imprinting of a Non-pheromonal Cue and Its Protective Effect on Alien Male-Induced Implantation Failure in Mice.

Chem Senses. 2018 Jul 05;:

Authors: Kurisinkal JT, Prathapan PK, Sreedharan R

Abstract
Bruce effect or alien male-induced implantation failure is a well-studied phenomenon in mice. The presence of stud male during exposure to an alien male protects the female from implantation failure. The pheromones of the stud male are imprinted in the female at the time of mating and act as a luteotrophic agent. We tested whether a non-pheromonal cue exposed to the female during pericopulatory sensitive period could protect pregnancy in newly inseminated females exposed to alien males. Virgin females were allowed to mate in presence of a cotton ball smeared with groundnut oil as a non-pheromonal cue. When these females were exposed to alien males in presence of groundnut oil, the majority of the females retained their pregnancy. We evidenced that a non-pheromonal cue could possibly protect the female from alien male-induced implantation failure. The majority of the females exposed to the non-pheromonal cue during the pre-or post-copulatory interactions with the males, exhibited higher rate of pregnancy failure on re-exposure to the same cue at the time of exposure to alien males. The protective effect of the non-pheromonal cue is observed only when the female is exposed to it during the pericopulatory sensitive period.

PMID: 29982306 [PubMed - as supplied by publisher]



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TRPV4 Channel Signaling in Macrophages Promotes Gastrointestinal Motility via Direct Effects on Smooth Muscle Cells.

https:--linkinghub.elsevier.com-ihub-ima Related Articles

TRPV4 Channel Signaling in Macrophages Promotes Gastrointestinal Motility via Direct Effects on Smooth Muscle Cells.

Immunity. 2018 May 30;:

Authors: Luo J, Qian A, Oetjen LK, Yu W, Yang P, Feng J, Xie Z, Liu S, Yin S, Dryn D, Cheng J, Riehl TE, Zholos AV, Stenson WF, Kim BS, Hu H

Abstract
Intestinal macrophages are critical for gastrointestinal (GI) homeostasis, but our understanding of their role in regulating intestinal motility is incomplete. Here, we report that CX3C chemokine receptor 1-expressing muscularis macrophages (MMs) were required to maintain normal GI motility. MMs expressed the transient receptor potential vanilloid 4 (TRPV4) channel, which senses thermal, mechanical, and chemical cues. Selective pharmacologic inhibition of TRPV4 or conditional deletion of TRPV4 from macrophages decreased intestinal motility and was sufficient to reverse the GI hypermotility that is associated with chemotherapy treatment. Mechanistically, stimulation of MMs via TRPV4 promoted the release of prostaglandin E2 and elicited colon contraction in a paracrine manner via prostaglandin E receptor signaling in intestinal smooth muscle cells without input from the enteric nervous system. Collectively, our data identify TRPV4-expressing MMs as an essential component required for maintaining normal GI motility and provide potential drug targets for GI motility disorders.

PMID: 29958798 [PubMed - as supplied by publisher]



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Global study of social odor awareness.

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Global study of social odor awareness.

Chem Senses. 2018 Jun 27;:

Authors: Sorokowska A, Groyecka A, Karwowski M, Frackowiak T, Lansford JE, Ahmadi K, Alghraibeh AM, Aryeetey R, Bertoni A, Bettache K, Blumen S, Blazejewska M, Bortolini T, Butovskaya M, Cantarero K, Castro FN, Cetinkaya H, Chang L, Chen BB, Cunha D, David D, David OA, Dileym FA, Domínguez Espinosa ADC, Donato S, Dronova D, Dural S, Fialová J, Fisher M, Gulbetekin E, Hamamcioglu Akkaya A, Hilpert P, Hromatko I, Iafrate R, Iesyp M, James B, Jaranovic J, Jiang F, Kimamo CO, Kjelvik G, Koç F, Laar A, Lopes FA, Macbeth G, Marcano NM, Martinez R, Mesko N, Molodovskaya N, Moradi Qezeli K, Motahari Z, Mühlhauser A, Natividade JC, Ntayi J, Oberzaucher E, Ojedokun O, Omar-Fauzee M, Onyishi IE, Paluszak A, Pierce JD, Pillay U, Portugal A, Razumiejczyk E, Realo A, Relvas AP, Rivas M, Rizwan M, Salkicevic S, Sarmány-Schuller I, Schmehl S, Senyk O, Sinding C, Sorbring E, Stamkou E, Stoyanova S, Šukolová D, Sutresna N, Tadinac M, Tapanya S, Teras A, Tinoco Ponciano EL, Tripathi R, Tripathi N, Tripathi M, Uhryn O, Yamamoto ME, Yoo G, Sorokowski P

Abstract
Olfaction plays an important role in human social communication, including multiple domains in which people often rely on their sense of smell in the social context. The importance of the sense of smell and its role can however vary inter-individually and culturally. Despite the growing body of literature on differences in olfactory performance or hedonic preferences across the globe, the aspects of a given culture as well as culturally universal individual differences affecting odor awareness in human social life remain unknown. Here, we conducted a large-scale analysis of data collected from 10,794 participants from 52 study sites from 44 countries all over the world. The aim of our research was to explore the potential individual and country-level correlates of odor awareness in the social context. The results show that the individual characteristics were more strongly related than country-level factors to self-reported odor awareness in different social contexts. A model including individual-level predictors (gender, age, material situation, education and preferred social distance) provided a relatively good fit to the data, but adding country-level predictors (Human Development Index, population density and average temperature) did not improve model parameters. Although there were some cross-cultural differences in social odor awareness, the main differentiating role was played by the individual differences. This suggests that people living in different cultures and different climate conditions may still share some similar patterns of odor awareness if they share other individual-level characteristics.

PMID: 29955865 [PubMed - as supplied by publisher]



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Odors and incontinence: What does the nose know?

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Odors and incontinence: What does the nose know?

Proc Inst Mech Eng H. 2018 Jun 01;:954411918781409

Authors: Dalton P, Maute C

Abstract
The fear of producing malodors that can be detected by others is a daily cause of anxiety for millions of people with incontinence. For many, the risk-whether real or imagined-that leaked waste products will be detectable by odor is sufficiently concerning to result in limitations on many types of activities. However, worry about personal odors can sensitize our olfactory system and cause us to be more aware of odors that may otherwise not be perceptible. In addition, heightened olfactory attention can often lead to odor misattributions, such as when we erroneously identify our body as the source of an odor that may simply be present in the environment. Odors produced by our bodies (endogenous odors) do enjoy a greater access to emotional brain centers and are processed faster than general odors. Here we provide examples from both everyday life and laboratory studies to explain how and why the olfactory system is unique among our sensory systems and how this knowledge can provide insights to our concerns about smell and incontinence and inform the development of products and solutions for incontinence.

PMID: 29939101 [PubMed - as supplied by publisher]



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Comparison of chemoreceptive abilities of the hydrothermal shrimp Mirocaris fortunata and the coastal shrimp Palaemon elegans.

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Comparison of chemoreceptive abilities of the hydrothermal shrimp Mirocaris fortunata and the coastal shrimp Palaemon elegans.

Chem Senses. 2018 Jun 20;:

Authors: Machon J, Lucas P, Ravaux J, Zbinden M

Abstract
Chemoreception might play an important role for endemic shrimp that inhabit deep and dark hydrothermal vents to find food sources and to locate active edifices that release specific chemicals. We compared the chemosensory abilities of the hydrothermal shrimp Mirocaris fortunata and the coastal related species, Palaemon elegans. The detection of diverse ecologically relevant chemical stimuli by the antennal appendages was measured with electroantennography. The two species can detect food-related odor and sulfide, a short-distance stimulus, via both their antennae and antennules. Neither iron nor manganese, considered as long-distance stimuli, were detected by the antennal appendages. Investigation of the ultrastructure of aesthetasc sensilla revealed no specific features of the hydrothermal species regarding innervation by olfactory sensory neurons. Pore-like structures occurring in the aesthetasc cuticle and dense bacterial covering seem to be unique to hydrothermal species, but their potential link to chemoreception remains elusive.

PMID: 29931242 [PubMed - as supplied by publisher]



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Neural basis of trigeminal chemo- and thermonociception in brown treesnakes, Boiga irregularis (Squamata: Colubridae).

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Neural basis of trigeminal chemo- and thermonociception in brown treesnakes, Boiga irregularis (Squamata: Colubridae).

J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2018 Jun 21;:

Authors: Bryant BP, Kraus F

Abstract
To elucidate the nociceptive system of the brown treesnake, Boiga irregularis, we exposed isolated brown treesnake trigeminal neurons to thermal and chemical stimulation. We measured responses as changes in intracellular calcium using ratiometric fluorescent calcium imaging. Responses to aversive thermal and chemical identified several classes of putative nociceptors. Compounds that were aversive excited many trigeminal neurons, putative chemonociceptors. Identification as nociceptors was further supported by lack of activation by compounds that were not aversive. Brown treesnake neurons had thermal thresholds ranging from 32 to 49 °C. The distribution was discontinuous, with a population of thresholds from 32 to 45 °C and a population with thresholds > 48 °C. Thermal stimulation of 48 °C has been shown to be strongly aversive to brown treesnakes, is lethal, and suggests the presence of thermonociceptors. Thermal sensitivity of brown treesnake trigeminal neurons greatly overlaps with chemical sensitivity; only 1.1% of neurons were sensitive to only thermal stimulation. 50% of brown treesnake trigeminal neurons tested with both > 48 °C and cinnamaldehyde responded to both stimuli, identifying putative polymodal nociceptors. Although a previous study found brown treesnakes insensitive to capsicum extract containing capsaicin, brown treesnake trigeminal neurons responded to capsaicin. These findings are of evolutionary interest as well as providing potential insights into managing this significant pest species.

PMID: 29926181 [PubMed - as supplied by publisher]



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Flavor Alterations Associated with Miracle Fruit and Gymnema sylvestre.

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Flavor Alterations Associated with Miracle Fruit and Gymnema sylvestre.

Chem Senses. 2018 Jun 14;:

Authors: Hudson SD, Sims CA, Odabasi AZ, Colquhoun TA, Snyder DJ, Stamps JJ, Dotson SC, Puentes L, Bartoshuk LM

Abstract
Taste and flavor (retronasal olfaction) interact in the brain. The rules of that interaction are not well understood. This study uses 2 taste modifiers that alter sweet to examine the effects on flavors. Subjects used the Global Sensory Intensity Scale to assess the aroma, sweetness, sourness, and flavor of 10 foods. As previous work had shown, miracle fruit added sweetness to acids, which secondarily reduced sourness (mixture suppression) and Gymnema sylvestre reduced sweetness in sweet foods as well as the sweetness induced by miracle fruit. In this study, multiple regression showed that both sweet and sour contribute to flavor. Gymnema sylvestre reduced the perceived sweet of predominantly sweet foods (chocolate and maple syrup) as expected; reducing the sweet, reduced the flavor. The effects of miracle fruit were complicated by its dual action: intensification of sweet and reduction of sour. Predominantly sour foods (vinegar, lemon, mustard, pickle) were sweetened by miracle fruit but any flavor enhancement associated with the added sweet appears to have been countered by the flavor reduction associated with reduced sourness. Moderately sour foods that are also sweet (tomatoes, strawberries) were sweetened by miracle fruit and thus flavor was enhanced; flavor loss through sour reduction was apparently not sufficient to counter the flavor enhancement due to increased sweet so the net result was that tomato and strawberry flavors were enhanced. The flavors of control foods (not predominantly sweet or sour [sausage, peanuts]) showed only small changes.

PMID: 29905783 [PubMed - as supplied by publisher]



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The Intracellular Loop of the Na+/Ca2+ Exchanger Contains an "Awareness Ribbon"-Shaped Two-Helix Bundle Domain.

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The Intracellular Loop of the Na+/Ca2+ Exchanger Contains an "Awareness Ribbon"-Shaped Two-Helix Bundle Domain.

Biochemistry. 2018 Jul 03;:

Authors: Yuan J, Yuan C, Xie M, Yu L, Bruschweiler-Li L, Brüschweiler R

Abstract
The Na+/Ca2+ exchanger (NCX) is a ubiquitous single-chain membrane protein that plays a major role in regulating the intracellular Ca2+ homeostasis by the counter transport of Na+ and Ca2+ across the cell membrane. Other than its prokaryotic counterpart, which contains only the transmembrane domain and is self-sufficient as an active ion transporter, the eukaryotic NCX protein possesses in addition a large intracellular loop that senses intracellular calcium signals and controls the activation of ion transport across the membrane. This provides a necessary layer of regulation for the more complex function of eukaryotic cells. The Ca2+ sensor in the intracellular loop is known as the Ca2+-binding domain (CBD12). However, how the signaling of the allosteric intracellular Ca2+ binding propagates and results in transmembrane ion transportation still lacks a detailed explanation. Further structural and dynamics characterization of the intracellular loop flanking both sides of CBD12 is therefore imperative. Here, we report the identification and characterization of another structured domain that is N-terminal to CBD12 in the intracellular loop using solution nuclear magnetic resonance (NMR) spectroscopy. The atomistic structure of this domain reveals that two tandem long α-helices, connected by a short linker, form a stable crossover two-helix bundle (THB), resembling an "awareness ribbon". Considering the highly conserved amino acid sequence of the THB domain, the detailed structural and dynamics properties of the THB domain will be common among NCXs from different species and will contribute toward the understanding of the regulatory mechanism of eukaryotic Na+/Ca2+ exchangers.

PMID: 29898361 [PubMed - as supplied by publisher]



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Coupling Green Fluorescent Protein Expression with Chemical Modification to Probe Functionally Relevant Riboswitch Conformations in Live Bacteria.

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Coupling Green Fluorescent Protein Expression with Chemical Modification to Probe Functionally Relevant Riboswitch Conformations in Live Bacteria.

Biochemistry. 2018 Jun 26;:

Authors: Dutta D, Belashov IA, Wedekind JE

Abstract
Noncoding RNAs engage in numerous biological activities including gene regulation. To fully understand RNA function it is necessary to probe biologically relevant conformations in living cells. To address this challenge, we coupled RNA-mediated regulation of the green fluorescent protein (GFP)uv-reporter gene to icSHAPE (in cell Selective 2'-Hydroxyl Acylation analyzed by Primer Extension). Our transcript-specific approach provides sensitive, fluorescence-based readout of the regulatory-RNA status as a means to coordinate chemical modification experiments. We chose a plasmid-based reporter compatible with Escherichia coli to allow use of knockout strains that eliminate endogenous effector biosynthesis. The approach was piloted using the Lactobacillus rhamnosus ( Lrh) preQ1-II riboswitch, which senses the pyrrolopyrimidine metabolite preQ1. Using an E. coli Δ queF strain incapable of preQ1 anabolism, the Lrh riboswitch yielded nearly one log unit of GFPuv-gene repression resulting from exogenously added preQ1. We then subjected cells in gene "on" and "off" states to icSHAPE. The resulting differential analysis indicated reduction in Lrh riboswitch flexibility in the P3 helix of the pseudoknot, which comprises the ribosome-binding site (RBS) paired with the anti-RBS. Such expression platform modulation was not observed by in vitro chemical probing and demonstrates that the crowded cellular environment does not preclude detection of compact and loose RNA-regulatory conformations. Here we describe the design, methods, interpretation, and caveats of Reporter Coupled (ReCo) icSHAPE. We also describe mapping of the differential ReCo-icSHAPE results onto the Lrh riboswitch-preQ1 cocrystal structure. The approach should be readily applicable to functional RNAs triggered by effectors or environmental variations.

PMID: 29897738 [PubMed - as supplied by publisher]



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Synthetic Access to the Mandelalide Family of Macrolides: Development of an Anion Relay Chemistry Strategy.

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Synthetic Access to the Mandelalide Family of Macrolides: Development of an Anion Relay Chemistry Strategy.

J Org Chem. 2018 04 20;83(8):4287-4306

Authors: Nguyen MH, Imanishi M, Kurogi T, Wan X, Ishmael JE, McPhail KL, Smith AB

Abstract
The mandelalides comprise a family of structurally complex marine macrolides that display significant cytotoxicity against several human cancer cell lines. Presented here is a full account on the development of an Anion Relay Chemistry (ARC) strategy for the total synthesis of (-)-mandelalides A and L, the two most potent members of the mandelalide family. The design and implementation of a three-component type II ARC/cross-coupling protocol and a four-component type I ARC union permits rapid access respectively to the key tetrahydrofuran and tetrahydropyran structural motifs of these natural products. Other highlights of the synthesis include an osmium-catalyzed oxidative cyclization of an allylic 1,3-diol, a mild Yamaguchi esterification to unite the northern and southern hemispheres, and a late-stage Heck macrocyclization. Synthetic mandelalides A and L displayed potent cytotoxicity against human HeLa cervical cancer cells (EC50, 1.3 and 3.1 nM, respectively). This synthetic approach also provides access to several highly potent non-natural mandelalide analogs, including a biotin-tagged mandelalide probe for future biological investigation.

PMID: 29480727 [PubMed - indexed for MEDLINE]



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Design, Synthesis, and Application of Polymer-Supported Silicon-Transfer Agents for Cross-Coupling Reactions with Organolithium Reagents.

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Design, Synthesis, and Application of Polymer-Supported Silicon-Transfer Agents for Cross-Coupling Reactions with Organolithium Reagents.

J Org Chem. 2017 10 20;82(20):11056-11071

Authors: Nguyen MH, O'Brien KT, Smith AB

Abstract
The initial design, synthesis, and validation of polymer-supported siloxane transfer agents have been achieved that permit the direct use of organolithium reagents in the palladium-catalyzed cross-coupling reactions. Through rational design, two generations of polymer support were developed that significantly simplify product purification and the transfer agent recycling.

PMID: 28931273 [PubMed - indexed for MEDLINE]



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