MHC class II expression through a hitherto unknown pathway supports T helper cell-dependent immune responses: implications for MHC class II deficiency

NARCIS (Netherlands)

Buch, Thorsten; Polic, Bojan; Clausen, Björn E.; Weiss, Susanne; Akilli-Ozturk, Ozlem; Chang, Cheong-Hee; Flavell, Richard; Schulz, Ansgar; Jonjic, Stipan; Waisman, Ari; Förster, Irmgard

2006-01-01

MHC class II (MHCII) deficiency or bare lymphocyte syndrome (BLS) is a severe immunodeficiency characterized by deficient T helper (Th)-cell-dependent immunity. The disease is caused by defects of the MHCII promoter complex resulting in low or absent MHCII expression. We demonstrate in a murine

Salmonella Typhimurium induces SPI-1 and SPI-2 regulated and strain dependent downregulation of MHC II expression on porcine alveolar macrophages

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Van Parys Alexander

2012-06-01

Full Text Available Abstract Foodborne salmonellosis is one of the most important bacterial zoonotic diseases worldwide. Salmonella Typhimurium is the serovar most frequently isolated from persistently infected slaughter pigs in Europe. Circumvention of the host’s immune system by Salmonella might contribute to persistent infection of pigs. In the present study, we found that Salmonella Typhimurium strain 112910a specifically downregulated MHC II, but not MHC I, expression on porcine alveolar macrophages in a Salmonella pathogenicity island (SPI-1 and SPI-2 dependent way. Salmonella induced downregulation of MHC II expression and intracellular proliferation of Salmonella in macrophages were significantly impaired after opsonization with Salmonella specific antibodies prior to inoculation. Furthermore, the capacity to downregulate MHC II expression on macrophages differed significantly among Salmonella strains, independently of strain specific differences in invasion capacity, Salmonella induced cytotoxicity and altered macrophage activation status. The fact that strain specific differences in MHC II downregulation did not correlate with the extent of in vitro SPI-1 or SPI-2 gene expression indicates that other factors are involved in MHC II downregulation as well. Since Salmonella strain dependent interference with the pig’s immune response through downregulation of MHC II expression might indicate that certain Salmonella strains are more likely to escape serological detection, our findings are of major interest for Salmonella monitoring programs primarily based on serology.

Differential odor processing in two olfactory pathways in the honeybee

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Nobuhiro Yamagata

2009-12-01

Full Text Available An important component in understanding central olfactory processing and coding in the insect brain relates to the characterization of the functional divisions between morphologically distinct types of projection neurons (PN. Using calcium imaging, we investigated how the identity, concentration and mixtures of odors are represented in axon terminals (boutons of two types of PNs - lPN and mPN. In lPN boutons we found less concentration dependence, narrow tuning profiles at a high concentration, which may be optimized for fine, concentration-invariant odor discrimination. In mPN boutons, however, we found clear rising concentration dependence, broader tuning profiles at a high concentration, which may be optimized for concentration coding. In addition, we found more mixture suppression in lPNs than in mPNs, indicating lPNs better adaptation for synthetic mixture processing. These results suggest a functional division of odor processing in both PN types.

MHC and non-MHC genes regulate elimination of lymphocytic choriomeningitis virus and antiviral cytotoxic T lymphocyte and delayed-type hypersensitivity mediating T lymphocyte activity in parallel

DEFF Research Database (Denmark)

Thomsen, Allan Randrup; Marker, O

1989-01-01

with regard to all three parameters was recessive, indicating that natural tolerance is not the mechanism explaining non-MHC dependent low responsiveness in this system. The implications of these findings are discussed with specific reference to the role of MHC genes in controlling resistance to infectious......, indicating that both H-2 and non-H-2 genes may influence the elimination of this virus. Differences in virus spread prior to appearance of the immune response could not explain the observed differences in clearance rate. On the other hand, inefficient clearance always correlated with low T cell...

Peptide and Peptide-Dependent Motions in MHC Proteins: Immunological Implications and Biophysical Underpinnings

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Cory M. Ayres

2017-08-01

Full Text Available Structural biology of peptides presented by class I and class II MHC proteins has transformed immunology, impacting our understanding of fundamental immune mechanisms and allowing researchers to rationalize immunogenicity and design novel vaccines. However, proteins are not static structures as often inferred from crystallographic structures. Their components move and breathe individually and collectively over a range of timescales. Peptides bound within MHC peptide-binding grooves are no exception and their motions have been shown to impact recognition by T cell and other receptors in ways that influence function. Furthermore, peptides tune the motions of MHC proteins themselves, which impacts recognition of peptide/MHC complexes by other proteins. Here, we review the motional properties of peptides in MHC binding grooves and discuss how peptide properties can influence MHC motions. We briefly review theoretical concepts about protein motion and highlight key data that illustrate immunological consequences. We focus primarily on class I systems due to greater availability of data, but segue into class II systems as the concepts and consequences overlap. We suggest that characterization of the dynamic “energy landscapes” of peptide/MHC complexes and the resulting functional consequences is one of the next frontiers in structural immunology.

Influence of background noise on the performance in the odor sensitivity task: effects of noise type and extraversion.

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Seo, Han-Seok; Hähner, Antje; Gudziol, Volker; Scheibe, Mandy; Hummel, Thomas

2012-10-01

Recent research demonstrated that background noise relative to silence impaired subjects' performance in a cognitively driven odor discrimination test. The current study aimed to investigate whether the background noise can also modulate performance in an odor sensitivity task that is less cognitively loaded. Previous studies have shown that the effect of background noise on task performance can be different in relation to degree of extraversion and/or type of noise. Accordingly, we wanted to examine whether the influence of background noise on the odor sensitivity task can be altered as a function of the type of background noise (i.e., nonverbal vs. verbal noise) and the degree of extraversion (i.e., introvert vs. extrovert group). Subjects were asked to conduct an odor sensitivity task in the presence of either nonverbal noise (e.g., party sound) or verbal noise (e.g., audio book), or silence. Overall, the subjects' mean performance in the odor sensitivity task was not significantly different across three auditory conditions. However, with regard to the odor sensitivity task, a significant interaction emerged between the type of background noise and the degree of extraversion. Specifically, verbal noise relative to silence significantly impaired or improved the performance of the odor sensitivity task in the introvert or extrovert group, respectively; the differential effect of introversion/extraversion was not observed in the nonverbal noise-induced task performance. In conclusion, our findings provide new empirical evidence that type of background noise and degree of extraversion play an important role in modulating the effect of background noise on subjects' performance in an odor sensitivity task.

Insights into structural features determining odorant affinities to honey bee odorant binding protein 14.

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Schwaighofer, Andreas; Pechlaner, Maria; Oostenbrink, Chris; Kotlowski, Caroline; Araman, Can; Mastrogiacomo, Rosa; Pelosi, Paolo; Knoll, Wolfgang; Nowak, Christoph; Larisika, Melanie

2014-04-18

Molecular interactions between odorants and odorant binding proteins (OBPs) are of major importance for understanding the principles of selectivity of OBPs towards the wide range of semiochemicals. It is largely unknown on a structural basis, how an OBP binds and discriminates between odorant molecules. Here we examine this aspect in greater detail by comparing the C-minus OBP14 of the honey bee (Apis mellifera L.) to a mutant form of the protein that comprises the third disulfide bond lacking in C-minus OBPs. Affinities of structurally analogous odorants featuring an aromatic phenol group with different side chains were assessed based on changes of the thermal stability of the protein upon odorant binding monitored by circular dichroism spectroscopy. Our results indicate a tendency that odorants show higher affinity to the wild-type OBP suggesting that the introduced rigidity in the mutant protein has a negative effect on odorant binding. Furthermore, we show that OBP14 stability is very sensitive to the position and type of functional groups in the odorant. Copyright © 2014 Elsevier Inc. All rights reserved.

Reminiscence therapy using odor in alcohol-dependent patients--psychophysiological evaluation and psychological evaluation; power spectral analysis of heart rate variability.

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Arizono, H; Morita, N; Iizuka, S; Satoh, S; Nakatani, Y

2000-12-01

This research was based on the hypothesis that when alcohol-dependent patients describe themselves, awakening of emotion by affirmative odor stimulation may facilitate memory reframing focusing on more affirmative emotion and memories. To prove the hypothesis, physiological changes accompanied by emotional awakening were evaluated by measuring the autonomic activity. In addition, subjective evaluation by a self-report manner was examined to investigate the effectiveness of Reminiscence Therapy (RT) using odor in alcohol-dependent patients. Thirty-four patients who met the DSM-IV criteria of alcohol-related disorders and were hospitalized in a ward specialized to alcohol dependence therapy. Each patient underwent a one-to-one interview twice. For counterbalance, one interview was performed with odor stimulation using an odor with a relaxing effect that recall pleasant emotion, and the other was without odor stimulation. As the evaluation indices of physiological changes accompanied by emotional awakening, index of autonomic function (HRV; Heart rate variability) for objective evaluation and psychological indices (STAI; State-Trait Anxiety Inventory VAS; Visual Analog Scale) for subjective evaluation were measured. 1) Objective evaluation: Regarding the evaluation index of the autonomic function, the sympathetic nervous system activity (LF/HF; low frequency component/high frequency component ratio) was significantly inhibited by odor stimulation (p Subjective evaluation: Compared to the state prior to interview, state anxiety judged by STAI was significantly decreased after interview (p subjective evaluation, but the objective evaluation suggested that the odor inhibited the sympathetic nervous system. Thus, it was suggested that odor can be used in RT, that is, emotional changes due to stimulation of odor may be applicable in RT.

The mere exposure effect depends on an odor's initial pleasantness.

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Delplanque, Sylvain; Coppin, Géraldine; Bloesch, Laurène; Cayeux, Isabelle; Sander, David

2015-01-01

The mere exposure phenomenon refers to improvement of one's attitude toward an a priori neutral stimulus after its repeated exposure. The extent to which such a phenomenon influences evaluation of a priori emotional stimuli remains under-investigated. Here we investigated this question by presenting participants with different odors varying in a priori pleasantness during different sessions spaced over time. Participants were requested to report each odor's pleasantness, intensity, and familiarity. As expected, participants became more familiar with all stimuli after the repetition procedure. However, while neutral and mildly pleasant odors showed an increase in pleasantness ratings, unpleasant and very pleasant odors remained unaffected. Correlational analyses revealed an inverse U-shape between the magnitude of the mere exposure effect and the initial pleasantness of the odor. Consequently, the initial pleasantness of the stimuli appears to modulate the impact of repeated exposures on an individual's attitude. These data underline the limits of mere exposure effect and are discussed in light of the biological relevance of odors for individual survival.

Odors: appetizing or satiating? Development of appetite during odor exposure over time.

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Ramaekers, M G; Boesveldt, S; Lakemond, C M M; van Boekel, M A J S; Luning, P A

2014-05-01

Exposure to palatable food odors influences appetite responses, either promoting or inhibiting food intake. Possibly, food odors are appetizing after a short exposure (of circa 1-3 min), but become satiating over time (circa 10-20 min). To investigate the effect of odor exposure on general appetite and sensory-specific appetite (SSA) over time. In a cross-over study, 21 unrestrained women (age: 18-45 years; BMI: 18.5-25 kg m(-2)) were exposed for 20 min to eight different odor types: five food odors, two nonfood odors and no-odor. All odors were distributed in a test room at suprathreshold levels. General appetite, SSA and salivation were measured over time. All food odors significantly increased general appetite and SSA, compared with the no-odor condition. The nonfood odors decreased general appetite. All effects did not change over time during odor exposure. Savory odors increased the appetite for savory foods, but decreased appetite for sweet foods, and vice versa after exposure to sweet odors. Neither food odors nor nonfood odors affected salivation. Palatable food odors were appetizing during and after odor exposure and did not become satiating over a 20-min period. Food odors had a large impact on SSA and a small impact on general appetite. Moreover, exposure to food odors increased the appetite for congruent foods, but decreased the appetite for incongruent foods. It may be hypothesized that, once the body is prepared for intake of a certain food with a particular macronutrient composition, it is unfavorable to consume foods that are very different from the cued food.

MHC class I loaded ligands from breast cancer cell lines: A potential HLA-I-typed antigen collection

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Rozanov, Dmitri V.; Rozanov, Nikita D.; Chiotti, Kami; Reddy, Ashok; Wilmarth, Phillip A.; David, Larry L.; Cha, Seung W.; Woo, Sunghee; Pevzner, Pavel; Bafna, Vineet; Burrows, Gregory G.; Rantala, Juha K.; Levin, Trevor; Anur, Pavana; Johnson-Camacho, Katie; Tabatabaei, Shaadi; Munson, Daniel J.; Bruno, Tullia C.; Slansky, Jill E.; Kappler, John W.; Hirano, Naoto; Boegel, Sebastian; Fox, Bernard A.; Egelston, Colt; Simons, Diana L.; Jimenez, Grecia; Lee, Peter P.; Gray, Joe W.; Spellman, Paul T.

2018-01-01

Breast cancer therapy based on amplifying a patient’s antitumor immune response depends on the availability of appropriate MHC class I-restricted, breast cancer-specific epitopes. To build a catalog of peptides presented by breast cancer cells, we undertook systematic MHC class I immunoprecipitation followed by elution of MHC class I-loaded peptides in breast cancer cell lines. We determined the sequence of 3,196 MHC class I-bound peptides representing 1,921 proteins from a panel of 20 breast cancer cell lines including basal, luminal, and claudin-low subtypes. The data has been deposited to the ProteomeXchange with identifier PXD006406. After removing duplicate peptides, i.e., the same peptide eluted from more than one cell line, the total number of unique peptides was 2,740. Of the unique peptides eluted, more than 1,750 had been previously identified, and of these, sixteen have been shown to be immunogenic. Importantly, only 3 of these immunogenic peptides have been identified in breast cancer cells in earlier studies. MHC class I binding probability of eluted peptides was used to plot the distribution of MHC class I allele-specific peptides in accordance with the binding score for each breast cancer cell line. We also determined that the tested breast cancer cells presented 89 mutation-containing peptides and peptides derived from aberrantly translated genes, 7 of which were shared between four or two different cell lines. Overall, the high throughput identification of MHC class I-loaded peptides is an effective strategy for systematic characterization of cancer peptides, and could be employed for design of multi-peptide anticancer vaccines. PMID:29331515

Methods for MHC genotyping in non-model vertebrates.

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Babik, W

2010-03-01

Genes of the major histocompatibility complex (MHC) are considered a paradigm of adaptive evolution at the molecular level and as such are frequently investigated by evolutionary biologists and ecologists. Accurate genotyping is essential for understanding of the role that MHC variation plays in natural populations, but may be extremely challenging. Here, I discuss the DNA-based methods currently used for genotyping MHC in non-model vertebrates, as well as techniques likely to find widespread use in the future. I also highlight the aspects of MHC structure that are relevant for genotyping, and detail the challenges posed by the complex genomic organization and high sequence variation of MHC loci. Special emphasis is placed on designing appropriate PCR primers, accounting for artefacts and the problem of genotyping alleles from multiple, co-amplifying loci, a strategy which is frequently necessary due to the structure of the MHC. The suitability of typing techniques is compared in various research situations, strategies for efficient genotyping are discussed and areas of likely progress in future are identified. This review addresses the well established typing methods such as the Single Strand Conformation Polymorphism (SSCP), Denaturing Gradient Gel Electrophoresis (DGGE), Reference Strand Conformational Analysis (RSCA) and cloning of PCR products. In addition, it includes the intriguing possibility of direct amplicon sequencing followed by the computational inference of alleles and also next generation sequencing (NGS) technologies; the latter technique may, in the future, find widespread use in typing complex multilocus MHC systems. © 2009 Blackwell Publishing Ltd.

MHC-I-induced apoptosis in human B-lymphoma cells is dependent on protein tyrosine and serine/threonine kinases

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Pedersen, Anders Elm; Bregenholt, S; Johansen, B

1999-01-01

B lymphoma cells, is dependent on protein tyrosine kinases and the phosphatidylinositol 3 (PI-3) kinase. Functional studies showed that MHC-I crosslinking induced almost complete inhibition of the spontaneous proliferation of the B lymphoma cells as early as 6 h post-crosslinking and apoptosis 24 h...... post-crosslinking. Preincubation with either protein tyrosine kinase or protein serine/threonine kinase inhibitors reduced the MHC-I-induced apoptosis to background levels, whereas inhibition of PI-3 kinase had no effect. These data demonstrate a pivotal role for protein tyrosine and serine...

Haplotype specific alteration of diabetes MHC risk by olfactory receptor gene polymorphism.

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Jahromi, Mohamed M

2012-12-01

Evidence for genes associated with risk for Type 1 diabetes (T1D) in the extended region of the major histocompatibility complex (MHC) genes is accumulating. The aim of this study was to investigate the association pattern of the extended MHC region with T1D susceptibility to identify effects independent of well established DR/DQ genes. A total of 394 Europid families with T1D were genotyped for the single nucleotide polymorphism (SNP) in the olfactory receptor family 14, subfamily J, member 1 (OR14J1) gene, rs9257691, in the MHC telomeric region. The OR provides "an internal depiction of our external world" through the capture of odorant molecules in the main OR system by several large families of G-protein coupled receptors (GPCR). These receptors transduce and chemosignals into the central nervous system (CNS). This SNP was chosen to identify its association with T1D. Interestingly, OR14J1C allele was significantly associated with T1D that seems to go with DRB1*0401, Χ(2)=10.9, p=0.0003. However, by fixing both genes of DR*0401-DQB1*0302, high risk, the association of T1D with OR14J1C still existed, Χ(2)=7.4, p=0.005. The occurrence of association of the OR14J1C allele with T1D patients with DRB1*401/DQB1*0302 is an independent risk for T1D. As an accumulative report suggests the role of OR in the pathogenesis of diabetic microvascular and other diabetic complications, undoubtedly, this haplotype specific alteration of T1D risk is an independent risk for the disease and can address the promising MHC-linked gene other than DR/DQ. Moreover, there is nothing to hinder for that this might be a signal that identifies the role of OR gene in the pathogenesis of T1D in patients who are prone to diabetic complications. Copyright © 2012. Published by Elsevier B.V.

Stressors impair odor recognition memory via an olfactory bulb-dependent noradrenergic mechanism

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Laura C Manella

2013-12-01

Full Text Available Non-associative habituation and odor recognition tasks have been widely used to probe questions social recognition, odor memory duration, and odor memory specificity. Among others, these paradigms have provided valuable insight into how neuromodulation, and specifically norepinephrine/noradrenaline (NE influences odor memory. In general, NE levels are modulated by arousal, stress, and behavioral state, and there is sparse evidence of a direct relationship between NE and odor memory in adult rodents. The present study uses simple mild psychological stressors (bright light and sound, to modulate NE levels physiologically in order to probe its effect on olfactory memory. In rats with bilateral bulbar cannulations, we show that these stressors modulate olfactory memory and that this effect is at least partially mediated by olfactory bulb. Specifically, we show that the presence of stressors during the acquisition of odor memory suppresses memory for an odor when tested 30 minutes after the acquisition. This suppression is blocked by infusing NE antagonists into the olfactory bulb prior to odor acquisition. Additionally, we find that infusion of bulbar NE is sufficient to suppress odor memory in a manner mimicking that of our stressors. These effects are unlikely to be solely mediated by locomotor/exploratory changes produced by stressors, although these stressors influence certain behaviors not directly related to odor investigation. This study provides important information about how behaviorally relevant changes in NE can influence top-down sensory processing and odor memory.

Genetically-based olfactory signatures persist despite dietary variation.

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Jae Kwak

Full Text Available Individual mice have a unique odor, or odortype, that facilitates individual recognition. Odortypes, like other phenotypes, can be influenced by genetic and environmental variation. The genetic influence derives in part from genes of the major histocompatibility complex (MHC. A major environmental influence is diet, which could obscure the genetic contribution to odortype. Because odortype stability is a prerequisite for individual recognition under normal behavioral conditions, we investigated whether MHC-determined urinary odortypes of inbred mice can be identified in the face of large diet-induced variation. Mice trained to discriminate urines from panels of mice that differed both in diet and MHC type found the diet odor more salient in generalization trials. Nevertheless, when mice were trained to discriminate mice with only MHC differences (but on the same diet, they recognized the MHC difference when tested with urines from mice on a different diet. This indicates that MHC odor profiles remain despite large dietary variation. Chemical analyses of urinary volatile organic compounds (VOCs extracted by solid phase microextraction (SPME and analyzed by gas chromatography/mass spectrometry (GC/MS are consistent with this inference. Although diet influenced VOC variation more than MHC, with algorithmic training (supervised classification MHC types could be accurately discriminated across different diets. Thus, although there are clear diet effects on urinary volatile profiles, they do not obscure MHC effects.

MHC motif viewer

DEFF Research Database (Denmark)

Rapin, Nicolas Philippe Jean-Pierre; Hoof, Ilka; Lund, Ole

2008-01-01

. Algorithms that predict which peptides MHC molecules bind have recently been developed and cover many different alleles, but the utility of these algorithms is hampered by the lack of tools for browsing and comparing the specificity of these molecules. We have, therefore, developed a web server, MHC motif....... A special viewing feature, MHC fight, allows for display of the specificity of two different MHC molecules side by side. We show how the web server can be used to discover and display surprising similarities as well as differences between MHC molecules within and between different species. The MHC motif...

Patterns of MHC-G-Like and MHC-B Diversification in New World Monkeys.

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Juan S Lugo

Full Text Available The MHC class I (MHC-I region in New World monkeys (Platyrrhini has remained relatively understudied. To evaluate the diversification patterns and transcription behavior of MHC-I in Platyrrhini, we first analyzed public genomic sequences from the MHC-G-like subregion in Saimiri boliviensis, Ateles geoffroyi and Callicebus moloch, and from the MHC-B subregion in Saimiri boliviensis. While S. boliviensis showed multiple copies of both MHC-G-like (10 and -B (15 loci, A. geoffroyi and C. moloch had only three and four MHC-G-like genes, respectively, indicating that not all Platyrrhini species have expanded their MHC-I loci. We then sequenced MHC-G-like and -B cDNAs from nine Platyrrhini species, recovering two to five unique cDNAs per individual for both loci classes. In two Saguinus species, however, no MHC-B cDNAs were found. In phylogenetic trees, MHC-G-like cDNAs formed genus-specific clusters whereas the MHC-B cDNAs grouped by Platyrrhini families, suggesting a more rapid diversification of the former. Furthermore, cDNA sequencing in 12 capuchin monkeys showed that they transcribe at least four MHC-G-like and five MHC-B polymorphic genes, showing haplotypic diversity for gene copy number and signatures of positive natural selection at the peptide binding region. Finally, a quantitative index for MHC:KIR affinity was proposed and tested to predict putative interacting pairs. Altogether, our data indicate that i MHC-I genes has expanded differentially among Platyrrhini species, ii Callitrichinae (tamarins and marmosets MHC-B loci have limited or tissue-specific expression, iii MHC-G-like genes have diversified more rapidly than MHC-B genes, and iv the MHC-I diversity is generated mainly by genetic polymorphism and gene copy number variation, likely promoted by natural selection for ligand binding.

Combinatorial effects of odorants on mouse behavior

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Saraiva, Luis R.; Kondoh, Kunio; Ye, Xiaolan; Yoon, Kyoung-hye; Hernandez, Marcus; Buck, Linda B.

2016-01-01

The mechanisms by which odors induce instinctive behaviors are largely unknown. Odor detection in the mouse nose is mediated by >1, 000 different odorant receptors (ORs) and trace amine-associated receptors (TAARs). Odor perceptions are encoded combinatorially by ORs and can be altered by slight changes in the combination of activated receptors. However, the stereotyped nature of instinctive odor responses suggests the involvement of specific receptors and genetically programmed neural circuits relatively immune to extraneous odor stimuli and receptor inputs. Here, we report that, contrary to expectation, innate odor-induced behaviors can be context-dependent. First, different ligands for a given TAAR can vary in behavioral effect. Second, when combined, some attractive and aversive odorants neutralize one another’s behavioral effects. Both a TAAR ligand and a common odorant block aversion to a predator odor, indicating that this ability is not unique to TAARs and can extend to an aversive response of potential importance to survival. In vitro testing of single receptors with binary odorant mixtures indicates that behavioral blocking can occur without receptor antagonism in the nose. Moreover, genetic ablation of a single receptor prevents its cognate ligand from blocking predator odor aversion, indicating that the blocking requires sensory input from the receptor. Together, these findings indicate that innate odor-induced behaviors can depend on context, that signals from a single receptor can block innate odor aversion, and that instinctive behavioral responses to odors can be modulated by interactions in the brain among signals derived from different receptors. PMID:27208093

NMDA receptors in mouse anterior piriform cortex initialize early odor preference learning and L-type calcium channels engage for long-term memory.

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Mukherjee, Bandhan; Yuan, Qi

2016-10-14

The interactions of L-type calcium channels (LTCCs) and NMDA receptors (NMDARs) in memories are poorly understood. Here we investigated the specific roles of anterior piriform cortex (aPC) LTCCs and NMDARs in early odor preference memory in mice. Using calcium imaging in aPC slices, LTCC activation was shown to be dependent on NMDAR activation. Either D-APV (NMDAR antagonist) or nifedipine (LTCC antagonist) reduced somatic calcium transients in pyramidal cells evoked by lateral olfactory tract stimulation. However, nifedipine did not further reduce calcium in the presence of D-APV. In mice that underwent early odor preference training, blocking NMDARs in the aPC prevented short-term (3 hr) and long-term (24 hr) odor preference memory, and both memories were rescued when BayK-8644 (LTCC agonist) was co-infused. However, activating LTCCs in the absence of NMDARs resulted in loss of discrimination between the conditioned odor and a similar odor mixture at 3 hr. Elevated synaptic AMPAR expression at 3 hr was prevented by D-APV infusion but restored when LTCCs were directly activated, mirroring the behavioral outcomes. Blocking LTCCs prevented 24 hr memory and spared 3 hr memory. These results suggest that NMDARs mediate stimulus-specific encoding of odor memory while LTCCs mediate intracellular signaling leading to long-term memory.

Neuronal MHC Class I Expression Is Regulated by Activity Driven Calcium Signaling.

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Dan Lv

Full Text Available MHC class I (MHC-I molecules are important components of the immune system. Recently MHC-I have been reported to also play important roles in brain development and synaptic plasticity. In this study, we examine the molecular mechanism(s underlying activity-dependent MHC-I expression using hippocampal neurons. Here we report that neuronal expression level of MHC-I is dynamically regulated during hippocampal development after birth in vivo. Kainic acid (KA treatment significantly increases the expression of MHC-I in cultured hippocampal neurons in vitro, suggesting that MHC-I expression is regulated by neuronal activity. In addition, KA stimulation decreased the expression of pre- and post-synaptic proteins. This down-regulation is prevented by addition of an MHC-I antibody to KA treated neurons. Further studies demonstrate that calcium-dependent protein kinase C (PKC is important in relaying KA simulation activation signals to up-regulated MHC-I expression. This signaling cascade relies on activation of the MAPK pathway, which leads to increased phosphorylation of CREB and NF-κB p65 while also enhancing the expression of IRF-1. Together, these results suggest that expression of MHC-I in hippocampal neurons is driven by Ca2+ regulated activation of the MAPK signaling transduction cascade.

Social pairing of Seychelles warblers under reduced constraints: MHC, neutral heterozygosity, and age.

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Wright, David J; Brouwer, Lyanne; Mannarelli, Maria-Elena; Burke, Terry; Komdeur, Jan; Richardson, David S

2016-01-01

The prevalence and significance of precopulatory mate choice remains keenly debated. The major histocompatibility complex (MHC) plays a key role in vertebrate adaptive immunity, and variation at the MHC influences individual survival. Although MHC-dependent mate choice has been documented in certain species, many other studies find no such pattern. This may be, at least in part, because in natural systems constraints may reduce the choices available to individuals and prevent full expression of underlying preferences. We used translocations to previously unoccupied islands to experimentally reduce constraints on female social mate choice in the Seychelles warbler ( Acrocephalus sechellensis ), a species in which patterns of MHC-dependent extrapair paternity (EPP), but not social mate choice, have been observed. We find no evidence of MHC-dependent social mate choice in the new populations. Instead, we find that older males and males with more microsatellite heterozygosity are more likely to have successfully paired. Our data cannot resolve whether these patterns in pairing were due to male-male competition or female choice. However, our research does suggest that female Seychelles warblers do not choose social mates using MHC class I to increase fitness. It may also indicate that the MHC-dependent EPP observed in the source population is probably due to mechanisms other than female precopulatory mate choice based on MHC cues.

Predicting the response of olfactory sensory neurons to odor mixtures from single odor response

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Marasco, Addolorata; de Paris, Alessandro; Migliore, Michele

2016-04-01

The response of olfactory receptor neurons to odor mixtures is not well understood. Here, using experimental constraints, we investigate the mathematical structure of the odor response space and its consequences. The analysis suggests that the odor response space is 3-dimensional, and predicts that the dose-response curve of an odor receptor can be obtained, in most cases, from three primary components with specific properties. This opens the way to an objective procedure to obtain specific olfactory receptor responses by manipulating mixtures in a mathematically predictable manner. This result is general and applies, independently of the number of odor components, to any olfactory sensory neuron type with a response curve that can be represented as a sigmoidal function of the odor concentration.

Odor composition analysis and odor indicator selection during sewage sludge composting

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Zhu, Yan-li; Zheng, Guo-di; Gao, Ding; Chen, Tong-bin; Wu, Fang-kun; Niu, Ming-jie; Zou, Ke-hua

2016-01-01

ABSTRACT On the basis of total temperature increase, normal dehydration, and maturity, the odor compositions of surface and internal piles in a well-run sewage sludge compost plant were analyzed using gas chromatography–mass spectrometry with a liquid nitrogen cooling system and a portable odor detector. Approximately 80 types of substances were detected, including 2 volatile inorganic compounds, 4 sulfur organic compounds, 16 benzenes, 27 alkanes, 15 alkenes, and 19 halogenated compounds. Most pollutants were mainly produced in the mesophilic and pre-thermophilic periods. The sulfur volatile organic compounds contributed significantly to odor and should be controlled primarily. Treatment strategies should be based on the properties of sulfur organic compounds. Hydrogen sulfide, methyl mercaptan, dimethyl disulfide, dimethyl sulfide, ammonia, and carbon disulfide were selected as core indicators. Ammonia, hydrogen sulfide, carbon disulfide, dimethyl disulfide, methyl mercaptan, dimethylbenzene, phenylpropane, and isopentane were designated as concentration indicators. Benzene, m-xylene, p-xylene, dimethylbenzene, dichloromethane, toluene, chlorobenzene, trichloromethane, carbon tetrachloride, and ethylbenzene were selected as health indicators. According to the principle of odor pollution indicator selection, dimethyl disulfide was selected as an odor pollution indicator of sewage sludge composting. Monitoring dimethyl disulfide provides a highly scientific method for modeling and evaluating odor pollution from sewage sludge composting facilities. Implications: Composting is one of the most important methods for sewage sludge treatment and improving the low organic matter content of many agricultural soils. However, odors are inevitably produced during the composting process. Understanding the production and emission patterns of odors is important for odor control and treatment. Core indicators, concentration indicators, and health indicators provide an index

Odor composition analysis and odor indicator selection during sewage sludge composting.

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Zhu, Yan-Li; Zheng, Guo-di; Gao, Ding; Chen, Tong-Bin; Wu, Fang-Kun; Niu, Ming-Jie; Zou, Ke-Hua

2016-09-01

On the basis of total temperature increase, normal dehydration, and maturity, the odor compositions of surface and internal piles in a well-run sewage sludge compost plant were analyzed using gas chromatography-mass spectrometry with a liquid nitrogen cooling system and a portable odor detector. Approximately 80 types of substances were detected, including 2 volatile inorganic compounds, 4 sulfur organic compounds, 16 benzenes, 27 alkanes, 15 alkenes, and 19 halogenated compounds. Most pollutants were mainly produced in the mesophilic and pre-thermophilic periods. The sulfur volatile organic compounds contributed significantly to odor and should be controlled primarily. Treatment strategies should be based on the properties of sulfur organic compounds. Hydrogen sulfide, methyl mercaptan, dimethyl disulfide, dimethyl sulfide, ammonia, and carbon disulfide were selected as core indicators. Ammonia, hydrogen sulfide, carbon disulfide, dimethyl disulfide, methyl mercaptan, dimethylbenzene, phenylpropane, and isopentane were designated as concentration indicators. Benzene, m-xylene, p-xylene, dimethylbenzene, dichloromethane, toluene, chlorobenzene, trichloromethane, carbon tetrachloride, and ethylbenzene were selected as health indicators. According to the principle of odor pollution indicator selection, dimethyl disulfide was selected as an odor pollution indicator of sewage sludge composting. Monitoring dimethyl disulfide provides a highly scientific method for modeling and evaluating odor pollution from sewage sludge composting facilities. Composting is one of the most important methods for sewage sludge treatment and improving the low organic matter content of many agricultural soils. However, odors are inevitably produced during the composting process. Understanding the production and emission patterns of odors is important for odor control and treatment. Core indicators, concentration indicators, and health indicators provide an index system to odor evaluation

MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen

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Judith A. James

2012-12-01

Full Text Available Anthrax Lethal Toxin consists of Protective Antigen (PA and Lethal Factor (LF, and current vaccination strategies focus on eliciting antibodies to PA. In human vaccination, the response to PA can vary greatly, and the response is often directed toward non-neutralizing epitopes. Variable vaccine responses have been shown to be due in part to genetic differences in individuals, with both MHC class II and other genes playing roles. Here, we investigated the relative contribution of MHC class II versus non-MHC class II genes in the humoral response to PA and LF immunization using three immunized strains of inbred mice: A/J (H-2k at the MHC class II locus, B6 (H-2b, and B6.H2k (H-2k. IgG antibody titers to LF were controlled primarily by the MHC class II locus, whereas IgG titers to PA were strongly influenced by the non-MHC class II genetic background. Conversely, the humoral fine specificity of reactivity to LF appeared to be controlled primarily through non-MHC class II genes, while the specificity of reactivity to PA was more dependent on MHC class II. Common epitopes, reactive in all strains, occurred in both LF and PA responses. These results demonstrate that MHC class II differentially influences humoral immune responses to LF and PA.

Odorant transfer characteristics of white bread during baking.

Science.gov (United States)

Onishi, Masanobu; Inoue, Michiko; Araki, Tetsuya; Iwabuchi, Hisakatsu; Sagara, Yasuyuki

2011-01-01

The potent odorants in the crust and crumb of white bread were identified and quantified by gas chromatography-mass spectrometry and gas chromatography/olfactometry. The weight loss ratio of the samples baked at 220 °C was controlled in the range of 0-28%. The odorants were classified into 5 types by the transfer characteristics: i) All amounts of odorant transferred from the crust to external space (type-I). ii) All transferred from the crust to the crumb and external space (type-II). iii) Certain amount remaining in the crust and the rest transferred to the crumb and external space (type-III). iv) All transferred from the crumb to external space (type-IV). v) Certain amount remaining in the crumb and the rest transferred to the crust and external space (type-V). The odorants of type-IV were not apparent after the crust had formed. The results indicate that the crust could be a barrier to prevent the odorants from being transferred to external space.

The SysteMHC Atlas project.

Science.gov (United States)

Shao, Wenguang; Pedrioli, Patrick G A; Wolski, Witold; Scurtescu, Cristian; Schmid, Emanuel; Vizcaíno, Juan A; Courcelles, Mathieu; Schuster, Heiko; Kowalewski, Daniel; Marino, Fabio; Arlehamn, Cecilia S L; Vaughan, Kerrie; Peters, Bjoern; Sette, Alessandro; Ottenhoff, Tom H M; Meijgaarden, Krista E; Nieuwenhuizen, Natalie; Kaufmann, Stefan H E; Schlapbach, Ralph; Castle, John C; Nesvizhskii, Alexey I; Nielsen, Morten; Deutsch, Eric W; Campbell, David S; Moritz, Robert L; Zubarev, Roman A; Ytterberg, Anders Jimmy; Purcell, Anthony W; Marcilla, Miguel; Paradela, Alberto; Wang, Qi; Costello, Catherine E; Ternette, Nicola; van Veelen, Peter A; van Els, Cécile A C M; Heck, Albert J R; de Souza, Gustavo A; Sollid, Ludvig M; Admon, Arie; Stevanovic, Stefan; Rammensee, Hans-Georg; Thibault, Pierre; Perreault, Claude; Bassani-Sternberg, Michal; Aebersold, Ruedi; Caron, Etienne

2018-01-04

Mass spectrometry (MS)-based immunopeptidomics investigates the repertoire of peptides presented at the cell surface by major histocompatibility complex (MHC) molecules. The broad clinical relevance of MHC-associated peptides, e.g. in precision medicine, provides a strong rationale for the large-scale generation of immunopeptidomic datasets and recent developments in MS-based peptide analysis technologies now support the generation of the required data. Importantly, the availability of diverse immunopeptidomic datasets has resulted in an increasing need to standardize, store and exchange this type of data to enable better collaborations among researchers, to advance the field more efficiently and to establish quality measures required for the meaningful comparison of datasets. Here we present the SysteMHC Atlas (https://systemhcatlas.org), a public database that aims at collecting, organizing, sharing, visualizing and exploring immunopeptidomic data generated by MS. The Atlas includes raw mass spectrometer output files collected from several laboratories around the globe, a catalog of context-specific datasets of MHC class I and class II peptides, standardized MHC allele-specific peptide spectral libraries consisting of consensus spectra calculated from repeat measurements of the same peptide sequence, and links to other proteomics and immunology databases. The SysteMHC Atlas project was created and will be further expanded using a uniform and open computational pipeline that controls the quality of peptide identifications and peptide annotations. Thus, the SysteMHC Atlas disseminates quality controlled immunopeptidomic information to the public domain and serves as a community resource toward the generation of a high-quality comprehensive map of the human immunopeptidome and the support of consistent measurement of immunopeptidomic sample cohorts. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Learning-dependent and -independent enhancement of mitral/tufted cell glomerular odor responses following olfactory fear conditioning in awake mice.

Science.gov (United States)

Ross, Jordan M; Fletcher, Max L

2018-04-18

Associative fear learning produces fear toward the conditioned stimulus (CS) and often generalization, the expansion of fear from the CS to similar, unlearned stimuli. However, how fear learning affects early sensory processing of learned and unlearned stimuli in relation to behavioral fear responses to these stimuli remains unclear. We subjected male and female mice expressing the fluorescent calcium indicator GCaMP3 in olfactory bulb mitral and tufted cells to a classical olfactory fear conditioning paradigm. We then used awake, in vivo calcium imaging to quantify learning-induced changes in glomerular odor responses, which constitute the first site of olfactory processing in the brain. The results demonstrate that odor-shock pairing non-specifically enhances glomerular odor representations in a learning-dependent manner and increases representational similarity between the CS and non-conditioned odors, potentially priming the system towards generalization of learned fear. Additionally, CS-specific glomerular enhancements remain even when associative learning is blocked, suggesting two separate mechanisms lead to enhanced glomerular responses following odor-shock pairings. SIGNIFICANCE STATEMENT In the olfactory bulb (OB), odors are uniquely coded in a spatial map that represents odor identity, making the OB a unique model system for investigating how learned fear alters sensory processing. Classical fear conditioning causes fear of the conditioned stimulus (CS) and of neutral stimuli, known as generalization. Combining fear conditioning with fluorescent calcium imaging of OB glomeruli, we found enhanced glomerular responses of the CS as well as neutral stimuli in awake mice, which mirrors fear generalization. We report that CS and neutral stimuli enhancements are, respectively, learning- independent and learning-dependent. Together, these results reveal distinct mechanisms leading to enhanced OB processing of fear-inducing stimuli and provide important

MHC-Dependent Mate Selection within 872 Spousal Pairs of European Ancestry from the Health and Retirement Study

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Zhen Qiao

2018-01-01

Full Text Available Disassortative mating refers to the phenomenon in which individuals with dissimilar genotypes and/or phenotypes mate with one another more frequently than would be expected by chance. Although the existence of disassortative mating is well established in plant and animal species, the only documented example of negative assortment in humans involves dissimilarity at the major histocompatibility complex (MHC locus. Previous studies investigating mating patterns at the MHC have been hampered by limited sample size and contradictory findings. Inspired by the sparse and conflicting evidence, we investigated the role that the MHC region played in human mate selection using genome-wide association data from 872 European American spouses from the Health and Retirement Study (HRS. First, we treated the MHC region as a whole, and investigated genomic similarity between spouses using three levels of genomic variation: single-nucleotide polymorphisms (SNPs, classical human leukocyte antigen (HLA alleles (both four-digit and two-digit classifications, and amino acid polymorphisms. The extent of MHC dissimilarity between spouses was assessed using a permutation approach. Second, we investigated fine scale mating patterns by testing for deviations from random mating at individual SNPs, HLA genes, and amino acids in HLA molecules. Third, we assessed how extreme the spousal relatedness at the MHC region was compared to the rest of the genome, to distinguish the MHC-specific effects from genome-wide effects. We show that neither the MHC region, nor any single SNPs, classic HLA alleles, or amino acid polymorphisms within the MHC region, were significantly dissimilar between spouses relative to non-spouse pairs. However, dissimilarity in the MHC region was extreme relative to the rest of genome for both spousal and non-spouse pairs. Despite the long-standing controversy, our analyses did not support a significant role of MHC dissimilarity in human mate choice.

Post-eclosion odor experience modifies olfactory receptor neuron coding in Drosophila.

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Iyengar, Atulya; Chakraborty, Tuhin Subhra; Goswami, Sarit Pati; Wu, Chun-Fang; Siddiqi, Obaid

2010-05-25

Olfactory responses of Drosophila undergo pronounced changes after eclosion. The flies develop attraction to odors to which they are exposed and aversion to other odors. Behavioral adaptation is correlated with changes in the firing pattern of olfactory receptor neurons (ORNs). In this article, we present an information-theoretic analysis of the firing pattern of ORNs. Flies reared in a synthetic odorless medium were transferred after eclosion to three different media: (i) a synthetic medium relatively devoid of odor cues, (ii) synthetic medium infused with a single odorant, and (iii) complex cornmeal medium rich in odors. Recordings were made from an identified sensillum (type II), and the Jensen-Shannon divergence (D(JS)) was used to assess quantitatively the differences between ensemble spike responses to different odors. Analysis shows that prolonged exposure to ethyl acetate and several related esters increases sensitivity to these esters but does not improve the ability of the fly to distinguish between them. Flies exposed to cornmeal display varied sensitivity to these odorants and at the same time develop greater capacity to distinguish between odors. Deprivation of odor experience on an odorless synthetic medium leads to a loss of both sensitivity and acuity. Rich olfactory experience thus helps to shape the ORNs response and enhances its discriminative power. The experiments presented here demonstrate an experience-dependent adaptation at the level of the receptor neuron.

Cross-adaptation between olfactory responses induced by two subgroups of odorant molecules.

Science.gov (United States)

Takeuchi, Hiroko; Imanaka, Yukie; Hirono, Junzo; Kurahashi, Takashi

2003-09-01

It has long been believed that vertebrate olfactory signal transduction is mediated by independent multiple pathways (using cAMP and InsP3 as second messengers). However, the dual presence of parallel pathways in the olfactory receptor cell is still controversial, mainly because of the lack of information regarding the single-cell response induced by odorants that have been shown to produce InsP3 exclusively (but not cAMP) in the olfactory cilia. In this study, we recorded activities of transduction channels of single olfactory receptor cells to InsP3-producing odorants. When the membrane potential was held at -54 mV, application of InsP3-producing odorants to the ciliary region caused an inward current. The reversal potential was 0 +/- 7 mV (mean +/- SD, n = 10). Actually, InsP3-producing odorants generated responses in a smaller fraction of cells (lilial, 3.4%; lyral, 1.7%) than the cAMP-producing odorant (cineole, 26%). But, fundamental properties of responses were surprisingly homologous; namely, spatial distribution of the sensitivity, waveforms, I-V relation, and reversal potential, dose dependence, time integration of stimulus period, adaptation, and recovery. By applying both types of odorants alternatively to the same cell, furthermore, we observed cells to exhibit symmetrical cross-adaptation. It seems likely that even with odorants with different modalities adaptation occurs completely depending on the amount of current flow. The data will also provide evidence showing that olfactory response generation and adaptation are regulated by a uniform mechanism for a wide variety of odorants.

The functional neuroanatomy of odor evoked autobiographical memories cued by odors and words.

Science.gov (United States)

Arshamian, Artin; Iannilli, Emilia; Gerber, Johannes C; Willander, Johan; Persson, Jonas; Seo, Han-Seok; Hummel, Thomas; Larsson, Maria

2013-01-01

Behavioral evidence indicates that odor evoked autobiographical memories (OEAMs) are older, more emotional, less thought of and induce stronger time traveling characteristics than autobiographical memories (AMs) evoked by other modalities. The main aim of this study was to explore the neural correlates of AMs evoked by odors as a function of retrieval cue. Participants were screened for specific OEAMs and later presented with the odor cue and its verbal referent in an fMRI paradigm. Because the same OEAM was retrieved across both cue formats (odor and word), potential cue dependent brain activations were investigated. The overall results showed that odor and word cued OEAMs activated regions typically associated with recollection of autobiographical information. Although no odors were presented, a verbal cuing of the OEAMs activated areas associated with olfactory perception (e.g., piriform cortex). However, relative to word cuing, an odor cuing of OEAMs resulted in more activity in MTL regions such as the parahippocampus, and areas involved in visual vividness (e.g., occipital gyrus and precuneus). Furthermore, odor cues activated areas related to emotional processing, such as limbic and tempopolar regions significantly more. In contrast, word cues relative to odor cues recruited a more widespread and bilateral prefrontal activity. Hippocampus activity did not vary as function of the remoteness of the memory, but recollection of OEAMs from the 1(st) vs the 2(nd) decade of life showed specific activation in the right OFC, whereas the 2(nd) reflected a higher activation in the left inferior frontal gyrus. Copyright © 2012 Elsevier Ltd. All rights reserved.

Odors cue memory for odor-associated words

OpenAIRE

Stafford, Lorenzo; Salehi, S.; Waller, Bridget

2009-01-01

The ability of odors to cue vivid and emotionally intense memories is well-known. However, the majority of research has focused on the extent to which odors can act as environmental cues to memory, where odors are presented alongside the stimuli to be remembered, rather than the extent to which pre-existing associations between odor and odor-related stimuli might influence memory. In this study, participants (n = 45 females in each experiment) were presented with words (two groups of odor-ass...

The mere exposure effect depends on an odor?s initial pleasantness

OpenAIRE

Delplanque, Sylvain; Coppin, G?raldine; Bloesch, Laur?ne; Cayeux, Isabelle; Sander, David

2015-01-01

The mere exposure phenomenon refers to improvement of one’s attitude toward an a priori neutral stimulus after its repeated exposure. The extent to which such a phenomenon influences evaluation of a priori emotional stimuli remains under-investigated. Here we investigated this question by presenting participants with different odors varying in a priori pleasantness during different sessions spaced over time. Participants were requested to report each odor’s pleasantness, intensity, and famili...

Contrasting patterns of selection between MHC I and II across populations of Humboldt and Magellanic penguins

OpenAIRE

Sallaberry?Pincheira, Nicole; Gonz?lez?Acu?a, Daniel; Padilla, Pamela; Dantas, Gisele P. M.; Luna?Jorquera, Guillermo; Frere, Esteban; Vald?s?Vel?squez, Armando; Vianna, Juliana A.

2016-01-01

Abstract The evolutionary and adaptive potential of populations or species facing an emerging infectious disease depends on their genetic diversity in genes, such as the major histocompatibility complex (MHC). In birds, MHC class I deals predominantly with intracellular infections (e.g., viruses) and MHC class II with extracellular infections (e.g., bacteria). Therefore, patterns of MHC I and II diversity may differ between species and across populations of species depending on the relative e...

Chemotherapeutics and radiation stimulate MHC class I expression through elevated interferon-beta signaling in breast cancer cells.

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Shan Wan

Full Text Available Low doses of anticancer drugs have been shown to enhance antitumor immune response and increase the efficacy of immunotherapy. The molecular basis for such effects remains elusive, although selective depletion of T regulatory cells has been demonstrated. In the current studies, we demonstrate that topotecan (TPT, a topoisomerase I-targeting drug with a well-defined mechanism of action, stimulates major histocompatibility complex class I (MHC I expression in breast cancer cells through elevated expression/secretion of interferon-β (IFN-β and activation of type I IFN signaling. First, we show that TPT treatment elevates the expression of both total and cell-surface MHC I in breast cancer cells. Second, conditioned media from TPT-treated breast cancer ZR-75-1 cells induce elevated expression of cell-surface MHC I in drug-naïve recipient cells, suggesting the involvement of cytokines and/or other secreted molecules. Consistently, TPT-treated cells exhibit elevated expression of multiple cytokines such as IFN-β, TNF-α, IL-6 and IL-8. Third, either knocking down the type I interferon receptor subunit 1 (IFNAR1 or addition of neutralizing antibody against IFN-β results in reduced MHC I expression in TPT-treated cells. Together, these results suggest that TPT induces increased IFN-β autocrine/paracrine signaling through type I IFN receptor, resulting in the elevated MHC I expression in tumor cells. Studies have also demonstrated that other chemotherapeutic agents (e.g. etoposide, cisplatin, paclitaxel and vinblastine similarly induce increased IFN-β secretion and elevated MHC I expression. In addition, conditioned media from γ-irradiated donor cells are shown to induce IFN-β-dependent MHC I expression in unirradiated recipient cells. In the aggregate, our results suggest that many cancer therapeutics induce elevated tumor antigen presentation through MHC I, which could represent a common mechanism for enhanced antitumor immune response through

Two Parallel Pathways Assign Opposing Odor Valences during Drosophila Memory Formation

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Daisuke Yamazaki

2018-02-01

Full Text Available During olfactory associative learning in Drosophila, odors activate specific subsets of intrinsic mushroom body (MB neurons. Coincident exposure to either rewards or punishments is thought to activate extrinsic dopaminergic neurons, which modulate synaptic connections between odor-encoding MB neurons and MB output neurons to alter behaviors. However, here we identify two classes of intrinsic MB γ neurons based on cAMP response element (CRE-dependent expression, γCRE-p and γCRE-n, which encode aversive and appetitive valences. γCRE-p and γCRE-n neurons act antagonistically to maintain neutral valences for neutral odors. Activation or inhibition of either cell type upsets this balance, toggling odor preferences to either positive or negative values. The mushroom body output neurons, MBON-γ5β′2a/β′2mp and MBON-γ2α′1, mediate the actions of γCRE-p and γCRE-n neurons. Our data indicate that MB neurons encode valence information, as well as odor information, and this information is integrated through a process involving MBONs to regulate learning and memory.

An MHC II-Dependent Activation Loop between Adipose Tissue Macrophages and CD4+ T Cells Controls Obesity-Induced Inflammation

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Kae Won Cho

2014-10-01

Full Text Available An adaptive immune response triggered by obesity is characterized by the activation of adipose tissue CD4+ T cells by unclear mechanisms. We have examined whether interactions between adipose tissue macrophages (ATMs and CD4+ T cells contribute to adipose tissue metainflammation. Intravital microscopy identifies dynamic antigen-dependent interactions between ATMs and T cells in visceral fat. Mice deficient in major histocompatibility complex class II (MHC II showed protection from diet-induced obesity. Deletion of MHC II expression in macrophages led to an adipose tissue-specific decrease in the effector/memory CD4+ T cells, attenuation of CD11c+ ATM accumulation, and improvement in glucose intolerance by increasing adipose tissue insulin sensitivity. Ablation experiments demonstrated that the maintenance of proliferating conventional T cells is dependent on signals from CD11c+ ATMs in obese mice. These studies demonstrate the importance of MHCII-restricted signals from ATMs that regulate adipose tissue T cell maturation and metainflammation.

Assessment of odor activity value coefficient and odor contribution based on binary interaction effects in waste disposal plant

Science.gov (United States)

Wu, Chuandong; Liu, Jiemin; Yan, Luchun; Chen, Haiying; Shao, Huiqi; Meng, Tian

2015-02-01

Odor activity value (OAV) has been widely used for the assessment of odor pollution from various sources. However, little attention has been paid to the extreme OAV variation and potential inaccuracies of odor contribution assessment caused by odor interaction effects. The objective of this study is to assess the odor interaction effect for precise assessment of odor contribution. In this paper, samples were collected from a food waste disposal plant, and analyzed by instrumental and olfactory method to conclude odorants' occurrence and OAV. Then odor activity value coefficient (γ) was first proposed to evaluate the type and the level of binary interaction effects based on determination of OAV variation. By multiplying OAV and γ, odor activity factor (OAF) was used to reflect the real OAV. Correlation between the sum of OAF and odor concentration reached 80.0 ± 5.7%, which was 10 times higher than the sum of OAV used before. Results showed that hydrogen sulfide contributed most (annual average 66.4 ± 15.8%) to odor pollution in the waste disposal plant. However, as odor intensity of samples in summer rising, odor contribution of trimethylamine increased to 48.3 ± 3.7% by the strong synergistic interaction effect, while odor contribution of phenol decreased to 0.1 ± 0.02% for the increasing antagonistic interaction effect.

MHC class II polymorphisms, autoreactive T-cells and autoimmunity

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Sue eTsai

2013-10-01

Full Text Available Major histocompatibility complex (MHC genes, also known as human leukocyte antigen genes (HLA in humans, are the prevailing contributors of genetic susceptibility to autoimmune diseases such as Type 1 Diabetes (T1D, Multiple Sclerosis (MS, and Rheumatoid arthritis (RA, among others (Todd and Wicker, 2001;MacKay et al., 2002;Hafler et al., 2007. Although the pathways through which MHC molecules afford autoimmune risk or resistance remain to be fully mapped out, it is generally accepted that they do so by shaping the central and peripheral T cell repertoires of the host towards autoimmune proclivity or resistance, respectively. Disease-predisposing MHC alleles would both spare autoreactive thymocytes from central tolerance and bias their development towards a pathogenic phenotype. Protective MHC alleles, on the other hand, would promote central deletion of autoreactive thymocytes and skew their development towards non-pathogenic phenotypes. This interpretation of the data is at odds with two other observations: that in MHC-heterozygous individuals, resistance is dominant over susceptibility; and that it is difficult to understand how deletion of one or a few clonal autoreactive T cell types would suffice to curb autoimmune responses driven by hundreds if not thousands of autoreactive T cell specificities. This review provides an update on current advances in our understanding of the mechanisms underlying MHC class II-associated autoimmune disease susceptibility and/or resistance and attempts to reconcile these seemingly opposing concepts.

Contrasting patterns of selection between MHC I and II across populations of Humboldt and Magellanic penguins.

Science.gov (United States)

Sallaberry-Pincheira, Nicole; González-Acuña, Daniel; Padilla, Pamela; Dantas, Gisele P M; Luna-Jorquera, Guillermo; Frere, Esteban; Valdés-Velásquez, Armando; Vianna, Juliana A

2016-10-01

The evolutionary and adaptive potential of populations or species facing an emerging infectious disease depends on their genetic diversity in genes, such as the major histocompatibility complex (MHC). In birds, MHC class I deals predominantly with intracellular infections (e.g., viruses) and MHC class II with extracellular infections (e.g., bacteria). Therefore, patterns of MHC I and II diversity may differ between species and across populations of species depending on the relative effect of local and global environmental selective pressures, genetic drift, and gene flow. We hypothesize that high gene flow among populations of Humboldt and Magellanic penguins limits local adaptation in MHC I and MHC II, and signatures of selection differ between markers, locations, and species. We evaluated the MHC I and II diversity using 454 next-generation sequencing of 100 Humboldt and 75 Magellanic penguins from seven different breeding colonies. Higher genetic diversity was observed in MHC I than MHC II for both species, explained by more than one MHC I loci identified. Large population sizes, high gene flow, and/or similar selection pressures maintain diversity but limit local adaptation in MHC I. A pattern of isolation by distance was observed for MHC II for Humboldt penguin suggesting local adaptation, mainly on the northernmost studied locality. Furthermore, trans-species alleles were found due to a recent speciation for the genus or convergent evolution. High MHC I and MHC II gene diversity described is extremely advantageous for the long-term survival of the species.

Sympatric and allopatric divergence of MHC genes in threespine stickleback.

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Blake Matthews

2010-06-01

Full Text Available Parasites can strongly affect the evolution of their hosts, but their effects on host diversification are less clear. In theory, contrasting parasite communities in different foraging habitats could generate divergent selection on hosts and promote ecological speciation. Immune systems are costly to maintain, adaptable, and an important component of individual fitness. As a result, immune system genes, such as those of the Major Histocompatibility Complex (MHC, can change rapidly in response to parasite-mediated selection. In threespine stickleback (Gasterosteus aculeatus, as well as in other vertebrates, MHC genes have been linked with female mating preference, suggesting that divergent selection acting on MHC genes might influence speciation. Here, we examined genetic variation at MHC Class II loci of sticklebacks from two lakes with a limnetic and benthic species pair, and two lakes with a single species. In both lakes with species pairs, limnetics and benthics differed in their composition of MHC alleles, and limnetics had fewer MHC alleles per individual than benthics. Similar to the limnetics, the allopatric population with a pelagic phenotype had few MHC alleles per individual, suggesting a correlation between MHC genotype and foraging habitat. Using a simulation model we show that the diversity and composition of MHC alleles in a sympatric species pair depends on the amount of assortative mating and on the strength of parasite-mediated selection in adjacent foraging habitats. Our results indicate parallel divergence in the number of MHC alleles between sympatric stickleback species, possibly resulting from the contrasting parasite communities in littoral and pelagic habitats of lakes.

Odor Learning and Its Experience-Dependent Modulation in the South American Native Bumblebee Bombus atratus (Hymenoptera: Apidae)

Science.gov (United States)

Palottini, Florencia; Estravis Barcala, María C.; Farina, Walter M.

2018-01-01

Learning about olfactory stimuli is essential in bumblebees’ life since it is involved in orientation, recognition of nest sites, foraging efficiency and food yield for the colony as a whole. To evaluate associative learning abilities in bees under controlled environmental conditions, the proboscis extension response (PER) assay is a well-established method used in honey bees, stingless bees and successfully adapted to bumblebees of the genus Bombus. However, studies on the learning capacity of Bombus atratus (Hymenoptera: Apidae), one of the most abundant native species in South America, are non-existent. In this study, we examined the cognitive abilities of worker bees of this species, carrying out an olfactory PER conditioning experiment. Bumblebees were able to learn a pure odor when it was presented in paired association with sugared reward, but not when odor and reward were presented in an unpaired manner. Furthermore, if the bees were preexposed to the conditioned odor, the results differed depending on the presence of the scent either as a volatile in the rearing environment or diluted in the food. A decrement in learning performance results from the non-reinforced pre-exposure to the to-be-conditioned odor, showing a latent inhibition phenomenon. However, if the conditioned odor has been previously offered diluted in sugared reward, the food odor acts as a stimulus that improves the learning performance during PER conditioning. The native bumblebee B. atratus is thus a new hymenopteran species capable of being trained under controlled experimental conditions. Since it is an insect increasingly reared for pollination service, this knowledge could be useful in its management in crops. PMID:29755391

Neurons are MHC class I-dependent targets for CD8 T cells upon neurotropic viral infection.

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Grégoire Chevalier

2011-11-01

Full Text Available Following infection of the central nervous system (CNS, the immune system is faced with the challenge of eliminating the pathogen without causing significant damage to neurons, which have limited capacities of renewal. In particular, it was thought that neurons were protected from direct attack by cytotoxic T lymphocytes (CTL because they do not express major histocompatibility class I (MHC I molecules, at least at steady state. To date, most of our current knowledge on the specifics of neuron-CTL interaction is based on studies artificially inducing MHC I expression on neurons, loading them with exogenous peptide and applying CTL clones or lines often differentiated in culture. Thus, much remains to be uncovered regarding the modalities of the interaction between infected neurons and antiviral CD8 T cells in the course of a natural disease. Here, we used the model of neuroinflammation caused by neurotropic Borna disease virus (BDV, in which virus-specific CTL have been demonstrated as the main immune effectors triggering disease. We tested the pathogenic properties of brain-isolated CD8 T cells against pure neuronal cultures infected with BDV. We observed that BDV infection of cortical neurons triggered a significant up regulation of MHC I molecules, rendering them susceptible to recognition by antiviral CTL, freshly isolated from the brains of acutely infected rats. Using real-time imaging, we analyzed the spatio-temporal relationships between neurons and CTL. Brain-isolated CTL exhibited a reduced mobility and established stable contacts with BDV-infected neurons, in an antigen- and MHC-dependent manner. This interaction induced rapid morphological changes of the neurons, without immediate killing or impairment of electrical activity. Early signs of neuronal apoptosis were detected only hours after this initial contact. Thus, our results show that infected neurons can be recognized efficiently by brain-isolated antiviral CD8 T cells and

MHC protocols

National Research Council Canada - National Science Library

Powis, Stephen H; Vaughan, Robert W

2003-01-01

... because it contains genes encoding components of the complement pathway. The entire human MHC has recently been sequenced (1) and each subregion is now known to contain many other genes, a number of which have immunological functions. The study of polymorphism within the MHC is well established, because the region contains the highly polymorphic HLA genes. HLA polym...

Establishment of a quantitative ELISA capable of determining peptide - MHC class I interaction

DEFF Research Database (Denmark)

Sylvester-Hvid, C; Kristensen, N; Blicher, T

2002-01-01

dependent manner. Here, we exploit the availability of these molecules to generate a quantitative ELISA-based assay capable of measuring the affinity of the interaction between peptide and MHC-I. This assay is simple and sensitive, and one can easily envisage that the necessary reagents, standards......Many different assays for measuring peptide-MHC interactions have been suggested over the years. Yet, there is no generally accepted standard method available. We have recently generated preoxidized recombinant MHC class I molecules (MHC-I) which can be purified to homogeneity under denaturing...

Odor Emotional Quality Predicts Odor Identification.

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Bestgen, Anne-Kathrin; Schulze, Patrick; Kuchinke, Lars

2015-09-01

It is commonly agreed upon a strong link between emotion and olfaction. Odor-evoked memories are experienced as more emotional compared with verbal, visual, and tactile stimuli. Moreover, the emotional quality of odor cues increases memory performance, but contrary to this, odors are poor retrieval cues for verbal labels. To examine the relation between the emotional quality of an odor and its likelihood of identification, this study evaluates how normative emotion ratings based on the 3-dimensional affective space model (that includes valence, arousal, and dominance), using the Self-Assessment Manikin by Bradley and Lang (Bradley MM, Lang PJ. 1994. Measuring emotion: the Self-Assessment Manikin and the Semantic Differential. J Behav Ther Exp Psychiatry. 25(1):49-59.) and the Positive and Negative Affect Schedule (Watson D, Clark LA, Tellegen A. 1988. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 54(6):1063-1070.) predict the identification of odors in a multiple choice condition. The best fitting logistic regression model includes squared valence and dominance and thus, points to a significant role of specific emotional features of odors as a main clue for odor identification. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Existence of multiple receptors in single neurons: responses of single bullfrog olfactory neurons to many cAMP-dependent and independent odorants.

Science.gov (United States)

Kashiwayanagi, M; Shimano, K; Kurihara, K

1996-11-04

The responses of single bullfrog olfactory neurons to various odorants were measured with the whole-cell patch clamp which offers direct information on cellular events and with the ciliary recording technique to obtain stable quantitative data from many neurons. A large portion of single olfactory neurons (about 64% and 79% in the whole-cell recording and in the ciliary recording, respectively) responded to many odorants with quite diverse molecular structures, including both odorants previously indicated to be cAMP-dependent (increasing) and independent odorants. One odorant elicited a response in many cells; e.g. hedione and citralva elicited the response in 100% and 92% of total neurons examined with the ciliary recording technique. To confirm that a single neuron carries different receptors or transduction pathways, the cross-adaptation technique was applied to single neurons. Application of hedione to a single neuron after desensitization of the current in response to lyral or citralva induced an inward current with a similar magnitude to that applied alone. It was suggested that most single olfactory neurons carry multiple receptors and at least dual transduction pathways.

Real-time, high-throughput measurements of peptide-MHC-I dissociation using a scintillation proximity assay

DEFF Research Database (Denmark)

Harndahl, Mikkel; Rasmussen, Michael; Røder, Gustav Andreas

2011-01-01

and it is well suited for high-throughput screening. To exemplify this, we screened a panel of 384 high-affinity peptides binding to the MHC class I molecule, HLA-A*02:01, and observed the rates of dissociation that ranged from 0.1h to 46h depending on the peptide used.......Efficient presentation of peptide-MHC class I complexes to immune T cells depends upon stable peptide-MHC class I interactions. Theoretically, determining the rate of dissociation of a peptide-MHC class I complexes is straightforward; in practical terms, however, generating the accurate and closely...... timed data needed to determine the rate of dissociation is not simple. Ideally, one should use a homogenous assay involving an inexhaustible and label-free assay principle. Here, we present a homogenous, high-throughput peptide-MHC class I dissociation assay, which by and large fulfill these ideal...

MHC class I cross-talk with CD2 and CD28 induces specific intracellular signalling and leads to growth retardation and apoptosis via a p56(lck)-dependent mechanism

DEFF Research Database (Denmark)

Ruhwald, M; Pedersen, Anders Elm; Claesson, M H

1999-01-01

Ligation of the major histocompatibility complex class I molecules (MHC-I) on human T lymphoma cells (Jurkat) initiates p56(lck)-dependent intracellular signalling events (phosphotyrosine kinase activity; [Ca(2+)](i)) and leads to augmented growth inhibition and apoptosis. MHC-I ligation in concert...... of apoptosis. In parallel experiments with the p56(lck)-negative Jurkat mutant cell, JCaM1.6, cross-linking neither influenced cell signalling nor cellular growth functions, indicating a cardinal role of the src kinases in signal transduction via MHC-I, CD2 and CD28 molecules. The results presented here...... with ligation of CD2 or CD28 augments, changes or modifies the pattern of activation. Ligation of MHC-I and CD2 alone resulted in growth inhibition, whereas CD28 ligation alone had no effect on cell proliferation. Ligation of MHC-I together with CD2 augmented growth inhibition and enhanced the level...

The C-terminal amino acid of the MHC-I heavy chain is critical for binding to Derlin-1 in human cytomegalovirus US11-induced MHC-I degradation.

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Cho, Sunglim; Kim, Bo Young; Ahn, Kwangseog; Jun, Youngsoo

2013-01-01

Derlin-1 plays a critical role in endoplasmic reticulum-associated protein degradation (ERAD) of a particular subset of proteins. Although it is generally accepted that Derlin-1 mediates the export of ERAD substrates from the ER to the cytosol, little is known about how Derlin-1 interacts with these substrates. Human cytomegalovirus (HCMV) US11 exploits Derlin-1-dependent ERAD to degrade major histocompatibility complex class I (MHC-I) molecules and evade immune surveillance. US11 requires the cytosolic tail of the MHC-I heavy chain to divert MHC-I molecules into the ERAD pathway for degradation; however, the underlying mechanisms remain unknown. Here, we show that the cytosolic tail of the MHC-I heavy chain, although not required for interaction with US11, is required for tight binding to Derlin-1 and thus for US11-induced dislocation of the MHC-I heavy chain to the cytosol for proteasomal degradation. Surprisingly, deletion of a single C-terminal amino acid from the cytosolic tail disrupted the interaction between MHC-I molecules and Derlin-1, rendering mutant MHC-I molecules resistant to US11-induced degradation. Consistently, deleting the C-terminal cytosolic region of Derlin-1 prevented it from binding to MHC-I molecules. Taken together, these results suggest that the cytosolic region of Derlin-1 is involved in ERAD substrate binding and that this interaction is critical for the Derlin-1-mediated dislocation of the MHC-I heavy chain to the cytosol during US11-induced MHC-I degradation.

MPID-T2: a database for sequence-structure-function analyses of pMHC and TR/pMHC structures.

Science.gov (United States)

Khan, Javed Mohammed; Cheruku, Harish Reddy; Tong, Joo Chuan; Ranganathan, Shoba

2011-04-15

Sequence-structure-function information is critical in understanding the mechanism of pMHC and TR/pMHC binding and recognition. A database for sequence-structure-function information on pMHC and TR/pMHC interactions, MHC-Peptide Interaction Database-TR version 2 (MPID-T2), is now available augmented with the latest PDB and IMGT/3Dstructure-DB data, advanced features and new parameters for the analysis of pMHC and TR/pMHC structures. http://biolinfo.org/mpid-t2. shoba.ranganathan@mq.edu.au Supplementary data are available at Bioinformatics online.

Tubulation of class II MHC compartments is microtubule dependent and involves multiple endolysosomal membrane proteins in primary dendritic cells.

Science.gov (United States)

Vyas, Jatin M; Kim, You-Me; Artavanis-Tsakonas, Katerina; Love, J Christopher; Van der Veen, Annemarthe G; Ploegh, Hidde L

2007-06-01

Immature dendritic cells (DCs) capture exogenous Ags in the periphery for eventual processing in endolysosomes. Upon maturation by TLR agonists, DCs deliver peptide-loaded class II MHC molecules from these compartments to the cell surface via long tubular structures (endolysosomal tubules). The nature and rules that govern the movement of these DC compartments are unknown. In this study, we demonstrate that the tubules contain multiple proteins including the class II MHC molecules and LAMP1, a lysosomal resident protein, as well as CD63 and CD82, members of the tetraspanin family. Endolysosomal tubules can be stained with acidotropic dyes, indicating that they are extensions of lysosomes. However, the proper trafficking of class II MHC molecules themselves is not necessary for endolysosomal tubule formation. DCs lacking MyD88 can also form endolysosomal tubules, demonstrating that MyD88-dependent TLR activation is not necessary for the formation of this compartment. Endolysosomal tubules in DCs exhibit dynamic and saltatory movement, including bidirectional travel. Measured velocities are consistent with motor-based movement along microtubules. Indeed, nocodazole causes the collapse of endolysosomal tubules. In addition to its association with microtubules, endolysosomal tubules follow the plus ends of microtubules as visualized in primary DCs expressing end binding protein 1 (EB1)-enhanced GFP.

Assessment and remediation of odor emissions from a complex industrial facility (Ambient air odor regulations in Canada and the United States)

International Nuclear Information System (INIS)

Boose, T.; Reusing, G.

2002-01-01

This paper describes the findings of a review and presents examples of ambient air odor regulations in Canada and the United States. State and provincial odor regulations were reviewed and other metropolitan cities or counties (regions) that have separate odor regulations were also included. The key topics addressed in this paper include an assessment of the methods used for odor regulation and the methods used to evaluate the odor impact to determine compliance with the regulation. Three types of ambient air odor regulations were identified: 1. 28 States, Provinces and regions (jurisdictions) have specific odor regulations. These regulations generally define what constitutes an odor impact and typically provide requirements for remedial measures; 2. 25 jurisdictions regulate odors by a general prohibition regulation. These regulations define odor in ambient air as a condition of air pollution, nuisance or objectionable odor that would typically prevent persons from the enjoyment of life and property; and 3. 13 jurisdictions do not have specific or general prohibition regulations regarding odors. For the jurisdictions that have specific or general prohibition odor regulations, there are a number of different techniques used to define what constitutes an odor impact. Odor impacts are typically defined in a regulation by one (or more) of the following techniques: dilution to threshold, or odor unit limit; determination of odor emission rates; odor concentration limits for selected chemicals (ppm); comparison with the n-butanol intensity scale (1 to 8); and investigation by an agency investigator. Compliance with odor regulations is typically determined using one (or more) of the following field methods: odor stack testing and dispersion modelling; odor panel analysis of stack or ambient air samples; chemical monitoring (ppm); odor school certified / agency investigator; and scentometer. (author)

GPS-MBA: computational analysis of MHC class II epitopes in type 1 diabetes.

Science.gov (United States)

Cai, Ruikun; Liu, Zexian; Ren, Jian; Ma, Chuang; Gao, Tianshun; Zhou, Yanhong; Yang, Qing; Xue, Yu

2012-01-01

As a severe chronic metabolic disease and autoimmune disorder, type 1 diabetes (T1D) affects millions of people world-wide. Recent advances in antigen-based immunotherapy have provided a great opportunity for further treating T1D with a high degree of selectivity. It is reported that MHC class II I-A(g7) in the non-obese diabetic (NOD) mouse and human HLA-DQ8 are strongly linked to susceptibility to T1D. Thus, the identification of new I-A(g7) and HLA-DQ8 epitopes would be of great help to further experimental and biomedical manipulation efforts. In this study, a novel GPS-MBA (MHC Binding Analyzer) software package was developed for the prediction of I-A(g7) and HLA-DQ8 epitopes. Using experimentally identified epitopes as the training data sets, a previously developed GPS (Group-based Prediction System) algorithm was adopted and improved. By extensive evaluation and comparison, the GPS-MBA performance was found to be much better than other tools of this type. With this powerful tool, we predicted a number of potentially new I-A(g7) and HLA-DQ8 epitopes. Furthermore, we designed a T1D epitope database (TEDB) for all of the experimentally identified and predicted T1D-associated epitopes. Taken together, this computational prediction result and analysis provides a starting point for further experimental considerations, and GPS-MBA is demonstrated to be a useful tool for generating starting information for experimentalists. The GPS-MBA is freely accessible for academic researchers at: http://mba.biocuckoo.org.

The neurobiology of infant maternal odor learning

Directory of Open Access Journals (Sweden)

C. Raineki

2010-10-01

Full Text Available Infant rats must learn to identify their mother’s diet-dependent odor. Once learned, maternal odor controls pups’ approach to the mother, their social behavior and nipple attachment. Here we present a review of the research from four different laboratories, which suggests that neural and behavioral responses to the natural maternal odor and neonatal learned odors are similar. Together, these data indicate that pups have a unique learning circuit relying on the olfactory bulb for neural plasticity and on the hyperfunctioning noradrenergic locus coeruleus flooding the olfactory bulb with norepinephrine to support the neural changes. Another important factor making this system unique is the inability of the amygdala to become incorporated into the infant learning circuit. Thus, infant rats appear to be primed in early life to learn odors that will evoke approach responses supporting attachment to the caregiver.

Rejection of class I MHC-deficient haemopoietic cells by irradiated MHC-matched mice

International Nuclear Information System (INIS)

Bix, M.; Nanshih Liao; Raulet, D.; Zijlstra, M.; Loring, J.; Jaenisch, R.

1991-01-01

Irradiated MHC-heterozygous mice often reject bone marrow cells transplanted from one of the homozygous parental strains, a phenomenon ('hybrid resistance') that appears to violate the laws of transplantation. Rejection of parental and allogeneic marrow cells also differs from conventional T cell-mediated rejection mechanisms as it is effected by NK1.1 + cells. To account for the unusual specificity of bone marrow rejection, it has been proposed that NK1.1 + cells destroy marrow cells that fail to express the full complement of self MHC class I (MHC-I) molecules. We show here that NK1.1 + cells in normal mice reject haemopoietic transplants from mice that are deficient for normal cell-surface MHC-I expression because of a targeted mutation in the β 2 -microglobulin gene. These findings demonstrate that deficient expression of MHC-I molecules renders marrow cells susceptible to rejection. (author)

Adiponectin mediated MHC class II mismatched cardiac graft rejection in mice is IL-4 dependent.

Directory of Open Access Journals (Sweden)

Daxu Li

Full Text Available BACKGROUND: Adiponectin regulates glucose and fatty-acid metabolism but its role in chronic graft rejection mediated by Th2 cytokines remains ill-defined. METHODOLOGY/PRINCIPAL FINDINGS: Wild type and adiponectin-null mice were used as graft recipients in mouse MHC class II disparate cardiac transplantation (bm12 toB6 and the graft rejection was monitored. In adiponectin-null mice we observed that the cellular infiltrate of eosinophils, CD4(+ and CD8(+ T cells was reduced in grafts compared to the controls as was collagen deposition and vessel occlusion. A similar outcome was observed for skin transplants except that neutrophil infiltration was increased. Low levels of IL-4 were detected in the grafts and serum. The effect of adiponectin signaling on IL-4 expression was further investigated. Treatment with AMPK and p38 MAPK inhibitors blocked adiponectin enhanced T cell proliferation in mixed lymphocyte reactions. Inhibition of AMPK reduced eosinophil infiltration in skin grafts in wild type recipients and in contrast AMPK activation increased eosinophils in adiponectin-null recipients. The addition of adiponectin increased IL-4 production by the T cell line EL4 with augmented nuclear GATA-3 and phospho-STAT6 expression which were suppressed by knockdown of adiponectin receptor 1 and 2. CONCLUSIONS: Our results demonstrate a direct effect of adiponectin on IL-4 expression which contributes to Th2 cytokine mediated rejection in mouse MHC class II histoincompatible transplants. These results add to our understanding of the interrelationship of metabolism and immune regulation and raise the possibility that AMPK inhibitors may be beneficial in selected types of rejection.

The perception of odor objects in everyday life: a review on the processing of odor mixtures

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Thierry eThomas-Danguin

2014-06-01

Full Text Available Smelling monomolecular odors hardly ever occurs in everyday life, and the daily functioning of the sense of smell relies primarily on the processing of complex mixtures of volatiles that are present in the environment (e.g., emanating from food or conspecifics. Such processing allows for the instantaneous recognition and categorization of smells and also for the discrimination of odors among others to extract relevant information and to adapt efficiently in different contexts. The neurophysiological mechanisms underpinning this highly efficient analysis of complex mixtures of odorants is beginning to be unraveled and support the idea that olfaction, as vision and audition, relies on odor-objects encoding. This configural processing of odor mixtures, which is empirically subject to important applications in our societies (e.g., the art of perfumers, flavorists, and wine makers, has been scientifically studied only during the last decades. This processing depends on many individual factors, among which are the developmental stage, lifestyle, physiological and mood state, and cognitive skills; this processing also presents striking similarities between species. The present review gathers the recent findings, as observed in animals, healthy subjects, and/or individuals with affective disorders, supporting the perception of complex odor stimuli as odor objects. It also discusses peripheral to central processing, and cognitive and behavioral significance. Finally, this review highlights that the study of odor mixtures is an original window allowing for the investigation of daily olfaction and emphasizes the need for knowledge about the underlying biological processes, which appear to be crucial for our representation and adaptation to the chemical environment.

Food-Related Odors Activate Dopaminergic Brain Areas

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Agnieszka Sorokowska

2017-12-01

Full Text Available Food-associated cues of different sensory categories have often been shown to be a potent elicitor of cerebral activity in brain reward circuits. Smells influence and modify the hedonic qualities of eating experience, and in contrast to smells not associated with food, perception of food-associated odors may activate dopaminergic brain areas. In this study, we aimed to verify previous findings related to the rewarding value of food-associated odors by means of an fMRI design involving carefully preselected odors of edible and non-edible substances. We compared activations generated by three food and three non-food odorants matching in terms of intensity, pleasantness and trigeminal qualities. We observed that for our mixed sample of 30 hungry and satiated participants, food odors generated significantly higher activation in the anterior cingulate cortex (right and left, insula (right, and putamen (right than non-food odors. Among hungry subjects, regardless of the odor type, we found significant activation in the ventral tegmental area in response to olfactory stimulation. As our stimuli were matched in terms of various perceptual qualities, this result suggests that edibility of an odor source indeed generates specific activation in dopaminergic brain areas.

MHC class II expression through a hitherto unknown pathway supports T helper cell-dependent immune responses: implications for MHC class II deficiency.

Science.gov (United States)

Buch, Thorsten; Polic, Bojan; Clausen, Björn E; Weiss, Susanne; Akilli-Ozturk, Ozlem; Chang, Cheong-Hee; Flavell, Richard; Schulz, Ansgar; Jonjic, Stipan; Waisman, Ari; Förster, Irmgard

2006-02-15

MHC class II (MHCII) deficiency or bare lymphocyte syndrome (BLS) is a severe immunodeficiency characterized by deficient T helper (Th)-cell-dependent immunity. The disease is caused by defects of the MHCII promoter complex resulting in low or absent MHCII expression. We demonstrate in a murine model of MHCII deficiency (RFX5- or CIITA-deficient mice) that residual MHCII expression by professional antigen-presenting cells (APCs) is sufficient to support activation of adoptively transferred Th cells. Furthermore, upon transplantation of WT thymic epithelium, we observed development of endogenous Th cells with restoration of Th-cell-dependent antibody responses and immunity to cytomegalovirus infection, thus opening the possibility of an alternative treatment regimen for BLS. Residual MHCII expression was further induced by the presence of Th cells and also other stimuli. Analysis of CIITA/RFX5 double-deficient animals revealed that this inducible MHCII expression is genetically independent of the known promoter complex and thus constitutes an alternative MHCII expression pathway. In these experiments, we also detected a novel repressive function of the RFX complex in the absence of CIITA.

Maternal status regulates cortical responses to the body odor of newborns

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Johan N Lundström

2013-09-01

Full Text Available Studies in non-human mammals have identified olfactory signals as prime mediators of mother-infant bonding and they have been linked with maternal attitudes and behavior in our own species as well. However, although the neuronal network processing infant cues has been studied for visual and auditory signals; to date, no such information exists for chemosensory signals. We contrasted the cerebral activity underlying the processing of infant odor properties in 15 women newly given birth for the first time and 15 women not given birth while smelling the body odor of unfamiliar 2 day-old newborn infants. Maternal status-dependent activity was demonstrated in the thalamus when exposed to the body odor of a newly born infant. Subsequent regions of interest analyses indicated that dopaminergic neostriatal areas are active in maternal-dependent responses. Taken together, these data suggests that body odors from 2 day-old newborns elicit activation in reward-related cerebral areas in women, regardless of their maternal status. These tentative data suggests that certain body odors might act as a catalyst for bonding mechanisms and highlights the need for future research on odor-dependent mother-infant bonding using parametric designs controlling for biological saliency and general odor perception effects.

Epac Activation Initiates Associative Odor Preference Memories in the Rat Pup

Science.gov (United States)

Grimes, Matthew T.; Powell, Maria; Gutierrez, Sandra Mohammed; Darby-King, Andrea; Harley, Carolyn W.; McLean, John H.

2015-01-01

Here we examine the role of the exchange protein directly activated by cAMP (Epac) in ß-adrenergic-dependent associative odor preference learning in rat pups. Bulbar Epac agonist (8-pCPT-2-O-Me-cAMP, or 8-pCPT) infusions, paired with odor, initiated preference learning, which was selective for the paired odor. Interestingly, pairing odor with Epac…

NLRC5/MHC class I transactivator is a target for immune evasion in cancer.

Science.gov (United States)

Yoshihama, Sayuri; Roszik, Jason; Downs, Isaac; Meissner, Torsten B; Vijayan, Saptha; Chapuy, Bjoern; Sidiq, Tabasum; Shipp, Margaret A; Lizee, Gregory A; Kobayashi, Koichi S

2016-05-24

Cancer cells develop under immune surveillance, thus necessitating immune escape for successful growth. Loss of MHC class I expression provides a key immune evasion strategy in many cancers, although the molecular mechanisms remain elusive. MHC class I transactivator (CITA), known as "NLRC5" [NOD-like receptor (NLR) family, caspase recruitment (CARD) domain containing 5], has recently been identified as a critical transcriptional coactivator of MHC class I gene expression. Here we show that the MHC class I transactivation pathway mediated by CITA/NLRC5 constitutes a target for cancer immune evasion. In all the 21 tumor types we examined, NLRC5 expression was highly correlated with the expression of MHC class I, with cytotoxic T-cell markers, and with genes in the MHC class I antigen-presentation pathway, including LMP2/LMP7, TAP1, and β2-microglobulin. Epigenetic and genetic alterations in cancers, including promoter methylation, copy number loss, and somatic mutations, were most prevalent in NLRC5 among all MHC class I-related genes and were associated with the impaired expression of components of the MHC class I pathway. Strikingly, NLRC5 expression was significantly associated with the activation of CD8(+) cytotoxic T cells and patient survival in multiple cancer types. Thus, NLRC5 constitutes a novel prognostic biomarker and potential therapeutic target of cancers.

Structural properties of MHC class II ligands, implications for the prediction of MHC class II epitopes.

Directory of Open Access Journals (Sweden)

Kasper Winther Jørgensen

2010-12-01

Full Text Available Major Histocompatibility class II (MHC-II molecules sample peptides from the extracellular space allowing the immune system to detect the presence of foreign microbes from this compartment. Prediction of MHC class II ligands is complicated by the open binding cleft of the MHC class II molecule, allowing binding of peptides extending out of the binding groove. Furthermore, only a few HLA-DR alleles have been characterized with a sufficient number of peptides (100-200 peptides per allele to derive accurate description of their binding motif. Little work has been performed characterizing structural properties of MHC class II ligands. Here, we perform one such large-scale analysis. A large set of SYFPEITHI MHC class II ligands covering more than 20 different HLA-DR molecules was analyzed in terms of their secondary structure and surface exposure characteristics in the context of the native structure of the corresponding source protein. We demonstrated that MHC class II ligands are significantly more exposed and have significantly more coil content than other peptides in the same protein with similar predicted binding affinity. We next exploited this observation to derive an improved prediction method for MHC class II ligands by integrating prediction of MHC- peptide binding with prediction of surface exposure and protein secondary structure. This combined prediction method was shown to significantly outperform the state-of-the-art MHC class II peptide binding prediction method when used to identify MHC class II ligands. We also tried to integrate N- and O-glycosylation in our prediction methods but this additional information was found not to improve prediction performance. In summary, these findings strongly suggest that local structural properties influence antigen processing and/or the accessibility of peptides to the MHC class II molecule.

Odors and incontinence: What does the nose know?

Science.gov (United States)

Dalton, Pamela; Maute, Christopher

2018-06-01

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.

MHC Class II epitope predictive algorithms

DEFF Research Database (Denmark)

Nielsen, Morten; Lund, Ole; Buus, S

2010-01-01

Major histocompatibility complex class II (MHC-II) molecules sample peptides from the extracellular space, allowing the immune system to detect the presence of foreign microbes from this compartment. To be able to predict the immune response to given pathogens, a number of methods have been...... developed to predict peptide-MHC binding. However, few methods other than the pioneering TEPITOPE/ProPred method have been developed for MHC-II. Despite recent progress in method development, the predictive performance for MHC-II remains significantly lower than what can be obtained for MHC-I. One reason...

Tubulation of Class II MHC Compartments Is Microtubule Dependent and Involves Multiple Endolysosomal Membrane Proteins in Primary Dendritic Cells1

Science.gov (United States)

Vyas, Jatin M.; Kim, You-Me; Artavanis-Tsakonas, Katerina; Love, J. Christopher; Van der Veen, Annemarthe G.; Ploegh, Hidde L.

2009-01-01

Immature dendritic cells (DCs) capture exogenous Ags in the periphery for eventual processing in endolysosomes. Upon maturation by TLR agonists, DCs deliver peptide-loaded class II MHC molecules from these compartments to the cell surface via long tubular structures (endolysosomal tubules). The nature and rules that govern the movement of these DC compartments are unknown. In this study, we demonstrate that the tubules contain multiple proteins including the class II MHC molecules and LAMP1, a lysosomal resident protein, as well as CD63 and CD82, members of the tetraspanin family. Endolysosomal tubules can be stained with acidotropic dyes, indicating that they are extensions of lysosomes. However, the proper trafficking of class II MHC molecules themselves is not necessary for endolysosomal tubule formation. DCs lacking MyD88 can also form endolysosomal tubules, demonstrating that MyD88-dependent TLR activation is not necessary for the formation of this compartment. Endolysosomal tubules in DCs exhibit dynamic and saltatory movement, including bidirectional travel. Measured velocities are consistent with motor-based movement along microtubules. Indeed, nocodazole causes the collapse of endolysosomal tubules. In addition to its association with microtubules, endolysosomal tubules follow the plus ends of microtubules as visualized in primary DCs expressing end binding protein 1 (EB1)-enhanced GFP. PMID:17513769

Vaginal Odor

Science.gov (United States)

... normally occurring vaginal bacteria — is the most common vaginal infection that causes a vaginal odor. Trichomoniasis — a sexually transmitted infection — also can lead to vaginal odor. Chlamydia and gonorrhea infections usually don't cause vaginal odors. Neither do ...

The MHC motif viewer: a visualization tool for MHC binding motifs

DEFF Research Database (Denmark)

Rapin, Nicolas; Hoof, Ilka; Lund, Ole

2010-01-01

is hampered by the lack of tools for browsing and comparing specificity of these molecules. We have developed a Web server, MHC Motif Viewer, which allows the display of the binding motif for MHC class I proteins for human, chimpanzee, rhesus monkey, mouse, and swine, as well as HLA-DR protein sequences...

The combination of major histocompatibility complex (MHC) and non-MHC genes influences murine lymphocytic choriomeningitis virus pathogenesis

DEFF Research Database (Denmark)

Eyler, Y L; Pfau, C J; Broomhall, K S

1989-01-01

with the recessive disease phenotype. In all cases, susceptibility was dominant. In backcross progeny obtained from matings of parental strains differing in both major histocompatibility complex (MHC) and non-MHC (SWR; C3H), 90% of the challenged mice died, indicating that at least three loci controlled...... susceptibility to the disease. When the parental strains carried similar MHC haplotypes but dissimilar background genes (B10.BR; CBA), 78% of the backcross mice succumbed, indicating that at least two non-MHC loci influenced disease susceptibility. It is unlikely, however, that the same two non-MHC loci...... are critical in all genetic combinations, since F1 produced from two H-2 identical, resistant strains (B10.BR; C3H) were found to be fully susceptible. When congenic mice, differing only in the D-end of the MHC region, were analysed, 50% of the backcross animals died, indicating that one gene in the MHC region...

MHC class II expression in lung cancer.

Science.gov (United States)

He, Yayi; Rozeboom, Leslie; Rivard, Christopher J; Ellison, Kim; Dziadziuszko, Rafal; Yu, Hui; Zhou, Caicun; Hirsch, Fred R

2017-10-01

Immunotherapy is an exciting development in lung cancer research. In this study we described major histocompatibility complex (MHC) Class II protein expression in lung cancer cell lines and patient tissues. We studied MHC Class II (DP, DQ, DR) (CR3/43, Abcam) protein expression in 55 non-small cell lung cancer (NSCLC) cell lines, 42 small cell lung cancer (SCLC) cell lines and 278 lung cancer patient tissues by immunohistochemistry (IHC). Seven (12.7%) NSCLC cell lines were positive for MHC Class II. No SCLC cell lines were found to be MHC Class II positive. We assessed 139 lung cancer samples available in the Hirsch Lab for MHC Class II. There was no positive MHC Class II staining on SCLC tumor cells. MHC Class II expression on TILs in SCLC was significantly lower than that on TILs in NSCLC (P＜0.001). MHC Class II was also assessed in an additional 139 NSCLC tumor tissues from Medical University of Gdansk, Poland. Patients with positive staining of MHC Class II on TILs had longer regression-free survival (RFS) and overall survival (OS) than those whose TILs were MHC Class II negative (2.980 years, 95% CI 1.628-4.332 vs. 1.050 years, 95% CI 0.556-1.554, P=0.028) (3.230 years, 95% CI 2.617-3.843 vs. 1.390 years, 95% CI 0.629-2.151, P=0.014). MHC Class II was expressed both in NSCLC cell lines and tissues. However, MHC Class II was not detected in SCLC cell lines or tissue tumor cells. MHC Class II expression was lower on SCLC TILs than on NSCLC TILs. Loss of expression of MHC Class II on SCLC tumor cells and reduced expression on SCLC TILs may be a means of escaping anti-cancer immunity. Higher MHC Class II expression on TILs was correlated with better prognosis in patients with NSCLC. Copyright © 2017. Published by Elsevier B.V.

Ligation of MHC class I molecules on peripheral blood T lymphocytes induces new phenotypes and functions

DEFF Research Database (Denmark)

Bregenholt, S; Röpke, M; Skov, S

1996-01-01

of T cell-mediated cytotoxicity. Immediately following MHC-I ligation, the T cells responded with increased protein tyrosine phosphorylation, with new bands appearing in the SDS-PAGE. Exposure of T cells to immobilized anti-MHC-I Ab for 24 h induced an increased surface expression of the TCR/CD3 and CD......28 molecules. MHC-I-induced proliferation of purified T cells was dependent on cellular interactions with non-T cells. Under certain conditions, in which MHC-I was ligated by picogram concentrations of immobilized anti-MHC-I Ab, anti-TCR/CD3 Ab-induced proliferation of T cells was strongly inhibited....... These data clearly demonstrate that ligation of the MHC-I complex on T cells may induce both positive and negative signals. Since the physiologic ligands for MHC-I molecules are TCR and the CD8 molecules, our data may suggest that MHC-I molecules are instrumental in cellular interactions between T cells....

Protective influences on experimental autoimmune encephalomyelitis by MHC class I and class II alleles

DEFF Research Database (Denmark)

Mustafa, M; Vingsbo, C; Olsson, T

1994-01-01

are resistant. Interestingly, rats with the MHC u haplotype develop an immune response to the MBP 63-88, but do not get EAE. In this study we have used intra-MHC recombinant rat strains to compare the influences of the MHC u with the a haplotype. We discovered the following: 1) The class II region of the MHC...... a haplotype permits EAE and a Th1 type of immune response as measured by IFN-gamma production after in vitro challenge of in vivo-primed T cells with MBP 63-88. 2) The class II region of the u haplotype is associated with a disease-protective immune response characterized by production of not only IFN......Experimental autoimmune encephalomyelitis (EAE) is influenced by polymorphism of the MHC. We have previously found that Lewis rats with certain MHC haplotypes are susceptible to disease induced with the myelin basic protein (MBP) peptide 63-88, whereas Lewis rats with other MHC haplotypes...

Mechanisms underlying odorant-induced and spontaneous calcium signals in olfactory receptor neurons of spiny lobsters, Panulirus argus.

Science.gov (United States)

Tadesse, Tizeta; Derby, Charles D; Schmidt, Manfred

2014-01-01

We determined if a newly developed antennule slice preparation allows studying chemosensory properties of spiny lobster olfactory receptor neurons under in situ conditions with Ca(2+) imaging. We show that chemical stimuli reach the dendrites of olfactory receptor neurons but not their somata, and that odorant-induced Ca(2+) signals in the somata are sufficiently stable over time to allow stimulation with a substantial number of odorants. Pharmacological manipulations served to elucidate the source of odorant-induced Ca(2+) transients and spontaneous Ca(2+) oscillations in the somata of olfactory receptor neurons. Both Ca(2+) signals are primarily mediated by an influx of extracellular Ca(2+) through voltage-activated Ca(2+) channels that can be blocked by CoCl2 and the L-type Ca(2+) channel blocker verapamil. Intracellular Ca(2+) stores contribute little to odorant-induced Ca(2+) transients and spontaneous Ca(2+) oscillations. The odorant-induced Ca(2+) transients as well as the spontaneous Ca(2+) oscillations depend on action potentials mediated by Na(+) channels that are largely TTX-insensitive but blocked by the local anesthetics tetracaine and lidocaine. Collectively, these results corroborate the conclusion that odorant-induced Ca(2+) transients and spontaneous Ca(2+) oscillations in the somata of olfactory receptor neurons closely reflect action potential activity associated with odorant-induced phasic-tonic responses and spontaneous bursting, respectively. Therefore, both types of Ca(2+) signals represent experimentally accessible proxies of spiking.

Improved pan-specific MHC class I peptide-binding predictions using a novel representation of the MHC-binding cleft environment

DEFF Research Database (Denmark)

Carrasco Pro, S.; Zimic, M.; Nielsen, Morten

2014-01-01

of the current state-of-the-art methods for MHC class I is NetMHCpan, which has a core ingredient for the representation of the MHC class I molecule using a pseudo-sequence representation of the binding cleft amino acid environment. New and large MHC-peptide-binding data sets are constantly being made available...... of different MHC data sets including human leukocyte antigen (HLA), non-human primates (chimpanzee, macaque and gorilla) and other animal alleles (cattle, mouse and swine). From these constructs, we showed that by focusing on MHC sequence positions found to be polymorphic across the MHC molecules used to train...

Influence of the Chemical Structure on Odor Qualities and Odor Thresholds of Halogenated Guaiacol-Derived Odorants

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Florian Juhlke

2017-12-01

Full Text Available Chlorinated guaiacol derivatives are found in waste water of pulp mills using chlorine in the bleaching process of wood pulp. They can also be detected in fish tissue, possibly causing off-odors. To date, there is no systematic investigation on the odor properties of halogenated guaiacol derivatives. To close this gap, odor thresholds in air and odor qualities of 14 compounds were determined by gas chromatography-olfactometry. Overall, the investigated compounds elicited smells that are characteristic for guaiacol, namely smoky, sweet, vanilla-like, but also medicinal and plaster-like. Their odor thresholds in air were, however, very low, ranging from 0.00072 to 23 ng/Lair. The lowest thresholds were found for 5-chloro- and 5-bromoguaiacol, followed by 4,5-dichloro- and 6-chloroguaiacol. Moreover, some inter-individual differences in odor threshold values could be observed, with the highest variations having been recorded for the individual values of 5-iodo- and 4-bromoguaiacol.

Influence of the chemical structure on odor qualities and odor thresholds of halogenated guaiacol-derived odorants

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Juhlke, Florian; Lorber, Katja; Wagenstaller, Maria; Buettner, Andrea

2017-12-01

Chlorinated guaiacol derivatives are found in waste water of pulp mills using chlorine in the bleaching process of wood pulp. They can also be detected in fish tissue, possibly causing off-odors. To date, there is no systematic investigation on the odor properties of halogenated guaiacol derivatives. To close this gap, odor thresholds in air and odor qualities of 14 compounds were determined by gas chromatography-olfactometry. Overall, the investigated compounds elicited smells that are characteristic for guaiacol, namely smoky, sweet, vanilla-like, but also medicinal and plaster-like. Their odor thresholds in air were, however, very low, ranging from 0.00072 to 23 ng/Lair. The lowest thresholds were found for 5-chloro- and 5-bromoguaiacol, followed by 4,5-dichloro- and 6-chloroguaiacol. Moreover, some inter-individual differences in odor threshold values could be observed, with the highest variations having been recorded for the individual values of 5-iodo- and 4-bromoguaiacol.

α7-Nicotinic acetylcholine receptor: role in early odor learning preference in mice.

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Jennifer L Hellier

Full Text Available Recently, we have shown that mice with decreased expression of α7-nicotinic acetylcholine receptors (α7 in the olfactory bulb were associated with a deficit in odor discrimination compared to wild-type mice. However, it is unknown if mice with decreased α7-receptor expression also show a deficit in early odor learning preference (ELP, an enhanced behavioral response to odors with attractive value observed in rats. In this study, we modified ELP methods performed in rats and implemented similar conditions in mice. From post-natal days 5-18, wild-type mice were stroked simultaneously with an odor presentation (conditioned odor for 90 s daily. Control mice were only stroked, exposed to odor, or neither. On the day of testing (P21, mice that were stroked in concert with a conditioned odor significantly investigated the conditioned odor compared to a novel odor, as observed similarly in rats. However, mice with a decrease in α7-receptor expression that were stroked during a conditioned odor did not show a behavioral response to that odorant. These results suggest that decreased α7-receptor expression has a role in associative learning, olfactory preference, and/or sensory processing deficits.

MHC variability in heritage breeds of chickens.

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Fulton, J E; Lund, A R; McCarron, A M; Pinegar, K N; Korver, D R; Classen, H L; Aggrey, S; Utterbach, C; Anthony, N B; Berres, M E

2016-02-01

The chicken Major Histocompatibility Complex (MHC) is very strongly associated with disease resistance and thus is a very important region of the chicken genome. Historically, MHC (B locus) has been identified by the use of serology with haplotype specific alloantisera. These antisera can be difficult to produce and frequently cross-react with multiple haplotypes and hence their application is generally limited to inbred and MHC-defined lines. As a consequence, very little information about MHC variability in heritage chicken breeds is available. DNA-based methods are now available for examining MHC variability in these previously uncharacterized populations. A high density SNP panel consisting of 101 SNP that span a 230,000 bp region of the chicken MHC was used to examine MHC variability in 17 heritage populations of chickens from five universities from Canada and the United States. The breeds included 6 heritage broiler lines, 3 Barred Plymouth Rock, 2 New Hampshire and one each of Rhode Island Red, Light Sussex, White Leghorn, Dark Brown Leghorn, and 2 synthetic lines. These heritage breeds contained from one to 11 haplotypes per line. A total of 52 unique MHC haplotypes were found with only 10 of them identical to serologically defined haplotypes. Furthermore, nine MHC recombinants with their respective parental haplotypes were identified. This survey confirms the value of these non-commercially utilized lines in maintaining genetic diversity. The identification of multiple MHC haplotypes and novel MHC recombinants indicates that diversity is being generated and maintained within these heritage populations. © 2016 Poultry Science Association Inc.

High-throughput discovery of T cell epitopes in type 1 diabetes using DNA barcode labelledpeptide-MHC multimers

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Lyngaa, Rikke Birgitte; Bentzen, Amalie Kai; Overgaard, A. Julie

2016-01-01

applying a novel technology where the selection of MHC-multimer binding T cells is followed by amplification and sequencing of MHC multimer-associated DNA barcodes revealing their recognition. This technique enables simultaneous detection of >1000 specificities. Identifying post translational modifications...

MHC and Evolution in Teleosts

OpenAIRE

Grimholt, Unni

2016-01-01

Major histocompatibility complex (MHC) molecules are key players in initiating immune responses towards invading pathogens. Both MHC class I and class II genes are present in teleosts, and, using phylogenetic clustering, sequences from both classes have been classified into various lineages. The polymorphic and classical MHC class I and class II gene sequences belong to the U and A lineages, respectively. The remaining class I and class II lineages contain nonclassical gene sequences that, de...

IRF-4-mediated CIITA transcription is blocked by KSHV encoded LANA to inhibit MHC II presentation.

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Qiliang Cai

2013-10-01

Full Text Available Peptides presentation to T cells by MHC class II molecules is of importance in initiation of immune response to a pathogen. The level of MHC II expression directly influences T lymphocyte activation and is often targeted by various viruses. Kaposi's sarcoma-associated herpesvirus (KSHV encoded LANA is known to evade MHC class I peptide processing, however, the effect of LANA on MHC class II remains unclear. Here, we report that LANA down-regulates MHC II expression and presentation by inhibiting the transcription of MHC II transactivator (CIITA promoter pIII and pIV in a dose-dependent manner. Strikingly, although LANA knockdown efficiently disrupts the inhibition of CIITA transcripts from its pIII and pIV promoter region, the expression of HLA-DQβ but no other MHC II molecules was significantly restored. Moreover, we revealed that the presentation of HLA-DQβ enhanced by LANA knockdown did not help LANA-specific CD4+ T cell recognition of PEL cells, and the inhibition of CIITA by LANA is independent of IL-4 or IFN-γ signaling but dependent on the direct interaction of LANA with IRF-4 (an activator of both the pIII and pIV CIITA promoters. This interaction dramatically blocked the DNA-binding ability of IRF-4 on both pIII and pIV promoters. Thus, our data implies that LANA can evade MHC II presentation and suppress CIITA transcription to provide a unique strategy of KSHV escape from immune surveillance by cytotoxic T cells.

Quantifying the importance of pMHC valency, total pMHC dose and frequency on nanoparticle therapeutic efficacy.

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Sugarman, Jordan; Tsai, Sue; Santamaria, Pere; Khadra, Anmar

2013-05-01

Nanoparticles (NPs) coated with β-cell-specific peptide major histocompatibility complex (pMHC) class I molecules can effectively restore normoglycemia in spontaneously diabetic nonobese diabetic mice. They do so by expanding pools of cognate memory autoreactive regulatory CD8+ T cells that arise from naive low-avidity T-cell precursors to therapeutic levels. Here we develop our previously constructed mathematical model to explore the effects of compound design parameters (NP dose and pMHC valency) on therapeutic efficacy with the underlying hypothesis that the functional correlates of the therapeutic response (expansion of autoregulatory T cells and deletion of autoantigen-loaded antigen-presenting cells by these T cells) are biphasic. We show, using bifurcation analysis, that the model exhibits a 'resonance'-like behavior for a given range of NP dose in which bistability between the healthy state (possessing zero level of effector T-cell population) and autoimmune state (possessing elevated level of the same population) disappears. A heterogeneous population of model mice subjected to several treatment protocols under these new conditions is conducted to quantify both the average percentage of autoregulatory T cells in responsive and nonresponsive model mice, and the average valency-dependent minimal optimal dose needed for effective therapy. Our results reveal that a moderate increase (≥1.6-fold) in the NP-dependent expansion rate of autoregulatory T-cell population leads to a significant increase in the efficacy and the area corresponding to the effective treatment regimen, provided that NP dose ≥8 μg. We expect the model developed here to generalize to other autoimmune diseases and serve as a computational tool to understand and optimize pMHC-NP-based therapies.

The mRNA expression profile of metabolic genes relative to MHC isoform pattern in human skeletal muscles

DEFF Research Database (Denmark)

Plomgaard, Peter; Penkowa, Milena; Leick, Lotte

2006-01-01

The metabolic profile of rodent muscle is generally reflected in the myosin heavy chain (MHC) fiber-type composition. The present study was conducted to test the hypothesis that metabolic gene expression is not tightly coupled with MHC fiber-type composition for all genes in human skeletal muscle....... Triceps brachii, vastus lateralis quadriceps, and soleus muscle biopsies were obtained from normally physically active, healthy, young male volunteers, because these muscles are characterized by different fiber-type compositions. As expected, citrate synthase and 3-hydroxyacyl dehydrogenase activity...... of a broad range of metabolic genes. The triceps muscle had two- to fivefold higher MHC IIa, phosphofructokinase, and LDH A mRNA content and two- to fourfold lower MHC I, lipoprotein lipase, CD36, hormone-sensitive lipase, and LDH B and hexokinase II mRNA than vastus lateralis or soleus. Interestingly...

Scent marking behavior as an odorant communication in mice

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Arakawa, Hiroyuki; Blanchard, D. Caroline; Arakawa, Keiko; Dunlap, Christopher; Blanchard, Robert J.

2008-01-01

In rodents, where chemical signals play a particularly important role in determining intraspecies interactions including social dominance and intersexual relationships, various studies have shown that behavior is sensitive to conspecific odor cues. Mice use urinary scent marks for communication with individual conspecifics in many social contexts. Urinary scent involves genetic information about individuals such as species, sex, and individual identity as well as metabolic information such as social dominance, and reproductive and health status, which are mediated by chemical proteins in scent marks including the major histocompatibility complex and the major urinary proteins. The odor of the predator which can be considered to be a threatening signal for the prey also modulate mouse behavior in which scent marking is suppressed in response to the cat odor exposure in mice. These odorant chemicals are detected and recognized through two olfactory bulbs, the role of which in detection of chemosignals with biological relevant appears to be differential, but partly overlapped. Mice deposit scent marks toward conspecifics to maintain their social relationships, and inhibit scent marking in a context where natural predator, cat odor is contained. This suppression of scent marking is long-lasting (for at least 7 days) and context-dependent, while the odorant signaling to conspecifics tends to appear frequently (over 24 hrs but less than 7 days intervals) depending on the familiarity of each signal-recipient. It has been discussed that scent marking is a communicative behavior associated with territoriality toward conspecifics, indicating that the social signaling within species are sensitive to predator odor cues in terms of vulnerability to predation risk. PMID:18565582

Ability of human oral microbiota to produce wine odorant aglycones from odourless grape glycosidic aroma precursors.

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Muñoz-González, Carolina; Cueva, Carolina; Ángeles Pozo-Bayón, M; Victoria Moreno-Arribas, M

2015-11-15

Grape aroma precursors are odourless glycosides that represent a natural reservoir of potential active odorant molecules in wines. Since the first step of wine consumption starts in the oral cavity, the processing of these compounds in the mouth could be an important factor in influencing aroma perception. Therefore, the objective of this work has been to evaluate the ability of human oral microbiota to produce wine odorant aglycones from odourless grape glycosidic aroma precursors previously isolated from white grapes. To do so, two methodological approaches involving the use of typical oral bacteria or the whole oral microbiota isolated from human saliva were followed. Odorant aglycones released in the culture mediums were isolated and analysed by HS-SPME-GC/MS. Results showed the ability of oral bacteria to hydrolyse grape aroma precursors, releasing different types of odorant molecules (terpenes, benzenic compounds and lipid derivatives). The hydrolytic activity seemed to be bacteria-dependent and was subject to large inter-individual variability. Copyright © 2015 Elsevier Ltd. All rights reserved.

Innate lymphoid cells and the MHC.

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Robinette, M L; Colonna, M

2016-01-01

Innate lymphoid cells (ILCs) are a new class of immune cells that include natural killer (NK) cells and appear to be the innate counterparts to CD4(+) helper T cells and CD8(+) cytotoxic T cells based on developmental and functional similarities. Like T cells, both NK cells and other ILCs also show connections to the major histocompatibility complex (MHC). In human and mouse, NK cells recognize and respond to classical and nonclassical MHC I molecules as well as structural homologues, whereas mouse ILCs have recently been shown to express MHC II. We describe the history of MHC I recognition by NK cells and discuss emerging roles for MHC II expression by ILC subsets, making comparisons between both mouse and human when possible. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Exosomal cancer immunotherapy is independent of MHC molecules on exosomes.

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Hiltbrunner, Stefanie; Larssen, Pia; Eldh, Maria; Martinez-Bravo, Maria-Jose; Wagner, Arnika K; Karlsson, Mikael C I; Gabrielsson, Susanne

2016-06-21

Peptide-loaded exosomes are promising cancer treatment vehicles; however, moderate T cell responses in human clinical trials indicate a need to further understand exosome-induced immunity. We previously demonstrated that antigen-loaded exosomes carry whole protein antigens and require B cells for inducing antigen-specific T cells. Therefore, we investigated the relative importance of exosomal major histocompatibility complex (MHC) class I for the induction of antigen-specific T cell responses and tumour protection. We show that ovalbumin-loaded dendritic cell-derived exosomes from MHCI-/- mice induce antigen-specific T cells at the same magnitude as wild type exosomes. Furthermore, exosomes lacking MHC class I, as well as exosomes with both MHC class I and II mismatch, induced tumour infiltrating T cells and increased overall survival to the same extent as syngeneic exosomes in B16 melanoma. In conclusion, T cell responses are independent of exosomal MHC/peptide complexes if whole antigen is present. This establishes the prospective of using impersonalised exosomes, and will greatly increase the feasibility of designing exosome-based vaccines or therapeutic approaches in humans.

Schwann cells promote post-traumatic nerve inflammation and neuropathic pain through MHC class II.

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Hartlehnert, Maike; Derksen, Angelika; Hagenacker, Tim; Kindermann, David; Schäfers, Maria; Pawlak, Mathias; Kieseier, Bernd C; Meyer Zu Horste, Gerd

2017-10-02

The activation of T helper cells requires antigens to be exposed on the surface of antigen presenting cells (APCs) via MHC class II (MHC-II) molecules. Expression of MHC-II is generally limited to professional APCs, but other cell types can express MHC-II under inflammatory conditions. However, the importance of these conditional APCs is unknown. We and others have previously shown that Schwann cells are potentially conditional APCs, but the functional relevance of MHC-II expression by Schwann cells has not been studied in vivo. Here, we conditionally deleted the MHC-II β-chain from myelinating Schwann cells in mice and investigated how this influenced post-traumatic intraneural inflammation and neuropathic pain using the chronic constriction injury (CCI) model. We demonstrate that deletion of MHC-II in myelinating Schwann cells reduces thermal hyperalgesia and, to a lesser extent, also diminishes mechanical allodynia in CCI in female mice. This was accompanied by a reduction of intraneural CD4+ T cells and greater preservation of preferentially large-caliber axons. Activation of T helper cells by MHC-II on Schwann cells thus promotes post-traumatic axonal loss and neuropathic pain. Hence, we provide experimental evidence that Schwann cells gain antigen-presenting function in vivo and modulate local immune responses and diseases in the peripheral nerves.

Myosin isoform fiber type and fiber size in the tail of the Virginia opossum (Didelphis virginiana).

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Hazimihalis, P J; Gorvet, M A; Butcher, M T

2013-01-01

Muscle fiber type is a well studied property in limb muscles, however, much less is understood about myosin heavy chain (MHC) isoform expression in caudal muscles of mammalian tails. Didelphid marsupials are an interesting lineage in this context as all species have prehensile tails, but show a range of tail-function depending on either their arboreal or terrestrial locomotor habits. Differences in prehensility suggest that MHC isoform fiber types may also be different, in that terrestrial opossums may have a large distribution of oxidative fibers for object carrying tasks instead of faster, glycolytic fiber types expected in mammals with long tails. To test this hypothesis, MHC isoform fiber type and their regional distribution (proximal/transitional/distal) were determined in the tail of the Virginia opossum (Didelphis virginiana). Fiber types were determined by a combination of myosin-ATPase histochemistry, immunohistochemistry, and SDS-PAGE. Results indicate a predominance of the fast MHC-2A and -2X isoforms in each region of the tail. The presence of two fast isoforms, in addition to the slow MHC-1 isoform, was confirmed by SDS-PAGE analysis. The overall MHC isoform fiber type distribution for the tail was: 25% MHC-1, 71% MHC-2A/X hybrid, and 4% MHC-1/2A hybrid. Oxidative MHC-2A/X isoform fibers were found to be relatively large in cross-section compared to slow, oxidative MHC-1 and MHC-1/2A hybrid fibers. A large percentage of fast MHC-2A/X hybrids fibers may be suggestive of an evolutionary transition in MHC isoform distribution (fast-to-slow fiber type) in the tail musculature of an opossum with primarily a terrestrial locomotor habit and adaptive tail-function. Copyright © 2012 Wiley Periodicals, Inc.

Forming a complex with MHC class I molecules interferes with mouse CD1d functional expression.

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Renukaradhya J Gourapura

Full Text Available CD1d molecules are structurally similar to MHC class I, but present lipid antigens as opposed to peptides. Here, we show that MHC class I molecules physically associate with (and regulate the functional expression of mouse CD1d on the surface of cells. Low pH (3.0 acid stripping of MHC class I molecules resulted in increased surface expression of murine CD1d on antigen presenting cells as well as augmented CD1d-mediated antigen presentation to NKT cells. Consistent with the above results, TAP1-/- mice were found to have a higher percentage of type I NKT cells as compared to wild type mice. Moreover, bone marrow-derived dendritic cells from TAP1-/- mice showed increased antigen presentation by CD1d compared to wild type mice. Together, these results suggest that MHC class I molecules can regulate NKT cell function, in part, by masking CD1d.

Leukocyte Ig-Like Receptors – a model for MHC class I disease associations

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Rachel Louise Allen

2016-07-01

Full Text Available MHC class I (MHC-I polymorphisms are associated with the outcome of some viral infections and autoimmune diseases. MHC-I proteins present antigenic peptides and are recognised by receptors on Natural Killer cells and Cytotoxic T lymphocytes, thus enabling the immune system to detect self-antigens and eliminate targets lacking self or expressing foreign antigens. Recognition of MHC-I, however, extends beyond receptors on cytotoxic leukocytes. Members of the Leukocyte Ig-like receptor (LILR family are expressed on monocytic cells and can recognise both classical and non-classical MHC-I alleles. Despite their relatively broad specificity when compared to the T Cell Receptor or Killer Ig-like Receptors, variations in the strength of LILR binding between different MHC-I alleles have recently been shown to correlate with control of HIV infection. We suggest that LILR recognition may mediate MHC-I disease association in a manner that does not depend on a binary discrimination of self/non-self by cytotoxic cells. Instead, the effects of LILR activity following engagement by MHC-I may represent a degrees of self model, whereby strength of binding to different alleles determines the degree of influence exerted by these receptors on immune cell functions. LILR are expressed by myelomonocytic cells and lymphocytes, extending their influence across antigen presenting cell subsets including dendritic cells, macrophages and B cells. They have been identified as important players in the response to infection, inflammatory diseases and cancer, with recent literature to indicate that MHC-I recognition by these receptors and consequent allelic effects could extend an influence beyond the immune system.

Odor memories regulate olfactory receptor expression in the sensory periphery.

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Claudianos, Charles; Lim, Julianne; Young, Melanie; Yan, Shanzhi; Cristino, Alexandre S; Newcomb, Richard D; Gunasekaran, Nivetha; Reinhard, Judith

2014-05-01

Odor learning induces structural and functional modifications throughout the olfactory system, but it is currently unknown whether this plasticity extends to the olfactory receptors (Or) in the sensory periphery. Here, we demonstrate that odor learning induces plasticity in olfactory receptor expression in the honeybee, Apis mellifera. Using quantitative RT-PCR analysis, we show that six putative floral scent receptors were differentially expressed in the bee antennae depending on the scent environment that the bees experienced. Or151, which we characterized using an in vitro cell expression system as a broadly tuned receptor binding floral odorants such as linalool, and Or11, the specific receptor for the queen pheromone 9-oxo-decenoic acid, were significantly down-regulated after honeybees were conditioned with the respective odorants in an olfactory learning paradigm. Electroantennogram recordings showed that the neural response of the antenna was similarly reduced after odor learning. Long-term odor memory was essential for inducing these changes, suggesting that the molecular mechanisms involved in olfactory memory also regulate olfactory receptor expression. Our study demonstrates for the first time that olfactory receptor expression is experience-dependent and modulated by scent conditioning, providing novel insight into how molecular regulation at the periphery contributes to plasticity in the olfactory system. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Mammalian odorant receptor tuning breadth persists across distinct odorant panels.

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Devin Kepchia

Full Text Available The molecular receptive range (MRR of a mammalian odorant receptor (OR is the set of odorant structures that activate the OR, while the distribution of these odorant structures across odor space is the tuning breadth of the OR. Variation in tuning breadth is thought to be an important property of ORs, with the MRRs of these receptors varying from narrowly to broadly tuned. However, defining the tuning breadth of an OR is a technical challenge. For practical reasons, a screening panel that broadly covers odor space must be limited to sparse coverage of the many potential structures in that space. When screened with such a panel, ORs with different odorant specificities, but equal tuning breadths, might appear to have different tuning breadths due to chance. We hypothesized that ORs would maintain their tuning breadths across distinct odorant panels. We constructed a new screening panel that was broadly distributed across an estimated odor space and contained compounds distinct from previous panels. We used this new screening panel to test several murine ORs that were previously characterized as having different tuning breadths. ORs were expressed in Xenopus laevis oocytes and assayed by two-electrode voltage clamp electrophysiology. MOR256-17, an OR previously characterized as broadly tuned, responded to nine novel compounds from our new screening panel that were structurally diverse and broadly dispersed across an estimated odor space. MOR256-22, an OR previously characterized as narrowly tuned, responded to a single novel compound that was structurally similar to a previously known ligand for this receptor. MOR174-9, a well-characterized receptor with a narrowly tuned MRR, did not respond to any novel compounds in our new panel. These results support the idea that variation in tuning breadth among these three ORs is not an artifact of the screening protocol, but is an intrinsic property of the receptors.

Disentangling the roles of natural selection and genetic drift in shaping variation at MHC immunity genes.

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Sutton, Jolene T; Nakagawa, Shinichi; Robertson, Bruce C; Jamieson, Ian G

2011-11-01

The major histocompatibility complex (MHC) forms an integral component of the vertebrate immune response and, due to strong selection pressures, is one of the most polymorphic regions of the entire genome. Despite over 15 years of research, empirical studies offer highly contradictory explanations of the relative roles of different evolutionary forces, selection and genetic drift, acting on MHC genes during population bottlenecks. Here, we take a meta-analytical approach to quantify the results of studies into the effects of bottlenecks on MHC polymorphism. We show that the consequences of selection acting on MHC loci prior to a bottleneck event, combined with drift during the bottleneck, will result in overall loss of MHC polymorphism that is ∼15% greater than loss of neutral genetic diversity. These results are counter to general expectations that selection should maintain MHC polymorphism, but do agree with the results of recent simulation models and at least two empirical studies. Notably, our results suggest that negative frequency-dependent selection could be more important than overdominance for maintaining high MHC polymorphism in pre-bottlenecked populations. © 2011 Blackwell Publishing Ltd.

An olfactory cocktail party: figure-ground segregation of odorants in rodents.

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Rokni, Dan; Hemmelder, Vivian; Kapoor, Vikrant; Murthy, Venkatesh N

2014-09-01

In odorant-rich environments, animals must be able to detect specific odorants of interest against variable backgrounds. However, studies have found that both humans and rodents are poor at analyzing the components of odorant mixtures, suggesting that olfaction is a synthetic sense in which mixtures are perceived holistically. We found that mice could be easily trained to detect target odorants embedded in unpredictable and variable mixtures. To relate the behavioral performance to neural representation, we imaged the responses of olfactory bulb glomeruli to individual odors in mice expressing the Ca(2+) indicator GCaMP3 in olfactory receptor neurons. The difficulty of segregating the target from the background depended strongly on the extent of overlap between the glomerular responses to target and background odors. Our study indicates that the olfactory system has powerful analytic abilities that are constrained by the limits of combinatorial neural representation of odorants at the level of the olfactory receptors.

Dimeric MHC-peptides inserted into an immunoglobulin scaffold as new immunotherapeutic agents

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Goldberg, Burt; Bona, Constantin

2011-01-01

Abstract The interactions of the T cell receptor (TCR) with cognate MHC-peptide and co-stimulatory molecules expressed at surface of antigen presenting cells (APC) leads to activation or tolerance of T cells. The development of molecular biological tools allowed for the preparation of soluble MHC-peptide molecules as surrogate for the APC. A decade ago a monomeric class II MHC molecule in which the peptide was covalently linked to β-chain of class II molecule was generated. This type of molecule had a low-binding affinity and did not cause the multimerization of TCR. The requirement of multimerization of TCR led to development of a new class of reagents, chimeric peptides covalently linked to MHC that was dimerized via Fc fragment of an immunoglobulin and linked to 3′ end of the β-chain of MHC class II molecule. These soluble dimerized MHC-peptide chimeric molecules display high affinity for the TCR and caused multimerization of TCR without processing by an APC. Because dimeric molecules are devoid of co-stimulatory molecules interacting with CD28, a second signal, they induce anergy rather the activation of T cells. In this review, we compare the human and murine dimerized MHC class II-peptides and their effect on CD4+ T cells, particularly the generation of T regulatory cells, which make these chimeric molecules an appealing approach for the treatment of autoimmune diseases. PMID:21435177

No evidence for the effect of MHC on male mating success in the brown bear.

Science.gov (United States)

Kuduk, Katarzyna; Babik, Wieslaw; Bellemain, Eva; Valentini, Alice; Zedrosser, Andreas; Taberlet, Pierre; Kindberg, Jonas; Swenson, Jon E; Radwan, Jacek

2014-01-01

Mate choice is thought to contribute to the maintenance of the spectacularly high polymorphism of the Major Histocompatibility Complex (MHC) genes, along with balancing selection from parasites, but the relative contribution of the former mechanism is debated. Here, we investigated the association between male MHC genotype and mating success in the brown bear. We analysed fragments of sequences coding for the peptide-binding region of the highly polymorphic MHC class I and class II DRB genes, while controlling for genome-wide effects using a panel of 18 microsatellite markers. Male mating success did not depend on the number of alleles shared with the female or amino-acid distance between potential mates at either locus. Furthermore, we found no indication of female mating preferences for MHC similarity being contingent on the number of alleles the females carried. Finally, we found no significant association between the number of MHC alleles a male carried and his mating success. Thus, our results provided no support for the role of mate choice in shaping MHC polymorphism in the brown bear.

Immunization alters body odor.

Science.gov (United States)

Kimball, Bruce A; Opiekun, Maryanne; Yamazaki, Kunio; Beauchamp, Gary K

2014-04-10

Infections have been shown to alter body odor. Because immune activation accompanies both infection and immunization, we tested the hypothesis that classical immunization might similarly result in the alteration of body odors detectable by trained biosensor mice. Using a Y-maze, we trained biosensor mice to distinguish between urine odors from rabies-vaccinated (RV) and unvaccinated control mice. RV-trained mice generalized this training to mice immunized with the equine West Nile virus (WNV) vaccine compared with urine of corresponding controls. These results suggest that there are similarities between body odors of mice immunized with these two vaccines. This conclusion was reinforced when mice could not be trained to directly discriminate between urine odors of RV- versus WNV-treated mice. Next, we trained biosensor mice to discriminate the urine odors of mice treated with lipopolysaccharide (LPS; a general elicitor of innate immunological responses) from the urine of control mice. These LPS-trained biosensors could distinguish between the odors of LPS-treated mouse urine and RV-treated mouse urine. Finally, biosensor mice trained to distinguish between the odors of RV-treated mouse urine and control mouse urine did not generalize this training to discriminate between the odors of LPS-treated mouse urine and control mouse urine. From these experiments, we conclude that: (1) immunization alters urine odor in similar ways for RV and WNV immunizations; and (2) immune activation with LPS also alters urine odor but in ways different from those of RV and WNV. Published by Elsevier Inc.

Efficacy of Odor Scavengers in Reducing Odor Compounds in Water, Milk, and Soymilk

OpenAIRE

Norton, Jenny Lynn

2003-01-01

Odor detection thresholds of hexanal, 2-heptenal, 2-pentanone, and 2,4-nonadienal were determined in spring water, high temperature short time (HTST) 2% fat milk, and extended shelf life soymilk. The efficacy of odor scavenger's beta-cyclodextrin, D-sorbitol, and nylon 6 in removing these odors was also determined. The odor thresholds of the different odor and media combinations were as follows: hexanal in spring water, milk, and soymilk were 585, 339, and 536 ppb respectively; 2-heptenal ...

Positive regulation of plasmacytoid dendritic cell function via Ly49Q recognition of class I MHC

Science.gov (United States)

Tai, Lee-Hwa; Goulet, Marie-Line; Belanger, Simon; Toyama-Sorimachi, Noriko; Fodil-Cornu, Nassima; Vidal, Silvia M.; Troke, Angela D.; McVicar, Daniel W.; Makrigiannis, Andrew P.

2008-01-01

Plasmacytoid dendritic cells (pDCs) are an important source of type I interferon (IFN) during initial immune responses to viral infections. In mice, pDCs are uniquely characterized by high-level expression of Ly49Q, a C-type lectin-like receptor specific for class I major histocompatibility complex (MHC) molecules. Despite having a cytoplasmic immunoreceptor tyrosine-based inhibitory motif, Ly49Q was found to enhance pDC function in vitro, as pDC cytokine production in response to the Toll-like receptor (TLR) 9 agonist CpG-oligonucleotide (ODN) could be blocked using soluble monoclonal antibody (mAb) to Ly49Q or H-2Kb. Conversely, CpG-ODN–dependent IFN-α production by pDCs was greatly augmented upon receptor cross-linking using immobilized anti-Ly49Q mAb or recombinant H-2Kb ligand. Accordingly, Ly49Q-deficient pDCs displayed a severely reduced capacity to produce cytokines in response to TLR7 and TLR9 stimulation both in vitro and in vivo. Finally, TLR9-dependent antiviral responses were compromised in Ly49Q-null mice infected with mouse cytomegalovirus. Thus, class I MHC recognition by Ly49Q on pDCs is necessary for optimal activation of innate immune responses in vivo. PMID:19075287

C57BL/6 mice need MHC class II Aq to develop collagen-induced arthritis dependent on autoreactive T cells.

Science.gov (United States)

Bäcklund, Johan; Li, Cuiqin; Jansson, Erik; Carlsen, Stefan; Merky, Patrick; Nandakumar, Kutty-Selva; Haag, Sabrina; Ytterberg, Jimmy; Zubarev, Roman A; Holmdahl, Rikard

2013-07-01

Collagen-induced arthritis (CIA) has traditionally been performed in MHC class II A(q)-expressing mice, whereas most genetically modified mice are on the C57BL/6 background (expressing the b haplotype of the major histocompatibility complex (MHC) class II region). However, C57BL/6 mice develop arthritis after immunisation with chicken-derived collagen type II (CII), but arthritis susceptibility has been variable, and the immune specificity has not been clarified. To establish a CIA model on the C57BL/6 background with a more predictable and defined immune response to CII. Both chicken and rat CII were arthritogenic in C57BL/6 mice provided they were introduced with high doses of Mycobacterium tuberculosis adjuvant. However, contaminating pepsin was strongly immunogenic and was essential for arthritis development. H-2(b)-restricted T cell epitopes on chicken or rat CII could not be identified, but expression of A(q) on the C57BL/6 background induced T cell response to the CII260-270 epitope, and also prolonged the arthritis to be more chronic. The putative (auto)antigen and its arthritogenic determinants in C57BL/6 mice remains undisclosed, questioning the value of the model for addressing T cell-driven pathological pathways in arthritis. To circumvent this impediment, we recommend MHC class II congenic C57BL/6N.Q mice, expressing A(q), with which T cell determinants have been thoroughly characterised.

H pylori receptor MHC class II contributes to the dynamic gastric epithelial apoptotic response

Science.gov (United States)

Bland, David A; Suarez, Giovanni; Beswick, Ellen J; Sierra, Johanna C; Reyes, Victor E

2006-01-01

AIM: To investigate the role of MHC class II in the modulation of gastric epithelial cell apoptosis induced by H pylori infection. METHODS: After stimulating a human gastric epithelial cell line with bacteria or agonist antibodies specific for MHC class II and CD95, the quantitation of apoptotic and anti-apoptotic events, including caspase activation, BCL-2 activation, and FADD recruitment, was performed with a fluorometric assay, a cytometric bead array, and confocal microscopy, respectively. RESULTS: Pretreatment of N87 cells with the anti-MHC class II IgM antibody RFD1 resulted in a reduction in global caspase activation at 24 h of H pylori infection. When caspase 3 activation was specifically measured, crosslinking of MHC class II resulted in a marked reduced caspase activation, while simple ligation of MHC class II did not. Crosslinking of MHC class II also resulted in an increased activation of the anti-apoptosis molecule BCL-2 compared to simple ligation. Confocal microscope analysis demonstrated that the pretreatment of gastric epithelial cells with a crosslinking anti-MHC class II IgM blocked the recruitment of FADD to the cell surface. CONCLUSION: The results presented here demonstrate that the ability of MHC class II to modulate gastric epithelial apoptosis is at least partially dependent on its crosslinking. Furthermore, while previous research has demonstrated that MHC class II signaling can be pro-apoptotic during extended ligation, we have shown that the crosslinking of this molecule has anti-apoptotic effects during the earlier time points of H pylori infection. This effect is possibly mediated by the ability of MHC class II to modulate the activation of the pro-apoptotic receptor Fas by blocking the recruitment of the accessory molecule FADD, and this delay in apoptosis induction could allow for prolonged cytokine secretion by H pylori-infected gastric epithelial cells. PMID:16981259

Inhibition of MHC-I by Brucella abortus is an early event during infection and involves EGFR pathway.

Science.gov (United States)

Velásquez, Lis N; Milillo, M Ayelén; Delpino, M Victoria; Trotta, Aldana; Mercogliano, M Florencia; Pozner, Roberto G; Schillaci, Roxana; Elizalde, Patricia V; Giambartolomei, Guillermo H; Barrionuevo, Paula

2017-04-01

Brucella abortus is able to persist inside the host despite the development of potent CD8 + T-cell responses. We have recently reported the ability of B. abortus to inhibit the interferon-γ-induced major histocompatibility complex (MHC)-I cell surface expression on human monocytes. This phenomenon was due to the B. abortus-mediated retention of MHC-I molecules within the Golgi apparatus and was dependent on bacterial viability. However, the implications of bacterial virulence or replicative capacity and the signaling pathways remained unknown. Here we demonstrated that the B. abortus mutant strains RB51 and virB10 - are able to inhibit MHC-I expression in the same manner as wild-type B. abortus, even though they are unable to persist inside human monocytes for a long period of time. Consistent with this, the phenomenon was triggered early in time and could be observed at 8 h postinfection. At 24 and 48 h, it was even stronger. Regarding the signaling pathway, targeting epidermal growth factor (EGF) receptor (EGFR), ErbB2 (HER2) or inhibition of tumor necrosis factor-α-converting enzyme, one of the enzymes which generates soluble EGF-like ligands, resulted in partial recovery of MHC-I surface expression. Moreover, recombinant EGF and transforming growth factor-α as well as the combination of both were also able to reproduce the B. abortus-induced MHC-I downmodulation. Finally, when infection was performed in the presence of an extracellular signal-regulated kinase 1/2 (Erk1/2) inhibitor, MHC-I surface expression was significantly recovered. Overall, these results describe how B. abortus evades CD8 + T-cell responses early during infection and exploits the EGFR-ERK signaling pathway to escape from the immune system and favor chronicity.

Research on odor interaction between aldehyde compounds via a partial differential equation (PDE) model.

Science.gov (United States)

Yan, Luchun; Liu, Jiemin; Qu, Chen; Gu, Xingye; Zhao, Xia

2015-01-28

In order to explore the odor interaction of binary odor mixtures, a series of odor intensity evaluation tests were performed using both individual components and binary mixtures of aldehydes. Based on the linear relation between the logarithm of odor activity value and odor intensity of individual substances, the relationship between concentrations of individual constituents and their joint odor intensity was investigated by employing a partial differential equation (PDE) model. The obtained results showed that the binary odor interaction was mainly influenced by the mixing ratio of two constituents, but not the concentration level of an odor sample. Besides, an extended PDE model was also proposed on the basis of the above experiments. Through a series of odor intensity matching tests for several different binary odor mixtures, the extended PDE model was proved effective at odor intensity prediction. Furthermore, odorants of the same chemical group and similar odor type exhibited similar characteristics in the binary odor interaction. The overall results suggested that the PDE model is a more interpretable way of demonstrating the odor interactions of binary odor mixtures.

Understanding TR binding to pMHC complexes: how does a TR scan many pMHC complexes yet preferentially bind to one.

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Javed Mohammed Khan

Full Text Available Understanding the basis of the binding of a T cell receptor (TR to the peptide-MHC (pMHC complex is essential due to the vital role it plays in adaptive immune response. We describe the use of computed binding (free energy (BE, TR paratope, pMHC epitope, molecular surface electrostatic potential (MSEP and calculated TR docking angle (θ to analyse 61 TR/pMHC crystallographic structures to comprehend TR/pMHC interaction. In doing so, we have successfully demonstrated a novel/rational approach for θ calculation, obtained a linear correlation between BE and θ without any "codon" or amino acid preference, provided an explanation for TR ability to scan many pMHC ligands yet specifically bind one, proposed a mechanism for pMHC recognition by TR leading to T cell activation and illustrated the importance of the peptide in determining TR specificity, challenging the "germline bias" theory.

An odor interaction model of binary odorant mixtures by a partial differential equation method.

Science.gov (United States)

Yan, Luchun; Liu, Jiemin; Wang, Guihua; Wu, Chuandong

2014-07-09

A novel odor interaction model was proposed for binary mixtures of benzene and substituted benzenes by a partial differential equation (PDE) method. Based on the measurement method (tangent-intercept method) of partial molar volume, original parameters of corresponding formulas were reasonably displaced by perceptual measures. By these substitutions, it was possible to relate a mixture's odor intensity to the individual odorant's relative odor activity value (OAV). Several binary mixtures of benzene and substituted benzenes were respectively tested to establish the PDE models. The obtained results showed that the PDE model provided an easily interpretable method relating individual components to their joint odor intensity. Besides, both predictive performance and feasibility of the PDE model were proved well through a series of odor intensity matching tests. If combining the PDE model with portable gas detectors or on-line monitoring systems, olfactory evaluation of odor intensity will be achieved by instruments instead of odor assessors. Many disadvantages (e.g., expense on a fixed number of odor assessors) also will be successfully avoided. Thus, the PDE model is predicted to be helpful to the monitoring and management of odor pollutions.

Kinase activity in the olfactory bulb is required for odor memory consolidation.

Science.gov (United States)

Tong, Michelle T; Kim, Tae-Young P; Cleland, Thomas A

2018-05-01

Long-term fear memory formation in the hippocampus and neocortex depends upon brain-derived neurotrophic factor (BDNF) signaling after acquisition. Incremental, appetitive odor discrimination learning is thought to depend substantially on the differentiation of adult-born neurons within the olfactory bulb (OB)-a process that is closely associated with BDNF signaling. We sought to elucidate the role of neurotrophin signaling within the OB on odor memory consolidation. Male mice were trained on odor-reward associative discriminations after bilateral infusion of the kinase inhibitor K252a, or vehicle control, into the OB. K252a is a partially selective inhibitor of tyrosine kinase (Trk) receptors, including the TrkB receptor for BDNF, though it also inhibits other plasticity-related kinases such as PKC and CaMKII/IV. K252a infusion into the OB did not impair odor acquisition or short-term (2 h) memory for the learned discriminations, but significantly impaired long-term (48 h) odor memory (LTM). This LTM deficit also was associated with reduced selectivity for the conditioned odorant in a reward-seeking digging task. Infusions of K252a immediately prior to testing did not impair LTM recall. These results indicate that kinase activation in the OB is required for the consolidation of odor memory of incrementally acquired information. © 2018 Tong et al.; Published by Cold Spring Harbor Laboratory Press.

Orf virus interferes with MHC class I surface expression by targeting vesicular transport and Golgi

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Rohde Jörg

2012-07-01

Full Text Available Abstract Background The Orf virus (ORFV, a zoonotic Parapoxvirus, causes pustular skin lesions in small ruminants (goat and sheep. Intriguingly, ORFV can repeatedly infect its host, despite the induction of a specific immunity. These immune modulating and immune evading properties are still unexplained. Results Here, we describe that ORFV infection of permissive cells impairs the intracellular transport of MHC class I molecules (MHC I as a result of structural disruption and fragmentation of the Golgi apparatus. Depending on the duration of infection, we observed a pronounced co-localization of MHC I and COP-I vesicular structures as well as a reduction of MHC I surface expression of up to 50%. These subversion processes are associated with early ORFV gene expression and are accompanied by disturbed carbohydrate trimming of post-ER MHC I. The MHC I population remaining on the cell surface shows an extended half-life, an effect that might be partially controlled also by late ORFV genes. Conclusions The presented data demonstrate that ORFV down-regulates MHC I surface expression in infected cells by targeting the late vesicular export machinery and the structure and function of the Golgi apparatus, which might aid to escape cellular immune recognition.

The Mouse Solitary Odorant Receptor Gene Promoters as Models for the Study of Odorant Receptor Gene Choice.

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Andrea Degl'Innocenti

Full Text Available In vertebrates, several anatomical regions located within the nasal cavity mediate olfaction. Among these, the main olfactory epithelium detects most conventional odorants. Olfactory sensory neurons, provided with cilia exposed to the air, detect volatile chemicals via an extremely large family of seven-transmembrane chemoreceptors named odorant receptors. Their genes are expressed in a monogenic and monoallelic fashion: a single allele of a single odorant receptor gene is transcribed in a given mature neuron, through a still uncharacterized molecular mechanism known as odorant receptor gene choice.Odorant receptor genes are typically arranged in genomic clusters, but a few are isolated (we call them solitary from the others within a region broader than 1 Mb upstream and downstream with respect to their transcript's coordinates. The study of clustered genes is problematic, because of redundancy and ambiguities in their regulatory elements: we propose to use the solitary genes as simplified models to understand odorant receptor gene choice.Here we define number and identity of the solitary genes in the mouse genome (C57BL/6J, and assess the conservation of the solitary status in some mammalian orthologs. Furthermore, we locate their putative promoters, predict their homeodomain binding sites (commonly present in the promoters of odorant receptor genes and compare candidate promoter sequences with those of wild-caught mice. We also provide expression data from histological sections.In the mouse genome there are eight intact solitary genes: Olfr19 (M12, Olfr49, Olfr266, Olfr267, Olfr370, Olfr371, Olfr466, Olfr1402; five are conserved as solitary in rat. These genes are all expressed in the main olfactory epithelium of three-day-old mice. The C57BL/6J candidate promoter of Olfr370 has considerably varied compared to its wild-type counterpart. Within the putative promoter for Olfr266 a homeodomain binding site is predicted. As a whole, our findings

The Smell of Age: Perception and Discrimination of Body Odors of Different Ages

OpenAIRE

Mitro, Susanna; Gordon, Amy R.; Olsson, Mats J.; Lundström, Johan N.

2012-01-01

Our natural body odor goes through several stages of age-dependent changes in chemical composition as we grow older. Similar changes have been reported for several animal species and are thought to facilitate age discrimination of an individual based on body odors, alone. We sought to determine whether humans are able to discriminate between body odor of humans of different ages. Body odors were sampled from three distinct age groups: Young (20-30 years old), Middle-age (45-55), and Old-age (...

DNA sequence of the Peromyscus leucopus MHC class II gene Aa (MhcPeleAa)

Energy Technology Data Exchange (ETDEWEB)

Crew, M.D.; Bates, L.M. [Univ. of Arkansas for Medical Sciences, Little Rock, AR (United States)

1996-09-01

The genus Peromyscus has been extensively studied by populations biologists and ecologists for over eighty years, with P. leucopus (the white-footed mouse) being one of the most intensively investigated species. Polymorphic major histocompatibility complex (MHC) genes have proven useful in population genetic studies and might be helpful in understanding the population dynamics of Peromyscus species which are ubiquitously distributed over North and Central America. Polymorphism of P. leucopus MHC (MhcPele) class II genes was evident by restriction fragment length polymorphism (RFLP) analyses using human and mouse probes and Pele class II loci exhibited degrees of polymorphism similar to H2 class II genes (A-like>E-like). 8 refs., 2 figs.

Functional neuronal processing of body odors differs from that of similar common odors.

Science.gov (United States)

Lundström, Johan N; Boyle, Julie A; Zatorre, Robert J; Jones-Gotman, Marilyn

2008-06-01

Visual and auditory stimuli of high social and ecological importance are processed in the brain by specialized neuronal networks. To date, this has not been demonstrated for olfactory stimuli. By means of positron emission tomography, we sought to elucidate the neuronal substrates behind body odor perception to answer the question of whether the central processing of body odors differs from perceptually similar nonbody odors. Body odors were processed by a network that was distinctly separate from common odors, indicating a separation in the processing of odors based on their source. Smelling a friend's body odor activated regions previously seen for familiar stimuli, whereas smelling a stranger activated amygdala and insular regions akin to what has previously been demonstrated for fearful stimuli. The results provide evidence that social olfactory stimuli of high ecological relevance are processed by specialized neuronal networks similar to what has previously been demonstrated for auditory and visual stimuli.

Intranasal localizability of odorants: influence of stimulus volume.

Science.gov (United States)

Frasnelli, J; Hummel, T; Berg, J; Huang, G; Doty, R L

2011-05-01

When an odorant is presented to one side of the nose and air to the other, the ability to localize which side received the odorant depends upon trigeminal nerve stimulation. It has been shown that performance on this lateralization task increases as stimulus concentration increases. In this study, we determined the influences of stimulus volume and sex on the ability to localize each of 8 odorants presented at neat concentrations: anethole, geraniol, limonene, linalool, menthol, methyl salicylate, phenyl ethanol, and vanillin. At a low stimulus volume (11 mL), only menthol was localized at an above-chance level. At a high stimulus volume (21 mL), above-chance localization occurred for all odorants except vanillin. Women were significantly better than men in localizing menthol. Stimuli rated as most intense were those that were most readily localized. The detection performance measures, as well as rated intensity values, significantly correlated with earlier findings of the trigeminal detectability of odorants presented to anosmic and normosmic subjects. This study suggests that differences in stimulus volume may explain some discrepant findings within the trigeminal chemosensory literature and supports the concept that vanillin may be a "relatively pure" olfactory stimulus.

Antigen processing of glycoconjugate vaccines; the polysaccharide portion of the pneumococcal CRM(197) conjugate vaccine co-localizes with MHC II on the antigen processing cell surface.

Science.gov (United States)

Lai, Zengzu; Schreiber, John R

2009-05-21

Pneumococcal (Pn) polysaccharides (PS) are T-independent (TI) antigens and do not induce immunological memory or antibodies in infants. Conjugation of PnPS to the carrier protein CRM(197) induces PS-specific antibody in infants, and memory similar to T-dependent (Td) antigens. Conjugates have improved immunogenicity via antigen processing and presentation of carrier protein with MHC II and recruitment of T cell help, but the fate of the PS attached to the carrier is unknown. To determine the location of the PS component of PnPS-CRM(197) in the APC, we separately labeled PS and protein and tracked their location. The PS of types 14-CRM(197) and 19F-CRM(197) was specifically labeled by Alexa Fluor 594 hydrazide (red). The CRM(197) was separately labeled red in a reaction that did not label PS. Labeled antigens were incubated with APC which were fixed, permeabilized and incubated with anti-MHC II antibody labeled green by Alexa Fluor 488, followed by confocal microscopy. Labeled CRM(197) was presented on APC surface and co-localized with MHC II (yellow). Labeled unconjugated 14 or 19F PS did not go to the APC surface, but PS labeled 14-CRM(197) and 19F-CRM(197) was internalized and co-localized with MHC II. Monoclonal antibody to type 14 PS bound to intracellular type 14 PS and PS-CRM(197). Brefeldin A and chloroquine blocked both CRM(197) and PS labeled 14-CRM(197) and 19F-CRM(197) from co-localizing with MHC II. These data suggest that the PS component of the CRM(197) glycoconjugate enters the endosome, travels with CRM(197) peptides to the APC surface and co-localizes with MHC II.

An Odor Interaction Model of Binary Odorant Mixtures by a Partial Differential Equation Method

Directory of Open Access Journals (Sweden)

Luchun Yan

2014-07-01

Full Text Available A novel odor interaction model was proposed for binary mixtures of benzene and substituted benzenes by a partial differential equation (PDE method. Based on the measurement method (tangent-intercept method of partial molar volume, original parameters of corresponding formulas were reasonably displaced by perceptual measures. By these substitutions, it was possible to relate a mixture’s odor intensity to the individual odorant’s relative odor activity value (OAV. Several binary mixtures of benzene and substituted benzenes were respectively tested to establish the PDE models. The obtained results showed that the PDE model provided an easily interpretable method relating individual components to their joint odor intensity. Besides, both predictive performance and feasibility of the PDE model were proved well through a series of odor intensity matching tests. If combining the PDE model with portable gas detectors or on-line monitoring systems, olfactory evaluation of odor intensity will be achieved by instruments instead of odor assessors. Many disadvantages (e.g., expense on a fixed number of odor assessors also will be successfully avoided. Thus, the PDE model is predicted to be helpful to the monitoring and management of odor pollutions.

An artificial odor recognition system is developed for discriminating odors

Directory of Open Access Journals (Sweden)

Wisnu Jatmiko

2002-12-01

Full Text Available This artificial system consisted of 16 quartz resonator crystals as the sensor array, a frequency modulator and a frequency counter for each sensor that are connected directly to a microcomputer. We have already shown that the artificial odor recognition system with 4 sensors is high enough to discriminate simple odor correctly, however, when it was used to discriminate compound odors, the recognition capability of this system is dropped significantly to be about 40%. Results of experiments show that the developed artificial system with 16 sensors could discriminate compound aroma based on 6 gradient of alcohol concentrations with high recognition rate of 89.9% for non batch processing system, and 82.4% for batch processing of the classes of odors.

Odors: appetizing or satiating? Development of appetite during odor exposure over time

NARCIS (Netherlands)

Ramaekers, M.G.; Boesveldt, S.; Lakemond, C.M.M.; Boekel, van M.A.J.S.; Luning, P.A.

2014-01-01

Background: Exposure to palatable food odors influences appetite responses, either promoting or inhibiting food intake. Possibly, food odors are appetizing after a short exposure (of circa 1–3¿min), but become satiating over time (circa 10–20¿min). Objective: To investigate the effect of odor

Wild western lowland gorillas signal selectively using odor.

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Michelle Klailova

Full Text Available Mammals communicate socially through visual, auditory and chemical signals. The chemical sense is the oldest sense and is shared by all organisms including bacteria. Despite mounting evidence for social chemo-signaling in humans, the extent to which it modulates behavior is debated and can benefit from comparative models of closely related hominoids. The use of odor cues in wild ape social communication has been only rarely explored. Apart from one study on wild chimpanzee sniffing, our understanding is limited to anecdotes. We present the first study of wild gorilla chemo-communication and the first analysis of olfactory signaling in relation to arousal levels and odor strength in wild apes. If gorilla scent is used as a signaling mechanism instead of only a sign of arousal or stress, odor emission should be context specific and capable of variation as a function of the relationships between the emitter and perceiver(s. Measured through a human pungency scale, we determined the factors that predicted extreme levels of silverback odor for one wild western lowland gorilla (Gorilla gorilla gorilla group silverback. Extreme silverback odor was predicted by the presence and intensity of inter-unit interactions, silverback anger, distress and long-calling auditory rates, and the absence of close proximity between the silverback and mother of the youngest infant. Odor strength also varied according to the focal silverback's strategic responses during high intensity inter-unit interactions. Silverbacks appear to use odor as a modifiable form of communication; where odor acts as a highly flexible, context dependent signaling mechanism to group members and extra-group units. The importance of olfaction to ape social communication may be especially pertinent in Central African forests where limited visibility may necessitate increased reliance on other senses.

The importance of immune gene variability (MHC in evolutionary ecology and conservation

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Sommer Simone

2005-10-01

Full Text Available Abstract Genetic studies have typically inferred the effects of human impact by documenting patterns of genetic differentiation and levels of genetic diversity among potentially isolated populations using selective neutral markers such as mitochondrial control region sequences, microsatellites or single nucleotide polymorphism (SNPs. However, evolutionary relevant and adaptive processes within and between populations can only be reflected by coding genes. In vertebrates, growing evidence suggests that genetic diversity is particularly important at the level of the major histocompatibility complex (MHC. MHC variants influence many important biological traits, including immune recognition, susceptibility to infectious and autoimmune diseases, individual odours, mating preferences, kin recognition, cooperation and pregnancy outcome. These diverse functions and characteristics place genes of the MHC among the best candidates for studies of mechanisms and significance of molecular adaptation in vertebrates. MHC variability is believed to be maintained by pathogen-driven selection, mediated either through heterozygote advantage or frequency-dependent selection. Up to now, most of our knowledge has derived from studies in humans or from model organisms under experimental, laboratory conditions. Empirical support for selective mechanisms in free-ranging animal populations in their natural environment is rare. In this review, I first introduce general information about the structure and function of MHC genes, as well as current hypotheses and concepts concerning the role of selection in the maintenance of MHC polymorphism. The evolutionary forces acting on the genetic diversity in coding and non-coding markers are compared. Then, I summarise empirical support for the functional importance of MHC variability in parasite resistance with emphasis on the evidence derived from free-ranging animal populations investigated in their natural habitat. Finally, I

Health effects of indoor odorants.

Science.gov (United States)

Cone, J E; Shusterman, D

1991-11-01

People assess the quality of the air indoors primarily on the basis of its odors and on their perception of associated health risk. The major current contributors to indoor odorants are human occupant odors (body odor), environmental tobacco smoke, volatile building materials, bio-odorants (particularly mold and animal-derived materials), air fresheners, deodorants, and perfumes. These are most often present as complex mixtures, making measurement of the total odorant problem difficult. There is no current method of measuring human body odor, other than by human panel studies of expert judges of air quality. Human body odors have been quantitated in terms of the "olf" which is the amount of air pollution produced by the average person. Another quantitative unit of odorants is the "decipol," which is the perceived level of pollution produced by the average human ventilated by 10 L/sec of unpolluted air or its equivalent level of dissatisfaction from nonhuman air pollutants. The standard regulatory approach, focusing on individual constituents or chemicals, is not likely to be successful in adequately controlling odorants in indoor air. Besides the current approach of setting minimum ventilation standards to prevent health effects due to indoor air pollution, a standard based on the olf or decipol unit might be more efficacious as well as simpler to measure.

Odor Perception by Dogs: Evaluating Two Training Approaches for Odor Learning of Sniffer Dogs.

Science.gov (United States)

Fischer-Tenhagen, Carola; Johnen, Dorothea; Heuwieser, Wolfgang; Becker, Roland; Schallschmidt, Kristin; Nehls, Irene

2017-06-01

In this study, a standardized experimental set-up with various combinations of herbs as odor sources was designed. Two training approaches for sniffer dogs were compared; first, training with a pure reference odor, and second, training with a variety of odor mixtures with the target odor as a common denominator. The ability of the dogs to identify the target odor in a new context was tested. Six different herbs (basil, St. John's wort, dandelion, marjoram, parsley, ribwort) were chosen to produce reference materials in various mixtures with (positive) and without (negative) chamomile as the target odor source. The dogs were trained to show 1 of 2 different behaviors, 1 for the positive, and 1 for the negative sample as a yes/no task. Tests were double blind with one sample presented at a time. In both training approaches, dogs were able to detect chamomile as the target odor in any presented mixture with an average sensitivity of 72% and a specificity of 84%. Dogs trained with odor mixture containing the target odor had more correct indications in the transfer task. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

MHC classⅠ gene in two duck lines

Indian Academy of Sciences (India)

Navya

Weishan Ma duck (WS) is the eugenic endemic breed, one of the four famous ducks in China, as well Cherry Valley duck (CV) is the largest number of breeding variety. WS is egg strain and CV is meat type. The two duck lines mainly support the. Chinese waterfowl industry. In this study, MHC class Ⅰ genes of WS and CV ...

Olfactory systems and neural circuits that modulate predator odor fear

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Lorey K. Takahashi

2014-03-01

Full Text Available When prey animals detect the odor of a predator a constellation of fear-related autonomic, endocrine, and behavioral responses rapidly occur to facilitate survival. How olfactory sensory systems process predator odor and channel that information to specific brain circuits is a fundamental issue that is not clearly understood. However, research in the last 15 years has begun to identify some of the essential features of the sensory detection systems and brain structures that underlie predator odor fear. For instance, the main (MOS and accessory olfactory systems (AOS detect predator odors and different types of predator odors are sensed by specific receptors located in either the MOS or AOS. However, complex predator chemosignals may be processed by both the MOS and AOS, which complicate our understanding of the specific neural circuits connected directly and indirectly from the MOS and AOS to activate the physiological and behavioral components of unconditioned and conditioned fear. Studies indicate that brain structures including the dorsal periaqueductal gray, paraventricular nucleus of the hypothalamus, and the medial amygdala appear to be broadly involved in predator odor induced autonomic activity and hypothalamic-pituitary-adrenal stress hormone secretion. The medial amygdala also plays a key role in predator odor unconditioned fear behavior and retrieval of contextual fear memory associated with prior predator odor experiences. Other neural structures including the bed nucleus of the stria terminalis and the ventral hippocampus appear prominently involve in predator odor fear behavior. The basolateral amygdala, medial hypothalamic nuclei, and medial prefrontal cortex are also activated by some but not all predator odors. Future research that characterizes how distinct predator odors are uniquely processed in olfactory systems and neural circuits will provide significant insights into the differences of how diverse predator odors activate

Olfactory systems and neural circuits that modulate predator odor fear

Science.gov (United States)

Takahashi, Lorey K.

2014-01-01

When prey animals detect the odor of a predator a constellation of fear-related autonomic, endocrine, and behavioral responses rapidly occur to facilitate survival. How olfactory sensory systems process predator odor and channel that information to specific brain circuits is a fundamental issue that is not clearly understood. However, research in the last 15 years has begun to identify some of the essential features of the sensory detection systems and brain structures that underlie predator odor fear. For instance, the main (MOS) and accessory olfactory systems (AOS) detect predator odors and different types of predator odors are sensed by specific receptors located in either the MOS or AOS. However, complex predator chemosignals may be processed by both the MOS and AOS, which complicate our understanding of the specific neural circuits connected directly and indirectly from the MOS and AOS to activate the physiological and behavioral components of unconditioned and conditioned fear. Studies indicate that brain structures including the dorsal periaqueductal gray (DPAG), paraventricular nucleus (PVN) of the hypothalamus, and the medial amygdala (MeA) appear to be broadly involved in predator odor induced autonomic activity and hypothalamic-pituitary-adrenal (HPA) stress hormone secretion. The MeA also plays a key role in predator odor unconditioned fear behavior and retrieval of contextual fear memory associated with prior predator odor experiences. Other neural structures including the bed nucleus of the stria terminalis and the ventral hippocampus (VHC) appear prominently involved in predator odor fear behavior. The basolateral amygdala (BLA), medial hypothalamic nuclei, and medial prefrontal cortex (mPFC) are also activated by some but not all predator odors. Future research that characterizes how distinct predator odors are uniquely processed in olfactory systems and neural circuits will provide significant insights into the differences of how diverse predator

NLRC5: a newly discovered MHC class I transactivator (CITA)

OpenAIRE

Meissner, Torsten B.; Li, Amy; Kobayashi, Koichi S.

2011-01-01

Major histocompatibility complex (MHC) class I and class II are crucial for the function of the human adaptive immune system. An NLR protein, CIITA (MHC class II transactivator), is a master regulator of MHC class II gene expression as well as of some of the genes involved in MHC class II antigen presentation. It has recently been discovered that another member of the NLR protein family, NLRC5, transcriptionally activates MHC class I genes, and thus acts as “CITA” (MHC class I transactivator)...

Expressing exogenous functional odorant receptors in cultured olfactory sensory neurons

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Fomina Alla F

2008-09-01

Full Text Available Abstract Background Olfactory discrimination depends on the large numbers of odorant receptor genes and differential ligand-receptor signaling among neurons expressing different receptors. In this study, we describe an in vitro system that enables the expression of exogenous odorant receptors in cultured olfactory sensory neurons. Olfactory sensory neurons in the culture express characteristic signaling molecules and, therefore, provide a system to study receptor function within its intrinsic cellular environment. Results We demonstrate that cultured olfactory sensory neurons express endogenous odorant receptors. Lentiviral vector-mediated gene transfer enables successful ectopic expression of odorant receptors. We show that the ectopically expressed mouse I7 is functional in the cultured olfactory sensory neurons. When two different odorant receptors are ectopically expressed simultaneously, both receptor proteins co-localized in the same olfactory sensory neurons up to 10 days in vitro. Conclusion This culture technique provided an efficient method to culture olfactory sensory neurons whose morphology, molecular characteristics and maturation progression resembled those observed in vivo. Using this system, regulation of odorant receptor expression and its ligand specificity can be studied in its intrinsic cellular environment.

Pollution odorante par les moteurs Diesel. Mesure des odeurs d'échappement Odorous Pollution by Diesel Engines. Measuring Exhaust Odors

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Degobert P.

2006-11-01

Full Text Available Les études de mesure d'odeur Diesel ont commencé en 1956 aux États-Unis, en particulier pour réduire le niveau odorant des autobus. Cet article expose d'abord les mécanismes de formation des odorants puis les études américaines, qui ont abouti en 1973 à l'odorimètre Arthur D. Little, basé sur l'analyse par chromatographie liquide de l'échappement, et ses corrélations avec les données sensorielles recueillies dans des conditions particulières. Les économies d'énergie dans les villes européennes entraînent un accroissement du nombre de véhicules Diesel, ce qui peut amener un niveau odorant incompatible avec le bien-être. C'est pourquoi l'Institut Français du Pétrole (IFP étudie actuellement les odeurs Diesel, pour mettre au point des méthodes de mesure fiables, partant de la chromatographie liquide type Arthur D. Little (ADL et de l'évaluation sensorielle. Les résultats actuels montrent qu'à moins de progrès importants en analyse chimique, l'évaluation sensorielle reste la méthode la plus fiable. Les perspectives futures basées sur l'olfactomètre différentiel Mac Leod sont présentées. Research was beg un in the United States in 1956 on the medsurementof diesel engine odors, and especially on reducing the odor from diesel city buses. This article begins by describing the mechanisms of odor formation and then goes on ta, review US research which resulted in the Arthur D. Little odormeter in 1973, based on a liquid chromatography analysis of exhaust and its corrélations with sensory data gathered under specific conditions. Energy conservation in European cities is tending ta, increase the number of diesel vehicles and possibly ta, create an odor level that is incompatible with humal well-being. This is why Institut Français du Pétrole (IFP is now investigating diesel eng ine odors for the purpose of developing reliable measuring methods based on liquid chromatography of the Arthur D. Little (ADl type and on

Analysis of chickens for recombination within the MHC (B-complex)

DEFF Research Database (Denmark)

Skjødt, K; Koch, C; Crone, M

1985-01-01

In an attempt to further map the chicken MHC (the B complex), a systematic search for genetic recombinants within the B complex was performed by serotyping the progeny from F2 crosses of chickens by means of specific anti-class I, anti-class II, and anti-class IV alloantisera. Two recombinant B......-haplotypes (B21r and B15r) were found by analysing 2,656 F2 chickens representing 5,312 informative typings. In either case, the B-G (class IV) allele was recombined with both the B-F and B-L alleles of the opposite haplotype. MLC typings, tests for direct compatibility by GVH reactions, and absorption analyses...... confirmed the original serological typing of the two recombinant B haplotypes. No recombination between B-F (class I) and B-L (class II) loci was found. This very low frequency of recombination within the B complex as compared with recombination frequencies found in mammalian MHC's is discussed...

Olfactory aversive conditioning alters olfactory bulb mitral/tufted cell glomerular odor responses

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Max L Fletcher

2012-03-01

Full Text Available The anatomical organization of receptor neuron input into the olfactory bulb (OB allows odor information to be transformed into an odorant-specific spatial map of mitral/tufted cell glomerular activity at the upper level of the olfactory bulb. In other sensory systems, neuronal representations of stimuli can be reorganized or enhanced following learning. While the mammalian OB has been shown to undergo experience-dependent plasticity at the glomerular level, it is still unclear if similar representational change occurs within mitral/tufted cell glomerular odor representations following learning. To address this, odorant-evoked glomerular activity patterns were imaged in mice expressing a GFP-based calcium indicator (GCaMP2 in OB mitral/tufted cells. Glomerular odor responses were imaged before and after olfactory associative conditioning to aversive foot shock. Following conditioning, we found no overall reorganization of the glomerular representation. Training, however, did significantly alter the amplitudes of individual glomeruli within the representation in mice in which the odor was presented together with foot shock. Further, the specific pairing of foot shock with odor presentations lead to increased responses primarily in initially weakly activated glomeruli. Overall, these results suggest that associative conditioning can enhance the initial representation of odors within the olfactory bulb by enhancing responses to the learned odor in some glomeruli.

Characterization of MHC class I and II genes in a subantarctic seabird, the blue petrel, Halobaena caerulea (Procellariiformes).

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Strandh, Maria; Lannefors, Mimi; Bonadonna, Francesco; Westerdahl, Helena

2011-10-01

The great polymorphism observed in the major histocompatibility complex (MHC) genes is thought to be maintained by pathogen-mediated selection possibly combined with MHC-disassortative mating, guided by MHC-determined olfactory cues. Here, we partly characterize the MHC class I and II B of the blue petrel, Halobaena caerulea (Procellariiformes), a bird with significant olfactory abilities that lives under presumably low pathogen burdens in Subantarctica. Blue petrels are long-lived, monogamous birds which suggest the necessity of an accurate mate choice process. The species is ancestral to songbirds (Passeriformes; many MHC loci), although not to gamefowls (Galliformes; few MHC loci). Considering the phylogenetic relationships and the low subantarctic pathogen burden, we expected few rather than many MHC loci in the blue petrel. However, when we analysed partial MHC class I and class II B cDNA and gDNA sequences we found evidence for as many as at least eight MHC class I loci and at least two class II B loci. These class I and II B sequences showed classical MHC characteristics, e.g. high nucleotide diversity, especially in putative peptide-binding regions where signatures of positive selection was detected. Trans-species polymorphism was found between MHC class II B sequences of the blue petrel and those of thin-billed prion, Pachyptila belcheri, two species that diverged ∼25 MYA. The observed MHC allele richness in the blue petrel may well serve as a basis for mate choice, especially since olfactory discrimination of MHC types may be possible in this species.

Preliminary analysis of odor legal solutions and study on their implementation possibilities in Poland

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Sówka, Izabela; Karski, Leszek

2018-01-01

The problem of odor nuisance requires undertaking legal means that aim towards implementation of regulations in order to improve the odor-related quality of air in selected areas in Poland. So far the works carried out in the country were concluded by drawing up `The guidelines for the bill on counteracting the odor nuisance'. However, as a result of completed social consultations in Poland, the Ministry of Environment, in 2015, resigned from implementing of so called anti-odor act. Currently, the legislature is taking steps which aim at undertaking specific actions in order to introduce solutions, which would directly regulate the issues of odors and the odor nuisance, to the national system. In the countries of the European Union, the issues related to odors are solved in diversified ways and the system still lacks of a uniform proposition, among others related to odor standards. In connection with the above, actions that are taken on a national level should fundamentally aim at developing national odor standards which would take into account the type / the kind of economic activity being a source of odor emission (e.g. clearly separated for existing objects and planned investments), at establishing a procedure and also legal and operational requirements related to determination and the types of zones with defined values of acceptable concentration and determination of reference methodology in monitoring, and modeling the dispersion of odors e.g. including strictly defined frequency of necessary tests. In addition, the process should be accompanied by a creation of financial mechanisms and streams in range of investments related to the development of technology and methods used to limit emission of odors.

Tolerance to MHC class II disparate allografts through genetic modification of bone marrow

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Jindra, Peter T.; Tripathi, Sudipta; Tian, Chaorui; Iacomini, John; Bagley, Jessamyn

2012-01-01

Induction of molecular chimerism through genetic modification of bone marrow is a powerful tool for the induction of tolerance. Here we demonstrate for the first time that expression of an allogeneic MHC class II gene in autologous bone marrow cells, resulting in a state of molecular chimerism, induces tolerance to MHC class II mismatched skin grafts, a stringent test of transplant tolerance. Reconstitution of recipients with syngeneic bone marrow transduced with retrovirus encoding H-2I-Ab (I-Ab) resulted the long-term expression of the retroviral gene product on the surface of MHC class II-expressing bone marrow derived cell types. Mechanistically, tolerance was maintained by the presence of regulatory T cells, which prevented proliferation and cytokine production by alloreactive host T cells. Thus, the introduction of MHC class II genes into bone marrow derived cells through genetic engineering results in tolerance. These results have the potential to extend the clinical applicability of molecular chimerism for tolerance induction. PMID:22833118

The E5 protein of human papillomavirus type 16 perturbs MHC class II antigen maturation in human foreskin keratinocytes treated with interferon-γ

International Nuclear Information System (INIS)

Zhang Benyue; Li Ping; Wang Exing; Brahmi, Zacharie; Dunn, Kenneth W.; Blum, Janice S.; Roman, Ann

2003-01-01

Major histocompatibility complex (MHC) class II antigens are expressed on human foreskin keratinocytes (HFKs) following exposure to interferon gamma. The expression of MHC class II proteins on the cell surface may allow keratinocytes to function as antigen-presenting cells and induce a subsequent immune response to virus infection. Invariant chain (Ii) is a chaperone protein which plays an important role in the maturation of MHC class II molecules. The sequential degradation of Ii within acidic endocytic compartments is a key process required for the successful loading of antigenic peptide onto MHC class II molecules. Since human papillomavirus (HPV) 16 E5 can inhibit the acidification of late endosomes in HFKs, the E5 protein may be able to affect proper peptide loading onto the MHC class II molecule. To test this hypothesis, HFKs were infected with either control virus or a recombinant virus expressing HPV16 E5 and the infected cells were subsequently treated with interferon-γ. ELISAs revealed a decrease of MHC class II expression on the surface of E5-expressing cells compared with control virus-infected cells after interferon treatment. Western blot analysis showed that, in cells treated with interferon gamma, E5 could prevent the breakdown of Ii and block the formation of peptide-loaded, SDS-stable mature MHC class II dimers, correlating with diminished surface MHC class II expression. These data suggest that HPV16 E5 may be able to decrease immune recognition of infected keratinocytes via disruption of MHC class II protein function

Irradiation of odor pollutant using powerful electron beam energy before discharge to the environment

International Nuclear Information System (INIS)

Mohd Nahar Othman; Muhd Noor Muhd Yunus; Khairul Zaman Mohd Dahlan; Norasalwa Zakaria; Ku Halim Ku Hamid

2008-08-01

The odour or odor complaints received by the Department of Environment of Malaysia in 2006 are about 1082 cases. The trend shows that odor problems have become more and more acute every year. The sources of odor complaints come from many types of industries such as animal raring industry, chemical industries, rubber processing industries, municipal solid wastes (MSW), sewage treatment plants, palm oil industries, petroleum industries and etc. The types of odor control technology used to solve the odor problem still cannot comply to the standard needed by the people. Some of the problems became more problematic because the sources are located in places which are populated. At the same time, there is no regulation concerning the specific odor parameter stated in the Environment Quality Acts 1974. Just recently the Department of Environment drafted a regulation in order to monitor this problem, relating to the nuisance coming from these industries. The aim of this paper is to introduce a new technique of treatment of odor pollutant by using Dimethyl Sulfide (DMS) as sample gas from MSW. The odor gases from Municipal solid waste is irradiated using electron beam irradiation that has been successfully carried out by the Malaysian Nuclear Agency and the result shows that this technique has good potential. (Author)

Comparative genome analyses reveal distinct structure in the saltwater crocodile MHC.

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Weerachai Jaratlerdsiri

Full Text Available The major histocompatibility complex (MHC is a dynamic genome region with an essential role in the adaptive immunity of vertebrates, especially antigen presentation. The MHC is generally divided into subregions (classes I, II and III containing genes of similar function across species, but with different gene number and organisation. Crocodylia (crocodilians are widely distributed and represent an evolutionary distinct group among higher vertebrates, but the genomic organisation of MHC within this lineage has been largely unexplored. Here, we studied the MHC region of the saltwater crocodile (Crocodylus porosus and compared it with that of other taxa. We characterised genomic clusters encompassing MHC class I and class II genes in the saltwater crocodile based on sequencing of bacterial artificial chromosomes. Six gene clusters spanning ∼452 kb were identified to contain nine MHC class I genes, six MHC class II genes, three TAP genes, and a TRIM gene. These MHC class I and class II genes were in separate scaffold regions and were greater in length (2-6 times longer than their counterparts in well-studied fowl B loci, suggesting that the compaction of avian MHC occurred after the crocodilian-avian split. Comparative analyses between the saltwater crocodile MHC and that from the alligator and gharial showed large syntenic areas (>80% identity with similar gene order. Comparisons with other vertebrates showed that the saltwater crocodile had MHC class I genes located along with TAP, consistent with birds studied. Linkage between MHC class I and TRIM39 observed in the saltwater crocodile resembled MHC in eutherians compared, but absent in avian MHC, suggesting that the saltwater crocodile MHC appears to have gene organisation intermediate between these two lineages. These observations suggest that the structure of the saltwater crocodile MHC, and other crocodilians, can help determine the MHC that was present in the ancestors of archosaurs.

Major Odorants Released as Urinary Volatiles by Urinary Incontinent Patients

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In Young Sa

2013-07-01

Full Text Available In this study, volatile urinary components were collected using three different types of samples from patients suffering from urinary incontinence (UI: (1 urine (A; (2 urine + non-used pad (B; and (3 urine + used pad (C. In addition, urine + non-used pad (D samples from non-patients were also collected as a reference. The collection of urinary volatiles was conducted with the aid of a glass impinger-based mini-chamber method. Each of the four sample types (A through D was placed in a glass impinger and incubated for 4 hours at 37 °C. Ultra pure air was then passed through the chamber, and volatile urine gas components were collected into Tedlar bags at the other end. These bag samples were then analyzed for a wide range of VOCs and major offensive odorants (e.g., reduced sulfur compounds (RSCs, carbonyls, trimethylamine (TMA, ammonia, etc.. Among the various odorants, sulfur compounds (methanethiol and hydrogen sulfide and aldehydes (acetaldehyde, butylaldehyde, and isovaleraldehyde were detected above odor threshold and predicted to contribute most effectively to odor intensity of urine incontinence.

Primordial linkage of β2-microglobulin to the MHC.

Science.gov (United States)

Ohta, Yuko; Shiina, Takashi; Lohr, Rebecca L; Hosomichi, Kazuyoshi; Pollin, Toni I; Heist, Edward J; Suzuki, Shingo; Inoko, Hidetoshi; Flajnik, Martin F

2011-03-15

β2-Microglobulin (β2M) is believed to have arisen in a basal jawed vertebrate (gnathostome) and is the essential L chain that associates with most MHC class I molecules. It contains a distinctive molecular structure called a constant-1 Ig superfamily domain, which is shared with other adaptive immune molecules including MHC class I and class II. Despite its structural similarity to class I and class II and its conserved function, β2M is encoded outside the MHC in all examined species from bony fish to mammals, but it is assumed to have translocated from its original location within the MHC early in gnathostome evolution. We screened a nurse shark bacterial artificial chromosome library and isolated clones containing β2M genes. A gene present in the MHC of all other vertebrates (ring3) was found in the bacterial artificial chromosome clone, and the close linkage of ring3 and β2M to MHC class I and class II genes was determined by single-strand conformational polymorphism and allele-specific PCR. This study satisfies the long-held conjecture that β2M was linked to the primordial MHC (Ur MHC); furthermore, the apparent stability of the shark genome may yield other genes predicted to have had a primordial association with the MHC specifically and with immunity in general.

Colonizing the world in spite of reduced MHC variation

Science.gov (United States)

Gangoso, L.; Alcaide, M.; Grande, J.M.; Muñoz, J.; Talbot, Sandra L.; Sonsthagen, Sarah A.; Sage, Kevin; Figuerola, J.

2012-01-01

Reduced immune gene diversity is thought to negatively affect the capacity of organisms to adapt to pathogen challenges, which represent a major force in natural selection. Genes of the Major Histocompatibility Complex (MHC) are the most widely invoked adaptive loci in conservation biology, and have become the most popular genetic markers to investigate pathogen-host interactions in vertebrates. Although MHC genes are the most polymorphic genes described in the vertebrate genome, the extent to which MHC diversity determines the long-term persistence of populations is, unclear and often debated, as recent studies have documented the occurrence of natural populations thriving even after a depletion of MHC diversity caused by genetic drift. Here, we show that some phylogenetically related species belonging to the Falco genus (Aves: Falconidae) present a dramatically low MHC variability that has not precluded, nevertheless, the successful colonization of almost all existing regions and habitats worldwide. We found evidence for two remarkably different patterns of MHC variation within the genus. While kestrels show a high MHC variation according to the general theory, falcons exhibit an ancestrally low intra- and inter-specific MHC allelic diversity. We provide compelling evidence that this pattern is not caused by the degeneration of functional genes into pseudogenes, the inadvertent analyses of paralogous MHC genes, or the devastating action of genetic drift. Instead, our results strongly support the idea of an evolutionary transition driven and maintained by natural selection from primarily highly variable towards low polymorphic, but functional and expressed, MHC genes with species-specific pathogen-recognition capabilities.

Does gently clearing the nasal passage affect odor identification?

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Mitchell G. Spring

2014-12-01

Full Text Available Identifying scents in a wine’s bouquet is considered one of the most important steps in the process of wine tasting. An individual’s ability to successfully do this is dependent on the sense of smell; thus, altering the nasal microenvironment could have a powerful effect on the wine tasting experience. In the present study, we examined olfactory performance in healthy participants who cleared their nasal cavity before odorant presentations. Fifty undergraduate participants were assessed with a standardized test of olfaction requiring the recognition of a battery of odors. Half of these participants cleared mucus from their nasal cavities (by gently blowing their noses prior to the assessment. No difference was found in performance between those who cleared their nasal passages and those who did not. Further, data were not different than known population data from the test. These data suggest that gently clearing the nasal cavity before presentation of odorants bears no effect on the ability to perceive those odor qualities.

New recombinants within the MHC (B-complex) of the chicken

DEFF Research Database (Denmark)

Koch, C; Skjødt, K; Toivanen, A

1983-01-01

In a search for genetic recombinations within the major histocompatibility complex (MHC) of the chicken, the B-complex, the offspring from matings between heterozygous B15/B21 and B4/B6 animals were analysed by red cell agglutination. Among the progeny, 8,912 informative typings were performed...... followed B-F/B-L. The mapping distance between the two loci B-F and B-G is in the range of 0.04 centimorgan. The lack of recombinants separating individual B-F loci in this study and in the studies of others might indicate that chicken MHC is less complex than those of mammalian species, but alternative...

Brucella abortus down-regulates MHC class II by the IL-6-dependent inhibition of CIITA through the downmodulation of IFN regulatory factor-1 (IRF-1).

Science.gov (United States)

Velásquez, Lis N; Milillo, M Ayelén; Delpino, M Victoria; Trotta, Aldana; Fernández, Pablo; Pozner, Roberto G; Lang, Roland; Balboa, Luciana; Giambartolomei, Guillermo H; Barrionuevo, Paula

2017-03-01

Brucella abortus is an intracellular pathogen capable of surviving inside of macrophages. The success of B. abortus as a chronic pathogen relies on its ability to orchestrate different strategies to evade the adaptive CD4 + T cell responses that it elicits. Previously, we demonstrated that B. abortus inhibits the IFN-γ-induced surface expression of MHC class II (MHC-II) molecules on human monocytes, and this phenomenon correlated with a reduction in antigen presentation. However, the molecular mechanisms, whereby B. abortus is able to down-regulate the expression of MHC-II, remained to be elucidated. In this study, we demonstrated that B. abortus infection inhibits the IFN-γ-induced transcription of MHC-II, transactivator (CIITA) and MHC-II genes. Accordingly, we observed that the synthesis of MHC-II proteins was also diminished. B. abortus was not only able to reduce the expression of mature MHC-II, but it also inhibited the expression of invariant chain (Ii)-associated immature MHC-II molecules. Outer membrane protein 19 (Omp19), a prototypical B. abortus lipoprotein, diminished the expression of MHC-II and CIITA transcripts to the same extent as B. abortus infection. IL-6 contributes to these down-regulatory phenomena. In addition, B. abortus and its lipoproteins, through IL-6 secretion, induced the transcription of the negative regulators of IFN-γ signaling, suppressor of cytokine signaling (SOCS)-1 and -3, without interfering with STAT1 activation. Yet, B. abortus lipoproteins via IL-6 inhibit the expression of IFN regulatory factor 1 (IRF-1), a critical regulatory transcription factor for CIITA induction. Overall, these results indicate that B. abortus inhibits the expression of MHC-II molecules at very early points in their synthesis and in this way, may prevent recognition by T cells establishing a chronic infection. © Society for Leukocyte Biology.

Predicting Odor Pleasantness from Odorant Structure: Pleasantness as a Reflection of the Physical World

Science.gov (United States)

2009-11-01

34 ( Engen , 1982). We next reduced the dimensionality of physico-chemical properties, and identified a primary axis of physico-chemical space. This axis...Berglund B, Berglund U, Engen T, Ekman G (1973) Multidimensional Analysis of 21 Odors. Scandinavian Journal of Psychology 14:131-137. Brennan PA...1984) Hedonics of odors and odor descriptors. J AIR POLLUT CONTROL ASSOC 34:752-776. Engen T (1982) The perception of odors. New York: Academic

Recovery of Agricultural Odors and Odorous Compounds from Polyvinyl Fluoride Film Bags

Science.gov (United States)

Parker, David B.; Perschbacher-Buser, Zena L.; Cole, N. Andy; Koziel, Jacek A.

2010-01-01

Accurate sampling methods are necessary when quantifying odor and volatile organic compound emissions at agricultural facilities. The commonly accepted methodology in the U.S. has been to collect odor samples in polyvinyl fluoride bags (PVF, brand name Tedlar®) and, subsequently, analyze with human panelists using dynamic triangular forced-choice olfactometry. The purpose of this research was to simultaneously quantify and compare recoveries of odor and odorous compounds from both commercial and homemade PVF sampling bags. A standard gas mixture consisting of p-cresol (40 μg m−3) and seven volatile fatty acids: acetic (2,311 μg m−3), propionic (15,800 μg m−3), isobutyric (1,686 μg m−3), butyric (1,049 μg m−3), isovaleric (1,236 μg m−3), valeric (643 μg m−3), and hexanoic (2,158 μg m−3) was placed in the PVF bags at times of 1 h, 1 d, 2 d, 3 d, and 7 d prior to compound and odor concentration analyses. Compound concentrations were quantified using sorbent tubes and gas chromatography/mass spectrometry. Odor concentration, intensity, and hedonic tone were measured using a panel of trained human subjects. Compound recoveries ranged from 2 to 40% after 1 h and 0 to 14% after 7 d. Between 1 h and 7 d, odor concentrations increased by 45% in commercial bags, and decreased by 39% in homemade bags. Minimal changes were observed in intensity and hedonic tone over the same time period. These results suggest that PVF bags can bias individual compound concentrations and odor as measured by dynamic triangular forced-choice olfactometry. PMID:22163671

The smell of age: perception and discrimination of body odors of different ages.

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Susanna Mitro

Full Text Available Our natural body odor goes through several stages of age-dependent changes in chemical composition as we grow older. Similar changes have been reported for several animal species and are thought to facilitate age discrimination of an individual based on body odors, alone. We sought to determine whether humans are able to discriminate between body odor of humans of different ages. Body odors were sampled from three distinct age groups: Young (20-30 years old, Middle-age (45-55, and Old-age (75-95 individuals. Perceptual ratings and age discrimination performance were assessed in 41 young participants. There were significant differences in ratings of both intensity and pleasantness, where body odors from the Old-age group were rated as less intense and less unpleasant than body odors originating from Young and Middle-age donors. Participants were able to discriminate between age categories, with body odor from Old-age donors mediating the effect also after removing variance explained by intensity differences. Similarly, participants were able to correctly assign age labels to body odors originating from Old-age donors but not to body odors originating from other age groups. This experiment suggests that, akin to other animals, humans are able to discriminate age based on body odor alone and that this effect is mediated mainly by body odors emitted by individuals of old age.

The smell of age: perception and discrimination of body odors of different ages.

Science.gov (United States)

Mitro, Susanna; Gordon, Amy R; Olsson, Mats J; Lundström, Johan N

2012-01-01

Our natural body odor goes through several stages of age-dependent changes in chemical composition as we grow older. Similar changes have been reported for several animal species and are thought to facilitate age discrimination of an individual based on body odors, alone. We sought to determine whether humans are able to discriminate between body odor of humans of different ages. Body odors were sampled from three distinct age groups: Young (20-30 years old), Middle-age (45-55), and Old-age (75-95) individuals. Perceptual ratings and age discrimination performance were assessed in 41 young participants. There were significant differences in ratings of both intensity and pleasantness, where body odors from the Old-age group were rated as less intense and less unpleasant than body odors originating from Young and Middle-age donors. Participants were able to discriminate between age categories, with body odor from Old-age donors mediating the effect also after removing variance explained by intensity differences. Similarly, participants were able to correctly assign age labels to body odors originating from Old-age donors but not to body odors originating from other age groups. This experiment suggests that, akin to other animals, humans are able to discriminate age based on body odor alone and that this effect is mediated mainly by body odors emitted by individuals of old age.

Taste and odor recognition memory: the emotional flavor of life.

Science.gov (United States)

Miranda, Maria Isabel

2012-01-01

In recent years, our knowledge of the neurobiology of taste and smell has greatly increased; by using several learning models, we now have a better understanding of the behavioral and neurochemical basis of memory recognition. Studies have provided new evidence of some processes that depend on prior experience with the specific combination of sensory stimuli. This review contains recent research related to taste and odor recognition memory, and the goal is to highlight the role of two prominent brain structures, the insular cortex and the amygdala. These structures have an important function during learning and memory and have been associated with the differences in learning induced by the diverse degrees of emotion during taste/odor memory formation, either aversive or appetitive or when taste and odor are combined and/or potentiated.Therefore, this review includes information about certain neurochemical transmitters and their interactions during appetitive or aversive taste memory formation,taste-potentiated odor aversion memory, and conditioned odor aversion, which might be able to maintain the complex processes necessary for flavor recognition memory.

Genetic influences on human body odor: from genes to the axillae.

Science.gov (United States)

Preti, George; Leyden, James J

2010-02-01

Several groups have identified the characteristic axillary odorants and how they arrive on the skin surface, pre-formed, bound to water-soluble odorless precursors in apocrine secretions. In the current issue, Martin et al., (2010) describe the relationship between the production of axillary odorants and variants in the ABCC11 gene. Individuals who are homozygotic for a SNP (538G>A) were found to have significantly less of the characteristic axillary odorants than either individuals who were heterozygotic for this change or those who had the wild-type gene. The 538G>A SNP predominates in Asians who have nearly complete loss of typical body odor. ABCC11 is expressed and localized in apocrine sweat glands. These findings are remarkably similar to the ethnic distribution and expression patterns for apocrine apoD, a previously identified carrier of a characteristic axillary odorant.

The SysteMHC Atlas project

DEFF Research Database (Denmark)

Shao, Wenguang; Pedrioli, Patrick G. A.; Wolski, Witold

2018-01-01

consisting of consensus spectra calculated from repeat measurements of the same peptide sequence, and links to other proteomics and immunology databases. The SysteMHC Atlas project was created and will be further expanded using a uniform and open computational pipeline that controls the quality of peptide......-scale generation of immunopeptidomic datasets and recent developments in MS-based peptide analysis technologies now support the generation of the required data. Importantly, the availability of diverse immunopeptidomic datasets has resulted in an increasing need to standardize, store and exchange this type of data...

Do Valenced Odors and Trait Body Odor Disgust Affect Evaluation of Emotion in Dynamic Faces?

Science.gov (United States)

Syrjänen, Elmeri; Liuzza, Marco Tullio; Fischer, Håkan; Olofsson, Jonas K

2017-12-01

Disgust is a core emotion evolved to detect and avoid the ingestion of poisonous food as well as the contact with pathogens and other harmful agents. Previous research has shown that multisensory presentation of olfactory and visual information may strengthen the processing of disgust-relevant information. However, it is not known whether these findings extend to dynamic facial stimuli that changes from neutral to emotionally expressive, or if individual differences in trait body odor disgust may influence the processing of disgust-related information. In this preregistered study, we tested whether a classification of dynamic facial expressions as happy or disgusted, and an emotional evaluation of these facial expressions, would be affected by individual differences in body odor disgust sensitivity, and by exposure to a sweat-like, negatively valenced odor (valeric acid), as compared with a soap-like, positively valenced odor (lilac essence) or a no-odor control. Using Bayesian hypothesis testing, we found evidence that odors do not affect recognition of emotion in dynamic faces even when body odor disgust sensitivity was used as moderator. However, an exploratory analysis suggested that an unpleasant odor context may cause faster RTs for faces, independent of their emotional expression. Our results further our understanding of the scope and limits of odor effects on facial perception affect and suggest further studies should focus on reproducibility, specifying experimental circumstances where odor effects on facial expressions may be present versus absent.

The Missing Link in Epstein-Barr Virus Immune Evasion: the BDLF3 Gene Induces Ubiquitination and Downregulation of Major Histocompatibility Complex Class I (MHC-I) and MHC-II.

Science.gov (United States)

Quinn, Laura L; Williams, Luke R; White, Claire; Forrest, Calum; Zuo, Jianmin; Rowe, Martin

2016-01-01

The ability of Epstein-Barr virus (EBV) to spread and persist in human populations relies on a balance between host immune responses and EBV immune evasion. CD8(+) cells specific for EBV late lytic cycle antigens show poor recognition of target cells compared to immediate early and early antigen-specific CD8(+) cells. This phenomenon is due in part to the early EBV protein BILF1, whose immunosuppressive activity increases with lytic cycle progression. However, published data suggest the existence of a hitherto unidentified immune evasion protein further enhancing protection against late EBV antigen-specific CD8(+) cells. We have now identified the late lytic BDLF3 gene as the missing link accounting for efficient evasion during the late lytic cycle. Interestingly, BDLF3 also contributes to evasion of CD4(+) cell responses to EBV. We report that BDLF3 downregulates expression of surface major histocompatibility complex (MHC) class I and class II molecules in the absence of any effect upon other surface molecules screened, including CD54 (ICAM-1) and CD71 (transferrin receptor). BDLF3 both enhanced internalization of surface MHC molecules and reduced the rate of their appearance at the cell surface. The reduced expression of surface MHC molecules correlated with functional protection against CD8(+) and CD4(+) T cell recognition. The molecular mechanism was identified as BDLF3-induced ubiquitination of MHC molecules and their subsequent downregulation in a proteasome-dependent manner. Immune evasion is a necessary feature of viruses that establish lifelong persistent infections in the face of strong immune responses. EBV is an important human pathogen whose immune evasion mechanisms are only partly understood. Of the EBV immune evasion mechanisms identified to date, none could explain why CD8(+) T cell responses to late lytic cycle genes are so infrequent and, when present, recognize lytically infected target cells so poorly relative to CD8(+) T cells specific for

A new polymorphic and multicopy MHC gene family related to nonmammalian class I

Energy Technology Data Exchange (ETDEWEB)

Leelayuwat, C.; Degli-Esposti, M.A.; Abraham, L.J. [Univ. of Western Australia, Perth (Australia); Townend, D.C. [Sir Charles Gairdner Hospital, Perth (Australia); Dawkins, R.L. [Royal Perth Hospital, Perth (Australia)]|[Univ. of Western Australia, Perth (Australia)]|[Sir Charles Gairdner Hospital, Perth (Australia)

1994-12-31

The authors have used genomic analysis to characterize a region of the central major histocompatibility complex (MHC) spanning {approximately} 300 kilobases (kb) between TNF and HLA-B. This region has been suggested to carry genetic factors relevant to the development of autoimmune diseases such as myasthenia gravis (MG) and insulin dependent diabetes mellitus (IDDM). Genomic sequence was analyzed for coding potential, using two neural network programs, GRAIL and GeneParser. A genomic probe, JAB, containing putative coding sequences (PERB11) located 60 kb centromeric of HLA-B, was used for northern analysis of human tissues. Multiple transcripts were detected. Southern analysis of genomic DNA and overlapping YAC clones, covering the region from BAT1 to HLA-F, indicated that there are at least five copies of PERB11, four of which are located within this region of the MHC. The partial cDNA sequence of PERB11 was obtained from poly-A RNA derived from skeletal muscle. The putative amino acid sequence of PERB11 shares {approximately} 30% identity to MHC class I molecules from various species, including reptiles, chickens, and frogs, as well as to other MHC class I-like molecules, such as the IgG FcR of the mouse and rat and the human Zn-{alpha}2-glycoprotein. From direct comparison of amino acid sequences, it is concluded that PERB11 is a distinct molecule more closely related to nonmammalian than known mammalian MHC class I molecules. Genomic sequence analysis of PERB11 from five MHC ancestral haplotypes (AH) indicated that the gene is polymorphic at both DNA and protein level. The results suggest that the authors have identified a novel polymorphic gene family with multiple copies within the MHC. 48 refs., 10 figs., 2 tabs.

Cross-cultural color-odor associations.

Directory of Open Access Journals (Sweden)

Carmel A Levitan

Full Text Available Colors and odors are associated; for instance, people typically match the smell of strawberries to the color pink or red. These associations are forms of crossmodal correspondences. Recently, there has been discussion about the extent to which these correspondences arise for structural reasons (i.e., an inherent mapping between color and odor, statistical reasons (i.e., covariance in experience, and/or semantically-mediated reasons (i.e., stemming from language. The present study probed this question by testing color-odor correspondences in 6 different cultural groups (Dutch, Netherlands-residing-Chinese, German, Malay, Malaysian-Chinese, and US residents, using the same set of 14 odors and asking participants to make congruent and incongruent color choices for each odor. We found consistent patterns in color choices for each odor within each culture, showing that participants were making non-random color-odor matches. We used representational dissimilarity analysis to probe for variations in the patterns of color-odor associations across cultures; we found that US and German participants had the most similar patterns of associations, followed by German and Malay participants. The largest group differences were between Malay and Netherlands-resident Chinese participants and between Dutch and Malaysian-Chinese participants. We conclude that culture plays a role in color-odor crossmodal associations, which likely arise, at least in part, through experience.

Cross-Cultural Color-Odor Associations

Science.gov (United States)

Levitan, Carmel A.; Ren, Jiana; Woods, Andy T.; Boesveldt, Sanne; Chan, Jason S.; McKenzie, Kirsten J.; Dodson, Michael; Levin, Jai A.; Leong, Christine X. R.; van den Bosch, Jasper J. F.

2014-01-01

Colors and odors are associated; for instance, people typically match the smell of strawberries to the color pink or red. These associations are forms of crossmodal correspondences. Recently, there has been discussion about the extent to which these correspondences arise for structural reasons (i.e., an inherent mapping between color and odor), statistical reasons (i.e., covariance in experience), and/or semantically-mediated reasons (i.e., stemming from language). The present study probed this question by testing color-odor correspondences in 6 different cultural groups (Dutch, Netherlands-residing-Chinese, German, Malay, Malaysian-Chinese, and US residents), using the same set of 14 odors and asking participants to make congruent and incongruent color choices for each odor. We found consistent patterns in color choices for each odor within each culture, showing that participants were making non-random color-odor matches. We used representational dissimilarity analysis to probe for variations in the patterns of color-odor associations across cultures; we found that US and German participants had the most similar patterns of associations, followed by German and Malay participants. The largest group differences were between Malay and Netherlands-resident Chinese participants and between Dutch and Malaysian-Chinese participants. We conclude that culture plays a role in color-odor crossmodal associations, which likely arise, at least in part, through experience. PMID:25007343

Predicting the response of olfactory sensory neurons to odor mixtures from single odor response

OpenAIRE

Marasco, Addolorata; De Paris, Alessandro; Migliore, Michele

2016-01-01

The response of olfactory receptor neurons to odor mixtures is not well understood. Here, using experimental constraints, we investigate the mathematical structure of the odor response space and its consequences. The analysis suggests that the odor response space is 3-dimensional, and predicts that the dose-response curve of an odor receptor can be obtained, in most cases, from three primary components with specific properties. This opens the way to an objective procedure to obtain specific o...

Investigation of indoor chemical pollutants and perceived odor in an area with complaints of unpleasant odors

Energy Technology Data Exchange (ETDEWEB)

Peng, Chiung-Yu.; Wu, Tzong-Jer [Graduate Institute of Occupational Safety and Health, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, Kaohsiung 807 (China); Lan, Cheng-Hang [Department of Occupational Safety and Health, Chung-Hwa University of Medical Technology, Tai-Nan County 717 (China)

2009-10-15

An uncomfortable smell was reported by employees of an IT office (information technological office) in a medical center. This problem started two years ago when the office was refurbished. The objectives of this study are to characterize the indoor air quality of this complaint area in terms of chemical pollutants and odor characteristics, and identify possible sources of this foul smell. Carbonyl chemicals and volatile organic compounds (VOCs) were investigated in this study, since these two groups are associated with odors and health effects. Additionally, the odor was evaluated by odor assessors (non-smokers) who recorded odor characters that appeared in offices. By comparing chemical measurements between complaint and non-complaint areas, calculating odor indices, and correlating odor and chemical measurements, we got results showing that a higher correlation coefficient is found between odor presence frequencies and VOC concentrations. Further investigating found nonanal and decanal are possible chemicals for malodors. The concentration levels of these two chemicals in the complaint area are higher than those in the non-complaint areas and exceeding odor thresholds. Possible sources of these long-chain aldehydes are formed during the oxidation degradations of fatty acids like linoleic acid, linolenic acid and oleic acid which are ingredients for many building products like linoleum and surface coating. In order to mitigate this malodor problem, extra and effective ventilation flow rate should be provided to reduce the concentrations of odorous chemicals and the precursors for these odorous chemicals. (author)

Behavioral responses to mammalian blood odor and a blood odor component in four species of large carnivores.

Directory of Open Access Journals (Sweden)

Sara Nilsson

Full Text Available Only little is known about whether single volatile compounds are as efficient in eliciting behavioral responses in animals as the whole complex mixture of a behaviorally relevant odor. Recent studies analysing the composition of volatiles in mammalian blood, an important prey-associated odor stimulus for predators, found the odorant trans-4,5-epoxy-(E-2-decenal to evoke a typical "metallic, blood-like" odor quality in humans. We therefore assessed the behavior of captive Asian wild dogs (Cuon alpinus, African wild dogs (Lycaon pictus, South American bush dogs (Speothos venaticus, and Siberian tigers (Panthera tigris altaica when presented with wooden logs that were impregnated either with mammalian blood or with the blood odor component trans-4,5-epoxy-(E-2-decenal, and compared it to their behavior towards a fruity odor (iso-pentyl acetate and a near-odorless solvent (diethyl phthalate as control. We found that all four species displayed significantly more interactions with the odorized wooden logs such as sniffing, licking, biting, pawing, and toying, when they were impregnated with the two prey-associated odors compared to the two non-prey-associated odors. Most importantly, no significant differences were found in the number of interactions with the wooden logs impregnated with mammalian blood and the blood odor component in any of the four species. Only one of the four species, the South American bush dogs, displayed a significant decrease in the number of interactions with the odorized logs across the five sessions performed per odor stimulus. Taken together, the results demonstrate that a single blood odor component can be as efficient in eliciting behavioral responses in large carnivores as the odor of real blood, suggesting that trans-4,5-epoxy-(E-2-decenal may be perceived by predators as a "character impact compound" of mammalian blood odor. Further, the results suggest that odorized wooden logs are a suitable manner of environmental

IMGT unique numbering for MHC groove G-DOMAIN and MHC superfamily (MhcSF) G-LIKE-DOMAIN

DEFF Research Database (Denmark)

Lefranc, Marie-Paule; Duprat, E.; Kaas, Quentin

2005-01-01

IMGT, the international ImMunoGeneTics information system® (http://imgt.cines.fr) provides a common access to expertly annotated data on the genome, proteome, genetics and structure of immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC), and related proteins...

Odor and odorous chemical emissions from animal buildings: part 1 - project overview, collection methods, and quality control

Science.gov (United States)

Livestock facilities have historically generated public concerns due to their emissions of odorous air and various chemical pollutants. Odor emission factors and identification of principal odorous chemicals are needed to better understand the problem. Applications of odor emission factors include i...

A broad diversity of volatile carboxylic acids, released by a bacterial aminoacylase from axilla secretions, as candidate molecules for the determination of human-body odor type.

Science.gov (United States)

Natsch, Andreas; Derrer, Samuel; Flachsmann, Felix; Schmid, Joachim

2006-01-01

Human body odor is to a large part determined by secretions of glands in the axillary regions. Two key odoriferous principles, 3-methylhex-2-enoic acid (3MH2; 4/5) and 3-hydroxy-3-methylhexanoic acid (HMHA; 6) have been shown to be released from glutamine conjugates secreted in the axilla by a specific N(alpha)-acyl-glutamine aminoacylase (N-AGA) obtained from axilla isolates of Corynebacteria sp. However, the low number of different odorants reported in humans stands in contrast to the observed high inter-individual variability in body odors. Axilla secretions of individual donors were, therefore, analyzed in detail. The secretions were treated with N-AGA, analyzed by GC/MS, and compared to undigested controls. Over 28 different carboxylic acids were released by this enzyme from odorless axilla secretions (Table 1). Many of these body odorants have not been reported before from a natural source, and they include several aliphatic 3-hydroxy acids with 4-Me branches, 3,4-unsaturated, 4-Et-branched aliphatic acids, and a variety of degradation products of amino acids. The odor threshold of some of the acids was found to be in the range of 1 ng. Most of these compounds were present in all donors tested, but in highly variable relative amounts, and they are, thus, candidate molecules as key components of a 'compound odor' determining the individual types of human body odor.

Altered olfactory processing of stress-related body odors and artificial odors in patients with panic disorder.

Science.gov (United States)

Wintermann, Gloria-Beatrice; Donix, Markus; Joraschky, Peter; Gerber, Johannes; Petrowski, Katja

2013-01-01

Patients with Panic Disorder (PD) direct their attention towards potential threat, followed by panic attacks, and increased sweat production. Onés own anxiety sweat odor influences the attentional focus, and discrimination of threat or non-threat. Since olfactory projection areas overlap with neuronal areas of a panic-specific fear network, the present study investigated the neuronal processing of odors in general and of stress-related sweat odors in particular in patients with PD. A sample of 13 patients with PD with/ without agoraphobia and 13 age- and gender-matched healthy controls underwent an fMRI investigation during olfactory stimulation with their stress-related sweat odors (TSST, ergometry) as well as artificial odors (peach, artificial sweat) as non-fearful non-body odors. The two groups did not differ with respect to their olfactory identification ability. Independent of the kind of odor, the patients with PD showed activations in fronto-cortical areas in contrast to the healthy controls who showed activations in olfaction-related areas such as the amygdalae and the hippocampus. For artificial odors, the patients with PD showed a decreased neuronal activation of the thalamus, the posterior cingulate cortex and the anterior cingulate cortex. Under the presentation of sweat odor caused by ergometric exercise, the patients with PD showed an increased activation in the superior temporal gyrus, the supramarginal gyrus, and the cingulate cortex which was positively correlated with the severity of the psychopathology. For the sweat odor from the anxiety condition, the patients with PD showed an increased activation in the gyrus frontalis inferior, which was positively correlated with the severity of the psychopathology. The results suggest altered neuronal processing of olfactory stimuli in PD. Both artificial odors and stress-related body odors activate specific parts of a fear-network which is associated with an increased severity of the psychopathology.

Altered olfactory processing of stress-related body odors and artificial odors in patients with panic disorder.

Directory of Open Access Journals (Sweden)

Gloria-Beatrice Wintermann

Full Text Available Patients with Panic Disorder (PD direct their attention towards potential threat, followed by panic attacks, and increased sweat production. Onés own anxiety sweat odor influences the attentional focus, and discrimination of threat or non-threat. Since olfactory projection areas overlap with neuronal areas of a panic-specific fear network, the present study investigated the neuronal processing of odors in general and of stress-related sweat odors in particular in patients with PD.A sample of 13 patients with PD with/ without agoraphobia and 13 age- and gender-matched healthy controls underwent an fMRI investigation during olfactory stimulation with their stress-related sweat odors (TSST, ergometry as well as artificial odors (peach, artificial sweat as non-fearful non-body odors.The two groups did not differ with respect to their olfactory identification ability. Independent of the kind of odor, the patients with PD showed activations in fronto-cortical areas in contrast to the healthy controls who showed activations in olfaction-related areas such as the amygdalae and the hippocampus. For artificial odors, the patients with PD showed a decreased neuronal activation of the thalamus, the posterior cingulate cortex and the anterior cingulate cortex. Under the presentation of sweat odor caused by ergometric exercise, the patients with PD showed an increased activation in the superior temporal gyrus, the supramarginal gyrus, and the cingulate cortex which was positively correlated with the severity of the psychopathology. For the sweat odor from the anxiety condition, the patients with PD showed an increased activation in the gyrus frontalis inferior, which was positively correlated with the severity of the psychopathology.The results suggest altered neuronal processing of olfactory stimuli in PD. Both artificial odors and stress-related body odors activate specific parts of a fear-network which is associated with an increased severity of the

The differential mice response to cat and snake odor.

Science.gov (United States)

de Oliveira Crisanto, Karen; de Andrade, Wylqui Mikael Gomes; de Azevedo Silva, Kayo Diogenes; Lima, Ramón Hypolito; de Oliveira Costa, Miriam Stela Maris; de Souza Cavalcante, Jeferson; de Lima, Ruthnaldo Rodrigues Melo; do Nascimento, Expedito Silva; Cavalcante, Judney Cley

2015-12-01

Studies from the last two decades have pointed to multiple mechanisms of fear. For responding to predators, there is a group of highly interconnected hypothalamic nuclei formed by the anterior hypothalamic nucleus, the ventromedial hypothalamic nucleus and the dorsal premammillary nucleus—the predator-responsive hypothalamic circuit. This circuit expresses Fos in response to predator presence or its odor. Lesion of any component of this system blocks or reduces the expression of fear and consequently defensive behavior when faced with a predator or its cue. However, most of the knowledge about that circuit has been obtained using the rat as a model of prey and the cat as a source of predator cues. In the present study, we exposed mice to strong cat or snake odors, two known mice predators, and then we used the rat exposure test (RET) to study their behavior when confronted with the same predator's odor. Our data point to a differential response of mice exposed to these odors. When Swiss mice were exposed to the cat odor, they show defensive behavior and the predator-responsive hypothalamic circuit expressed Fos. The opposite was seen when they faced snake's odor. The acute odor exposure was not sufficient to activate the mouse predator-responsive hypothalamic circuit and the mice acted like they were not in a stressful situation, showing almost no sign of fear or defensive posture. This leads us to the conclusion that not all the predator cues are sufficient to activate the predator-responsive hypothalamic circuit of mice and that their response depends on the danger that these predators represent in the natural history of the prey.

Mechanical Stress Downregulates MHC Class I Expression on Human Cancer Cell Membrane

KAUST Repository

La Rocca, Rosanna; Tallerico, Rossana; Talib Hassan, Almosawy; Das, Gobind; Tadepally, Lakshmikanth; Matteucci, Marco; Liberale, Carlo; Mesuraca, Maria; Scumaci, Domenica; Gentile, Francesco; Cojoc, Gheorghe; Perozziello, Gerardo; Ammendolia, Antonio; Gallo, Adriana; Kä rre, Klas; Cuda, Giovanni; Candeloro, Patrizio; Di Fabrizio, Enzo M.; Carbone, Ennio

2014-01-01

bar (1 bar = 100.000 Pascal), depending on the devices used. Moreover, Raman spectroscopy analysis, after mechanical treatment, in the range between 700–1800 cm−1, indicated a relative concentration variation of MHC class I. PCA analysis was also

Seeing odors in color: Cross-modal associations in children and adults from two cultural environments.

Science.gov (United States)

Goubet, Nathalie; Durand, Karine; Schaal, Benoist; McCall, Daniel D

2018-02-01

We investigated the occurrence and underlying processes of odor-color associations in French and American 6- to 10-year-old children (n = 386) and adults (n = 137). Nine odorants were chosen according to their familiarity to either cultural group. Participants matched each odor with a color, gave hedonic and familiarity judgments, and identified each odor. By 6 years of age, children displayed culture-specific odor-color associations, but age differences were noted in the type of associations. Children and adults in both cultural groups shared common associations and formed associations that were unique to their environment, underscoring the importance of exposure learning in odor-color associations. Copyright © 2017 Elsevier Inc. All rights reserved.

Prediction of antigenic epitopes and MHC binders of neurotoxin ...

African Journals Online (AJOL)

PRECIOUS

2009-12-01

Dec 1, 2009 ... scorpion chlorotoxin-like short-chain neurotoxins (SCNs). *Corresponding ... Protein sequence analysis. Here we ... MHC/peptide binding is a log-transformed value related to the IC50 values in nM ..... porter. Adducts of MHC and peptide complexes are the ligands for T cell receptors (TCR) (Table-1). MHC.

MHCcluster, a method for functional clustering of MHC molecules

DEFF Research Database (Denmark)

Thomsen, Martin Christen Frølund; Lundegaard, Claus; Buus, Søren

2013-01-01

The identification of peptides binding to major histocompatibility complexes (MHC) is a critical step in the understanding of T cell immune responses. The human MHC genomic region (HLA) is extremely polymorphic comprising several thousand alleles, many encoding a distinct molecule. The potentially...... binding specificity. The method has a flexible web interface that allows the user to include any MHC of interest in the analysis. The output consists of a static heat map and graphical tree-based visualizations of the functional relationship between MHC variants and a dynamic TreeViewer interface where...

Identification of agonists for a group of human odorant receptors

Directory of Open Access Journals (Sweden)

Daniela eGonzalez-Kristeller

2015-03-01

Full Text Available Olfaction plays a critical role in several aspects of the human life. Odorants are detected by hundreds of odorant receptors (ORs which belong to the superfamily of G protein-coupled receptors. These receptors are expressed in the olfactory sensory neurons of the nose. The information provided by the activation of different combinations of ORs in the nose is transmitted to the brain, leading to odorant perception and emotional and behavioral responses. There are ~400 intact human ORs, and to date only a small percentage of these receptors (~10% have known agonists. The determination of the specificity of the human ORs will contribute to a better understanding of how odorants are discriminated by the olfactory system. In this work, we aimed to identify human specific ORs, that is, ORs that are present in humans but absent from other species, and their corresponding agonists. To do this, we first selected 22 OR gene sequences from the human genome with no counterparts in the mouse, rat or dog genomes. Then we used a heterologous expression system to screen a subset of these human ORs against a panel of odorants of biological relevance, including foodborne aroma volatiles. We found that different types of odorants are able to activate some of these previously uncharacterized human ORs.

Red junglefowl have individual body odors.

Science.gov (United States)

Karlsson, Anna-Carin; Jensen, Per; Elgland, Mathias; Laur, Katriann; Fyrner, Timmy; Konradsson, Peter; Laska, Matthias

2010-05-01

Olfaction may play an important role in regulating bird behavior, and has been suggested to be involved in feather-pecking. We investigated possible differences in the body odors of red junglefowl females by using an automated olfactometer which assessed the ability of trained mice to discriminate between the odors of uropygial gland secretions (the main carrier of potential individual odors in chickens) of six feather-pecked and six non-pecked birds. All mice were clearly able to discriminate between all individual red junglefowl odors, showing that each bird has an individual body odor. We analyzed whether it was more difficult to discriminate between the odors of two feather-pecked, or two non-pecked birds, than it was to discriminate between the odors of two randomly selected birds. This was not the case, suggesting that feather-pecked birds did not share a common odor signature. Analyses using gas chromatography and mass spectrometry showed that the composition of aliphatic carboxylic acids in uropygial gland secretions differed consistently between individuals. However, chemical composition did not vary according to feather-pecking status. We conclude that red junglefowl have individual body odors which appear to be largely based on differences in the relative abundance of aliphatic carboxylic acids, but there is no evidence of systematic differences between the body odors of pecked and non-pecked birds.

Ontogeny of Odor-LiCl vs. Odor-Shock Learning: Similar Behaviors but Divergent Ages of Functional Amygdala Emergence

Science.gov (United States)

Raineki, Charlis; Shionoya, Kiseko; Sander, Kristin; Sullivan, Regina M.

2009-01-01

Both odor-preference and odor-aversion learning occur in perinatal pups before the maturation of brain structures that support this learning in adults. To characterize the development of odor learning, we compared three learning paradigms: (1) odor-LiCl (0.3M; 1% body weight, ip) and (2) odor-1.2-mA shock (hindlimb, 1sec)--both of which…

Simulation of Major Histocompatibility Complex (MHC Structure and Peptide Loading into an MHC Binding Pocket with Teachers’Hands

Directory of Open Access Journals (Sweden)

Mojtaba Sankian

2013-10-01

Full Text Available Molecular understanding of three-dimensional (3D peptide: MHC models require both basic knowledge of computational modeling and skilled visual perception, which are not possessed by all students. The present model aims to simulate MHC molecular structure with the hands and make a profound impression on the students.

NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8-11.

Science.gov (United States)

Lundegaard, Claus; Lamberth, Kasper; Harndahl, Mikkel; Buus, Søren; Lund, Ole; Nielsen, Morten

2008-07-01

NetMHC-3.0 is trained on a large number of quantitative peptide data using both affinity data from the Immune Epitope Database and Analysis Resource (IEDB) and elution data from SYFPEITHI. The method generates high-accuracy predictions of major histocompatibility complex (MHC): peptide binding. The predictions are based on artificial neural networks trained on data from 55 MHC alleles (43 Human and 12 non-human), and position-specific scoring matrices (PSSMs) for additional 67 HLA alleles. As only the MHC class I prediction server is available, predictions are possible for peptides of length 8-11 for all 122 alleles. artificial neural network predictions are given as actual IC(50) values whereas PSSM predictions are given as a log-odds likelihood scores. The output is optionally available as download for easy post-processing. The training method underlying the server is the best available, and has been used to predict possible MHC-binding peptides in a series of pathogen viral proteomes including SARS, Influenza and HIV, resulting in an average of 75-80% confirmed MHC binders. Here, the performance is further validated and benchmarked using a large set of newly published affinity data, non-redundant to the training set. The server is free of use and available at: http://www.cbs.dtu.dk/services/NetMHC.

Complex Mhc-based mate choice in a wild passerine

Science.gov (United States)

Bonneaud, Camille; Chastel, Olivier; Federici, Pierre; Westerdahl, Helena; Sorci, Gabriele

2006-01-01

The extreme polymorphism of the vertebrate major histocompatibility complex (Mhc) is famous for protecting hosts against constantly evolving pathogens. Mate choice is often evoked as a means of maintaining Mhc variability through avoidance of partners with similar Mhc alleles or preference for heterozygotes. Evidence for these two hypotheses mostly comes from studies on humans and laboratory mice. Here, we tested these hypotheses in a wild outbred population of house sparrows (Passer domesticus). Females were not more or less closely related to the males they paired with when considering neutral genetic variation. However, males failed to form breeding pairs when they had too few Mhc alleles and when they were too dissimilar from females at Mhc loci (i.e. had no common alleles). Furthermore, pairs did not form at random as Mhc diversity positively correlated in mating pairs. These results suggest that mate choice evolves in response to (i) benefits in terms of parasite resistance acquired from allelic diversity, and (ii) costs associated with the disruption of co-adapted genes. PMID:16600889

Central insulin administration improves odor-cued reactivation of spatial memory in young men.

Science.gov (United States)

Brünner, Yvonne F; Kofoet, Anja; Benedict, Christian; Freiherr, Jessica

2015-01-01

Insulin receptors are ubiquitously found in the human brain, comprising the olfactory bulb, essential for odor processing, and the hippocampus, important for spatial memory processing. The present study aimed at examining if intranasal insulin, which is known to transiently increase brain insulin levels in humans, would improve odor-cued reactivation of spatial memory in young men. We applied a double-blind, placebo-controlled, counterbalanced within-subject design. The study was conducted at the research unit of a university hospital. Interventions/Participants/Main Outcome Measures: Following intranasal administration of either insulin (40 I.U.) or placebo, male subjects (n = 18) were exposed to eight odors. During each odor exposure, a green-colored field was presented on a 17-in. computer screen. During immediate recall (comprising 3 runs), the participants were re-exposed to each odor cue, and were asked to select the corresponding field (with visual feedback after each response). The delayed recall was scheduled ∼10 min later (without feedback). To test if insulin's putative effect on odor-place memory would be domain-specific, participants also performed a separate place and odor recognition task. Intranasal insulin improved the delayed but not immediate odor-cued recall of spatial memory. This effect was independent of odor type and in the absence of systemic side effects (eg, fasting plasma glucose levels remained unaltered). Place and odor recognition were unaffected by the insulin treatment. These findings suggest that acute intranasal insulin improves odor-cued reactivation of spatial memory in young men.

High levels of diversity characterize mandrill (Mandrillus sphinx) Mhc-DRB sequences.

Science.gov (United States)

Abbott, Kristin M; Wickings, E Jean; Knapp, Leslie A

2006-08-01

The major histocompatibility complex (MHC) is highly polymorphic in most primate species studied thus far. The rhesus macaque (Macaca mulatta) has been studied extensively and the Mhc-DRB region demonstrates variability similar to humans. The extent of MHC diversity is relatively unknown for other Old World monkeys (OWM), especially among genera other than Macaca. A molecular survey of the Mhc-DRB region in mandrills (Mandrillus sphinx) revealed extensive variability, suggesting that other OWMs may also possess high levels of Mhc-DRB polymorphism. In the present study, 33 Mhc-DRB loci were identified from only 13 animals. Eleven were wild-born and presumed to be unrelated and two were captive-born twins. Two to seven different sequences were identified for each individual, suggesting that some mandrills may have as many as four Mhc-DRB loci on a single haplotype. From these sequences, representatives of at least six Mhc-DRB loci or lineages were identified. As observed in other primates, some new lineages may have arisen through the process of gene conversion. These findings indicate that mandrills have Mhc-DRB diversity not unlike rhesus macaques and humans.

MHC Class II and CD9 in Human Eosinophils Localize to Detergent-Resistant Membrane Microdomains

Science.gov (United States)

Akuthota, Praveen; Melo, Rossana C. N.; Spencer, Lisa A.

2012-01-01

Eosinophils function in murine allergic airways inflammation as professional antigen-presenting cells (APCs). In murine professional APC cell types, optimal functioning of MHC Class II depends on its lateral association in plasma membranes and colocalization with the tetraspanin CD9 into detergent-resistant membrane microdomains (DRMs). With human eosinophils, we evaluated the localization of MHC Class II (HLA-DR) to DRMs and the functional significance of such localization. In granulocyte-macrophage colony-stimulating factor–stimulated human eosinophils, antibody cross-linked HLA-DR colocalized by immunofluorescence microscopy focally on plasma membranes with CD9 and the DRM marker ganglioside GM1. In addition, HLA-DR coimmunoprecipitates with CD9 after chemical cross-linking of CD9. HLA-DR and CD9 were localized by Western blotting in eosinophil DRM subcellular fractions. DRM disruption with the cholesterol-depleting agent methyl-β-cyclodextrin decreased eosinophil surface expression of HLA-DR and CD9. We show that CD9 is abundant on the surface of eosinophils, presenting the first electron microscopy data of the ultrastructural immunolocalization of CD9 in human eosinophils. Disruption of HLA-DR–containing DRMs decreased the ability of superantigen-loaded human eosinophils to stimulate CD4+ T-cell activation (CD69 expression), proliferation, and cytokine production. Our results, which demonstrate that eosinophil MHC Class II localizes to DRMs in association with CD9 in a functionally significant manner, represent a novel insight into the organization of the antigen presentation complex of human eosinophils. PMID:21885678

MHC Class II and CD9 in human eosinophils localize to detergent-resistant membrane microdomains.

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Akuthota, Praveen; Melo, Rossana C N; Spencer, Lisa A; Weller, Peter F

2012-02-01

Eosinophils function in murine allergic airways inflammation as professional antigen-presenting cells (APCs). In murine professional APC cell types, optimal functioning of MHC Class II depends on its lateral association in plasma membranes and colocalization with the tetraspanin CD9 into detergent-resistant membrane microdomains (DRMs). With human eosinophils, we evaluated the localization of MHC Class II (HLA-DR) to DRMs and the functional significance of such localization. In granulocyte-macrophage colony-stimulating factor-stimulated human eosinophils, antibody cross-linked HLA-DR colocalized by immunofluorescence microscopy focally on plasma membranes with CD9 and the DRM marker ganglioside GM1. In addition, HLA-DR coimmunoprecipitates with CD9 after chemical cross-linking of CD9. HLA-DR and CD9 were localized by Western blotting in eosinophil DRM subcellular fractions. DRM disruption with the cholesterol-depleting agent methyl-β-cyclodextrin decreased eosinophil surface expression of HLA-DR and CD9. We show that CD9 is abundant on the surface of eosinophils, presenting the first electron microscopy data of the ultrastructural immunolocalization of CD9 in human eosinophils. Disruption of HLA-DR-containing DRMs decreased the ability of superantigen-loaded human eosinophils to stimulate CD4(+) T-cell activation (CD69 expression), proliferation, and cytokine production. Our results, which demonstrate that eosinophil MHC Class II localizes to DRMs in association with CD9 in a functionally significant manner, represent a novel insight into the organization of the antigen presentation complex of human eosinophils.

Meta-genome-wide association studies identify a locus on chromosome 1 and multiple variants in the MHC region for serum C-peptide in type 1 diabetes.

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Roshandel, Delnaz; Gubitosi-Klug, Rose; Bull, Shelley B; Canty, Angelo J; Pezzolesi, Marcus G; King, George L; Keenan, Hillary A; Snell-Bergeon, Janet K; Maahs, David M; Klein, Ronald; Klein, Barbara E K; Orchard, Trevor J; Costacou, Tina; Weedon, Michael N; Oram, Richard A; Paterson, Andrew D

2018-05-01

The aim of this study was to identify genetic variants associated with beta cell function in type 1 diabetes, as measured by serum C-peptide levels, through meta-genome-wide association studies (meta-GWAS). We performed a meta-GWAS to combine the results from five studies in type 1 diabetes with cross-sectionally measured stimulated, fasting or random C-peptide levels, including 3479 European participants. The p values across studies were combined, taking into account sample size and direction of effect. We also performed separate meta-GWAS for stimulated (n = 1303), fasting (n = 2019) and random (n = 1497) C-peptide levels. In the meta-GWAS for stimulated/fasting/random C-peptide levels, a SNP on chromosome 1, rs559047 (Chr1:238753916, T>A, minor allele frequency [MAF] 0.24-0.26), was associated with C-peptide (p = 4.13 × 10 -8 ), meeting the genome-wide significance threshold (p C>T, MAF 0.07-0.10, p = 8.43 × 10 -8 ). In the stimulated C-peptide meta-GWAS, rs61211515 (Chr6:30100975, T/-, MAF 0.17-0.19) in the MHC region was associated with stimulated C-peptide (β [SE] = - 0.39 [0.07], p = 9.72 × 10 -8 ). rs61211515 was also associated with the rate of stimulated C-peptide decline over time in a subset of individuals (n = 258) with annual repeated measures for up to 6 years (p = 0.02). In the meta-GWAS of random C-peptide, another MHC region, SNP rs3135002 (Chr6:32668439, C>A, MAF 0.02-0.06), was associated with C-peptide (p = 3.49 × 10 -8 ). Conditional analyses suggested that the three identified variants in the MHC region were independent of each other. rs9260151 and rs3135002 have been associated with type 1 diabetes, whereas rs559047 and rs61211515 have not been associated with a risk of developing type 1 diabetes. We identified a locus on chromosome 1 and multiple variants in the MHC region, at least some of which were distinct from type 1 diabetes risk loci, that were associated with C

Unexpected plant odor responses in a moth pheromone system

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Angéla eRouyar

2015-05-01

Full Text Available Male moths rely on olfactory cues to find females for reproduction. Males also use volatile plant compounds (VPCs to find food sources and might use host-plant odor cues to identify the habitat of calling females. Both the sex pheromone released by conspecific females and VPCs trigger well-described oriented flight behavior towards the odor source. Whereas detection and central processing of pheromones and VPCs have been thought for a long time to be highly separated from each other, recent studies have shown that interactions of both types of odors occur already early at the periphery of the olfactory pathway. Here we show that detection and early processing of VPCs and pheromone can overlap between the two sub-systems. Using complementary approaches, i.e. single-sensillum recording of olfactory receptor neurons, in vivo calcium imaging in the antennal lobe, intracellular recordings of neurons in the macroglomerular complex (MGC and flight tracking in a wind tunnel, we show that some plant odorants alone, such as heptanal, activate the pheromone-specific pathway in male Agrotis ipsilon at peripheral and central levels. To our knowledge, this is the first report of a plant odorant with no chemical similarity to the molecular structure of the pheromone, acting as a partial agonist of a moth sex pheromone.

CD4+ T cell-mediated rejection of MHC class II-positive tumor cells is dependent on antigen secretion and indirect presentation on host APCs.

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Haabeth, Ole Audun Werner; Fauskanger, Marte; Manzke, Melanie; Lundin, Katrin U; Corthay, Alexandre; Bogen, Bjarne; Tveita, Anders Aune

2018-05-11

Tumor-specific CD4+ T cells have been shown to mediate efficient anti-tumor immune responses against cancer. Such responses can occur through direct binding to MHC class II (MHC II)-expressing tumor cells or indirectly via activation of professional antigen-presenting cells (APC) that take up and present the tumor antigen. We have previously shown that CD4+ T cells reactive against an epitope within the Ig light chain variable region of a murine B cell lymphoma can reject established tumors. Given the presence of MHC II molecules at the surface of lymphoma cells, we investigated whether MHC II-restricted antigen presentation on tumor cells alone was required for rejection. Variants of the A20 B lymphoma cell line that either secreted or intracellularly retained different versions of the tumor-specific antigen revealed that antigen secretion by the MHC II-expressing tumor cells was essential both for the priming and effector phase of CD4+ T cell-driven anti-tumor immune responses. Consistent with this, genetic ablation of MHC II in tumor cells, both in the case of B lymphoma and B16 melanoma, did not preclude rejection of tumors by tumor antigen-specific CD4+ T cells in vivo. These findings demonstrate that MHC class II expression on tumor cells themselves is not required for CD4+ T cell-mediated rejection, and that indirect display on host APC is sufficient for effective tumor elimination. These results support the importance of tumor-infiltrating APC as mediators of tumor cell killing by CD4+ T cells. Copyright ©2018, American Association for Cancer Research.

Identification and quantification of glue-like off-odors in elastic therapeutic tapes.

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Denk, Philipp; Buettner, Andrea

2018-05-01

Elastic therapeutic tapes are an important tool in the field of physical therapy and medicine. These tapes contain types of adhesive. However, sensory evaluations revealed the release of pronounced and irritating odors of the tapes. Negative odors were, amongst others, reported in elastic therapeutic tapes containing acrylic adhesives. In this study, the odor of four different tape samples was evaluated applying a descriptive analysis approach carried out by a trained sensory panel. Afterwards, the volatile compounds were recovered from the samples by solvent extraction and isolated by solvent-assisted flavor evaporation (SAFE). The obtained distillates were subsequently analyzed by gas chromatography-olfactometry (GC-O) and two-dimensional GC-O coupled with mass spectrometry (2D-GC-MS/O). To determine the most potent odorants in the distillates, odor extract dilution analyses (OEDA) were carried out. Thirty-one odorants were successfully identified using this approach, which were all described for the first time as odorants in tapes. Amongst the set of volatiles, unsaturated and saturated aldehydes were present, eliciting fatty, soapy, and citrus-like odor impressions, as well as a range of glue-like, moldy, and fruity smelling odor-active volatiles, such as 2-ethyl-1-hexanol, butyl benzoate, and 3-phenyltoluene. Based on their relative intensities, the concentrations of the glue-like smelling substances were determined: 2-ethyl-1-hexanol, present in all samples, was determined with concentrations ranging from 10 to 200 mg/kg in the investigated tapes.

Odor management in petroleum refining units; Gerenciamento de odores em refinaria de petroleo

Energy Technology Data Exchange (ETDEWEB)

Gutierres, Ricardo; Evangelho, Mauro Rocha; Moreira, Andrea Cristina de Castro Araujo [PETROBRAS, Rio de Janeiro, RJ (Brazil). Centro de Pesquisas (CENPES). P e D de Energia e Desenvolvimento Sustentavel (PDEDS)

2004-07-01

Odor emissions can cause serious annoyance in the neighbourhood of the emissions sources related to industrial processes and effluent and wastewater treatments. Jointly with the industrial control for reducing the odor, the emissions monitoring becomes convenient for identification and quantification of compounds responsible for the odors. To reach this objective, they are proposed analytical and olfactometric methodologies. The analytical procedures are based on the application of methods of sampling and analysis in gas chromatography-mass spectrometry, accepted for environmental agencies. The olfactometric methodology is based on the use of procedures that consider the subjective manner with that the odors are felt and evaluated by the people. This work describes as these methodologies can be applied in petroleum refining units. (author)

Optimization of the Odor Microclimate

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M. V. Jokl

2002-01-01

Full Text Available The odor microclimate is formed by gaseous airborne components perceived either as an unpleasant smell or as a pleasant smell. Smells enter the building interior partly from outdoors (exhaust fumes - flower fragrance and partly from indoors (building materials, smoking cigarettes - cosmetics, dishes. They affect the human organism through the olfactory center which is connected to the part of brain that is responsible for controlling people's emotions and sexual feelings: smells therefore participate to a high level in mood formation. Sweet smells have a positive impact on human feelings and on human performance. Criteria for odor microclimate appraisal are presented together with ways of improving the odor microclimate (by stopping odors from spreading within a building, ventilation, air filtration, odor removal by plants, deodorization, etc., including so-called AIR DESIGN.

Detection of new MHC mutations in mice by skin grafting, tumor transplantation and monoclonal antibodies: a comparison

International Nuclear Information System (INIS)

Egorov, I.K.; Egorov, O.S.

1988-01-01

Two mechanisms of major histocompatibility complex (MHC) mutations have been described in mice: gene conversion and homologous but unequal recombination. However, the knowledge of mutations in MHC is incomplete because studies have been limited almost exclusively to two haplotypes, H-2/sup b/ and H-2/sup d/, while hundreds of haplotypes exist in nature; it has been biased by the use of only one procedure of screening for mutation, skin grafting. The authors used three procedures to screen for MHC mutations: (1) conventional techniques of skin grafting, (2) syngeneic tumor transplantation and (3) typing with monoclonal anti-MHC antibodies (mAbs) and complement. The faster technique of tumor transplantation detected mutants similar to those discovered by skin grafting technique. Screening with mAbs allowed us to detect both mutants that are capable of rejecting standard skin grafts and those that are silent in skin grafting tests, and which therefore resulted in a higher apparent mutation frequency. Two mutants of the H-2/sup a/ haplotype were found that carry concomitant class I and class II antigenic alterations. Both MHC mutants silent in skin grafting tests and mutants carrying concomitant class I and class II alterations have never been studied before and are expected to reveal new mechanisms of generating MHC mutations. 1-Ethyl-1-nitrosourea (ENU) failed to induce de novo MHC mutations in our skin grafting series

ER stress affects processing of MHC class I-associated peptides

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Meloche Sylvain

2009-02-01

Full Text Available Abstract Background Viral infection and neoplastic transformation trigger endoplasmic reticulum (ER stress. Thus, a large proportion of the cells that must be recognized by the immune system are stressed cells. Cells respond to ER stress by launching the unfolded protein response (UPR. The UPR regulates the two key processes that control major histocompatibility complex class I (MHC I-peptide presentation: protein synthesis and degradation. We therefore asked whether and how the UPR impinges on MHC I-peptide presentation. Results We evaluated the impact of the UPR on global MHC I expression and on presentation of the H2Kb-associated SIINFEKL peptide. EL4 cells stably transfected with vectors coding hen egg lysozyme (HEL-SIINFEKL protein variants were stressed with palmitate or exposed to glucose deprivation. UPR decreased surface expression of MHC I but did not affect MHC I mRNA level nor the total amount of intracellular MHC I proteins. Impaired MHC I-peptide presentation was due mainly to reduced supply of peptides owing to an inhibition of overall protein synthesis. Consequently, generation of H2Kb-SIINFEKL complexes was curtailed during ER stress, illustrating how generation of MHC I peptide ligands is tightly coupled to ongoing protein synthesis. Notably, the UPR-induced decline of MHC I-peptide presentation was more severe when the protein source of peptides was localized in the cytosol than in the ER. This difference was not due to changes in the translation rates of the precursor proteins but to increased stability of the cytosolic protein during ER stress. Conclusion Our results demonstrate that ER stress impairs MHC I-peptide presentation, and that it differentially regulates expression of ER- vs. cytosol-derived peptides. Furthermore, this work illustrates how ER stress, a typical feature of infected and malignant cells, can impinge on cues for adaptive immune recognition.

Smell your way back to childhood: autobiographical odor memory.

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Willander, Johan; Larsson, Maria

2006-04-01

This study addressed age distributions and experiential qualities of autobiographical memories evoked by different sensory cues. Ninety-three older adults were presented with one of three cue types (word, picture, or odor) and were asked to relate any autobiographical event for the given cue. The main aims were to explore whether (1) the age distribution of olfactory-evoked memories differs from memories cued by words and pictures and (2) the experiential qualities of the evoked memories vary over the different cues. The results showed that autobiographical memories triggered by olfactory information were older than memories associated with verbal and visual information. Specifically, most odor-cued memories were located to the first decade of life (memories associated with verbal and visual cues peaked in early adulthood (11-20 years). Also, odor-evoked memories were associated with stronger feelings of being brought back in time and had been thought of less often than memories evoked by verbal and visual information. This pattern of findings suggests that odor-evoked memories may be different from other memory experiences.

Enhancement of retronasal odors by taste.

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Green, Barry G; Nachtigal, Danielle; Hammond, Samuel; Lim, Juyun

2012-01-01

Psychophysical studies of interactions between retronasal olfaction and taste have focused most often on the enhancement of tastes by odors, which has been attributed primarily to a response bias (i.e., halo dumping). Based upon preliminary evidence that retronasal odors could also be enhanced by taste, the present study measured both forms of enhancement using appropriate response categories. In the first experiment, subjects rated taste ("sweet," "sour," "salty," and "bitter") and odor ("other") intensity for aqueous samples of 3 tastants (sucrose, NaCl, and citric acid) and 3 odorants (vanillin, citral, and furaneol), both alone and in taste-odor mixtures. The results showed that sucrose, but not the other taste stimuli, significantly increased the perceived intensity of all 3 odors. Enhancement of tastes by odors was inconsistent and generally weaker than enhancement of odors by sucrose. A second experiment used a flavored beverage and a custard dessert to test whether the findings from the first experiment would hold for the perception of actual foods. Adding sucrose significantly enhanced the intensity of "cherry" and "vanilla" flavors, whereas adding vanillin did not significantly enhance the intensity of sweetness. It is proposed that enhancement of retronasal odors by a sweet stimulus results from an adaptive sensory mechanism that serves to increase the salience of the flavor of nutritive foods. © The Author 2011. Published by Oxford University Press. All rights reserved.

Expression and phylogenetic analyses reveal paralogous lineages of putatively classical and non-classical MHC-I genes in three sparrow species (Passer).

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Drews, Anna; Strandh, Maria; Råberg, Lars; Westerdahl, Helena

2017-06-26

The Major Histocompatibility Complex (MHC) plays a central role in immunity and has been given considerable attention by evolutionary ecologists due to its associations with fitness-related traits. Songbirds have unusually high numbers of MHC class I (MHC-I) genes, but it is not known whether all are expressed and equally important for immune function. Classical MHC-I genes are highly expressed, polymorphic and present peptides to T-cells whereas non-classical MHC-I genes have lower expression, are more monomorphic and do not present peptides to T-cells. To get a better understanding of the highly duplicated MHC genes in songbirds, we studied gene expression in a phylogenetic framework in three species of sparrows (house sparrow, tree sparrow and Spanish sparrow), using high-throughput sequencing. We hypothesize that sparrows could have classical and non-classical genes, as previously indicated though never tested using gene expression. The phylogenetic analyses reveal two distinct types of MHC-I alleles among the three sparrow species, one with high and one with low level of polymorphism, thus resembling classical and non-classical genes, respectively. All individuals had both types of alleles, but there was copy number variation both within and among the sparrow species. However, the number of highly polymorphic alleles that were expressed did not vary between species, suggesting that the structural genomic variation is counterbalanced by conserved gene expression. Overall, 50% of the MHC-I alleles were expressed in sparrows. Expression of the highly polymorphic alleles was very variable, whereas the alleles with low polymorphism had uniformly low expression. Interestingly, within an individual only one or two alleles from the polymorphic genes were highly expressed, indicating that only a single copy of these is highly expressed. Taken together, the phylogenetic reconstruction and the analyses of expression suggest that sparrows have both classical and non

Human skeletal muscle: transition between fast and slow fibre types.

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Neunhäuserer, Daniel; Zebedin, Michaela; Obermoser, Magdalena; Moser, Gerhard; Tauber, Mark; Niebauer, Josef; Resch, Herbert; Galler, Stefan

2011-05-01

Human skeletal muscles consist of different fibre types: slow fibres (slow twitch or type I) containing the myosin heavy chain isoform (MHC)-I and fast fibres (fast twitch or type II) containing MHC-IIa (type IIA) or MHC-IId (type IID). The following order of decreasing kinetics is known: type IID > type IIA > type I. This order is especially based on the kinetics of stretch activation, which is the most discriminative property among fibre types. In this study we tested if hybrid fibres containing both MHC-IIa and MHC-I (type C fibres) provide a transition in kinetics between fast (type IIA) and slow fibres (type I). Our data of stretch activation kinetics suggest that type C fibres, with different ratios of MHC-IIa and MHC-I, do not provide a continuous transition. Instead, a specialized group of slow fibres, which we called "transition fibres", seems to provide a transition. Apart of their kinetics of stretch activation, which is most close to that of type IIA, the transition fibres are characterized by large cross-sectional areas and low maximal tensions. The molecular cause for the mechanical properties of the transition fibres is unknown. It is possible that the transition fibres contain an unknown slow MHC isoform, which cannot be separated by biochemical methods. Alternatively, or in addition, isoforms of myofibrillar proteins, other than MHC, and posttranslational modifications of myofibrillar proteins could play a role regarding the characteristics of the transition fibres.

A hybrid approach for predicting promiscuous MHC class I restricted ...

Indian Academy of Sciences (India)

Prakash

2006-09-15

Sep 15, 2006 ... with existing MHC binder prediction methods for alleles studied by both ... in locating the promiscuous MHC binding regions from antigen sequence. ... Artificial neural network; MHC class I alleles; promiscuous binders; ... this problem by developing methods for prediction for ... In case equal number of.

Recovery of agricultural odors and odorous compounds from polyvinyl fluoride film bags

Science.gov (United States)

Accurate sampling methods are necessary when quantifying odor and volatile organic compound emissions at agricultural facilities. The commonly accepted methodology in the U.S. has been to collect odor samples in polyvinyl fluoride bags (PVF, brand name Tedlar®) and, subsequently, analyze with human ...

HPLC analysis of aldehydes in automobile exhaust gas: Comparison of exhaust odor and irritation in different types of gasoline and diesel engines

International Nuclear Information System (INIS)

Roy, Murari Mohon

2008-01-01

This study investigated high performance liquid chromatography (HPLC) to identify and measure aldehydes from automobile exhaust gas. Four aldehydes: formaldehyde (HCHO), acetaldehyde (CH 3 CHO), acrolein (H 2 C=CHCHO) and propionaldehyde (CH 3 CH 2 CHO) and one ketone, acetone (CH 3 ) 2 CO are separated. The other higher aldehydes in exhaust gas are very small and cannot be separated. A new method of gas sampling, hereafter called bag sampling in HPLC is introduced instead of the trapping gas sampling method. The superiority of the bag sampling method is its transient gas checking capability. In the second part of this study, HPLC results are applied to compare exhaust odor and irritation of exhaust gases in different types of gasoline and diesel engines. Exhaust odor, irritation and aldehydes are found worst in direct injection (DI) diesel engines and best in some good multi-point injection (MPI) gasoline and direct injection gasoline (DIG) engines. Indirect injection (IDI) diesel engines showed odor, irritation and aldehydes in between the levels of MPI gasoline, DIG and DI diesel engines

The participation of cortical amygdala in innate, odor-driven behavior

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Root, Cory M.; Denny, Christine A.; Hen, René; Axel, Richard

2014-01-01

Innate behaviors are observed in naïve animals without prior learning or experience, suggesting that the neural circuits that mediate these behaviors are genetically determined and stereotyped. The neural circuits that convey olfactory information from the sense organ to the cortical and subcortical olfactory centers have been anatomically defined1-3 but the specific pathways responsible for innate responses to volatile odors have not been identified. We have devised genetic strategies that demonstrate that a stereotyped neural circuit that transmits information from the olfactory bulb to cortical amygdala is necessary for innate aversive and appetitive behaviors. Moreover, we have employed the promoter of the activity-dependent gene, arc, to express the photosensitive ion channel, channelrhodopsin, in neurons of the cortical amygdala activated by odors that elicit innate behaviors. Optical activation of these neurons leads to appropriate behaviors that recapitulate the responses to innate odors. These data indicate that the cortical amygdala plays a critical role in the generation of innate odor-driven behaviors but do not preclude the participation of cortical amygdala in learned olfactory behaviors. PMID:25383519

A caspase-2-RFXANK interaction and its implication for MHC class II expression.

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Forsberg, Jeremy; Li, Xinge; Akpinar, Birce; Salvatori, Roger; Ott, Martin; Zhivotovsky, Boris; Olsson, Magnus

2018-01-23

Despite recent achievements implicating caspase-2 in tumor suppression, the enzyme stands out from the apoptotic caspase family as a factor whose function requires further clarification. To specify enzyme characteristics through the definition of interacting proteins in apoptotic or non-apoptotic settings, a yeast 2-hybrid (Y2H) screen was performed using the full-length protein as bait. The current report describes the analysis of a captured prey and putative novel caspase-2 interacting factor, the regulatory factor X-associated ankyrin-containing protein (RFXANK), previously associated with CIITA, the transactivator regulating cell-type specificity and inducibility of MHC class II gene expression. The interaction between caspase-2 and RFXANK was verified by co-immunoprecipitations using both exogenous and endogenous proteins, where the latter approach suggested that binding of the components occurs in the cytoplasm. Cellular co-localization was confirmed by transfection of fluorescently conjugated proteins. Enhanced caspase-2 processing in RFXANK-overexpressing HEK293T cells treated with chemotherapeutic agents further supported Y2H data. Yet, no distinct differences with respect to MHC class II expression were observed in plasma membranes of antigen-presenting cells derived from wild type and caspase-2 -/- mice. In contrast, increased levels of the total MHC class II protein was evident in protein lysates from caspase-2 RNAi-silenced leukemia cell lines and B-cells isolated from gene-targeted mice. Together, these data identify a novel caspase-2-interacting factor, RFXANK, and indicate a potential non-apoptotic role for the enzyme in the control of MHC class II gene regulation.

Circuit oscillations in odor perception and memory.

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Kay, Leslie M

2014-01-01

Olfactory system neural oscillations as seen in the local field potential have been studied for many decades. Recent research has shown that there is a functional role for the most studied gamma oscillations (40-100Hz in rats and mice, and 20Hz in insects), without which fine odor discrimination is poor. When these oscillations are increased artificially, fine discrimination is increased, and when rats learn difficult and highly overlapping odor discriminations, gamma is increased in power. Because of the depth of study on this oscillation, it is possible to point to specific changes in neural firing patterns as represented by the increase in gamma oscillation amplitude. However, we know far less about the mechanisms governing beta oscillations (15-30Hz in rats and mice), which are best associated with associative learning of responses to odor stimuli. These oscillations engage every part of the olfactory system that has so far been tested, plus the hippocampus, and the beta oscillation frequency band is the one that is most reliably coherent with other regions during odor processing. Respiratory oscillations overlapping with the theta frequency band (2-12Hz) are associated with odor sniffing and normal breathing in rats. They also show coupling in some circumstances between olfactory areas and rare coupling between the hippocampus and olfactory bulb. The latter occur in specific learning conditions in which coherence strength is negatively or positively correlated with performance, depending on the task. There is still much to learn about the role of neural oscillations in learning and memory, but techniques that have been brought to bear on gamma oscillations (current source density, computational modeling, slice physiology, behavioral studies) should deliver much needed knowledge of these events. © 2014 Elsevier B.V. All rights reserved.

Odors Bias Time Perception in Visual and Auditory Modalities.

Science.gov (United States)

Yue, Zhenzhu; Gao, Tianyu; Chen, Lihan; Wu, Jiashuang

2016-01-01

Previous studies have shown that emotional states alter our perception of time. However, attention, which is modulated by a number of factors, such as emotional events, also influences time perception. To exclude potential attentional effects associated with emotional events, various types of odors (inducing different levels of emotional arousal) were used to explore whether olfactory events modulated time perception differently in visual and auditory modalities. Participants were shown either a visual dot or heard a continuous tone for 1000 or 4000 ms while they were exposed to odors of jasmine, lavender, or garlic. Participants then reproduced the temporal durations of the preceding visual or auditory stimuli by pressing the spacebar twice. Their reproduced durations were compared to those in the control condition (without odor). The results showed that participants produced significantly longer time intervals in the lavender condition than in the jasmine or garlic conditions. The overall influence of odor on time perception was equivalent for both visual and auditory modalities. The analysis of the interaction effect showed that participants produced longer durations than the actual duration in the short interval condition, but they produced shorter durations in the long interval condition. The effect sizes were larger for the auditory modality than those for the visual modality. Moreover, by comparing performance across the initial and the final blocks of the experiment, we found odor adaptation effects were mainly manifested as longer reproductions for the short time interval later in the adaptation phase, and there was a larger effect size in the auditory modality. In summary, the present results indicate that odors imposed differential impacts on reproduced time durations, and they were constrained by different sensory modalities, valence of the emotional events, and target durations. Biases in time perception could be accounted for by a framework of

Predator odor avoidance as a rodent model of anxiety: learning-mediated consequences beyond the initial exposure.

Science.gov (United States)

Staples, Lauren G

2010-11-01

Prey animals such as rats display innate defensive responses when exposed to the odor of a predator, providing a valuable means of studying the neurobiology of anxiety. While the unconditioned behavioral and neural responses to a single predator odor exposure have been well documented, the paradigm can also be used to study learning-dependent adaptations that occur following repeated exposure to a stressor or associated stimuli. In developing preclinical models for human anxiety disorders this is advantageous, as anxiety disorders seldom involve a single acute experience of anxiety, but rather are chronic and/or recurring illnesses. Part 1 of this review summarizes current research on the three most commonly used predator-related odors: cat odor, ferret odor, and trimethylthiazoline (a component of fox odor). Part 2 reviews the learning-based behavioral and neural adaptations that underlie predator odor-induced context conditioning, one-trial tolerance, sensitization, habituation and dishabituation. Copyright © 2010 Elsevier Inc. All rights reserved.

Identification, inheritance, and linkage of B-G-like and MHC class I genes in cranes

Science.gov (United States)

Jarvi, S.I.; Goto, R.M.; Gee, G.F.; Briles, W.E.; Miller, M.M.

1999-01-01

We identified B-G-like genes in the whooping and Florida sandhill cranes and linked them to the major histocompatibility complex (MHC). We evaluated the inheritance of B-G-like genes in families of whooping and Florida sandhill cranes using restriction fragment patterns (RFPs). Two B-G-like genes, designated wcbgl and wcbg2, were located within 8 kb of one another. The fully sequenced wcbg2 gene encodes a B-G IgV-like domain, an additional Ig-like domain, a transmembrane domain, and a single heptad domain typical of '-helical coiled coils. Patterns of restriction fragments in DNA from the whooping crane and from a number of other species indicate that the B-G-like gene families of cranes are large with diverse sequences. Segregation of RFPs in families of Florida sandhill cranes provide evidence for genetic polymorphism in the B-G-like genes. The restriction fragments generally segregated in concert with MHC haplotypes assigned by serological typing and by single stranded conformational polymorphism (SSCP) assays based in the second exon of the crane MHC class I genes. This study supports the concept of a long-term association of polymorphic B-G-like genes with the MHC. It also establishes SSCP as a means for evaluating MHC genetic variability in cranes.

Identification, inheritance, and linkage of B-G-like and MHC class I genes in cranes.

Science.gov (United States)

Jarvi, S I; Goto, R M; Gee, G F; Briles, W E; Miller, M M

1999-01-01

We identified B-G-like genes in the whooping and Florida sandhill cranes and linked them to the major histocompatibility complex (MHC). We evaluated the inheritance of B-G-like genes in families of whooping and Florida sandhill cranes using restriction fragment patterns (RFPs). Two B-G-like genes, designated wcbg1 and wcbg2, were located within 8 kb of one another. The fully sequenced wcbg2 gene encodes a B-G IgV-like domain, an additional Ig-like domain, a transmembrane domain, and a single heptad domain typical of alpha-helical coiled coils. Patterns of restriction fragments in DNA from the whooping crane and from a number of other species indicate that the B-G-like gene families of cranes are large with diverse sequences. Segregation of RFPs in families of Florida sandhill cranes provide evidence for genetic polymorphism in the B-G-like genes. The restriction fragments generally segregated in concert with MHC haplotypes assigned by serological typing and by single stranded conformational polymorphism (SSCP) assays based in the second exon of the crane MHC class I genes. This study supports the concept of a long-term association of polymorphic B-G-like genes with the MHC. It also establishes SSCP as a means for evaluating MHC genetic variability in cranes.

Do ambient urban odors evoke basic emotions?

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Sandra Theresia Weber-Glass

2014-04-01

Full Text Available Fragrances, such as plant odors, have been shown to evoke autonomic response patterns associated with Ekman’s (Ekman et al., 1983 basic emotions happiness, surprise, anger, fear, sadness and disgust. Inducing positive emotions by odors in highly frequented public spaces could serve to improve the quality of life in urban environments. Thus, the present study evaluated the potency of ambient odors connoted with an urban environment to evoke basic emotions on an autonomic and cognitive response level. Synthetic mixtures representing the odors of disinfectant, candles / bees wax, summer air, burnt smell, vomit and musty smell as well as odorless water as a control were presented five times in random order to 30 healthy, non-smoking human subjects with intact sense of smell. Skin temperature, skin conductance, breathing rate, forearm muscle activity, blink rate and heart rate were recorded simultaneously. Subjects rated the odors in terms of pleasantness, intensity and familiarity and gave verbal labels to each odor as well as cognitive associations with the basic emotions. The results showed that the amplitude of the skin conductance response varied as a function of odor presentation. Burnt smell and vomit elicited significantly higher electrodermal responses than summer air. Also, a negative correlation was revealed between the amplitude of the skin conductance response and hedonic odor valence indicating that the magnitude of the electrodermal response increased with odor unpleasantness. The analysis of the cognitive associations between odors and basic emotions showed that candles / bees wax and summer air were specifically associated with happiness whereas burnt smell and vomit were uniquely associated with disgust. Our findings suggest that city odors may evoke specific cognitive associations of basic emotions and that autonomic activity elicited by such odors is related to odor hedonics.

Protein tyrosine kinases p53/56lyn and p72syk in MHC class I-mediated signal transduction in B lymphoma cells

DEFF Research Database (Denmark)

Pedersen, Anders Elm; Bregenholt, S; Skov, S

1998-01-01

syk are among the tyrosine-phosphorylated proteins. The kinetics of phosphorylation of these kinases after MHC-I crosslinking differ from the kinetics observed after crosslinking of the B cell antigen receptor (BCR). Additional experiments were performed with chicken lyn- and syk-negative DT40 B cells...... mobilization of intracellular free calcium compared with MHC-I crosslinking of wild-type DT40 cells. Thus, expression of BCR at the cell surface is likely to be important for the signal cascade initiated by MHC-I crosslinking. Our data suggest that signal transduction initiated through ligation of the MHC...

Analysis and control of odors from petroleum refineries

International Nuclear Information System (INIS)

O'Brien, M.A.; Duffee, R.A.; Ostojic, N.

1992-01-01

This paper presents a proven approach used to effectively solve odor problems associated with atmospheric emissions from petroleum refineries. A systematic evaluation is first conducted to identify all emissions with the potential for off-site odor impacts. Sampling is then conducted and dynamic dilution olfactometry is used to quantify the odor emission rates of each source. Community odor surveys are performed simultaneously with the source sampling to quantitatively document the downwind odor impacts. Atmospheric dispersion modeling specifically designed for odor is then used to predict instantaneous odor occurrences at various receptor sites under meteorological conditions not actually encountered during the field study. The findings make it possible to rank sources by their odor emission rates and potential for odor impacts in the community. It is then possible to determine how much odor reduction is required to bring the present odor impacts of the individual sources to an acceptable level under worst-case meteorological conditions. Once the degree of control required is determined, control alternatives are selected and evaluated. Case histories have been selected to illustrate the application of this approach at petroleum refineries. They provide descriptions of odor assessment and abatement studies conducted specifically for refinery effluent treatment plant sources as well as process unit emission sources. The sources identified as needing control and the odor abatement measures taken are discussed

MHC Intratumoral Heterogeneity May Predict Cancer Progression and Response to Immunotherapy

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Irene Romero

2018-01-01

Full Text Available An individual tumor can present intratumoral phenotypic heterogeneity, containing tumor cells with different phenotypes that do not present irreversible genetic alterations. We have developed a mouse cancer model, named GR9, derived from a methylcholanthrene-induced fibrosarcoma that was adapted to tissue culture and cloned into different tumor cell lines. The clones showed diverse MHC-I phenotypes, ranging from highly positive to weakly positive MHC-I expression. These MHC-I alterations are due to reversible molecular mechanisms, because surface MHC-I could be recovered by IFN-γ treatment. Cell clones with high MHC-I expression demonstrated low local oncogenicity and high spontaneous metastatic capacity, whereas MHC-I-low clones showed high local oncogenicity and no spontaneous metastatic capacity. Although MHC-I-low clones did not metastasize, they produced MHC-I-positive dormant micrometastases controlled by the host immune system, i.e., in a state of immunodormancy. The metastatic capacity of each clone was directly correlated with the host T-cell subpopulations; thus, a strong decrease in cytotoxic and helper T lymphocytes was observed in mice with numerous metastases derived from MHC-I positive tumor clones but a strong increase was observed in those with dormant micrometastases. Immunotherapy was administered to the hosts after excision of the primary tumor, producing a recovery in their immune status and leading to the complete eradication of overt spontaneous metastases or their decrease. According to these findings, the combination of MHC-I surface expression in primary tumor and metastases with host T-cell subsets may be a decisive indicator of the clinical outcome and response to immunotherapy in metastatic disease, allowing the identification of responders to this approach.

Changes in Olfactory Sensory Neuron Physiology and Olfactory Perceptual Learning After Odorant Exposure in Adult Mice.

Science.gov (United States)

Kass, Marley D; Guang, Stephanie A; Moberly, Andrew H; McGann, John P

2016-02-01

The adult olfactory system undergoes experience-dependent plasticity to adapt to the olfactory environment. This plasticity may be accompanied by perceptual changes, including improved olfactory discrimination. Here, we assessed experience-dependent changes in the perception of a homologous aldehyde pair by testing mice in a cross-habituation/dishabituation behavioral paradigm before and after a week-long ester-odorant exposure protocol. In a parallel experiment, we used optical neurophysiology to observe neurotransmitter release from olfactory sensory neuron (OSN) terminals in vivo, and thus compared primary sensory representations of the aldehydes before and after the week-long ester-odorant exposure in individual animals. Mice could not discriminate between the aldehydes during pre-exposure testing, but ester-exposed subjects spontaneously discriminated between the homologous pair after exposure, whereas home cage control mice cross-habituated. Ester exposure did not alter the spatial pattern, peak magnitude, or odorant-selectivity of aldehyde-evoked OSN input to olfactory bulb glomeruli, but did alter the temporal dynamics of that input to make the time course of OSN input more dissimilar between odorants. Together, these findings demonstrate that odor exposure can induce both physiological and perceptual changes in odor processing, and suggest that changes in the temporal patterns of OSN input to olfactory bulb glomeruli could induce differences in odor quality. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Modification of CO2 avoidance behaviour in Drosophila by inhibitory odorants.

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Turner, Stephanie Lynn; Ray, Anandasankar

2009-09-10

The fruitfly Drosophila melanogaster exhibits a robust and innate olfactory-based avoidance behaviour to CO(2), a component of odour emitted from stressed flies. Specialized neurons in the antenna and a dedicated neuronal circuit in the higher olfactory system mediate CO(2) detection and avoidance. However, fruitflies need to overcome this avoidance response in some environments that contain CO(2) such as ripening fruits and fermenting yeast, which are essential food sources. Very little is known about the molecular and neuronal basis of this unique, context-dependent modification of innate olfactory avoidance behaviour. Here we identify a new class of odorants present in food that directly inhibit CO(2)-sensitive neurons in the antenna. Using an in vivo expression system we establish that the odorants act on the Gr21a/Gr63a CO(2) receptor. The presence of these odorants significantly and specifically reduces CO(2)-mediated avoidance behaviour, as well as avoidance mediated by 'Drosophila stress odour'. We propose a model in which behavioural avoidance to CO(2) is directly influenced by inhibitory interactions of the novel odours with CO(2) receptors. Furthermore, we observe differences in the temporal dynamics of inhibition: the effect of one of these odorants lasts several minutes beyond the initial exposure. Notably, animals that have been briefly pre-exposed to this odorant do not respond to the CO(2) avoidance cue even after the odorant is no longer present. We also show that related odorants are effective inhibitors of the CO(2) response in Culex mosquitoes that transmit West Nile fever and filariasis. Our findings have broader implications in highlighting the important role of inhibitory odorants in olfactory coding, and in their potential to disrupt CO(2)-mediated host-seeking behaviour in disease-carrying insects like mosquitoes.

MHC class II DQB diversity in the Japanese black bear, Ursus thibetanus japonicus

Science.gov (United States)

2012-01-01

Background The major histocompatibility complex (MHC) genes are one of the most important genetic systems in the vertebrate immune response. The diversity of MHC genes may directly influence the survival of individuals against infectious disease. However, there has been no investigation of MHC diversity in the Asiatic black bear (Ursus thibetanus). Here, we analyzed 270-bp nucleotide sequences of the entire exon 2 region of the MHC DQB gene by using 188 samples from the Japanese black bear (Ursus thibetanus japonicus) from 12 local populations. Results Among 185 of 188 samples, we identified 44 MHC variants that encoded 31 different amino acid sequences (allotypes) and one putative pseudogene. The phylogenetic analysis suggests that MHC variants detected from the Japanese black bear are derived from the DQB locus. One of the 31 DQB allotypes, Urth-DQB*01, was found to be common to all local populations. Moreover, this allotype was shared between the black bear on the Asian continent and the Japanese black bear, suggesting that Urth-DQB*01 might have been maintained in the ancestral black bear population for at least 300,000 years. Our findings, from calculating the ratio of non-synonymous to synonymous substitutions, indicate that balancing selection has maintained genetic variation of peptide-binding residues at the DQB locus of the Japanese black bear. From examination of genotype frequencies among local populations, we observed a considerably lower level of observed heterozygosity than expected. Conclusions The low level of observed heterozygosity suggests that genetic drift reduced DQB diversity in the Japanese black bear due to a bottleneck event at the population or species level. The decline of DQB diversity might have been accelerated by the loss of rare variants that have been maintained by negative frequency-dependent selection. Nevertheless, DQB diversity of the black bear appears to be relatively high compared with some other endangered mammalian

MHC class II DQB diversity in the Japanese black bear, Ursus thibetanus japonicus

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Yasukochi Yoshiki

2012-11-01

Full Text Available Abstract Background The major histocompatibility complex (MHC genes are one of the most important genetic systems in the vertebrate immune response. The diversity of MHC genes may directly influence the survival of individuals against infectious disease. However, there has been no investigation of MHC diversity in the Asiatic black bear (Ursus thibetanus. Here, we analyzed 270-bp nucleotide sequences of the entire exon 2 region of the MHC DQB gene by using 188 samples from the Japanese black bear (Ursus thibetanus japonicus from 12 local populations. Results Among 185 of 188 samples, we identified 44 MHC variants that encoded 31 different amino acid sequences (allotypes and one putative pseudogene. The phylogenetic analysis suggests that MHC variants detected from the Japanese black bear are derived from the DQB locus. One of the 31 DQB allotypes, Urth-DQB*01, was found to be common to all local populations. Moreover, this allotype was shared between the black bear on the Asian continent and the Japanese black bear, suggesting that Urth-DQB*01 might have been maintained in the ancestral black bear population for at least 300,000 years. Our findings, from calculating the ratio of non-synonymous to synonymous substitutions, indicate that balancing selection has maintained genetic variation of peptide-binding residues at the DQB locus of the Japanese black bear. From examination of genotype frequencies among local populations, we observed a considerably lower level of observed heterozygosity than expected. Conclusions The low level of observed heterozygosity suggests that genetic drift reduced DQB diversity in the Japanese black bear due to a bottleneck event at the population or species level. The decline of DQB diversity might have been accelerated by the loss of rare variants that have been maintained by negative frequency-dependent selection. Nevertheless, DQB diversity of the black bear appears to be relatively high compared with some other

MHC class II DQB diversity in the Japanese black bear, Ursus thibetanus japonicus.

Science.gov (United States)

Yasukochi, Yoshiki; Kurosaki, Toshifumi; Yoneda, Masaaki; Koike, Hiroko; Satta, Yoko

2012-11-29

The major histocompatibility complex (MHC) genes are one of the most important genetic systems in the vertebrate immune response. The diversity of MHC genes may directly influence the survival of individuals against infectious disease. However, there has been no investigation of MHC diversity in the Asiatic black bear (Ursus thibetanus). Here, we analyzed 270-bp nucleotide sequences of the entire exon 2 region of the MHC DQB gene by using 188 samples from the Japanese black bear (Ursus thibetanus japonicus) from 12 local populations. Among 185 of 188 samples, we identified 44 MHC variants that encoded 31 different amino acid sequences (allotypes) and one putative pseudogene. The phylogenetic analysis suggests that MHC variants detected from the Japanese black bear are derived from the DQB locus. One of the 31 DQB allotypes, Urth-DQB*01, was found to be common to all local populations. Moreover, this allotype was shared between the black bear on the Asian continent and the Japanese black bear, suggesting that Urth-DQB*01 might have been maintained in the ancestral black bear population for at least 300,000 years. Our findings, from calculating the ratio of non-synonymous to synonymous substitutions, indicate that balancing selection has maintained genetic variation of peptide-binding residues at the DQB locus of the Japanese black bear. From examination of genotype frequencies among local populations, we observed a considerably lower level of observed heterozygosity than expected. The low level of observed heterozygosity suggests that genetic drift reduced DQB diversity in the Japanese black bear due to a bottleneck event at the population or species level. The decline of DQB diversity might have been accelerated by the loss of rare variants that have been maintained by negative frequency-dependent selection. Nevertheless, DQB diversity of the black bear appears to be relatively high compared with some other endangered mammalian species. This result suggests that

Functional neuronal processing of human body odors.

Science.gov (United States)

Lundström, Johan N; Olsson, Mats J

2010-01-01

Body odors carry informational cues of great importance for individuals across a wide range of species, and signals hidden within the body odor cocktail are known to regulate several key behaviors in animals. For a long time, the notion that humans may be among these species has been dismissed. We now know, however, that each human has a unique odor signature that carries information related to his or her genetic makeup, as well as information about personal environmental variables, such as diet and hygiene. Although a substantial number of studies have investigated the behavioral effects of body odors, only a handful have studied central processing. Recent studies have, however, demonstrated that the human brain responds to fear signals hidden within the body odor cocktail, is able to extract kin specific signals, and processes body odors differently than other perceptually similar odors. In this chapter, we provide an overview of the current knowledge of how the human brain processes body odors and the potential importance these signals have for us in everyday life. Copyright © 2010 Elsevier Inc. All rights reserved.

The Scent of Roses and beyond: Molecular Structures, Analysis, and Practical Applications of Odorants

Science.gov (United States)

Mannschreck, Albrecht; von Angerer, Erwin

2011-01-01

A few odorous compounds found in roses are chosen to arouse the reader's interest in their molecular structures. This article differs from some similar reports on odorants mainly by combining the structural description with the presentation of the following types of isomers: constitutional isomers, enantiomers, and diastereomers. The preparation…

A Novel Therapeutic Vaccine for Metastatic Mammary Carcinoma: Focusing MHC/Peptide Complexes to Lipid Rafts

Science.gov (United States)

2006-11-01

reportable outcomes). Briefly, the T cell lymphoma EL4 and the immortalized fibroblast cell line DAP (both expressing ova) were used to measure...and Use Committee. Cells , transfections, and antibodies B16.BL6 8.2, A20, EL4 and EL4 /ova were cultured as described (20-22). NIH3T3 cells were...types can donate MHC class I molecules to DC. To determine if the levels of MHC class I on the donor cell affected the efficiency of transfer, EL4 /ova

Fine-mapping analysis of the MHC region for vitiligo based on a new Han-MHC reference panel.

Science.gov (United States)

Yang, Chao; Wu, Juan; Zhang, Xuelei; Wen, Leilei; Sun, Jingying; Cheng, Yuyan; Tang, Xianfa; Liang, Bo; Chen, Gang; Zhou, Fusheng; Cui, Yong; Zhang, Anping; Zhang, Xuejun; Zheng, Xiaodong; Yang, Sen; Sun, Liangdan

2018-03-30

Vitiligo is an immune-related disease with patchy depigmentation of skin and hair caused by selective destruction of melanocytes. In recent decades, many studies have shown the association between vitiligo and HLA genes; however, the results of Han Chinese are scarce. In this study, we performed a fine-mapping analysis of the MHC region in 2818 Han Chinese subjects through a widely used HLA imputation method with a newly built large-scale Han-MHC reference panel. Three new four-digit HLA alleles (HLA-DQB1 ∗ 02:02, HLA-DQA1 ∗ 02:01 and HLA-DPB1 ∗ 17:01) were identified to be associated with the risk of vitiligo, and four previously reported alleles were confirmed. Further conditional analysis revealed that two important variants, HLA-DQβ1 amino acid position 135 (OR = 1.79, P = 1.87 × 10 -11 ) and HLA-B amino acid positions 45-46 (OR = 1.44, P = 5.61 × 10 -11 ), conferred most of the MHC associations. Three-dimension ribbon models showed that the former is located within the β2 domain of the HLA-DQβ1 molecule, and the latter lies in the α1 domain of the HLA-B molecule, while both are involved in specific antigen presenting process. Finally, we summarized all significant signals in the MHC region to clarify their complex relationships, and 8.60% of phenotypic variance could be explained based on all reported variants in Han Chinese so far. Our findings highlight the complex genetic architecture of the MHC region for vitiligo in Han Chinese population and expand our understanding of the roles of HLA coding variants in the etiology of vitiligo. Copyright © 2018. Published by Elsevier B.V.

Virus encoded MHC-like decoys diversify the inhibitory KIR repertoire.

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Paola Carrillo-Bustamante

Full Text Available Natural killer (NK cells are circulating lymphocytes that play an important role in the control of viral infections and tumors. Their functions are regulated by several activating and inhibitory receptors. A subset of these receptors in human NK cells are the killer immunoglobulin-like receptors (KIRs, which interact with the highly polymorphic MHC class I molecules. One important function of NK cells is to detect cells that have down-regulated MHC expression (missing-self. Because MHC molecules have non polymorphic regions, their expression could have been monitored with a limited set of monomorphic receptors. Surprisingly, the KIR family has a remarkable genetic diversity, the function of which remains poorly understood. The mouse cytomegalovirus (MCMV is able to evade NK cell responses by coding "decoy" molecules that mimic MHC class I. This interaction was suggested to have driven the evolution of novel NK cell receptors. Inspired by the MCMV system, we develop an agent-based model of a host population infected with viruses that are able to evolve MHC down-regulation and decoy molecules. Our simulations show that specific recognition of MHC class I molecules by inhibitory KIRs provides excellent protection against viruses evolving decoys, and that the diversity of inhibitory KIRs will subsequently evolve as a result of the required discrimination between host MHC molecules and decoy molecules.

Generation of a genomic tiling array of the human Major Histocompatibility Complex (MHC and its application for DNA methylation analysis

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Ottaviani Diego

2008-05-01

Full Text Available Abstract Background The major histocompatibility complex (MHC is essential for human immunity and is highly associated with common diseases, including cancer. While the genetics of the MHC has been studied intensively for many decades, very little is known about the epigenetics of this most polymorphic and disease-associated region of the genome. Methods To facilitate comprehensive epigenetic analyses of this region, we have generated a genomic tiling array of 2 Kb resolution covering the entire 4 Mb MHC region. The array has been designed to be compatible with chromatin immunoprecipitation (ChIP, methylated DNA immunoprecipitation (MeDIP, array comparative genomic hybridization (aCGH and expression profiling, including of non-coding RNAs. The array comprises 7832 features, consisting of two replicates of both forward and reverse strands of MHC amplicons and appropriate controls. Results Using MeDIP, we demonstrate the application of the MHC array for DNA methylation profiling and the identification of tissue-specific differentially methylated regions (tDMRs. Based on the analysis of two tissues and two cell types, we identified 90 tDMRs within the MHC and describe their characterisation. Conclusion A tiling array covering the MHC region was developed and validated. Its successful application for DNA methylation profiling indicates that this array represents a useful tool for molecular analyses of the MHC in the context of medical genomics.

Problems in instrumentation for S-odorant emissions

International Nuclear Information System (INIS)

Hall, H.J.

1974-01-01

Instrumentation to measure sulfur-containing odorants in stack emissions is much more difficult than in the ambient atmosphere, and must be matched to the specific source: key components aside from H 2 S are methyl mercaptan in paper mills, COS/CS 2 in a refinery Claus plant, and SO 2 /SO 3 in a combustion stack. Satisfactory operation for a period of six months was not achieved by any instrument in this service, in a lab and field evaluation of eight instruments of three types commercially available as of 1971. The effects of interferent gases H 2 O, SO 2 , CO 2 /CO and particulates which are diluted in ambient samples are greatly aggravated in stack gases, where the ratio of odorant to interferent may be 1:1000 or less, due to the very great sensitivity of human receptors to S-odorants. The most serious problem proved to be the analysis for odorless carbonyl sulfide, which is commonly formed where S compounds are oxidized in a reducing atmosphere. This COS has been undetected or mistaken for odorous H 2 S in most analyses. A field instrument for the general case would provide exactly simultaneous readings at five minute intervals or less for the five components H 2 S, SO 2 , COS, CSH, and total S, or their equivalent. This may be simplified to four components or less only when the composition of the sample gas is positively known

Blocking oxytocin receptors inhibits vaginal marking to male odors in female Syrian hamsters.

Science.gov (United States)

Martinez, Luis A; Albers, H Elliott; Petrulis, Aras

2010-12-02

In Syrian hamsters (Mesocricetus auratus), precopulatory behaviors such as vaginal scent marking are essential for attracting a suitable mate. Vaginal marking is dependent on forebrain areas implicated in the neural regulation of reproductive behaviors in rodents, including the medial preoptic/anterior hypothalamus (MPOA-AH). Within MPOA-AH, the neuropeptide oxytocin (OT) acts to facilitate copulation (lordosis), as well as ultrasonic vocalizations towards males. It is not known, however, if OT in this area also facilitates vaginal marking. In the present study, a specific oxytocin receptor antagonist (OTA) was injected into MPOA-AH of intact female Syrian hamsters to determine if oxytocin receptor-dependent signaling is critical for the normal expression of vaginal marking elicited by male, female, and clean odors. OTA injections significantly inhibited vaginal marking in response to male odors compared with vehicle injections. There was no effect of OTA on marking in response to either female or clean odors. When injected into the bed nucleus of the stria terminalis (BNST), a nearby region to MPOA-AH, OTA was equally effective in decreasing marking. Finally, the effects of OTA appear to be specific to vaginal marking, as OTA injections in MPOA-AH or BNST did not alter general locomotor activity, flank marking, or social odor investigation. Considered together, these results suggest that OT in MPOA-AH and/or BNST normally facilitates male odor-induced vaginal marking, providing further evidence that OT generally supports prosocial interactions among conspecifics. Copyright © 2010 Elsevier Inc. All rights reserved.

MHC class II B diversity in blue tits : A preliminary study

NARCIS (Netherlands)

Rivero-de Aguilar, Juan; Schut, Elske; Merino, Santiago; Martinez, Javier; Komdeur, Jan; Westerdahl, Helena

In this study, we partly characterize major histocompatibility complex (MHC) class II B in the blue tit (Cyanistes caeruleus). A total of 22 individuals from three different European locations: Spain, The Netherlands, and Sweden were screened for MHC allelic diversity. The MHC genes were

Odors pulsed at wing beat frequencies are tracked by primary olfactory networks and enhance odor detection

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Shreejoy Tripathy

2010-03-01

Full Text Available Each down stroke of an insect’s wings accelerates axial airflow over the antennae. Modeling studies suggest that this can greatly enhance penetration of air and air-born odorants through the antennal sensilla thereby periodically increasing odorant-receptor interactions. Do these periodic changes result in entrainment of neural responses in the antenna and antennal lobe (AL? Does this entrainment affect olfactory acuity? To address these questions, we monitored antennal and AL responses in the moth Manduca sexta while odorants were pulsed at frequencies from 10-72 Hz, encompassing the natural wingbeat frequency. Power spectral density (PSD analysis was used to identify entrainment of neural activity. Statistical analysis of PSDs indicates that the antennal nerve tracked pulsed odor up to 30 Hz. Furthermore, at least 50% of AL local field potentials (LFPs and between 7-25% of unitary spiking responses also tracked pulsed odor up to 30 Hz in a frequency-locked manner. Application of bicuculline (200µM abolished pulse tracking in both LFP and unitary responses suggesting that GABAA receptor activation is necessary for pulse tracking within the AL. Finally, psychophysical measures of odor detection establish that detection thresholds are lowered when odor is pulsed at 20 Hz. These results suggest that AL networks can respond to the oscillatory dynamics of stimuli such as those imposed by the wing beat in a manner analogous to mammalian sniffing.

Odor Memory and Discrimination Covary as a Function of Delay between Encoding and Recall in Rats.

Science.gov (United States)

Hackett, Chelsea; Choi, Christina; O'Brien, Brenna; Shin, Philip; Linster, Christiane

2015-06-01

Nonassociative odor learning paradigms are often used to assess memory, social recognition and neuromodulation of olfactory pathways. We here use a modified object recognition paradigm to investigate how an important task parameter, delay between encoding and recall trials, affects the properties of this memory. We show that both memory for a previously investigated odorant and discrimination of a novel odorant decay with delay time and that rats can remember an odorant for up to 45min after a single trial encoding event. The number of odorants that can be encoded, as well as the specificity of the encoded memory, decrease with increased delay and also depend on stimulus concentration. Memory for an odorant and discrimination of a novel odorant decay at approximately the same rate, whereas the specificity of the formed memory decays faster than the memory itself. These results have important implications for the interpretation of behavioral data obtained with this paradigm. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Establishment of a quantitative ELISA capable of determining peptide - MHC class I interaction

DEFF Research Database (Denmark)

Sylvester-Hvid, C; Kristensen, N; Blicher, T

2002-01-01

dependent manner. Here, we exploit the availability of these molecules to generate a quantitative ELISA-based assay capable of measuring the affinity of the interaction between peptide and MHC-I. This assay is simple and sensitive, and one can easily envisage that the necessary reagents, standards...

Positive implicit attitudes toward odor words.

Science.gov (United States)

Bulsing, Patricia J; Smeets, Monique A M; van den Hout, Marcel A

2007-07-01

Associations between certain odors and for instance health effects may lead to positive or negative attitudes toward these odors. However, in experiments we conducted using the Implicit Association Test (IAT), we encountered attitudes even to odor "words." The IAT is based on the principle that reaction times measuring the association between words from a target dimension (in this case, odor vs. a neutral reference category) and an attribute dimension (i.e., positive or negative words) reflect the attitude to the target, where attitude-congruent associations between target and attribute are reflected by shorter reaction times. In a first experiment, we found distinctly positive attitudes to the concept odor in a student sample, which was replicated in a second experiment. In the main experiment, subjects in the aromatherapy group, who prefer using scented consumer products for relaxation purposes, showed a significantly more positive attitude toward odor words in the IAT than a control group, who did not have such a preference. The fact that results from the implicit test were not always associated with explicitly stated attitudes toward the odor words attests to the fact that the IAT measures the attitude of interest in a different way. As such, the IAT has added value in circumstances where explicit tests can be biased.

MHC-I affects infection intensity but not infection status with a frequent avian malaria parasite in blue tits.

Directory of Open Access Journals (Sweden)

Helena Westerdahl

Full Text Available Host resistance against parasites depends on three aspects: the ability to prevent, control and clear infections. In vertebrates the immune system consists of innate and adaptive immunity. Innate immunity is particularly important for preventing infection and eradicating established infections at an early stage while adaptive immunity is slow, but powerful, and essential for controlling infection intensities and eventually clearing infections. Major Histocompatibility Complex (MHC molecules are central in adaptive immunity, and studies on parasite resistance and MHC in wild animals have found effects on both infection intensity (parasite load and infection status (infected or not. It seems MHC can affect both the ability to control infection intensities and the ability to clear infections. However, these two aspects have rarely been considered simultaneously, and their relative importance in natural populations is therefore unclear. Here we investigate if MHC class I genotype affects infection intensity and infection status with a frequent avian malaria infection Haemoproteus majoris in a natural population of blue tits Cyanistes caeruleus. We found a significant negative association between a single MHC allele and infection intensity but no association with infection status. Blue tits that carry a specific MHC allele seem able to suppress H. majoris infection intensity, while we have no evidence that this allele also has an effect on clearance of the H. majoris infection, a result that is in contrast with some previous studies of MHC and avian malaria. A likely explanation could be that the clearance rate of avian malaria parasites differs between avian malaria lineages and/or between avian hosts.

MHC-I affects infection intensity but not infection status with a frequent avian malaria parasite in blue tits.

Science.gov (United States)

Westerdahl, Helena; Stjernman, Martin; Råberg, Lars; Lannefors, Mimi; Nilsson, Jan-Åke

2013-01-01

Host resistance against parasites depends on three aspects: the ability to prevent, control and clear infections. In vertebrates the immune system consists of innate and adaptive immunity. Innate immunity is particularly important for preventing infection and eradicating established infections at an early stage while adaptive immunity is slow, but powerful, and essential for controlling infection intensities and eventually clearing infections. Major Histocompatibility Complex (MHC) molecules are central in adaptive immunity, and studies on parasite resistance and MHC in wild animals have found effects on both infection intensity (parasite load) and infection status (infected or not). It seems MHC can affect both the ability to control infection intensities and the ability to clear infections. However, these two aspects have rarely been considered simultaneously, and their relative importance in natural populations is therefore unclear. Here we investigate if MHC class I genotype affects infection intensity and infection status with a frequent avian malaria infection Haemoproteus majoris in a natural population of blue tits Cyanistes caeruleus. We found a significant negative association between a single MHC allele and infection intensity but no association with infection status. Blue tits that carry a specific MHC allele seem able to suppress H. majoris infection intensity, while we have no evidence that this allele also has an effect on clearance of the H. majoris infection, a result that is in contrast with some previous studies of MHC and avian malaria. A likely explanation could be that the clearance rate of avian malaria parasites differs between avian malaria lineages and/or between avian hosts.

Purinergic receptor antagonists inhibit odorant-mediated CREB phosphorylation in sustentacular cells of mouse olfactory epithelium.

LENUS (Irish Health Repository)

Dooley, Ruth

2012-02-01

BACKGROUND: Extracellular nucleotides have long been known to play neuromodulatory roles and to be involved in intercellular signalling. In the olfactory system, ATP is released by olfactory neurons, and exogenous ATP can evoke an increase in intracellular calcium concentration in sustentacular cells, the nonneuronal supporting cells of the olfactory epithelium. Here we investigate the hypothesis that olfactory neurons communicate with sustentacular cells via extracellular ATP and purinergic receptor activation. RESULTS: Here we show that exposure of mice to a mixture of odorants induced a significant increase in the levels of the transcription factor CREB phosphorylated at Ser-133 in the nuclei of both olfactory sensory neurons and sustentacular cells. This activation was dependent on adenylyl cyclase III-mediated olfactory signaling and on activation of P2Y purinergic receptors on sustentacular cells. Purinergic receptor antagonists inhibited odorant-dependent CREB phosphorylation specifically in the nuclei of the sustentacular cells. CONCLUSION: Our results point to a possible role for extracellular nucleotides in mediating intercellular communication between the neurons and sustentacular cells of the olfactory epithelium in response to odorant exposure. Maintenance of extracellular ionic gradients and metabolism of noxious chemicals by sustentacular cells may therefore be regulated in an odorant-dependent manner by olfactory sensory neurons.

Purinergic receptor antagonists inhibit odorant-mediated CREB phosphorylation in sustentacular cells of mouse olfactory epithelium

LENUS (Irish Health Repository)

Dooley, Ruth

2011-08-22

Abstract Background Extracellular nucleotides have long been known to play neuromodulatory roles and to be involved in intercellular signalling. In the olfactory system, ATP is released by olfactory neurons, and exogenous ATP can evoke an increase in intracellular calcium concentration in sustentacular cells, the nonneuronal supporting cells of the olfactory epithelium. Here we investigate the hypothesis that olfactory neurons communicate with sustentacular cells via extracellular ATP and purinergic receptor activation. Results Here we show that exposure of mice to a mixture of odorants induced a significant increase in the levels of the transcription factor CREB phosphorylated at Ser-133 in the nuclei of both olfactory sensory neurons and sustentacular cells. This activation was dependent on adenylyl cyclase III-mediated olfactory signaling and on activation of P2Y purinergic receptors on sustentacular cells. Purinergic receptor antagonists inhibited odorant-dependent CREB phosphorylation specifically in the nuclei of the sustentacular cells. Conclusion Our results point to a possible role for extracellular nucleotides in mediating intercellular communication between the neurons and sustentacular cells of the olfactory epithelium in response to odorant exposure. Maintenance of extracellular ionic gradients and metabolism of noxious chemicals by sustentacular cells may therefore be regulated in an odorant-dependent manner by olfactory sensory neurons.

Purinergic receptor antagonists inhibit odorant-mediated CREB phosphorylation in sustentacular cells of mouse olfactory epithelium

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Hatt Hanns

2011-08-01

Full Text Available Abstract Background Extracellular nucleotides have long been known to play neuromodulatory roles and to be involved in intercellular signalling. In the olfactory system, ATP is released by olfactory neurons, and exogenous ATP can evoke an increase in intracellular calcium concentration in sustentacular cells, the nonneuronal supporting cells of the olfactory epithelium. Here we investigate the hypothesis that olfactory neurons communicate with sustentacular cells via extracellular ATP and purinergic receptor activation. Results Here we show that exposure of mice to a mixture of odorants induced a significant increase in the levels of the transcription factor CREB phosphorylated at Ser-133 in the nuclei of both olfactory sensory neurons and sustentacular cells. This activation was dependent on adenylyl cyclase III-mediated olfactory signaling and on activation of P2Y purinergic receptors on sustentacular cells. Purinergic receptor antagonists inhibited odorant-dependent CREB phosphorylation specifically in the nuclei of the sustentacular cells. Conclusion Our results point to a possible role for extracellular nucleotides in mediating intercellular communication between the neurons and sustentacular cells of the olfactory epithelium in response to odorant exposure. Maintenance of extracellular ionic gradients and metabolism of noxious chemicals by sustentacular cells may therefore be regulated in an odorant-dependent manner by olfactory sensory neurons.

Basic emotions induced by odorants: a new approach based on autonomic pattern results.

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Vernet-Maury, E; Alaoui-Ismaïli, O; Dittmar, A; Delhomme, G; Chanel, J

1999-02-15

The aim of this study was to link the effects of odorants with the emotional process, through autonomic nervous system (ANS) responses. Taking Ekman's data and our previous results into account, we tried to verify a possible evocation by odorants of some basic emotions, i.e. anger, fear, sadness, surprise, disgust and happiness. The question investigated was: would it be possible to associate any of these emotions with a pattern of autonomic responses? A total of 15 subjects inhaled five odorants: lavender, ethyl aceto acetate, camphor, acetic acid and butyric acid acting as olfactory stimuli. After inhaling the odorant, subjects were requested to fill out an 11-point hedonic scale to rate its 'pleasantness' vs. 'unpleasantness'. ANS parameters monitored were skin potential and resistance, skin blood flow and temperature, instantaneous respiratory frequency and instantaneous heart rate. Simultaneous recording of these six autonomic parameters permitted the analysis of phasic responses through specific ANS patterns. An analysis of variance made it possible to differentiate among the five odorants. Two-by-two odorant comparisons for autonomic responses using Tukey's HSD multiple comparison test only permitted differentiation between 'pleasant' and 'unpleasant' odors. Camphor was differentiated from both types. For instance, long duration responses were associated with 'unpleasant' odors whereas camphor elicited intermediate responses. Taking into account each subject's preferential channel, it was possible to associate each ANS pattern with a basic emotion by means of a decision tree. The computation of subjects' responses made it possible to associate an odorant with a basic emotion, over the whole group: lavender elicited mostly 'happiness', as did, to a lesser degree ethyl aceto acetate; camphor induced either 'happiness', 'surprise' or 'sadness' according to subjects' past histories; butyric and acetic acids mainly induced negative emotions: 'anger' and 'disgust

Cheetah paradigm revisited: MHC diversity in the world's largest free-ranging population.

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Castro-Prieto, Aines; Wachter, Bettina; Sommer, Simone

2011-04-01

For more than two decades, the cheetah (Acinonyx jubatus) has been considered a paradigm of disease vulnerability associated with low genetic diversity, particularly at the immune genes of the major histocompatibility complex (MHC). Cheetahs have been used as a classic example in numerous conservation genetics textbooks as well as in many related scientific publications. However, earlier studies used methods with low resolution to quantify MHC diversity and/or small sample sizes. Furthermore, high disease susceptibility was reported only for captive cheetahs, whereas free-ranging cheetahs show no signs of infectious diseases and a good general health status. We examined whether the diversity at MHC class I and class II-DRB loci in 149 Namibian cheetahs was higher than previously reported using single-strand conformation polymorphism analysis, cloning, and sequencing. MHC genes were examined at the genomic and transcriptomic levels. We detected ten MHC class I and four class II-DRB alleles, of which nine MHC class I and all class II-DRB alleles were expressed. Phylogenetic analyses and individual genotypes suggested that the alleles belong to four MHC class I and three class II-DRB putative loci. Evidence of positive selection was detected in both MHC loci. Our study indicated that the low number of MHC class I alleles previously observed in cheetahs was due to a smaller sample size examined. On the other hand, the low number of MHC class II-DRB alleles previously observed in cheetahs was further confirmed. Compared with other mammalian species including felids, cheetahs showed low levels of MHC diversity, but this does not seem to influence the immunocompetence of free-ranging cheetahs in Namibia and contradicts the previous conclusion that the cheetah is a paradigm species of disease vulnerability.

Nurse odor perception in various Japanese hospital settings

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Masami Horiguchi

2015-12-01

Full Text Available Because unpleasant hospital odors affect the nursing environment, we investigated nurses' perceptions of the odors of various hospital settings: hospital rooms, nurse stations, and human waste disposal rooms to discard the urine, stools and diapers. A questionnaire based on the Japanese Ministry of the Environment's guidelines on odor index regulation was used to assess nurses' perceptions of odor intensity, comfort, tolerability, and description in the aforementioned settings. Questionnaires were distributed to nursing department directors at three Japanese hospitals, who then disseminated the questionnaires to nursing staff. Of the 1,151 questionnaires distributed, 496 nurses participated. Human waste disposal rooms had greater odor intensity and were perceived as more uncomfortable than the other settings. Unpleasant odors in disposal rooms, hospital rooms, and nurse stations were rated as slightly intolerable in comparison. Hospital and disposal rooms were mainly described as having a “pungent odor such as of urine and stool.” In contrast, nurse stations were described as having other unpleasant odors, such as chemical, human-body-related, or sewage-like odors. Given that nurses spend much of their time in hospital rooms and nurse stations, odor management in these two settings would likely improve nurses' working conditions at hospitals. Improving odors at nurse stations is feasible. Such improvements could have indirect effects on nurse turnover and burnout.

An odor flux model for cattle feedlots

Energy Technology Data Exchange (ETDEWEB)

Ormerod, R.J. [Dames & Moore, Brisbane (Australia)

1994-12-31

Odor nuisance associated with cattle feedlots has been an issue of major interest and concern to regulators, rural communities and the beef industry in Australia over the past decade. Methods of assessing the likely impacts of new feedlots on community odor exposure are still being developed, but in the past few years much has been learnt about the processes of odor generation, flux and dispersion as well as the acceptability of feedlot odor to exposed communities. This paper outlines a model which simulates the complex physical and chemical processes leading to odor emissions in a simple and practical framework. The model, named BULSMEL, has been developed as a response to regulatory requirements for quantitative assessments of odor impact. It will continue to be refined as more data are gathered.

Isoamyl alcohol odor promotes longevity and stress tolerance via DAF-16 in Caenorhabditis elegans.

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Kurino, Chiho; Furuhashi, Tsubasa; Sudoh, Kaori; Sakamoto, Kazuichi

2017-04-01

The possibility that odor plays a role in lifespan regulation through effects on the nervous system is indicated by research on Caenorhabditis elegans. In fact, ablation of AWA and AWC, which are suggested as olfactory neurons, has been shown to extend lifespan via DAF-16, a homolog of FoxO. However, the effects of odor stimuli on the lifespan still remain unclear. Thus, we here aimed to clarify the effect of attractive and repulsive odors on longevity and stress tolerance in C. elegans and to analyze the pathways thereof. We used isoamyl alcohol as an attractive odor, and acetic acid as a repellent component, as identified by chemotaxis assay. We found that isoamyl alcohol stimulus promoted longevity in a DAF-16-dependent manner. On the other hand, acetic acid stimulus promoted thermotolerance through mechanisms independent of DAF-16. Above all, our results indicate that odor stimuli affect the lifespan and stress tolerance of C. elegans, with attractive and repulsive odors exerting their effects through different mechanisms, and that longevity is induced by both activation and inactivation of olfactory neurons. Copyright © 2017 Elsevier Inc. All rights reserved.

Odors bias time perception in visual and auditory modalities

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Zhenzhu eYue

2016-04-01

Full Text Available Previous studies have shown that emotional states alter our perception of time. However, attention, which is modulated by a number of factors, such as emotional events, also influences time perception. To exclude potential attentional effects associated with emotional events, various types of odors (inducing different levels of emotional arousal were used to explore whether olfactory events modulated time perception differently in visual and auditory modalities. Participants were shown either a visual dot or heard a continuous tone for 1000 ms or 4000 ms while they were exposed to odors of jasmine, lavender, or garlic. Participants then reproduced the temporal durations of the preceding visual or auditory stimuli by pressing the spacebar twice. Their reproduced durations were compared to those in the control condition (without odor. The results showed that participants produced significantly longer time intervals in the lavender condition than in the jasmine or garlic conditions. The overall influence of odor on time perception was equivalent for both visual and auditory modalities. The analysis of the interaction effect showed that participants produced longer durations than the actual duration in the short interval condition, but they produced shorter durations in the long interval condition. The effect sizes were larger for the auditory modality than those for the visual modality. Moreover, by comparing performance across the initial and the final blocks of the experiment, we found odor adaptation effects were mainly manifested as longer reproductions for the short time interval later in the adaptation phase, and there was a larger effect size in the auditory modality. In summary, the present results indicate that odors imposed differential impacts on reproduced time durations, and they were constrained by different sensory modalities, valence of the emotional events, and target durations. Biases in time perception could be accounted for by a

Predator cat odors activate sexual arousal pathways in brains of Toxoplasma gondii infected rats.

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Patrick K House

Full Text Available Cat odors induce rapid, innate and stereotyped defensive behaviors in rats at first exposure, a presumed response to the evolutionary pressures of predation. Bizarrely, rats infected with the brain parasite Toxoplasma gondii approach the cat odors they typically avoid. Since the protozoan Toxoplasma requires the cat to sexually reproduce, this change in host behavior is thought to be a remarkable example of a parasite manipulating a mammalian host for its own benefit. Toxoplasma does not influence host response to non-feline predator odor nor does it alter behavior on olfactory, social, fear or anxiety tests, arguing for specific manipulation in the processing of cat odor. We report that Toxoplasma infection alters neural activity in limbic brain areas necessary for innate defensive behavior in response to cat odor. Moreover, Toxoplasma increases activity in nearby limbic regions of sexual attraction when the rat is exposed to cat urine, compelling evidence that Toxoplasma overwhelms the innate fear response by causing, in its stead, a type of sexual attraction to the normally aversive cat odor.

Predator cat odors activate sexual arousal pathways in brains of Toxoplasma gondii infected rats.

Science.gov (United States)

House, Patrick K; Vyas, Ajai; Sapolsky, Robert

2011-01-01

Cat odors induce rapid, innate and stereotyped defensive behaviors in rats at first exposure, a presumed response to the evolutionary pressures of predation. Bizarrely, rats infected with the brain parasite Toxoplasma gondii approach the cat odors they typically avoid. Since the protozoan Toxoplasma requires the cat to sexually reproduce, this change in host behavior is thought to be a remarkable example of a parasite manipulating a mammalian host for its own benefit. Toxoplasma does not influence host response to non-feline predator odor nor does it alter behavior on olfactory, social, fear or anxiety tests, arguing for specific manipulation in the processing of cat odor. We report that Toxoplasma infection alters neural activity in limbic brain areas necessary for innate defensive behavior in response to cat odor. Moreover, Toxoplasma increases activity in nearby limbic regions of sexual attraction when the rat is exposed to cat urine, compelling evidence that Toxoplasma overwhelms the innate fear response by causing, in its stead, a type of sexual attraction to the normally aversive cat odor.

Development switch in neural circuitry underlying odor-malaise learning.

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Shionoya, Kiseko; Moriceau, Stephanie; Lunday, Lauren; Miner, Cathrine; Roth, Tania L; Sullivan, Regina M

2006-01-01

Fetal and infant rats can learn to avoid odors paired with illness before development of brain areas supporting this learning in adults, suggesting an alternate learning circuit. Here we begin to document the transition from the infant to adult neural circuit underlying odor-malaise avoidance learning using LiCl (0.3 M; 1% of body weight, ip) and a 30-min peppermint-odor exposure. Conditioning groups included: Paired odor-LiCl, Paired odor-LiCl-Nursing, LiCl, and odor-saline. Results showed that Paired LiCl-odor conditioning induced a learned odor aversion in postnatal day (PN) 7, 12, and 23 pups. Odor-LiCl Paired Nursing induced a learned odor preference in PN7 and PN12 pups but blocked learning in PN23 pups. 14C 2-deoxyglucose (2-DG) autoradiography indicated enhanced olfactory bulb activity in PN7 and PN12 pups with odor preference and avoidance learning. The odor aversion in weanling aged (PN23) pups resulted in enhanced amygdala activity in Paired odor-LiCl pups, but not if they were nursing. Thus, the neural circuit supporting malaise-induced aversions changes over development, indicating that similar infant and adult-learned behaviors may have distinct neural circuits.

Sex-specific selection for MHC variability in Alpine chamois

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Schaschl Helmut

2012-02-01

Full Text Available Abstract Background In mammals, males typically have shorter lives than females. This difference is thought to be due to behavioural traits which enhance competitive abilities, and hence male reproductive success, but impair survival. Furthermore, in many species males usually show higher parasite burden than females. Consequently, the intensity of selection for genetic factors which reduce susceptibility to pathogens may differ between sexes. High variability at the major histocompatibility complex (MHC genes is believed to be advantageous for detecting and combating the range of infectious agents present in the environment. Increased heterozygosity at these immune genes is expected to be important for individual longevity. However, whether males in natural populations benefit more from MHC heterozygosity than females has rarely been investigated. We investigated this question in a long-term study of free-living Alpine chamois (Rupicapra rupicapra, a polygynous mountain ungulate. Results Here we show that male chamois survive significantly (P = 0.022 longer if heterozygous at the MHC class II DRB locus, whereas females do not. Improved survival of males was not a result of heterozygote advantage per se, as background heterozygosity (estimated across twelve microsatellite loci did not change significantly with age. Furthermore, reproductively active males depleted their body fat reserves earlier than females leading to significantly impaired survival rates in this sex (P Conclusions Increased MHC class II DRB heterozygosity with age in males, suggests that MHC heterozygous males survive longer than homozygotes. Reproductively active males appear to be less likely to survive than females most likely because of the energetic challenge of the winter rut, accompanied by earlier depletion of their body fat stores, and a generally higher parasite burden. This scenario renders the MHC-mediated immune response more important for males than for females

Body odor quality predicts behavioral attractiveness in humans.

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Roberts, S Craig; Kralevich, Alexandra; Ferdenzi, Camille; Saxton, Tamsin K; Jones, Benedict C; DeBruine, Lisa M; Little, Anthony C; Havlicek, Jan

2011-12-01

Growing effort is being made to understand how different attractive physical traits co-vary within individuals, partly because this might indicate an underlying index of genetic quality. In humans, attention has focused on potential markers of quality such as facial attractiveness, axillary odor quality, the second-to-fourth digit (2D:4D) ratio and body mass index (BMI). Here we extend this approach to include visually-assessed kinesic cues (nonverbal behavior linked to movement) which are statistically independent of structural physical traits. The utility of such kinesic cues in mate assessment is controversial, particularly during everyday conversational contexts, as they could be unreliable and susceptible to deception. However, we show here that the attractiveness of nonverbal behavior, in 20 male participants, is predicted by perceived quality of their axillary body odor. This finding indicates covariation between two desirable traits in different sensory modalities. Depending on two different rating contexts (either a simple attractiveness rating or a rating for long-term partners by 10 female raters not using hormonal contraception), we also found significant relationships between perceived attractiveness of nonverbal behavior and BMI, and between axillary odor ratings and 2D:4D ratio. Axillary odor pleasantness was the single attribute that consistently predicted attractiveness of nonverbal behavior. Our results demonstrate that nonverbal kinesic cues could reliably reveal mate quality, at least in males, and could corroborate and contribute to mate assessment based on other physical traits.

F pocket flexibility influences the tapasin dependence of two differentially disease-associated MHC Class I proteins.

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Abualrous, Esam T; Fritzsche, Susanne; Hein, Zeynep; Al-Balushi, Mohammed S; Reinink, Peter; Boyle, Louise H; Wellbrock, Ursula; Antoniou, Antony N; Springer, Sebastian

2015-04-01

The human MHC class I protein HLA-B*27:05 is statistically associated with ankylosing spondylitis, unlike HLA-B*27:09, which differs in a single amino acid in the F pocket of the peptide-binding groove. To understand how this unique amino acid difference leads to a different behavior of the proteins in the cell, we have investigated the conformational stability of both proteins using a combination of in silico and experimental approaches. Here, we show that the binding site of B*27:05 is conformationally disordered in the absence of peptide due to a charge repulsion at the bottom of the F pocket. In agreement with this, B*27:05 requires the chaperone protein tapasin to a greater extent than the conformationally stable B*27:09 in order to remain structured and to bind peptide. Taken together, our data demonstrate a method to predict tapasin dependence and physiological behavior from the sequence and crystal structure of a particular class I allotype. Also watch the Video Abstract. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preservation of Essential Odor-Guided Behaviors and Odor-Based Reversal Learning after Targeting Adult Brain Serotonin Synthesis.

Science.gov (United States)

Carlson, Kaitlin S; Whitney, Meredith S; Gadziola, Marie A; Deneris, Evan S; Wesson, Daniel W

2016-01-01

The neurotransmitter serotonin (5-HT) is considered a powerful modulator of sensory system organization and function in a wide range of animals. The olfactory system is innervated by midbrain 5-HT neurons into both its primary and secondary odor-processing stages. Facilitated by this circuitry, 5-HT and its receptors modulate olfactory system function, including odor information input to the olfactory bulb. It is unknown, however, whether the olfactory system requires 5-HT for even its most basic behavioral functions. To address this question, we established a conditional genetic approach to specifically target adult brain tryptophan hydroxylase 2 ( Tph2 ), encoding the rate-limiting enzyme in brain 5-HT synthesis, and nearly eliminate 5-HT from the mouse forebrain. Using this novel model, we investigated the behavior of 5-HT-depleted mice during performance in an olfactory go/no-go task. Surprisingly, the near elimination of 5-HT from the forebrain, including the olfactory bulbs, had no detectable effect on the ability of mice to perform the odor-based task. Tph2 -targeted mice not only were able to learn the task, but also had levels of odor acuity similar to those of control mice when performing coarse odor discrimination. Both groups of mice spent similar amounts of time sampling odors during decision-making. Furthermore, odor reversal learning was identical between 5-HT-depleted and control mice. These results suggest that 5-HT neurotransmission is not necessary for the most essential aspects of olfaction, including odor learning, discrimination, and certain forms of cognitive flexibility.

Body odors promote automatic imitation in autism.

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Parma, Valentina; Bulgheroni, Maria; Tirindelli, Roberto; Castiello, Umberto

2013-08-01

Autism spectrum disorders comprise a range of neurodevelopmental pathologies characterized, among other symptoms, by impaired social interactions. Individuals with this diagnosis are reported to often identify people by repetitively sniffing pieces of clothing or the body odor of family members. Since body odors are known to initiate and mediate many different social behaviors, smelling the body odor of a family member might constitute a sensory-based action promoting social contact. In light of this, we hypothesized that the body odor of a family member would facilitate the appearance of automatic imitation, an essential social skill known to be impaired in autism. We recruited 20 autistic and 20 typically developing children. Body odors were collected from the children's mothers' axillae. A child observed a model (their mother or a stranger mother) execute (or not) a reach-to-grasp action toward an object. Subsequently, she performed the same action. The object was imbued with the child's mother's odor, a stranger mother's odor, or no odor. The actions were videotaped, and movement time was calculated post hoc via a digitalization technique. Automatic imitation effects-expressed in terms of total movement time reduction-appear in autistic children only when exposed to objects paired with their own mother's odor. The maternal odor, which conveys a social message otherwise neglected, helps autistic children to covertly imitate the actions of others. Our results represent a starting point holding theoretical and practical relevance for the development of new strategies to enhance communication and social behavior among autistic individuals. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Body Odor (For Young Men)

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... Sexual Health Medical Conditions Nutrition & Fitness Emotional Health Body Odor Posted under Health Guides . Updated 23 March 2017. + ... every guy has to deal with. What causes body odor? During puberty, your sweat glands become much more ...

Semi-empirical quantum evaluation of peptide - MHC class II binding

Science.gov (United States)

González, Ronald; Suárez, Carlos F.; Bohórquez, Hugo J.; Patarroyo, Manuel A.; Patarroyo, Manuel E.

2017-01-01

Peptide presentation by the major histocompatibility complex (MHC) is a key process for triggering a specific immune response. Studying peptide-MHC (pMHC) binding from a structural-based approach has potential for reducing the costs of investigation into vaccine development. This study involved using two semi-empirical quantum chemistry methods (PM7 and FMO-DFTB) for computing the binding energies of peptides bonded to HLA-DR1 and HLA-DR2. We found that key stabilising water molecules involved in the peptide binding mechanism were required for finding high correlation with IC50 experimental values. Our proposal is computationally non-intensive, and is a reliable alternative for studying pMHC binding interactions.

Effects of Odor on Emotion, with Implications

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Mikiko eKadohisa

2013-10-01

Full Text Available The sense of smell is found widely in the animal kingdom. Human and animal studies show that odor perception is modulated by experience and/or physiological state (such as hunger, and that some odors can arouse emotion, and can lead to the recall of emotional memories. Further, odors can influence psychological and physiological states. Individual odorants are mapped via gene-specified receptors to corresponding glomeruli in the olfactory bulb, which directly projects to the piriform cortex and the amygdala without a thalamic relay. The odors to which a glomerulus responds reflect the chemical structure of the odorant. The piriform cortex and the amygdala both project to the orbitofrontal cortex which with the amygdala is involved in emotion and associative learning, and to the entorhinal/hippocampal system which is involved in long-term memory including episodic memory. Evidence that some odors can modulate emotion and cognition is described, and the possible implications for the treatment of psychological problems, for example in reducing the effects of stress, are considered.

B. abortus RNA is the component involved in the down-modulation of MHC-I expression on human monocytes via TLR8 and the EGFR pathway

Science.gov (United States)

Milillo, M. Ayelén; Velásquez, Lis N.; Trotta, Aldana; Delpino, M. Victoria; Balboa, Luciana; Vermeulen, Mónica; Espindola, Sonia L.; Rodriguez-Rodrigues, Nahuel; Fernández, Gabriela C.; Oliveira, Sergio Costa; Giambartolomei, Guillermo H.

2017-01-01

Despite eliciting a potent CD8+ T cell response, Brucella abortus is able to persist and establish a chronic infection inside its host. We have previously reported that the infection of human monocytes/macrophages with B. abortus inhibits the IFN-γ-induced MHC-I cell surface expression down-modulating cytotoxic CD8+ T cell responses. MHC-I down-modulation depends on bacterial viability and results from the capacity of B. abortus to retain the MHC-I molecules within the Golgi apparatus. Furthermore, we recently demonstrated that epidermal growth factor receptor (EGFR) pathway is involved in this phenomenon and that this is an early event during infection. However, the components and mechanisms whereby B. abortus is able to down-modulate MHC-I remained to be elucidated. In this study we demonstrated that the down-modulation of MHC-I expression is not mediated by well-known Brucella virulence factors but instead by B. abortus RNA, a PAMP associated to viability (vita-PAMP). Surprisingly, completely degraded RNA was also able to inhibit MHC-I expression to the same extent as intact RNA. Accordingly, B. abortus RNA and its degradation products were able to mimic the MHC-I intracellular retention within the Golgi apparatus observed upon infection. We further demonstrated that TLR8, a single-stranded RNA and RNA degradation products sensor, was involved in MHC-I inhibition. On the other hand, neutralization of the EGFR reversed the MHC-I inhibition, suggesting a connection between the TLR8 and EGFR pathways. Finally, B. abortus RNA-treated macrophages display diminished capacity of antigen presentation to CD8+ T cells. Overall, our results indicate that the vita-PAMP RNA as well as its degradation products constitute novel virulence factors whereby B. abortus, by a TLR8-dependent mechanism and through the EGFR pathway, inhibits the IFN-γ-induced MHC-I surface expression on human monocytes/macrophages. Thus, bacteria can hide within infected cells and avoid the

B. abortus RNA is the component involved in the down-modulation of MHC-I expression on human monocytes via TLR8 and the EGFR pathway.

Directory of Open Access Journals (Sweden)

M Ayelén Milillo

2017-08-01

Full Text Available Despite eliciting a potent CD8+ T cell response, Brucella abortus is able to persist and establish a chronic infection inside its host. We have previously reported that the infection of human monocytes/macrophages with B. abortus inhibits the IFN-γ-induced MHC-I cell surface expression down-modulating cytotoxic CD8+ T cell responses. MHC-I down-modulation depends on bacterial viability and results from the capacity of B. abortus to retain the MHC-I molecules within the Golgi apparatus. Furthermore, we recently demonstrated that epidermal growth factor receptor (EGFR pathway is involved in this phenomenon and that this is an early event during infection. However, the components and mechanisms whereby B. abortus is able to down-modulate MHC-I remained to be elucidated. In this study we demonstrated that the down-modulation of MHC-I expression is not mediated by well-known Brucella virulence factors but instead by B. abortus RNA, a PAMP associated to viability (vita-PAMP. Surprisingly, completely degraded RNA was also able to inhibit MHC-I expression to the same extent as intact RNA. Accordingly, B. abortus RNA and its degradation products were able to mimic the MHC-I intracellular retention within the Golgi apparatus observed upon infection. We further demonstrated that TLR8, a single-stranded RNA and RNA degradation products sensor, was involved in MHC-I inhibition. On the other hand, neutralization of the EGFR reversed the MHC-I inhibition, suggesting a connection between the TLR8 and EGFR pathways. Finally, B. abortus RNA-treated macrophages display diminished capacity of antigen presentation to CD8+ T cells. Overall, our results indicate that the vita-PAMP RNA as well as its degradation products constitute novel virulence factors whereby B. abortus, by a TLR8-dependent mechanism and through the EGFR pathway, inhibits the IFN-γ-induced MHC-I surface expression on human monocytes/macrophages. Thus, bacteria can hide within infected cells and

MHC class II+ (HLA-DP-like) cells in the cow reproductive tract: II. Immunolocalization of MHC class II+ cells in oviduct and vagina.

Science.gov (United States)

Eren, U; Kum, S; Sandikçi, M; Eren, V; Ilhan, F

2009-08-01

The aim of this study was to determine and examine the distribution of major frequency MHC II+ cells in the oviduct and vagina of cows during the oestrous and dioestrus phases. Right oviduct (ampulla, isthmus) and vaginal samples taken from a total of twenty seven multiparous cows were used. Tissue samples were processed to obtain both cryostat and paraffin sections. Sections were stained immunocytochemically using StreptABC method using a specific monoclonal antibody to MHC II+ cell population. Intra-epithelial and subepithelial areas along with lamina propria, muscularis mucosae and serosa of both ampulla and isthmus and intra-epithelial/subepithelial areas and mucosae of vagina were examined for the presence of MHC II+ cells. The density of immune positive cells was determined using a subjective scoring system. MHC II+ cells were demonstrated in all areas examined in both oestrus and dioestrus. In oestrus, the density of MHC II+ cells decreased in subepithelial areas (in between the epithelial cells and the basal membrane) of isthmus, whereas the density of immune positive cells was increased in muscularis mucosae of isthmus (P < 0.05), lamina propria and muscularis mucosae of ampulla (P < 0.05) as well as in the mucosae of vagina (P MHC II+ cells observed in the oviduct and vagina increases in the majority of areas examined due to the effect of oestrogen.

pH dependence of the interaction between immunogenic peptides and MHC class II molecules. Evidence for an acidic intracellular compartment being the organelle of interaction

DEFF Research Database (Denmark)

Mouritsen, S; Buus, Anette Stryhn; Petersen, B L

1992-01-01

and most notably in the endosome-lysosome compartment in which Ag processing is thought to occur. Thus, Ag processing and interaction with MHC class II molecules can potentially happen in the very same compartment. This yet undefined acidic compartment would have to contain proteolytic enzymes and MHC...

Polymorphism at Expressed DQ and DR Loci in Five Common Equine MHC Haplotypes

Science.gov (United States)

Miller, Donald; Tallmadge, Rebecca L.; Binns, Matthew; Zhu, Baoli; Mohamoud, Yasmin Ali; Ahmed, Ayeda; Brooks, Samantha A.; Antczak, Douglas F.

2016-01-01

The polymorphism of Major Histocompatibility Complex (MHC) class II DQ and DR genes in five common Equine Leukocyte Antigen (ELA) haplotypes was determined through sequencing of mRNA transcripts isolated from lymphocytes of eight ELA homozygous horses. Ten expressed MHC class II genes were detected in horses of the ELA-A3 haplotype carried by the donor horses of the equine Bacterial Artificial Chromosome (BAC) library and the reference genome sequence: four DR genes and six DQ genes. The other four ELA haplotypes contained at least eight expressed polymorphic MHC class II loci. Next Generation Sequencing (NGS) of genomic DNA of these four MHC haplotypes revealed stop codons in the DQA3 gene in the ELA-A2, ELA-A5, and ELA-A9 haplotypes. Few NGS reads were obtained for the other MHC class II genes that were not amplified in these horses. The amino acid sequences across haplotypes contained locus-specific residues, and the locus clusters produced by phylogenetic analysis were well supported. The MHC class II alleles within the five tested haplotypes were largely non-overlapping between haplotypes. The complement of equine MHC class II DQ and DR genes appears to be well conserved between haplotypes, in contrast to the recently described variation in class I gene loci between equine MHC haplotypes. The identification of allelic series of equine MHC class II loci will aid comparative studies of mammalian MHC conservation and evolution and may also help to interpret associations between the equine MHC class II region and diseases of the horse. PMID:27889800

BG1 has a major role in MHC-linked resistance to malignant lymphoma in the chicken.

Science.gov (United States)

Goto, Ronald M; Wang, Yujun; Taylor, Robert L; Wakenell, Patricia S; Hosomichi, Kazuyoshi; Shiina, Takashi; Blackmore, Craig S; Briles, W Elwood; Miller, Marcia M

2009-09-29

Pathogen selection is postulated to drive MHC allelic diversity at loci for antigen presentation. However, readily apparent MHC infectious disease associations are rare in most species. The strong link between MHC-B haplotype and the occurrence of virally induced tumors in the chicken provides a means for defining the relationship between pathogen selection and MHC polymorphism. Here, we verified a significant difference in resistance to gallid herpesvirus-2 (GaHV-2)-induced lymphomas (Marek's disease) conferred by two closely-related recombinant MHC-B haplotypes. We mapped the crossover breakpoints that distinguish these haplotypes to the highly polymorphic BG1 locus. BG1 encodes an Ig-superfamily type I transmembrane receptor-like protein that contains an immunoreceptor tyrosine-based inhibition motif (ITIM), which undergoes phosphorylation and is recognized by Src homology 2 domain-containing protein tyrosine phosphatase (SHP-2). The recombinant haplotypes are identical, except for differences within the BG1 3'-untranslated region (3'-UTR). The 3'-UTR of the BG1 allele associated with increased lymphoma contains a 225-bp insert of retroviral origin and showed greater inhibition of luciferase reporter gene translation compared to the other allele. These findings suggest that BG1 could affect the outcome of GaHV-2 infection through modulation of the lymphoid cell responsiveness to infection, a condition that is critical for GaHV-2 replication and in which the MHC-B haplotype has been previously implicated. This work provides a mechanism by which MHC-B region genetics contributes to the incidence of GaHV-2-induced malignant lymphoma in the chicken and invites consideration of the possibility that similar mechanisms might affect the incidence of lymphomas associated with other oncogenic viral infections.

MHC class II deficiency: Report of a novel mutation and special review.

Science.gov (United States)

Farrokhi, S; Shabani, M; Aryan, Z; Zoghi, S; Krolo, A; Boztug, K; Rezaei, N

The MHC II deficiency is a rare autosomal recessive primary immunodeficiency syndrome with increased susceptibility to respiratory and gastrointestinal infections, failure to thrive and early mortality. This syndrome is caused by mutations in transcription regulators of the MHC II gene and results in development of blind lymphocytes due to the lack of indicatory MHC II molecules. Despite homogeneity of clinical manifestations of patients with MHC II deficiency, the genetic defects underlying this disease are heterogeneous. Herein, we report an Iranian patient with MHC II deficiency harbouring a novel mutation in RFXANK and novel misleading clinical features. He had ataxic gait and dysarthria from 30 months of age. Epidemiology, clinical and immunological features, therapeutic options and prognosis of patients with MHC II are reviewed in this paper. Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

Quantitative method to determine the regional drinking water odorant regulation goals based on odor sensitivity distribution: illustrated using 2-MIB.

Science.gov (United States)

Yu, Jianwei; An, Wei; Cao, Nan; Yang, Min; Gu, Junong; Zhang, Dong; Lu, Ning

2014-07-01

Taste and odor (T/O) in drinking water often cause consumer complaints and are thus regulated in many countries. However, people in different regions may exhibit different sensitivities toward T/O. This study proposed a method to determine the regional drinking water odorant regulation goals (ORGs) based on the odor sensitivity distribution of the local population. The distribution of odor sensitivity to 2-methylisoborneol (2-MIB) by the local population in Beijing, China was revealed by using a normal distribution function/model to describe the odor complaint response to a 2-MIB episode in 2005, and a 2-MIB concentration of 12.9 ng/L and FPA (flavor profile analysis) intensity of 2.5 was found to be the critical point to cause odor complaints. Thus the Beijing ORG for 2-MIB was determined to be 12.9 ng/L. Based on the assumption that the local FPA panel can represent the local population in terms of sensitivity to odor, and that the critical FPA intensity causing odor complaints was 2.5, this study tried to determine the ORGs for seven other cities of China by performing FPA tests using an FPA panel from the corresponding city. ORG values between 12.9 and 31.6 ng/L were determined, showing that a unified ORG may not be suitable for drinking water odor regulations. This study presents a novel approach for setting drinking water odor regulations. Copyright © 2014. Published by Elsevier B.V.

Female perception of male body odor.

Science.gov (United States)

Sergeant, Mark J T

2010-01-01

Olfaction is one of the most crucial forms of communication among nonhuman animals. Historically, olfaction has been perceived as being of limited importance for humans, but recent research has documented that not only do humans have sensitive olfactory abilities, but also odors have the potential to influence our physiology and behavior. This chapter reviews research on olfactory communication among humans, focusing on the effects of male bodily odors on female physiology and behavior. The process of body odor production and the detection of olfactory signals are reviewed, focusing on potential sex differences in these abilities. The effects of male body odors on female physiological and behavioral effects of body odors are considered. Finally, with specific regard to female mate choice, evidence regarding the influence of the major histocompatibility complex and fluctuating asymmetry on male olfactory cues is reviewed. Copyright © 2010 Elsevier Inc. All rights reserved.

Altered Olfactory Processing of Stress Related Body Odors and Artificial Odors in Patients with Panic Disorder

OpenAIRE

Wintermann, Gloria-Beatrice; Donix, Markus; Joraschky, Peter; Gerber, Johannes; Petrowski, Katja

2014-01-01

Background: Patients with Panic Disorder (PD) direct their attention towards potential threat, followed by panic attacks, and increased sweat production. Onés own anxiety sweat odor influences the attentional focus, and discrimination of threat or non-threat. Since olfactory projection areas overlap with neuronal areas of a panic-specific fear network, the present study investigated the neuronal processing of odors in general and of stress-related sweat odors in particular in patients with PD...

The systems biology of MHC class II antigen presentation

NARCIS (Netherlands)

Paul, Petra

2012-01-01

Major histocompatibility class II molecules (MHC class II) are one of the key regulators of adaptive immunity because of their specific expression by professional antigen presenting cells (APC). They present peptides derived from endocytosed material to T helper lymphocytes. Consequently, MHC class

MHC2NNZ: A novel peptide binding prediction approach for HLA DQ molecules

Science.gov (United States)

Xie, Jiang; Zeng, Xu; Lu, Dongfang; Liu, Zhixiang; Wang, Jiao

2017-07-01

The major histocompatibility complex class II (MHC-II) molecule plays a crucial role in immunology. Computational prediction of MHC-II binding peptides can help researchers understand the mechanism of immune systems and design vaccines. Most of the prediction algorithms for MHC-II to date have made large efforts in human leukocyte antigen (HLA, the name of MHC in Human) molecules encoded in the DR locus. However, HLA DQ molecules are equally important and have only been made less progress because it is more difficult to handle them experimentally. In this study, we propose an artificial neural network-based approach called MHC2NNZ to predict peptides binding to HLA DQ molecules. Unlike previous artificial neural network-based methods, MHC2NNZ not only considers sequence similarity features but also captures the chemical and physical properties, and a novel method incorporating these properties is proposed to represent peptide flanking regions (PFR). Furthermore, MHC2NNZ improves the prediction accuracy by combining with amino acid preference at more specific positions of the peptides binding core. By evaluating on 3549 peptides binding to six most frequent HLA DQ molecules, MHC2NNZ is demonstrated to outperform other state-of-the-art MHC-II prediction methods.

Identification of T1D susceptibility genes within the MHC region by combining protein interaction networks and SNP genotyping data

DEFF Research Database (Denmark)

Brorsson, C.; Hansen, Niclas Tue; Hansen, Kasper Lage

2009-01-01

genes. We have developed a novel method that combines single nucleotide polymorphism (SNP) genotyping data with protein-protein interaction (ppi) networks to identify disease-associated network modules enriched for proteins encoded from the MHC region. Approximately 2500 SNPs located in the 4 Mb MHC......To develop novel methods for identifying new genes that contribute to the risk of developing type 1 diabetes within the Major Histocompatibility Complex (MHC) region on chromosome 6, independently of the known linkage disequilibrium (LD) between human leucocyte antigen (HLA)-DRB1, -DQA1, -DQB1...... region were analysed in 1000 affected offspring trios generated by the Type 1 Diabetes Genetics Consortium (T1DGC). The most associated SNP in each gene was chosen and genes were mapped to ppi networks for identification of interaction partners. The association testing and resulting interacting protein...

The effect of meat consumption on body odor attractiveness.

Science.gov (United States)

Havlicek, Jan; Lenochova, Pavlina

2006-10-01

Axillary body odor is individually specific and potentially a rich source of information about its producer. Odor individuality partly results from genetic individuality, but the influence of ecological factors such as eating habits are another main source of odor variability. However, we know very little about how particular dietary components shape our body odor. Here we tested the effect of red meat consumption on body odor attractiveness. We used a balanced within-subject experimental design. Seventeen male odor donors were on "meat" or "nonmeat" diet for 2 weeks wearing axillary pads to collect body odor during the final 24 h of the diet. Fresh odor samples were assessed for their pleasantness, attractiveness, masculinity, and intensity by 30 women not using hormonal contraceptives. We repeated the same procedure a month later with the same odor donors, each on the opposite diet than before. Results of repeated measures analysis of variance showed that the odor of donors when on the nonmeat diet was judged as significantly more attractive, more pleasant, and less intense. This suggests that red meat consumption has a negative impact on perceived body odor hedonicity.

Cell surface appearance of unexpected host MHC determinants on thymocytes from radiation bone marrow chimeras

International Nuclear Information System (INIS)

Sharrow, S.O.; Mathieson, B.J.; Singer, A.

1981-01-01

The phenotypic appearance of cell surface antigens on murine thymocytes from long-term radiation bone marrow chimeras was analyzed using indirect immunofluorescence and flow microfluorometry. Cells maturing in the thymi of these mice were typed for MHC (Kk, I-Ak, H-2b, Kb, and Ib) and non-MHC (Lty 1, Ly 9, and TL) determinants. All cells were of donor origin as determined by non-MHC (Ly) phenotype in P1 leads to P2, P1 x P2 leads to P1, and P1 leads to P2 radiation chimeras. In contrast, the MHC phenotypes of these thymocytes were markedly affected by the host environment. Specifically, H-2 and I-A determinants of both parental phenotypes were detected on thymocytes from P1 leads to P1 x P2 chimeras; I-A determinants of host phenotype were present, whereas I-A determinants of donor phenotype were reduced on thymocytes from P1 x P2 leads to P1 chimeras; and thymocytes from P1 leads to P2 chimeras possessed H-2 and I-A determinants of host phenotype but showed reduction of donor I-A phenotype determinants. The appearance of host cell surface H-2 and I-A determinants on thymocytes from chimeras closely parallels the functional recognition of MHC determinants by T cells from chimeric mice and thus may be significantly related to the development of the self-recognition repertoire by maturing T cells

Unpleasant odors increase aversion to monetary losses.

Science.gov (United States)

Stancak, Andrej; Xie, Yuxin; Fallon, Nicholas; Bulsing, Patricia; Giesbrecht, Timo; Thomas, Anna; Pantelous, Athanasios A

2015-04-01

Loss aversion is the tendency to prefer avoiding losses over acquiring gains of equal nominal values. Unpleasant odors not only influence affective state but have also been shown to activate brain regions similar to those mediating loss aversion. Therefore, we hypothesized a stronger loss aversion in a monetary gamble task if gambles were associated with an unpleasant as opposed to pleasant odor. In thirty human subjects, unpleasant (methylmercaptan), pleasant (jasmine), and neutral (clean air) odors were presented for 4 s. At the same time, uncertain gambles offering an equal chance of gain or loss of a variable amount of money, or a prospect of an assured win were displayed. One hundred different gambles were presented three times, each time paired with a different odor. Loss aversion, risk aversion, and logit sensitivity were evaluated using non-linear fitting of individual gamble decisions. Loss aversion was larger when prospects were displayed in the presence of methylmercaptan compared to jasmine or clean air. Moreover, individual differences in changes in loss aversion to the unpleasant as compared to pleasant odor correlated with odor pleasantness but not with odor intensity. Skin conductance responses to losses during the outcome period were larger when gambles were associated with methylmercaptan compared to jasmine. Increased loss aversion while perceiving an unpleasant odor suggests a dynamic adjustment of loss aversion toward greater sensitivity to losses. Given that odors are biological signals of hazards, such adjustment of loss aversion may have adaptive value in situations entailing threat or danger. Copyright © 2015 Elsevier B.V. All rights reserved.

Thymic repopulation following intrathymic injection of mouse bone marrow cells in MHC matched and mismatched recipients

International Nuclear Information System (INIS)

Chervenak, R.

1986-01-01

T cell precursors (pre-T cells) have traditionally been detected by their ability to repopulate the thymus of heavily irradiated mice following intravenous injection. Recently, Goldschneider et. al. developed an assay system which involves the direct injection of pre-T cells into the thymus. The authors used this technique to evaluate the ability of bone marrow cells to repopulate thymuses in various donor-host strain combinations. Sub-lethally irradiated (600R) mice were injected intrathymically with 2 x 10 6 bone marrow cells which differed from the recipient with respect to their Thy 1 allotype. The percentage of thymus cells expressing either the donor or recipient type Thy 1 marker was determined 14 to 21 days after injection. These experiments showed that in MHC matched donor-host combinations (AKR/cum → AKR/J and CBA/J → AKR/J), cells derived from the donor inoculum accounted for 40% to 75% of the total thymus population. MHC mismatched donor-host combinations (C57BL/6J → AKR/J and Balb/c → AKR/J) resulted in significantly less donor-type repopulation of the thymus. In these cases, donor repopulation typically ranged from 0% to 4%. The ability of the pre-T cells detected by intrathymic injection to proliferate in the thymic environment, therefore, appears to be influenced by the MHC. This may reflect commitment of pre-T cells to MHC haplotype recognition prior to their migration to the thymus

Absence of linkage between MHC and a gene involved in susceptibility to human schistosomiasis

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Chiarella J.M.

1998-01-01

Full Text Available Six hundred million people are at risk of infection by Schistosoma mansoni. MHC haplotypes have been reported to segregate with susceptibility to schistosomiasis in murine models. In humans, a major gene related to susceptibility/resistance to infection by S. mansoni (SM1 and displaying the mean fecal egg count as phenotype was detected by segregation analysis. This gene displayed a codominant mode of inheritance with an estimated frequency of 0.20-0.25 for the deleterious allele and accounted for more than 50% of the variance of infection levels. To determine if the SM1 gene segregates with the human MHC chromosomal region, we performed a linkage study by the lod score method. We typed for HLA-A, B, C, DR and DQ antigens in 11 informative families from an endemic area for schistosomiasis in Bahia, Brazil, by the microlymphocytotoxicity technique. HLA-DR typing by the polymerase chain reaction with sequence-specific primers (PCR-SSP and HLA-DQ were confirmed by PCR-sequence-specific oligonucleotide probes (PCR-SSOP. The lod scores for the different q values obtained clearly indicate that there is no physical linkage between HLA and SM1 genes. Thus, susceptibility or resistance to schistosomiasis, as defined by mean fecal egg count, is not primarily dependent on the host's HLA profile. However, if the HLA molecule plays an important role in specific immune responses to S. mansoni, this may involve the development of the different clinical aspects of the disease such as granuloma formation and development of hepatosplenomegaly.

TMEM129 is a Derlin-1 associated ERAD E3 ligase essential for virus-induced degradation of MHC-I.

Science.gov (United States)

van den Boomen, Dick J H; Timms, Richard T; Grice, Guinevere L; Stagg, Helen R; Skødt, Karsten; Dougan, Gordon; Nathan, James A; Lehner, Paul J

2014-08-05

The US11 gene product of human cytomegalovirus promotes viral immune evasion by hijacking the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway. US11 initiates dislocation of newly translocated MHC I from the ER to the cytosol for proteasome-mediated degradation. Despite the critical role for ubiquitin in this degradation pathway, the responsible E3 ligase is unknown. In a forward genetic screen for host ERAD components hijacked by US11 in near-haploid KBM7 cells, we identified TMEM129, an uncharacterized polytopic membrane protein. TMEM129 is essential and rate-limiting for US11-mediated MHC-I degradation and acts as a novel ER resident E3 ubiquitin ligase. TMEM129 contains an unusual cysteine-only RING with intrinsic E3 ligase activity and is recruited to US11 via Derlin-1. Together with its E2 conjugase Ube2J2, TMEM129 is responsible for the ubiquitination, dislocation, and subsequent degradation of US11-associated MHC-I. US11 engages two degradation pathways: a Derlin-1/TMEM129-dependent pathway required for MHC-I degradation and a SEL1L/HRD1-dependent pathway required for "free" US11 degradation. Our data show that TMEM129 is a novel ERAD E3 ligase and the central component of a novel mammalian ERAD complex.

NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8-11

DEFF Research Database (Denmark)

Lundegaard, Claus; Lamberth, K; Harndahl, M

2008-01-01

NetMHC-3.0 is trained on a large number of quantitative peptide data using both affinity data from the Immune Epitope Database and Analysis Resource (IEDB) and elution data from SYFPEITHI. The method generates high-accuracy predictions of major histocompatibility complex (MHC): peptide binding...

The olfactory tubercle encodes odor valence in behaving mice.

Science.gov (United States)

Gadziola, Marie A; Tylicki, Kate A; Christian, Diana L; Wesson, Daniel W

2015-03-18

Sensory information acquires meaning to adaptively guide behaviors. Despite odors mediating a number of vital behaviors, the components of the olfactory system responsible for assigning meaning to odors remain unclear. The olfactory tubercle (OT), a ventral striatum structure that receives monosynaptic input from the olfactory bulb, is uniquely positioned to transform odor information into behaviorally relevant neural codes. No information is available, however, on the coding of odors among OT neurons in behaving animals. In recordings from mice engaged in an odor discrimination task, we report that the firing rate of OT neurons robustly and flexibly encodes the valence of conditioned odors over identity, with rewarded odors evoking greater firing rates. This coding of rewarded odors occurs before behavioral decisions and represents subsequent behavioral responses. We predict that the OT is an essential region whereby odor valence is encoded in the mammalian brain to guide goal-directed behaviors. Copyright © 2015 the authors 0270-6474/15/354515-13$15.00/0.

An MHC class I immune evasion gene of Marek׳s disease virus.

Science.gov (United States)

Hearn, Cari; Preeyanon, Likit; Hunt, Henry D; York, Ian A

2015-01-15

Marek׳s disease virus (MDV) is a widespread α-herpesvirus of chickens that causes T cell tumors. Acute, but not latent, MDV infection has previously been shown to lead to downregulation of cell-surface MHC class I (Virology 282:198-205 (2001)), but the gene(s) involved have not been identified. Here we demonstrate that an MDV gene, MDV012, is capable of reducing surface expression of MHC class I on chicken cells. Co-expression of an MHC class I-binding peptide targeted to the endoplasmic reticulum (bypassing the requirement for the TAP peptide transporter) partially rescued MHC class I expression in the presence of MDV012, suggesting that MDV012 is a TAP-blocking MHC class I immune evasion protein. This is the first unique non-mammalian MHC class I immune evasion gene identified, and suggests that α-herpesviruses have conserved this function for at least 100 million years. Copyright © 2014 Elsevier Inc. All rights reserved.

A Genome-wide multidimensional RNAi screen reveals pathways controlling MHC class II antigen presentation

NARCIS (Netherlands)

Paul, Petra; van den Hoorn, Tineke; Jongsma, Marlieke L. M.; Bakker, Mark J.; Hengeveld, Rutger; Janssen, Lennert; Cresswell, Peter; Egan, David A.; van Ham, Marieke; ten Brinke, Anja; Ovaa, Huib; Beijersbergen, Roderick L.; Kuijl, Coenraad; Neefjes, Jacques

2011-01-01

MHC class II molecules (MHC-II) present peptides to T helper cells to facilitate immune responses and are strongly linked to autoimmune diseases. To unravel processes controlling MHC-II antigen presentation, we performed a genome-wide flow cytometry-based RNAi screen detecting MHC-II expression and

Functional recombinant MHC class II molecules and high-throughput peptide-binding assays

DEFF Research Database (Denmark)

Justesen, Sune; Harndahl, Mikkel; Lamberth, Kasper

2009-01-01

BACKGROUND: Molecules of the class II major histocompability complex (MHC-II) specifically bind and present exogenously derived peptide epitopes to CD4+ T helper cells. The extreme polymorphism of the MHC-II hampers the complete analysis of peptide binding. It is also a significant hurdle......-II molecules and accompanying HTS peptide-binding assay were successfully developed for nine different MHC-II molecules including the DPA1*0103/DPB1*0401 (DP401) and DQA1*0501/DQB1*0201, where both alpha and beta chains are polymorphic, illustrating the advantages of producing the two chains separately....... CONCLUSION: We have successfully developed versatile MHC-II resources, which may assist in the generation of MHC class II -wide reagents, data, and tools....

Basic emotions evoked by eugenol odor differ according to the dental experience. A neurovegetative analysis.

Science.gov (United States)

Robin, O; Alaoui-Ismaïli, O; Dittmar, A; Vernet-Maury, E

1999-06-01

Subjective individual experiences seem to indicate that odors may form strong connections with memories, especially those charged with emotional significance. In the dental field, this could be the case with the odorant eugenol, responsible for the typical clinging odor impregnating the dental office. The odor of eugenol could evoke memories of unpleasant dental experiences and, therefore, negative feelings such as anxiety and fear, since eugenates (cements containing eugenol) are used in potentially painful restorative dentistry. This hypothesis was tested by evaluating the emotional impact of the odor of eugenol through autonomic nervous system (ANS) analysis. The simultaneous variations of six ANS parameters (two electrodermal, two thermovascular and two cardiorespiratory), induced by the inhalation of this odorant, were recorded on volunteer subjects. Vanillin (a pleasant odorant) and propionic acid (an unpleasant one) served as controls. After the experiment, subjects were asked to rate the pleasantness versus unpleasantness of each odorant on an 11-point hedonic scale. The patterns of autonomic responses, obtained for each odorant and each subject, were transcribed into one of the six basic emotions defined by Ekman et al. (happiness, surprise, sadness, fear, anger and disgust). Results were compared between two groups of subjects divided according to their dental experience (fearful and non-fearful dental care subjects) and showed significant differences only for eugenol. This odorant was rated as pleasant by non-fearful dental subjects but unpleasant by fearful dental subjects. The evoked autonomic responses were mainly associated with positive basic emotions (happiness and surprise) in non-fearful dental subjects and with negative basic emotions (fear, anger, disgust) in fearful dental subjects. These results suggest that eugenol can be responsible for different emotional states depending on the subjects' dental experience, which seems to confirm the

Friends and foes from an ant brain's point of view--neuronal correlates of colony odors in a social insect.

Science.gov (United States)

Brandstaetter, Andreas Simon; Rössler, Wolfgang; Kleineidam, Christoph Johannes

2011-01-01

Successful cooperation depends on reliable identification of friends and foes. Social insects discriminate colony members (nestmates/friends) from foreign workers (non-nestmates/foes) by colony-specific, multi-component colony odors. Traditionally, complex processing in the brain has been regarded as crucial for colony recognition. Odor information is represented as spatial patterns of activity and processed in the primary olfactory neuropile, the antennal lobe (AL) of insects, which is analogous to the vertebrate olfactory bulb. Correlative evidence indicates that the spatial activity patterns reflect odor-quality, i.e., how an odor is perceived. For colony odors, alternatively, a sensory filter in the peripheral nervous system was suggested, causing specific anosmia to nestmate colony odors. Here, we investigate neuronal correlates of colony odors in the brain of a social insect to directly test whether they are anosmic to nestmate colony odors and whether spatial activity patterns in the AL can predict how odor qualities like "friend" and "foe" are attributed to colony odors. Using ant dummies that mimic natural conditions, we presented colony odors and investigated their neuronal representation in the ant Camponotus floridanus. Nestmate and non-nestmate colony odors elicited neuronal activity: In the periphery, we recorded sensory responses of olfactory receptor neurons (electroantennography), and in the brain, we measured colony odor specific spatial activity patterns in the AL (calcium imaging). Surprisingly, upon repeated stimulation with the same colony odor, spatial activity patterns were variable, and as variable as activity patterns elicited by different colony odors. Ants are not anosmic to nestmate colony odors. However, spatial activity patterns in the AL alone do not provide sufficient information for colony odor discrimination and this finding challenges the current notion of how odor quality is coded. Our result illustrates the enormous challenge

Influence of Body Odors and Gender on Perceived Genital Arousal.

Science.gov (United States)

Alves-Oliveira, Patrícia; Carvalho, Joana; Ferreira, Jacqueline; Alho, Laura; Nobre, Pedro; Olsson, Mats J; Soares, Sandra C

2018-04-01

Olfaction is often linked to mating behavior in nonhumans. Additionally, studies in mating behavior have shown that women seem to be more affected by odor cues than men. However, the relationship between odor cues and sexual response-specifically, sexual arousal-has not been studied yet. The aim of this study was to evaluate the impact of the exposure to human body odors (from individuals of the opposite gender) on perceived genital arousal, while these were presented concomitantly to sexually explicit video clips. Eighty university students (40 women) rated their perceived genital arousal (perceived degree of erection/genital lubrication) in response to an audiovisual sexual stimulus, while simultaneously exposed to a body odor from an opposite-gender donor or no odor. Participants also rated each odor sample's (body odor and no odor) perceived pleasantness, intensity, and familiarity. Findings indicated that odor condition had an effect on women's (but not men's) perceived genital arousal, with women showing higher levels of perceived genital arousal in the no odor condition. Also, results showed that women rated body odors as less pleasant than no odor. Notwithstanding, the odor ratings do not seem to explain the association between body odor and perceived genital arousal. The current results support the hypothesis that women, rather than men, are sensitive to odors in the context of sexual response. The findings of this study have relevance for the understanding of human sexuality with respect to chemosensory communication.

NetMHCpan-4.0: Improved Peptide-MHC Class I Interaction Predictions Integrating Eluted Ligand and Peptide Binding Affinity Data.

Science.gov (United States)

Jurtz, Vanessa; Paul, Sinu; Andreatta, Massimo; Marcatili, Paolo; Peters, Bjoern; Nielsen, Morten

2017-11-01

Cytotoxic T cells are of central importance in the immune system's response to disease. They recognize defective cells by binding to peptides presented on the cell surface by MHC class I molecules. Peptide binding to MHC molecules is the single most selective step in the Ag-presentation pathway. Therefore, in the quest for T cell epitopes, the prediction of peptide binding to MHC molecules has attracted widespread attention. In the past, predictors of peptide-MHC interactions have primarily been trained on binding affinity data. Recently, an increasing number of MHC-presented peptides identified by mass spectrometry have been reported containing information about peptide-processing steps in the presentation pathway and the length distribution of naturally presented peptides. In this article, we present NetMHCpan-4.0, a method trained on binding affinity and eluted ligand data leveraging the information from both data types. Large-scale benchmarking of the method demonstrates an increase in predictive performance compared with state-of-the-art methods when it comes to identification of naturally processed ligands, cancer neoantigens, and T cell epitopes. Copyright © 2017 by The American Association of Immunologists, Inc.

Avian influenza infection alters fecal odor in mallards.

Directory of Open Access Journals (Sweden)

Bruce A Kimball

Full Text Available Changes in body odor are known to be a consequence of many diseases. Much of the published work on disease-related and body odor changes has involved parasites and certain cancers. Much less studied have been viral diseases, possibly due to an absence of good animal model systems. Here we studied possible alteration of fecal odors in animals infected with avian influenza viruses (AIV. In a behavioral study, inbred C57BL/6 mice were trained in a standard Y-maze to discriminate odors emanating from feces collected from mallard ducks (Anas platyrhynchos infected with low-pathogenic avian influenza virus compared to fecal odors from non-infected controls. Mice could discriminate odors from non-infected compared to infected individual ducks on the basis of fecal odors when feces from post-infection periods were paired with feces from pre-infection periods. Prompted by this indication of odor change, fecal samples were subjected to dynamic headspace and solvent extraction analyses employing gas chromatography/mass spectrometry to identify chemical markers indicative of AIV infection. Chemical analyses indicated that AIV infection was associated with a marked increase of acetoin (3-hydroxy-2-butanone in feces. These experiments demonstrate that information regarding viral infection exists via volatile metabolites present in feces. Further, they suggest that odor changes following virus infection could play a role in regulating behavior of conspecifics exposed to infected individuals.

The insular taste cortex contributes to odor quality coding

Directory of Open Access Journals (Sweden)

Maria G Veldhuizen

2010-07-01

Full Text Available Despite distinct peripheral and central pathways, stimulation of both the olfactory and the gustatory systems may give rise to the sensation of sweetness. Whether there is a common central mechanism producing sweet quality sensations or two discrete mechanisms associated independently with gustatory and olfactory stimuli is currently unknown. Here we used fMRI to determine whether odor sweetness is represented in the piriform olfactory cortex, which is thought to code odor quality, or in the insular taste cortex, which is thought to code taste quality. Fifteen participants sampled two concentrations of a pure sweet taste (sucrose, two sweet food odors (chocolate and strawberry, and two sweet floral odors (lilac and rose. Replicating prior work we found that olfactory stimulation activated the piriform, orbitofrontal and insular cortices. Of these regions, only the insula also responded to sweet taste. More importantly, the magnitude of the response to the food odors, but not to the non-food odors, in this region of insula was positively correlated with odor sweetness rating. These findings demonstrate that insular taste cortex contributes to odor quality coding by representing the taste-like aspects of food odors. Since the effect was specific to the food odors, and only food odors are experienced with taste, we suggest this common central mechanism develops as a function of experiencing flavors.

Effects of odors on behaviors of captive Amur leopards Panthera pardus orientalis

Directory of Open Access Journals (Sweden)

Shangying YU

2009-02-01

Full Text Available Captive environments often fail to resemble the wild environment in respects of limited space, unchanging habitat, lack of stimulus and contingency. Common animal welfare problems which occur in captive animals include low behavioral diversity, abnormal behavior and excessive inactivity. Environmental enrichment, as an effective strategy to tackle these problems and promote mental health of captive animals, has been recognized as an important principal for captive animal management. Among all the enrichment techniques, olfactory enrichment is a simple and effective method for improving the well-being of the olfactory sensitive felids. Behavioral problems were observed in six Amur leopards Panthera pardus orientalis at Beijing Zoological Garden. These were held in the older type exhibits which have now been rebuilt. These behaviors include stereotypic behavior and excessive inactivity caused by the spatially limited enclosures with low levels of stimuli. To determine the effects of predator, prey, and herb odors as potential enrichment materials for captive leopards, we conducted olfactory enrichment experiments for the leopards and tested the effects of nutmeg Myristica fragrans, feces of roe deer Capreolus capreolus and urine of Amur tiger Panthera tigris altaica to test for an increase in behavioral repertoire and activity. Odors provided in this study were also believed to improve the psychological and physiological health of individuals. To standardize the method of presentation the odors were introduced to the enclosures by rubbing or spraying onto a clean towel. Our results show that the selected three odors effectively increased the behavioral diversity. Ten new behavior types were observed in the nutmeg experiment, eight in the feces of roe deer experiment and six in the tiger urine experiment. Among the three odors, cats responded to nutmeg for the longest duration, followed by tiger urine and feces of roe deer. Leopards showed more

RSCA genotyping of MHC for high-throughput evolutionary studies in the model organism three-spined stickleback Gasterosteus aculeatus

Science.gov (United States)

Lenz, Tobias L; Eizaguirre, Christophe; Becker, Sven; Reusch, Thorsten BH

2009-01-01

Background In all jawed vertebrates, highly polymorphic genes of the major histocompatibility complex (MHC) encode antigen presenting molecules that play a key role in the adaptive immune response. Their polymorphism is composed of multiple copies of recently duplicated genes, each possessing many alleles within populations, as well as high nucleotide divergence between alleles of the same species. Experimental evidence is accumulating that MHC polymorphism is a result of balancing selection by parasites and pathogens. In order to describe MHC diversity and analyse the underlying mechanisms that maintain it, a reliable genotyping technique is required that is suitable for such highly variable genes. Results We present a genotyping protocol that uses Reference Strand-mediated Conformation Analysis (RSCA), optimised for recently duplicated MHC class IIB genes that are typical for many fish and bird species, including the three-spined stickleback, Gasterosteus aculeatus. In addition we use a comprehensive plasmid library of MHC class IIB alleles to determine the nucleotide sequence of alleles represented by RSCA allele peaks. Verification of the RSCA typing by cloning and sequencing demonstrates high congruency between both methods and provides new insight into the polymorphism of classical stickleback MHC genes. Analysis of the plasmid library additionally reveals the high resolution and reproducibility of the RSCA technique. Conclusion This new RSCA genotyping protocol offers a fast, but sensitive and reliable way to determine the MHC allele repertoire of three-spined sticklebacks. It therefore provides a valuable tool to employ this highly polymorphic and adaptive marker in future high-throughput studies of host-parasite co-evolution and ecological speciation in this emerging model organism. PMID:19291291

RSCA genotyping of MHC for high-throughput evolutionary studies in the model organism three-spined stickleback Gasterosteus aculeatus

Directory of Open Access Journals (Sweden)

Becker Sven

2009-03-01

Full Text Available Abstract Background In all jawed vertebrates, highly polymorphic genes of the major histocompatibility complex (MHC encode antigen presenting molecules that play a key role in the adaptive immune response. Their polymorphism is composed of multiple copies of recently duplicated genes, each possessing many alleles within populations, as well as high nucleotide divergence between alleles of the same species. Experimental evidence is accumulating that MHC polymorphism is a result of balancing selection by parasites and pathogens. In order to describe MHC diversity and analyse the underlying mechanisms that maintain it, a reliable genotyping technique is required that is suitable for such highly variable genes. Results We present a genotyping protocol that uses Reference Strand-mediated Conformation Analysis (RSCA, optimised for recently duplicated MHC class IIB genes that are typical for many fish and bird species, including the three-spined stickleback, Gasterosteus aculeatus. In addition we use a comprehensive plasmid library of MHC class IIB alleles to determine the nucleotide sequence of alleles represented by RSCA allele peaks. Verification of the RSCA typing by cloning and sequencing demonstrates high congruency between both methods and provides new insight into the polymorphism of classical stickleback MHC genes. Analysis of the plasmid library additionally reveals the high resolution and reproducibility of the RSCA technique. Conclusion This new RSCA genotyping protocol offers a fast, but sensitive and reliable way to determine the MHC allele repertoire of three-spined sticklebacks. It therefore provides a valuable tool to employ this highly polymorphic and adaptive marker in future high-throughput studies of host-parasite co-evolution and ecological speciation in this emerging model organism.

Honey bee odorant-binding protein 14: effects on thermal stability upon odorant binding revealed by FT-IR spectroscopy and CD measurements.

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Schwaighofer, Andreas; Kotlowski, Caroline; Araman, Can; Chu, Nam; Mastrogiacomo, Rosa; Becker, Christian; Pelosi, Paolo; Knoll, Wolfgang; Larisika, Melanie; Nowak, Christoph

2014-03-01

In the present work, we study the effect of odorant binding on the thermal stability of honey bee (Apis mellifera L.) odorant-binding protein 14. Thermal denaturation of the protein in the absence and presence of different odorant molecules was monitored by Fourier transform infrared spectroscopy (FT-IR) and circular dichroism (CD). FT-IR spectra show characteristic bands for intermolecular aggregation through the formation of intermolecular β-sheets during the heating process. Transition temperatures in the FT-IR spectra were evaluated using moving-window 2D correlation maps and confirmed by CD measurements. The obtained results reveal an increase of the denaturation temperature of the protein when bound to an odorant molecule. We could also discriminate between high- and low-affinity odorants by determining transition temperatures, as demonstrated independently by the two applied methodologies. The increased thermal stability in the presence of ligands is attributed to a stabilizing effect of non-covalent interactions between odorant-binding protein 14 and the odorant molecule.

Sensing of Scent, Fragrance, Smell, and Odor Emissions from Biota Sources

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Ki-Hyun Kim

2014-04-01

Full Text Available People encounter enormous numbers of chemicals present in the outdoor atmosphere and/or in the various facilities they use daily. Despite such diversity, not many of them have necessarily the potential to draw human’s nasal attraction if their perception thresholds are in general not sufficiently low enough, regardless of abundance. In this sense, many types of scents, musks, fragrances, smells, odors, and pheromones are unique enough to draw a great deal of attention mainly by their presence at or near threshold levels which are far lower than those of common chemicals with poor odorant characteristics. It is known that most of the diverse characters of odor-related ingredients or expressions are commonly produced from various biota sources present in the biosphere, e.g., fauna, flora, bacteria, fruits, flowers, trees, meats, fresh/decaying foods, etc.

Red junglefowl have individual body odors

OpenAIRE

Karlsson, Anna-Carin; Jensen, Per; Elgland, Mathias; Laur, Katriann; Fyrner, Timmy; Konradsson, Peter; Laska, Matthias

2010-01-01

Olfaction may play an important role in regulating bird behavior, and has been suggested to be involved in feather-pecking. We investigated possible differences in the body odors of red junglefowl females by using an automated olfactometer which assessed the ability of trained mice to discriminate between the odors of uropygial gland secretions (the main carrier of potential individual odors in chickens) of six feather-pecked and six non-pecked birds. All mice were clearly able to discriminat...

Molecular Basis of Natural Killer Cell Tumor Target Recognition: The NKr/MHC Class I Complex

National Research Council Canada - National Science Library

Hasemann, Charles

1999-01-01

.... We have pursued this via the heterologous expression of wild type and mutant NK receptors for the purpose of the determination of the atomic structure of an NK receptor/ class I MHC complex via X-ray crystallography...

Identification of pleasant, neutral, and unpleasant odors in schizophrenia.

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Kamath, Vidyulata; Turetsky, Bruce I; Moberg, Paul J

2011-05-15

Recent work on odor hedonics in schizophrenia has indicated that patients display abnormalities in hedonic judgments of odors in comparison to healthy comparison participants. In the current study, identification accuracy for pleasant, neutral, and unpleasant odors in individuals with schizophrenia and healthy controls was examined. Thirty-three schizophrenia patients (63% male) and thirty-one healthy volunteers (65% male) were recruited. The groups were well matched on age, sex, and smoking status. Participants were administered the University of Pennsylvania Smell Identification Test, which was subsequently divided into 16 pleasant, 15 neutral, and 9 unpleasant items. Analysis of identification z-scores for pleasant, neutral, and unpleasant odors revealed a significant diagnosis by valence interaction. Post-hoc analysis revealed that schizophrenia participants made more identification errors on pleasant and neutral odors compared to healthy controls, with no differences observed for unpleasant odors. No effect was seen for sex. The findings from the current investigation suggest that odor identification accuracy in patients is influenced by odor valence. This pattern of results parallels a growing body of literature indicating that patients display aberrant pleasantness ratings for pleasant odors and highlights the need for additional research on the influence of odor valence on olfactory identification performance in individuals with schizophrenia. Copyright © 2010 Elsevier Ltd. All rights reserved.

Cutting Edge: Impaired MHC Class I Expression in Mice Deficient for Nlrc5/CITA

OpenAIRE

Biswas, Amlan; Meissner, Torsten B.; Taro Kawai,; Kobayashi, Koichi S.

2012-01-01

MHC class I and class II are crucial for the adaptive immune system. Although regulation of MHC class II expression by CIITA (class II transactivator) has long been recognized, the mechanism of MHC class I transactivation has been largely unknown until the recent discovery of NLRC5/CITA. Here we show using Nlrc5-deficient mice that NLRC5 is required for both constitutive and inducible MHC class I expression. Loss of Nlrc5 resulted in severe reduction in the expression of MHC class I and relat...

Complex assembly, crystallization and preliminary X-ray crystallographic studies of duck MHC class I molecule

International Nuclear Information System (INIS)

Zhang, Jianhua; Chen, Yong; Gao, Feng; Chen, Weihong; Qi, Jianxun; Xia, Chun

2009-01-01

Using a peptide derived from H5N1, a complex of duck MHC class I molecule (DuMHC I) with duck β 2 -microglobulin (Duβ 2 m) was assembled and crystallized. Initial structure analysis indicated that the crystals did not contain the complete DuMHC I complex but instead contained DuMHC I α3-domain and Duβ 2 m subunits. In order to understand the biological properties of the immune systems of waterfowl and to establish a system for structural studies of duck class I major histocompatibility complex (DuMHC I), a complex of DuMHC I with duck β 2 -microglobulin (Duβ 2 m) and the peptide AEIEDLIF (AF8) derived from H5N1 NP residues 251–258 was assembled. The complex was crystallized; the crystals belonged to space group C222 1 , with unit-cell parameters a = 54.7, b = 72.4, c = 102.2 Å, and diffracted to 2.3 Å resolution. Matthews coefficient calculation and initial structure determination by molecular replacement showed that the crystals did not contain the whole DuMHC I complex, but instead contained the DuMHC I α3 domain and a Duβ2m molecule (DuMHC I α3+β2m). Another complex of DuMHC I with the peptide IDWFDGKE derived from a chicken fusion protein also generated the same results. The stable structure of DuMHC I α3+β2m may reflect some unique characteristics of DuMHC I and pave the way for novel MHC structure-related studies in the future

Low genetic variation in the MHC class II DRB gene and MHC-linked microsatellites in endangered island populations of the leopard cat (Prionailurus bengalensis) in Japan.

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Saka, Toshinori; Nishita, Yoshinori; Masuda, Ryuichi

2018-02-01

Isolated populations of the leopard cat (Prionailurus bengalensis) on Tsushima and Iriomote islands in Japan are classified as subspecies P. b. euptilurus and P. b. iriomotensis, respectively. Because both populations have decreased to roughly 100, an understanding of their genetic diversity is essential for conservation. We genotyped MHC class II DRB exon 2 and MHC-linked microsatellite loci to evaluate the diversity of MHC genes in the Tsushima and Iriomote cat populations. We detected ten and four DRB alleles in these populations, respectively. A phylogenetic analysis showed DRB alleles from both populations to be closely related to those in other felid DRB lineages, indicating trans-species polymorphism. The MHC-linked microsatellites were more polymorphic in the Tsushima than in the Iriomote population. The MHC diversity of both leopard cat populations is much lower than in the domestic cat populations on these islands, probably due to inbreeding associated with founder effects, geographical isolation, or genetic drift. Our results predict low resistance of the two endangered populations to new pathogens introduced to the islands.

Enhancement of Retronasal Odors by Taste

OpenAIRE

Green, Barry G.; Nachtigal, Danielle; Hammond, Samuel; Lim, Juyun

2011-01-01

Psychophysical studies of interactions between retronasal olfaction and taste have focused most often on the enhancement of tastes by odors, which has been attributed primarily to a response bias (i.e., halo dumping). Based upon preliminary evidence that retronasal odors could also be enhanced by taste, the present study measured both forms of enhancement using appropriate response categories. In the first experiment, subjects rated taste (“sweet,” “sour,” “salty,” and “bitter”) and odor (“ot...

Odor and odorous chemical emissions from dairy and swine facilities: Part 5-Simultaneous chemical and sensory analysis with Gas Chromatography - Mass Spectrometry - Olfactometry

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Simultaneous chemical and sensory analyses using gas chromatography-mass spectrometry-olfactometry (GC-MS-O) for air samples collected at barn exhaust fans were used for quantification and ranking of odor impact of target odorous gases. Fifteen target odorous VOCs (odorants) were selected. Air sampl...

Sibling rivalry: competition between MHC class II family members inhibits immunity.

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Denzin, Lisa K; Cresswell, Peter

2013-01-01

Peptide loading of major histocompatibility complex (MHC) class II molecules in the endosomes and lysosomes of antigen-presenting cells is catalyzed by human leukocyte antigen-DM (HLA-DM) and modulated by HLA-DO. In a structural study in this issue, Guce et al. show that HLA-DO is an MHC class II mimic and functions as a competitive and essentially irreversible inhibitor of HLA-DM activity, thereby inhibiting MHC class II antigen presentation.

Blue petrels recognize the odor of their egg.

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Leclaire, Sarah; Bourret, Vincent; Bonadonna, Francesco

2017-09-01

Most studies on avian olfactory communication have focused on mate choice, and the importance of olfaction in subsequent nesting stages has been poorly explored. In particular, the role of olfactory cues in egg recognition has received little attention, despite eggs potentially being spread with parental odorous secretions known to elicit individual discrimination. Here, we used behavioral choice tests to determine whether female blue petrels ( Halobaena caerulea ) can discriminate the odor of their own egg from the odor of a conspecific egg. Females preferentially approached the odor of their own egg, suggesting that blue petrels can recognize their own egg using odor cues. This finding raises the question of the adaptive value of this mechanism, and may inspire further research on odor-based egg discrimination in species suffering brood parasitism. © 2017. Published by The Company of Biologists Ltd.

Evaluation of Odor-Reducing Commercial Products for Animal Waste

OpenAIRE

Shukla, Shuchi S.

1997-01-01

Six odor-reducing commercial products were tested for their efficacy in reducing odors from dairy and swine wastes. A sensory panel method was utilized for odor evaluations, in which the panel played an important part. Comparisons between products were made for agitated and unagitated conditions and effect of storage time (three weeks in which experiments were performed). Cotton pieces tied to the mouth of the sample jars were useful in absorbing the odors. Odor-treated jars were observed and...

Contribution of DA Signaling to Appetitive Odor Perception in a Drosophila Model.

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Pu, Yuhan; Palombo, Melissa Megan Masserant; Shen, Ping

2018-04-13

Understanding cognitive processes that translate chemically diverse olfactory stimuli to specific appetitive drives remains challenging. We have shown that food-related odors arouse impulsive-like feeding of food media that are palatable and readily accessible in well-nourished Drosophila larvae. Here we provide evidence that two assemblies of four dopamine (DA) neurons, one per brain hemisphere, contribute to perceptual processing of the qualitative and quantitative attributes of food scents. These DA neurons receive neural representations of chemically diverse food-related odors, and their combined neuronal activities become increasingly important as the chemical complexity of an appetizing odor stimulus increases. Furthermore, in each assembly of DA neurons, integrated odor signals are transformed to one-dimensional DA outputs that have no intrinsic reward values. Finally, a genetic analysis has revealed a D1-type DA receptor (Dop1R1)-gated mechanism in neuropeptide Y-like neurons that assigns appetitive significance to selected DA outputs. Our findings suggest that fly larvae provide a useful platform for elucidation of molecular and circuit mechanisms underlying cognitive processing of olfactory and possibly other sensory cues.

Odor-Sensing System to Support Social Participation of People Suffering from Incontinence

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Alvaro Ortiz Pérez

2016-12-01

Full Text Available This manuscript describes the design considerations, implementation, and laboratory validation of an odor sensing module whose purpose is to support people that suffer from incontinence. Because of the requirements expressed by the affected end-users the odor sensing unit is realized as a portable accessory that may be connected to any pre-existing smart device. We have opted for a low-cost, low-power consuming metal oxide based gas detection approach to highlight the viability of developing an inexpensive yet helpful odor recognition technology. The system consists of a hotplate employing, inkjet-printed p-type semiconducting layers of copper(II oxide, and chromium titanium oxide. Both functional layers are characterized with respect to their gas-sensitive behavior towards humidity, ammonia, methylmercaptan, and dimethylsulfide and we demonstrate detection limits in the parts-per-billion range for the two latter gases. Employing a temperature variation scheme that reads out the layer’s resistivity in a steady-state, we use each sensor chip as a virtual array. With this setup, we demonstrate the feasibility of detecting odors associated with incontinence.

Odor-Sensing System to Support Social Participation of People Suffering from Incontinence.

Science.gov (United States)

Ortiz Pérez, Alvaro; Kallfaß-de Frenes, Vera; Filbert, Alexander; Kneer, Janosch; Bierer, Benedikt; Held, Pirmin; Klein, Philipp; Wöllenstein, Jürgen; Benyoucef, Dirk; Kallfaß, Sigrid; Mescheder, Ulrich; Palzer, Stefan

2016-12-29

This manuscript describes the design considerations, implementation, and laboratory validation of an odor sensing module whose purpose is to support people that suffer from incontinence. Because of the requirements expressed by the affected end-users the odor sensing unit is realized as a portable accessory that may be connected to any pre-existing smart device. We have opted for a low-cost, low-power consuming metal oxide based gas detection approach to highlight the viability of developing an inexpensive yet helpful odor recognition technology. The system consists of a hotplate employing, inkjet-printed p-type semiconducting layers of copper(II) oxide, and chromium titanium oxide. Both functional layers are characterized with respect to their gas-sensitive behavior towards humidity, ammonia, methylmercaptan, and dimethylsulfide and we demonstrate detection limits in the parts-per-billion range for the two latter gases. Employing a temperature variation scheme that reads out the layer's resistivity in a steady-state, we use each sensor chip as a virtual array. With this setup, we demonstrate the feasibility of detecting odors associated with incontinence.

Leukemia prevention and long-term survival of AKR mice transplanted with MHC-matched or MHC-mismatched bone marrow

International Nuclear Information System (INIS)

Longley, R.E.; Good, R.A.

1986-01-01

The current studies were designed to evaluate the effectiveness of marrow transplantation within and outside the major histocompatibility complex (MHC) on the long-term survival and occurrence of spontaneous leukemia in AKR mice. AKR mice, which were lethally irradiated and received MHC-matched marrow from CBA/J mice (CBA----AKR), never developed leukemia and were alive and remained healthy for up to 280 days post-transplant. These long-term surviving chimeras possessed substantial immune vigor when both cell-mediated and humoral responses were tested. Lethally irradiated AKR mice, which had received MHC-mismatched marrow (anti-Thy-1.2 treated or nontreated) from C57BL/6J mice (B6----AKR), never developed leukemia and survived up to 170 days post-transplant. However, both groups of these chimeras began dying 180 to 270 days post-transplant due to a disease process which could not be readily identified. Histological analysis of B6----AKR chimeras revealed severe lymphoid cell depletion in thymus and spleen; however, none of these chimeras exhibited classical features of acute graft versus host disease. Concanavalin A mitogenesis, primary antibody responses to sheep red blood cells and the production of interleukin 2 (IL-2) were suppressed in B6----AKR chimeras. IL-2 treatment of B6----AKR chimeras was shown to partially correct these deficiencies without stimulating mixed lymphocyte responsiveness to donor or host lymphocytes. These studies indicate that the use of MHC-mismatched marrow for the prevention of spontaneous AKR leukemia may rely on augmentative IL-2 therapy for complete immune reconstitution of leukemia-free chimeras

Friends and Foes from an Ant Brain's Point of View – Neuronal Correlates of Colony Odors in a Social Insect

Science.gov (United States)

Brandstaetter, Andreas Simon; Rössler, Wolfgang; Kleineidam, Christoph Johannes

2011-01-01

Background Successful cooperation depends on reliable identification of friends and foes. Social insects discriminate colony members (nestmates/friends) from foreign workers (non-nestmates/foes) by colony-specific, multi-component colony odors. Traditionally, complex processing in the brain has been regarded as crucial for colony recognition. Odor information is represented as spatial patterns of activity and processed in the primary olfactory neuropile, the antennal lobe (AL) of insects, which is analogous to the vertebrate olfactory bulb. Correlative evidence indicates that the spatial activity patterns reflect odor-quality, i.e., how an odor is perceived. For colony odors, alternatively, a sensory filter in the peripheral nervous system was suggested, causing specific anosmia to nestmate colony odors. Here, we investigate neuronal correlates of colony odors in the brain of a social insect to directly test whether they are anosmic to nestmate colony odors and whether spatial activity patterns in the AL can predict how odor qualities like “friend” and “foe” are attributed to colony odors. Methodology/Principal Findings Using ant dummies that mimic natural conditions, we presented colony odors and investigated their neuronal representation in the ant Camponotus floridanus. Nestmate and non-nestmate colony odors elicited neuronal activity: In the periphery, we recorded sensory responses of olfactory receptor neurons (electroantennography), and in the brain, we measured colony odor specific spatial activity patterns in the AL (calcium imaging). Surprisingly, upon repeated stimulation with the same colony odor, spatial activity patterns were variable, and as variable as activity patterns elicited by different colony odors. Conclusions Ants are not anosmic to nestmate colony odors. However, spatial activity patterns in the AL alone do not provide sufficient information for colony odor discrimination and this finding challenges the current notion of how odor

AMisfit Theory of Spontaneous Conscious Odor Perception (MITSCOP: reflections on the role and function of odor memory in everyday life.

Directory of Open Access Journals (Sweden)

Egon P Köster

2014-02-01

Full Text Available Our senses have developed as an answer to the world we live in (Gibson, 1966 and so have the forms of memory that accompany them. All senses serve different purposes and do so in different ways. In vision, where orientation and object recognition are important, memory is strongly linked to identification. In olfaction, the guardian of vital functions such as breathing and food ingestion, perhaps the most important (and least noticed and researched role of odor memory is to help us not to notice the well-known odors or flavors in our everyday surroundings, but to react immediately to the unexpected ones. At the same time it provides us with a feeling of safety when our expectancies are met. All this happens without any smelling intention or conscious knowledge of our expectations. Identification by odor naming is not involved in this and people are notoriously bad at it. Odors are usually best identified via the episodic memory of the situation in which they once occurred. Spontaneous conscious odor perception normally only occurs in situations where attention is demanded, either because the inhaled air or the food smell is particularly good or particularly bad and people search for its source or because people want to actively enjoy the healthiness and pleasantness of their surroundings or food. Odor memory is concerned with novelty detection rather than with recollection of odors. In this paper, these points are illustrated with experimental results and their consequences for doing ecologically valid odor memory research are drawn. Furthermore, suggestions for ecologically valid research on everyday odor memory and some illustrative examples are given.

Semantic networks for odors and colors in Alzheimer's disease.

Science.gov (United States)

Razani, Jill; Chan, Agnes; Nordin, Steven; Murphy, Claire

2010-05-01

Impairment in odor-naming ability and in verbal and visual semantic networks raised the hypothesis of a breakdown in the semantic network for odors in Alzheimer's disease (AD). The current study addressed this hypothesis. Twenty-four individuals, half patients with probable AD and half control participants, performed triadic-similarity judgments for odors and colors, separately, which, utilizing the multidimensional scaling (MDS) technique of individual difference scaling analysis (INDSCAL), generated two-dimensional configurations of similarity. The abilities to match odors and colors with written name labels were assessed to investigate disease-related differences in ability to identify and conceptualize the stimuli. In addition, responses on attribute-sorting tasks, requiring the odor and color perceptions to be categorized as one polarity of a certain dimension, were obtained to allow for objective interpretation of the MDS spatial maps. Whereas comparison subjects generated spatial maps based predominantly on relatively abstract characteristics, patients with AD classified odors on perceptual characteristics. The maps for patients with AD also showed disorganized groupings and loose associations between odors. Their normal configurations for colors imply that the patients were able to comprehend the task per se. The data for label matching and for attribute sorting provide further evidence for a disturbance in semantic odor memory in AD. The patients performed poorer than controls on both these odor tasks, implying that the ability to identify and/or conceptualize odors is impaired in AD. The results provide clear evidence for deterioration of the structure of semantic knowledge for odors in AD.

The MHC-II transactivator CIITA, a restriction factor against oncogenic HTLV-1 and HTLV-2 retroviruses: similarities and differences in the inhibition of Tax-1 and Tax-2 viral transactivators

Science.gov (United States)

Forlani, Greta; Abdallah, Rawan; Accolla, Roberto S.; Tosi, Giovanna

2013-01-01

The activation of CD4+ T helper cells is strictly dependent on the presentation of antigenic peptides by MHC class II (MHC-II) molecules. MHC-II expression is primarily regulated at the transcriptional level by the AIR-1 gene product CIITA (class II transactivator). Thus, CIITA plays a pivotal role in the triggering of the adaptive immune response against pathogens. Besides this well known function, we recently found that CIITA acts as an endogenous restriction factor against HTLV-1 (human T cell lymphotropic virus type 1) and HTLV-2 oncogenic retroviruses by targeting their viral transactivators Tax-1 and Tax-2, respectively. Here we review our findings on CIITA-mediated inhibition of viral replication and discuss similarities and differences in the molecular mechanisms by which CIITA specifically counteracts the function of Tax-1 and Tax-2 molecules. The dual function of CIITA as a key regulator of adaptive and intrinsic immunity represents a rather unique example of adaptation of host-derived factors against pathogen infections during evolution. PMID:23986750

Circumsporozoite Protein-Specific Kd-Restricted CD8+ T Cells Mediate Protective Antimalaria Immunity in Sporozoite-Immunized MHC-I-Kd Transgenic Mice

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Jing Huang

2014-01-01

Full Text Available Although the roles of CD8+ T cells and a major preerythrocytic antigen, the circumsporozoite (CS protein, in contributing protective antimalaria immunity induced by radiation-attenuated sporozoites, have been shown by a number of studies, the extent to which these players contribute to antimalaria immunity is still unknown. To address this question, we have generated C57BL/6 (B6 transgenic (Tg mice, expressing Kd molecules under the MHC-I promoter, called MHC-I-Kd-Tg mice. In this study, we first determined that a single immunizing dose of IrPySpz induced a significant level of antimalaria protective immunity in MHC-I-Kd-Tg mice but not in B6 mice. Then, by depleting various T-cell subsets in vivo, we determined that CD8+ T cells are the main mediator of the protective immunity induced by IrPySpz. Furthermore, when we immunized (MHC-I-Kd-Tg × CS-Tg F1 mice with IrPySpz after crossing MHC-I-Kd-Tg mice with PyCS-transgenic mice (CS-Tg, which are unable to mount PyCS-specific immunity, we found that IrPySpz immunization failed to induce protective antimalaria immunity in (MHC-I-Kd-Tg × CS-Tg F1 mice, thus indicating the absence of PyCS antigen-dependent immunity in these mice. These results indicate that protective antimalaria immunity induced by IrPySpz in MHC-I-Kd-Tg mice is mediated by CS protein-specific, Kd-restricted CD8+ T cells.

Odor-induced recall of emotional memories in PTSD-Review and new paradigm for research.

Science.gov (United States)

Daniels, Judith K; Vermetten, Eric

2016-10-01

It is clinically well known that olfactory intrusions in PTSD can be a disabling phenomena due to the involuntary recall of odor memories. Odorants can trigger involuntary recall of emotional memories as well have the potential to help diminishing emotional arousal as grounding stimuli. Despite major advances in our understanding of the function of olfactory system, the study of the relation of olfaction and emotional memory is still relatively scarce. Odor memory is long thought to be different than other types of memories such as verbal or visual memories, being more strongly engraved and more closely related to strong emotions. Brain areas mediating smell memory including orbitofrontal cortex and other parts of medial prefrontal cortex, hippocampus and amygdala, have been implicated in learning and memory and are part of a neural circuitry that is involved in PTSD. The olfactory cortex itself also plays an important role in emotional processing. Clinical observations support the notion that odor-evoked memories can play a role in the symptomatology of PTSD. This paper reviews a re-emerging body of science linking odor processing to emotional processing in PTSD using the calming and grounding effect of odors as well as the use of odors in augmented exposure therapy. This results in converging evidence that olfaction is an excellent model for studying many questions germane to the field of human emotional memory processing. Copyright © 2016 Elsevier Inc. All rights reserved.

Child Odors and Parenting: A Survey Examination of the Role of Odor in Child-Rearing.

Science.gov (United States)

Okamoto, Masako; Shirasu, Mika; Fujita, Rei; Hirasawa, Yukei; Touhara, Kazushige

2016-01-01

Parental caregiving is critical for the survival of our young and continuation of our species. In humans, visual and auditory signals from offspring have been shown to be potent facilitators of parenting. However, whether odors emitted by our young also influence human parenting remains unclear. To explore this, we conducted a series of questionnaire surveys targeting parents with children under 6 years old. First, we collected episodes on experiencing odors/sniffing various parts of a child's body (n = 507). The prevalence of experiencing events described in those episodes was examined in a separate survey (n = 384). Based on those results, the Child Odor in Parenting scale (COPs) was developed, and subsequently used in the main survey (n = 888). We found COPs to have adequate content validity, concurrent validity, and reliability. Responses to the COPs demonstrated that parents, especially mothers with infants, are aware of odors from their offspring, and actively seek them in daily child-rearing. The factor structure and content of the COPs items indicated that child odors have both affective and instrumental roles. Affective experiences induce loving feeling and affectionate sniffing, while instrumental experiences pertain to specific hygienic needs. The head was the most frequent source of affective experiences, and the child's bottom of instrumental. Each was experienced by more than 90% of the mothers with a child below 1 year of age. Affective experiences significantly declined as the child grew older, possibly associated with the decline of physical proximity between parents and child. This age-related decline was not prominent for instrumental experiences, except for the bottom, which significantly declined after 3 years of age. The present findings suggest that child odors play roles in human parenting, and that their nature and significance change during the course of a child's development.

Child Odors and Parenting: A Survey Examination of the Role of Odor in Child-Rearing.

Directory of Open Access Journals (Sweden)

Masako Okamoto

Full Text Available Parental caregiving is critical for the survival of our young and continuation of our species. In humans, visual and auditory signals from offspring have been shown to be potent facilitators of parenting. However, whether odors emitted by our young also influence human parenting remains unclear. To explore this, we conducted a series of questionnaire surveys targeting parents with children under 6 years old. First, we collected episodes on experiencing odors/sniffing various parts of a child's body (n = 507. The prevalence of experiencing events described in those episodes was examined in a separate survey (n = 384. Based on those results, the Child Odor in Parenting scale (COPs was developed, and subsequently used in the main survey (n = 888. We found COPs to have adequate content validity, concurrent validity, and reliability. Responses to the COPs demonstrated that parents, especially mothers with infants, are aware of odors from their offspring, and actively seek them in daily child-rearing. The factor structure and content of the COPs items indicated that child odors have both affective and instrumental roles. Affective experiences induce loving feeling and affectionate sniffing, while instrumental experiences pertain to specific hygienic needs. The head was the most frequent source of affective experiences, and the child's bottom of instrumental. Each was experienced by more than 90% of the mothers with a child below 1 year of age. Affective experiences significantly declined as the child grew older, possibly associated with the decline of physical proximity between parents and child. This age-related decline was not prominent for instrumental experiences, except for the bottom, which significantly declined after 3 years of age. The present findings suggest that child odors play roles in human parenting, and that their nature and significance change during the course of a child's development.

Statistical deconvolution of enthalpic energetic contributions to MHC-peptide binding affinity

Directory of Open Access Journals (Sweden)

Drew Michael GB

2006-03-01

Full Text Available Abstract Background MHC Class I molecules present antigenic peptides to cytotoxic T cells, which forms an integral part of the adaptive immune response. Peptides are bound within a groove formed by the MHC heavy chain. Previous approaches to MHC Class I-peptide binding prediction have largely concentrated on the peptide anchor residues located at the P2 and C-terminus positions. Results A large dataset comprising MHC-peptide structural complexes was created by re-modelling pre-determined x-ray crystallographic structures. Static energetic analysis, following energy minimisation, was performed on the dataset in order to characterise interactions between bound peptides and the MHC Class I molecule, partitioning the interactions within the groove into van der Waals, electrostatic and total non-bonded energy contributions. Conclusion The QSAR techniques of Genetic Function Approximation (GFA and Genetic Partial Least Squares (G/PLS algorithms were used to identify key interactions between the two molecules by comparing the calculated energy values with experimentally-determined BL50 data. Although the peptide termini binding interactions help ensure the stability of the MHC Class I-peptide complex, the central region of the peptide is also important in defining the specificity of the interaction. As thermodynamic studies indicate that peptide association and dissociation may be driven entropically, it may be necessary to incorporate entropic contributions into future calculations.

Characterization of MHC class I in a long distance migratory wader, the Icelandic black-tailed godwit.

Science.gov (United States)

Pardal, Sara; Drews, Anna; Alves, José A; Ramos, Jaime A; Westerdahl, Helena

2017-07-01

The major histocompatibility complex (MHC) encodes proteins that are central for antigen presentation and pathogen elimination. MHC class I (MHC-I) genes have attracted a great deal of interest among researchers in ecology and evolution and have been partly characterized in a wide range of bird species. So far, the main focus has been on species within the bird orders Galliformes and Passeriformes, while Charadriiformes remain vastly underrepresented with only two species studied to date. These two Charadriiformes species exhibit striking differences in MHC-I characteristics and MHC-I diversity. We therefore set out to study a third species within Charadriiformes, the Icelandic subspecies of black-tailed godwits (Limosa limosa islandica). This subspecies is normally confined to parasite-poor environments, and we hence expected low MHC diversity. MHC-I was partially characterized first using Sanger sequencing and then using high-throughput sequencing (MiSeq) in 84 individuals. We verified 47 nucleotide alleles in open reading frame with classical MHC-I characteristics, and each individual godwit had two to seven putatively classical MHC alleles. However, in contrast to previous MHC-I data within Charadriiformes, we did not find any evidence of alleles with low sequence diversity, believed to represent non-classical MHC genes. The diversity and divergence of the godwits MHC-I genes to a large extent fell between the previous estimates within Charadriiformes. However, the MHC genes of the migratory godwits had few sites subject to positive selection, and one possible explanation could be a low exposure to pathogens.

Body odor based personality judgments: The effect of fragranced cosmetics

Directory of Open Access Journals (Sweden)

Agnieszka eSorokowska

2016-04-01

Full Text Available People can accurately assess various personality traits of others based on body odor alone. Previous studies have shown that correlations between odor ratings and self-assessed personality dimensions are evident for assessments of neuroticism and dominance. Here, we tested differences between assessments based on natural body odor alone, without the use of cosmetics and assessments based on the body odor of people who were allowed to use cosmetics following their daily routine. Sixty-seven female observers assessed samples of odors from 113 odor donors (each odor donor provided two samples – one with and one without cosmetic use; the donors provided their personality ratings, and the raters judged personality characteristics of the donors based on the provided odor samples. Correlations between observers’ ratings and self-rated neuroticism were stronger when raters assessed body odor in the natural body odor condition (natural BO condition; rs = .20 than in the cosmetics use condition (BO+cosmetics condition; rs = .15. Ratings of dominance significantly predicted self-assessed dominance in both conditions (rs = .34 for natural BO and rs = .21 for BO+cosmetics, whereas ratings of extraversion did not predict self-assessed extraversion in either condition. In addition, ratings of body odor attractiveness and pleasantness were significantly lower in natural BO condition than in BO+cosmetics condition, although the intensity of donors’ body odors was similar under both conditions. Our findings suggest that although olfaction seems to contribute to accurate first impression judgments of certain personality traits, cosmetic use can affect assessments of others based on body odor.

Ubiquitination regulates MHC class II-peptide complex retention and degradation in dendritic cells

OpenAIRE

Walseng, Even; Furuta, Kazuyuki; Bosch, Berta; Weih, Karis A.; Matsuki, Yohei; Bakke, Oddmund; Ishido, Satoshi; Roche, Paul A.

2010-01-01

The expression and turnover of MHC class II-peptide complexes (pMHC-II) on the surface of dendritic cells (DCs) is essential for their ability to activate CD4 T cells efficiently. The half-life of surface pMHC-II is significantly greater in activated (mature) DCs than in resting (immature) DCs, but the molecular mechanism leading to this difference remains unknown. We now show that ubiquitination of pMHC-II by the E3 ubiquitin ligase membrane-associated RING-CH 1 (March-I) regulates surface e...

Stability of odorants from pig production in sampling bags for olfactometry.

Science.gov (United States)

Hansen, Michael J; Adamsen, Anders P S; Feilberg, Anders; Jonassen, Kristoffer E N

2011-01-01

Odor from pig production facilities is typically measured with olfactometry, whereby odor samples are collected in sampling bags and assessed by human panelists within 30 h. In the present study, the storage stability of odorants in two types of sampling bags that are often used for olfactometry was investigated. The bags were made of Tedlar or Nalophan. In a field experiment, humid and dried air samples were collected from a pig production facility with growing-finishing pigs and analyzed with a gas chromatograph with an amperometric sulfur detector at 4, 8, 12, 28, 52, and 76 h after sampling. In a laboratory experiment, the bags were filled with a humid gas mixture containing carboxylic acids, phenols, indoles, and sulfur compounds and analyzed with proton-transfer-reaction mass spectrometry after 0, 4, 8, 12, and 24 h. The results demonstrated that the concentrations of carboxylic acids, phenols, and indoles decreased by 50 to >99% during the 24 h of storage in Tedlar and Nalophan bags. The concentration of hydrogen sulfide decreased by approximately 30% during the 24 h of storage in Nalophan bags, whereas in Tedlar bags the concentration of sulfur compounds decreased by bags, and the composition changes toward a higher relative presence of sulfur compounds. This can result in underestimation of odor emissions from pig production facilities and of the effect of odor reduction technologies. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Posttraining ablation of adult-generated olfactory granule cells degrades odor-reward memories.

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Arruda-Carvalho, Maithe; Akers, Katherine G; Guskjolen, Axel; Sakaguchi, Masanori; Josselyn, Sheena A; Frankland, Paul W

2014-11-19

Proliferation of neural progenitor cells in the subventricular zone leads to the continuous generation of new olfactory granule cells (OGCs) throughout life. These cells synaptically integrate into olfactory bulb circuits after ∼2 weeks and transiently exhibit heightened plasticity and responses to novel odors. Although these observations suggest that adult-generated OGCs play important roles in olfactory-related memories, global suppression of olfactory neurogenesis does not typically prevent the formation of odor-reward memories, perhaps because residual OGCs can compensate. Here, we used a transgenic strategy to selectively ablate large numbers of adult-generated OGCs either before or after learning in mice. Consistent with previous studies, pretraining ablation of adult-generated OGCs did not prevent the formation of an odor-reward memory, presumably because existing OGCs can support memory formation in their absence. However, ablation of a similar cohort of adult-generated OGCs after training impaired subsequent memory expression, indicating that if these cells are available at the time of training, they play an essential role in subsequent expression of odor-reward memories. Memory impairment was associated with the loss of adult-generated OGCs that were >10 d in age and did not depend on the developmental stage in which they were generated, suggesting that, once sufficiently mature, OGCs generated during juvenility and adulthood play similar roles in the expression of odor-reward memories. Finally, ablation of adult-generated OGCs 1 month after training did not produce amnesia, indicating that adult-generated OGCs play a time-limited role in the expression of odor-reward memories. Copyright © 2014 the authors 0270-6474/14/3415793-11$15.00/0.

Neuropeptide Y enhances olfactory mucosa responses to odorant in hungry rats.

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Negroni, Julia; Meunier, Nicolas; Monnerie, Régine; Salesse, Roland; Baly, Christine; Caillol, Monique; Congar, Patrice

2012-01-01

Neuropeptide Y (NPY) plays an important role in regulating appetite and hunger in vertebrates. In the hypothalamus, NPY stimulates food intake under the control of the nutritional status. Previous studies have shown the presence of NPY and receptors in rodent olfactory system, and suggested a neuroproliferative role. Interestingly, NPY was also shown to directly modulate olfactory responses evoked by a food-related odorant in hungry axolotls. We have recently demonstrated that another nutritional cue, insulin, modulates the odorant responses of the rat olfactory mucosa (OM). Therefore, the aim of the present study was to investigate the potential effect of NPY on rat OM responses to odorants, in relation to the animal's nutritional state. We measured the potential NPY modulation of OM responses to odorant, using electro-olfactogram (EOG) recordings, in fed and fasted adult rats. NPY application significantly and transiently increased EOG amplitudes in fasted but not in fed rats. The effects of specific NPY-receptor agonists were similarly quantified, showing that NPY operated mainly through Y1 receptors. These receptors appeared as heterogeneously expressed by olfactory neurons in the OM, and western blot analysis showed that they were overexpressed in fasted rats. These data provide the first evidence that NPY modulates the initial events of odorant detection in the rat OM. Because this modulation depends on the nutritional status of the animal, and is ascribed to NPY, the most potent orexigenic peptide in the central nervous system, it evidences a strong supplementary physiological link between olfaction and nutritional processes.

Evaluation method of offensive odor. Shuki no hyoka hoho

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Iwasaki, Y [The Tokyo Metropolitan Research Institute for Environmental Protection, Tokyo (Japan)

1991-06-01

As the evaluation method of offensive odor, two kinds of methods were outlined, a concentration measurement method for compounds emitting offensive odors and a sensory method by human olfactory organ. On the former, the method for measuring separately odors of twelve compounds controlled by the regulation act such as ammonia and hydrogen sulfide was outlined as well as the method for measuring odors of compound groups such as total reduced sulfur and total hydrocarbon. On the later, the evaluation scale of essential properties of odor such as quality, intensity, acceptability and pervasiveness was discussed. As typical sensory techniques, a scentometer, syringe method, odorless chamber method and olfactometer were outlined, and a triangle odor bag method widely used for the evaluation at present was described in detail which was developed to reduce demerits of a syringe method such as adsorption of odorants on a syringe surface. 24 refs., 6 figs., 3 tabs.

Cholesterol Corrects Altered Conformation of MHC-II Protein in Leishmania donovani Infected Macrophages: Implication in Therapy

Science.gov (United States)

Chakrabarti, Saikat; Roy, Syamal

2016-01-01

Background Previously we reported that Kala-azar patients show progressive decrease in serum cholesterol as a function of splenic parasite burden. Splenic macrophages (MΦ) of Leishmania donovani (LD) infected mice show decrease in membrane cholesterol, while LD infected macrophages (I-MΦ) show defective T cell stimulating ability that could be corrected by liposomal delivery of cholesterol. T helper cells recognize peptide antigen in the context of class II MHC molecule. It is known that the conformation of a large number of membrane proteins is dependent on membrane cholesterol. In this investigation we tried to understand the influence of decreased membrane cholesterol in I-MΦ on the conformation of MHC-II protein and peptide-MHC-II stability, and its bearing on the antigen specific T-cell activation. Methodology/Principal Findings MΦ of CBA/j mice were infected with Leishmania donovani (I-MΦ). Two different anti-Aκ mAbs were used to monitor the status of MHC-II protein under parasitized condition. One of them (11.5–2) was conformation specific, whereas the other one (10.2.16) was not. Under parasitized condition, the binding of 11.5–2 decreased significantly with respect to the normal counterpart, whereas that of 10.2.16 remained unaltered. The binding of 11.5–2 was restored to normal upon liposomal delivery of cholesterol in I-MΦ. By molecular dynamics (MD) simulation studies we found that there was considerable conformational fluctuation in the transmembrane domain of the MHC-II protein in the presence of membrane cholesterol than in its absence, which possibly influenced the distal peptide binding groove. This was evident from the faster dissociation of the cognate peptide from peptide-MHC complex under parasitized condition, which could be corrected by liposomal delivery of cholesterol in I-MΦ. Conclusion The decrease in membrane cholesterol in I-MΦ may lead to altered conformation of MHC II, and this may contribute to a faster dissociation of

Anatomical and molecular consequences of Unilateral Naris Closure on two populations of olfactory sensory neurons expressing defined odorant receptors.

Science.gov (United States)

Molinas, Adrien; Aoudé, Imad; Soubeyre, Vanessa; Tazir, Bassim; Cadiou, Hervé; Grosmaitre, Xavier

2016-07-28

Mammalian olfactory sensory neurons (OSNs), the primary elements of the olfactory system, are located in the olfactory epithelium lining the nasal cavity. Exposed to the environment, their lifespan is short. Consequently, OSNs are regularly regenerated and several reports show that activity strongly modulates their development and regeneration: the peripheral olfactory system can adjust to the amount of stimulus through compensatory mechanisms. Unilateral naris occlusion (UNO) was frequently used to investigate this mechanism at the entire epithelium level. However, there is little data regarding the effects of UNO at the cellular level, especially on individual neuronal populations expressing a defined odorant receptor. Here, using UNO during the first three postnatal weeks, we analyzed the anatomical and molecular consequences of sensory deprivation in OSNs populations expressing the MOR23 and M71 receptors. The density of MOR23-expressing neurons is decreased in the closed side while UNO does not affect the density of M71-expressing neurons. Using Real Time qPCR on isolated neurons, we observed that UNO modulates the transcript levels for transduction pathway proteins (odorant receptors, CNGA2, PDE1c). The transcripts modulated by UNO will differ between populations depending on the receptor expressed. These results suggest that sensory deprivation will have different effects on different OSNs' populations. As a consequence, early experience will shape the functional properties of OSNs differently depending on the type of odorant receptor they express. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Natural host genetic resistance to lentiviral CNS disease: a neuroprotective MHC class I allele in SIV-infected macaques.

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Joseph L Mankowski

Full Text Available Human immunodeficiency virus (HIV infection frequently causes neurologic disease even with anti-retroviral treatment. Although associations between MHC class I alleles and acquired immunodeficiency syndrome (AIDS have been reported, the role MHC class I alleles play in restricting development of HIV-induced organ-specific diseases, including neurologic disease, has not been characterized. This study examined the relationship between expression of the MHC class I allele Mane-A*10 and development of lentiviral-induced central nervous system (CNS disease using a well-characterized simian immunodeficiency (SIV/pigtailed macaque model. The risk of developing CNS disease (SIV encephalitis was 2.5 times higher for animals that did not express the MHC class I allele Mane-A*10 (P = 0.002; RR = 2.5. Animals expressing the Mane-A*10 allele had significantly lower amounts of activated macrophages, SIV RNA, and neuronal dysfunction in the CNS than Mane-A*10 negative animals (P<0.001. Mane-A*10 positive animals with the highest CNS viral burdens contained SIV gag escape mutants at the Mane-A*10-restricted KP9 epitope in the CNS whereas wild type KP9 sequences dominated in the brain of Mane-A*10 negative animals with comparable CNS viral burdens. These concordant findings demonstrate that particular MHC class I alleles play major neuroprotective roles in lentiviral-induced CNS disease.

Effect of fragrance use on discrimination of individual body odor

Science.gov (United States)

Allen, Caroline; Havlíček, Jan; Roberts, S. Craig

2015-01-01

Previous research suggests that artificial fragrances may be chosen to complement or enhance an individual’s body odor, rather than simply masking it, and that this may create an odor blend with an emergent quality that is perceptually distinguishable from body odor or fragrance alone. From this, it can be predicted that a new emergent odor might be more easily identified than an individual’s body odor in isolation. We used a triangle test paradigm to assess whether fragrance affects people’s ability to distinguish between individual odors. Six male and six female donors provided axillary odor samples in three conditions (without fragrance, wearing their own fragrance, and wearing an assigned fragrance). In total, 296 female and 131 male participants selected the odd one from three odor samples (two from one donor, one from another; both of the same sex). We found that participants could discriminate between the odors at above chance levels in all three odor conditions. Olfactory identification ability (measured using Sniffin’ Sticks) positively predicted discrimination performance, and sex differences in performance were also observed, with female raters being correct more often than men. Success rates were also higher for odors of male donors. Additionally, while performance was above chance in all conditions, individual odor discrimination varied across the three conditions. Discrimination rate was significantly higher in the “no fragrance” condition than either of the fragranced conditions. Importantly, however, discrimination rate was also significantly higher in the “own fragrance” condition than the “assigned fragrance” condition, suggesting that naturally occurring variance in body odor is more preserved when blended with fragrances that people choose for themselves, compared with other fragrances. Our data are consistent with the idea that fragrance choices are influenced by fragrance interactions with an individual’s own body odor

Population genetic segmentation of MHC-correlated perfume preferences.

Science.gov (United States)

Hämmerli, A; Schweisgut, C; Kaegi, M

2012-04-01

It has become difficult to find a matching perfume. An overwhelming number of 300 new perfumes launch each year, and marketing campaigns target pre-defined groups based on gender, age or income rather than on individual preferences. Recent evidence for a genetic basis of perfume preferences, however, could be the starting point for a novel population genetic approach to better match perfumes with people's preferences. With a total of 116 participants genotyped for alleles of three loci of the major histocompatibility complex (MHC), the aim of this study was to test whether common MHC alleles could be used as genetic markers to segment a given population into preference types. Significant deviations from random expectations for a set of 10 common perfume ingredients indicate how such segmentation could be achieved. In addition, preference patterns of participants confronted with images that contained a sexual communication context significantly differed in their ratings for some of the scents compared with participants confronted with images of perfume bottles. This strongly supports the assumption that genetically correlated perfume preferences evolved in the context of sexual communication. The results are discussed in the light of perfume customization. © 2011 The Authors. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Guarded dependent type theory with coinductive types

DEFF Research Database (Denmark)

Bizjak, Aleš; Grathwohl, Hans Bugge; Clouston, Ranald

2016-01-01

We present guarded dependent type theory, gDTT, an extensional dependent type theory with a later' modality and clock quantifiers for programming and proving with guarded recursive and coinductive types. The later modality is used to ensure the productivity of recursive definitions in a modular......, type based, way. Clock quantifiers are used for controlled elimination of the later modality and for encoding coinductive types using guarded recursive types. Key to the development of gDTT are novel type and term formers involving what we call delayed substitutions’. These generalise the applicative...... functor rules for the later modality considered in earlier work, and are crucial for programming and proving with dependent types. We show soundness of the type theory with respect to a denotational model....

A specialized odor memory buffer in primary olfactory cortex.

Science.gov (United States)

Zelano, Christina; Montag, Jessica; Khan, Rehan; Sobel, Noam

2009-01-01

The neural substrates of olfactory working memory are unknown. We addressed the questions of whether olfactory working memory involves a verbal representation of the odor, or a sensory image of the odor, or both, and the location of the neural substrates of these processes. We used functional magnetic resonance imaging to measure activity in the brains of subjects who were remembering either nameable or unnameable odorants. We found a double dissociation whereby remembering nameable odorants was reflected in sustained activity in prefrontal language areas, and remembering unnameable odorants was reflected in sustained activity in primary olfactory cortex. These findings suggest a novel dedicated mechanism in primary olfactory cortex, where odor information is maintained in temporary storage to subserve ongoing tasks.

Structure of a Pheromone Receptor-Associated Mhc Molecule With An Open And Empty Groove

Energy Technology Data Exchange (ETDEWEB)

Olson, R.; Huey-Tubman, K.E.; Dulac, C.; Bjorkman, P.J.; /Caltech /Harvard U.

2006-10-06

Neurons in the murine vomeronasal organ (VNO) express a family of class Ib major histocompatibility complex (MHC) proteins (M10s) that interact with the V2R class of VNO receptors. This interaction may play a direct role in the detection of pheromonal cues that initiate reproductive and territorial behaviors. The crystal structure of M10.5, an M10 family member, is similar to that of classical MHC molecules. However, the M10.5 counterpart of the MHC peptide-binding groove is open and unoccupied, revealing the first structure of an empty class I MHC molecule. Similar to empty MHC molecules, but unlike peptide-filled MHC proteins and non-peptide-binding MHC homologs, M10.5 is thermally unstable, suggesting that its groove is normally occupied. However, M10.5 does not bind endogenous peptides when expressed in mammalian cells or when offered a mixture of class I-binding peptides. The F pocket side of the M10.5 groove is open, suggesting that ligands larger than 8-10-mer class I-binding peptides could fit by extending out of the groove. Moreover, variable residues point up from the groove helices, rather than toward the groove as in classical MHC structures. These data suggest that M10s are unlikely to provide specific recognition of class I MHC-binding peptides, but are consistent with binding to other ligands, including proteins such as the V2Rs.

Structure of a pheromone receptor-associated MHC molecule with an open and empty groove.

Directory of Open Access Journals (Sweden)

2005-08-01

Full Text Available Neurons in the murine vomeronasal organ (VNO express a family of class Ib major histocompatibility complex (MHC proteins (M10s that interact with the V2R class of VNO receptors. This interaction may play a direct role in the detection of pheromonal cues that initiate reproductive and territorial behaviors. The crystal structure of M10.5, an M10 family member, is similar to that of classical MHC molecules. However, the M10.5 counterpart of the MHC peptide-binding groove is open and unoccupied, revealing the first structure of an empty class I MHC molecule. Similar to empty MHC molecules, but unlike peptide-filled MHC proteins and non-peptide-binding MHC homologs, M10.5 is thermally unstable, suggesting that its groove is normally occupied. However, M10.5 does not bind endogenous peptides when expressed in mammalian cells or when offered a mixture of class I-binding peptides. The F pocket side of the M10.5 groove is open, suggesting that ligands larger than 8-10-mer class I-binding peptides could fit by extending out of the groove. Moreover, variable residues point up from the groove helices, rather than toward the groove as in classical MHC structures. These data suggest that M10s are unlikely to provide specific recognition of class I MHC-binding peptides, but are consistent with binding to other ligands, including proteins such as the V2Rs.

Quantum chemical analysis explains hemagglutinin peptide-MHC Class II molecule HLA-DRβ1*0101 interactions

International Nuclear Information System (INIS)

Cardenas, Constanza; Villaveces, Jose Luis; Bohorquez, Hugo; Llanos, Eugenio; Suarez, Carlos; Obregon, Mateo; Patarroyo, Manuel Elkin

2004-01-01

We present a new method to explore interactions between peptides and major histocompatibility complex (MHC) molecules using the resultant vector of the three principal multipole terms of the electrostatic field expansion. Being that molecular interactions are driven by electrostatic interactions, we applied quantum chemistry methods to better understand variations in the electrostatic field of the MHC Class II HLA-DRβ1*0101-HA complex. Multipole terms were studied, finding strong alterations of the field in Pocket 1 of this MHC molecule, and weak variations in other pockets, with Pocket 1 >> Pocket 4 > Pocket 9 ∼ Pocket 7 > Pocket 6. Variations produced by 'ideal' amino acids and by other occupying amino acids were compared. Two types of interactions were found in all pockets: a strong unspecific one (global interaction) and a weak specific interaction (differential interaction). Interactions in Pocket 1, the dominant pocket for this allele, are driven mainly by the quadrupole term, confirming the idea that aromatic rings are important in these interactions. Multipolar analysis is in agreement with experimental results, suggesting quantum chemistry methods as an adequate methodology to understand these interactions

Fancy citrus, feel good: Positive judgment of citrus odor, but not the odor itself, is associated with elevated mood during experienced helplessness

Directory of Open Access Journals (Sweden)

Matthias eHoenen

2016-02-01

Full Text Available Aromatherapy claims that citrus essential oils exert mood lifting effects. Controlled studies, however, have yielded inconsistent results. Notably, studies so far did not control for odor pleasantness, although pleasantness is a critical determinant of emotional responses to odors. This study investigates mood lifting effects of d-(+-limonene, the most prominent substance in citrus essential oils, with respect to odor quality judgments.Negative mood was induced within 78 participants using a helplessness paradigm (unsolvable social discrimination task. During this task, participants were continuously (mean duration: 19.5 min exposed to d-(+-limonene (n = 25, vanillin (n = 26, or diethyl phthalate (n = 27. Participants described their mood (Self-Assessment-Manikin, basic emotion ratings and judged the odors’ quality (intensity, pleasantness, unpleasantness, familiarity prior to and following the helplessness induction. The participants were in a less positive mood after the helplessness induction (p < .001, irrespective of the odor condition. Still, the more pleasant the participants judged the odors, the less effective the helplessness induction was in reducing happiness (p = .019.The results show no odor specific mood lifting effect of d-(+-limonene, but indicate a positive effect of odor pleasantness on mood. The study highlights the necessity to evaluate odor judgments in aromatherapy research.

MHC Class II and Non-MHC Class II Genes Differentially Influence Humoral Immunity to Bacillus anthracis Lethal Factor and Protective Antigen

OpenAIRE

Garman, Lori; Dumas, Eric K.; Kurella, Sridevi; Hunt, Jonathan J.; Crowe, Sherry R.; Nguyen, Melissa L.; Cox, Philip M.; James, Judith A.; Farris, A. Darise

2012-01-01

Anthrax Lethal Toxin consists of Protective Antigen (PA) and Lethal Factor (LF), and current vaccination strategies focus on eliciting antibodies to PA. In human vaccination, the response to PA can vary greatly, and the response is often directed toward non-neutralizing epitopes. Variable vaccine responses have been shown to be due in part to genetic differences in individuals, with both MHC class II and other genes playing roles. Here, we investigated the relative contribution of MHC class I...

Odorants and malodors associated with land application of biosolids stabilized with lime and coal fly ash.

Science.gov (United States)

Laor, Yael; Naor, Moshe; Ravid, Uzi; Fine, Pinchas; Halachmi, Ilan; Chen, Yona; Baybikov, Rima

2011-01-01

Malodor emissions limit public acceptance of using municipal biosolids as natural organic resources in agricultural production. We aimed to identify major odorants and to evaluate odor concentrations associated with land application of anaerobically digested sewage sludges (Class B) and their alkaline (lime and coal fly ash)-stabilized products (Class A). These two types of biosolids were applied at 12.6 tonnes ha(-1) (dry weight) to microplots of very fine clayey Vertisol in the Jezreel Valley, northern Israel. The volatile organic compounds (VOCs) emitted from the biosolids before and during alkaline stabilization and after incorporation into the soil were analyzed by headspace solid-phase microextraction followed by gas chromatography-mass spectrometry. Odor concentrations at the plots were evaluated on site with a Nasal Ranger field olfactometer that sniffed over a defined land surface area through a static chamber. The odors emitted by anaerobically digested sewage sludges from three activated sludge water treatment plants had one characteristic chemical fingerprint. Alkaline stabilization emitted substantial odors associated with high concentrations of ammonia and release of nitrogen-containing VOCs and did not effectively reduce the potential odor annoyance. Odorous VOCs could be generated within the soil after biosolids incorporation, presumably because of anaerobic conditions within soil-biosolids aggregates. We propose that dimethyl disulfide and dimethyl trisulfide, which seem to be most related to the odor concentrations of biosolids-treated soil, be used as potential chemical markers for the odor annoyance associated with incorporation of anaerobically digested sewage sludges. by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II recepter HLA-DR1

Energy Technology Data Exchange (ETDEWEB)

Mullen, M.; Haan, K.M.; Longnecker, R.; Jardetzky, T.

2010-03-08

Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes long-term latent infections, and is associated with a variety of human tumors. The EBV gp42 glycoprotein binds MHC class II molecules, playing a critical role in infection of B lymphocytes. EBV gp42 belongs to the C-type lectin superfamily, with homology to NK receptors of the immune system. We report the crystal structure of gp42 bound to the human MHC class II molecule HLA-DR1. The gp42 binds HLA-DR1 using a surface site that is distinct from the canonical lectin and NK receptor ligand binding sites. At the canonical ligand binding site, gp42 forms a large hydrophobic groove, which could interact with other ligands necessary for EBV entry, providing a mechanism for coupling MHC recognition and membrane fusion.

Ghrelin, leptin and adiponectin as possible predictors of the hedonic value of odors.

Science.gov (United States)

Trellakis, Sokratis; Tagay, Sefik; Fischer, Cornelia; Rydleuskaya, Alena; Scherag, André; Bruderek, Kirsten; Schlegl, Sandra; Greve, Jens; Canbay, Ali E; Lang, Stephan; Brandau, Sven

2011-02-25

Several lines of evidence point to a close relationship between the hormones of energy homeostasis and the olfactory system. Examples are the localization of leptin and adiponectin receptors in the olfactory system or increased activation of brain regions related to the palatability and the hedonic value of food in response to food pictures after application of ghrelin. In this preliminary study, we tested in 31 subjects (17 male and 14 female) if and to what extent the peripheral blood concentrations of "satiety" hormones, such as leptin, adiponectin, and ghrelin (acyl and total), are correlated with the self-ratings of odor pleasantness and with the objective olfactory and gustatory ability. The hedonic values of some odors were found to be differently rated between donors depending on gender and body weight. The concentrations of leptin, adiponectin and total ghrelin were significantly associated with the hedonic value of pepper black oil, but failed to show significant correlations for 5 other odors tested. Except for a significant association between leptin and odor identification, hormone concentrations were not linked to the abilities of smell and taste. Peripheral adipokines and gut hormones may alter the perception and pleasantness of specific odors, presumably either directly through their receptors in the olfactory system or indirectly through central interfaces between the regulation systems of olfaction, appetite control, memory and motivation. Copyright © 2010 Elsevier B.V. All rights reserved.

Walking patterns induced by learned odors in the honeybee, Apis mellifera L.

Science.gov (United States)

Yamashita, Toshiya; Haupt, S Shuichi; Ikeno, Hidetoshi; Ai, Hiroyuki

2016-01-01

The odor localization strategy induced by odors learned via differential conditioning of the proboscis extension response was investigated in honeybees. In response to reward-associated but not non-reward-associated odors, learners walked longer paths than non-learners and control bees. When orange odor reward association was learned, the path length and the body turn angles were small during odor stimulation and greatly increased after stimulation ceased. In response to orange odor, bees walked locally with alternate left and right turns during odor stimulation to search for the reward-associated odor source. After odor stimulation, bees walked long paths with large turn angles to explore the odor plume. For clove odor, learning-related modulations of locomotion were less pronounced, presumably due to a spontaneous preference for orange in the tested population of bees. This study is the first to describe how an odor-reward association modulates odor-induced walking in bees. © 2016. Published by The Company of Biologists Ltd.

Tapasin-related protein TAPBPR is an additional component of the MHC class I presentation pathway

DEFF Research Database (Denmark)

Boyle, Louise H; Hermann, Clemens; Boname, Jessica M

2013-01-01

Tapasin is an integral component of the peptide-loading complex (PLC) important for efficient peptide loading onto MHC class I molecules. We investigated the function of the tapasin-related protein, TAPBPR. Like tapasin, TAPBPR is widely expressed, IFN-γ-inducible, and binds to MHC class I coupled...... with β2-microglobulin in the endoplasmic reticulum. In contrast to tapasin, TAPBPR does not bind ERp57 or calreticulin and is not an integral component of the PLC. β2-microglobulin is essential for the association between TAPBPR and MHC class I. However, the association between TAPBPR and MHC class I...... occurs in the absence of a functional PLC, suggesting peptide is not required. Expression of TAPBPR decreases the rate of MHC class I maturation through the secretory pathway and prolongs the association of MHC class I on the PLC. The TAPBPR:MHC class I complex trafficks through the Golgi apparatus...

Odors as effective retrieval cues for stressful episodes.

Science.gov (United States)

Wiemers, Uta S; Sauvage, Magdalena M; Wolf, Oliver T

2014-07-01

Olfactory information seems to play a special role in memory due to the fast and direct processing of olfactory information in limbic areas like the amygdala and the hippocampus. This has led to the assumption that odors can serve as effective retrieval cues for autobiographic memories, especially emotional memories. The current study sought to investigate whether an olfactory cue can serve as an effective retrieval cue for memories of a stressful episode. A total of 95 participants were exposed to a psychosocial stressor or a well matching but not stressful control condition. During both conditions were visual objects present, either bound to the situation (central objects) or not (peripheral objects). Additionally, an ambient odor was present during both conditions. The next day, participants engaged in an unexpected object recognition task either under the influence of the same odor as was present during encoding (congruent odor) or another odor (non-congruent odor). Results show that stressed participants show a better memory for all objects and especially for central visual objects if recognition took place under influence of the congruent odor. An olfactory cue thus indeed seems to be an effective retrieval cue for stressful memories. Copyright © 2013 Elsevier Inc. All rights reserved.

Emotion experienced during encoding enhances odor retrieval cue effectiveness.

Science.gov (United States)

Herz, R S

1997-01-01

Emotional potentiation may be a key variable in the formation of odor-associated memory. Two experiments were conducted in which a distinctive ambient odor was present or absent during encoding and retrieval sessions and subjects were in an anxious or neutral mood during encoding. Subjects' mood at retrieval was not manipulated. The laboratory mood induction used in Experiment 1 suggested that anxiety might increase the effectiveness of an odor retrieval cue. This trend was confirmed in Experiment 2 by capturing a naturally stressful situation. Subjects who had an ambient odor cue available and were in a preexam state during encoding recalled more words than subjects in any other group. These data are evidence that heightened emotion experienced during encoding with an ambient odor can enhance the effectiveness of an odor as a cue to memory.

Study on off-odor volatiles of irradiated packaged raw pork

International Nuclear Information System (INIS)

Lin Ruotai; Geng Shengrong; Liu Yangmin

2008-01-01

Analysing the compositions of off-odor volatiles in irradiated refrigerated vacuum-packaged pork and research on its origin. First, the off-odor volatiles were collected by a cooled via in liquid nitrogen, then the main composition of off-odor volatiles were analyzed by gas chromatograph mass spectrometry (GC-MS). The main composition of off-odor volatiles are dimethyl disulfide, dimethyl sulfide, dimethyl trisulfide, methanethiol and S-methyl thioacetate. The off-odor volatiles come from irradiated cystine, methionine and VB1. The main composition of off-odor volatiles are S-containing compounds from irradiated S-containing amino acid and VB1

Effect of fragrance use on discrimination of individual body odor

Directory of Open Access Journals (Sweden)

Caroline eAllen

2015-08-01

Full Text Available Previous research suggests that artificial fragrances may be chosen to complement or enhance an individual’s body odor, rather than simply masking it, and that this may create an odor blend with an emergent quality that is perceptually distinguishable from body odor or fragrance alone. From this, it can be predicted that a new emergent odor might be more easily identified than an individual’s body odor in isolation. We used a triangle test paradigm to assess whether fragrance affects people’s ability to distinguish between individual odors. Six male and six female donors provided axillary odor samples in three conditions (without fragrance, wearing their own fragrance, and wearing an assigned fragrance. In total, 296 female and 131 male participants selected the odd one out from three odor samples (two from one donor, one from another; both of the same sex. We found that participants could discriminate between the odors at above chance levels in all three odour conditions. Olfactory identification ability (measured using Sniffin’ Sticks positively predicted discrimination performance, and sex differences in performance were also observed, with female raters being correct more often than men. Success rates were also higher for odors of male donors. Additionally, while performance was above chance in all conditions, individual odor discrimination varied across the three conditions. Discrimination rate was significantly higher in the ‘no fragrance’ condition than either of the fragranced conditions. Importantly, however, discrimination rate was also significantly higher in the ‘own fragrance’ condition than the ‘assigned fragrance’ condition, suggesting that naturally occurring variance in body odor is more preserved when blended with fragrances that people choose for themselves, compared with other fragrances. Our data are consistent with the idea that fragrance choices are influenced by fragrance interactions with an

Gene transfer preferentially selects MHC class I positive tumour cells and enhances tumour immunogenicity.

Science.gov (United States)

Hacker, Ulrich T; Schildhauer, Ines; Barroso, Margarita Céspedes; Kofler, David M; Gerner, Franz M; Mysliwietz, Josef; Buening, Hildegard; Hallek, Michael; King, Susan B S

2006-05-01

The modulated expression of MHC class I on tumour tissue is well documented. Although the effect of MHC class I expression on the tumorigenicity and immunogenicity of MHC class I negative tumour cell lines has been rigorously studied, less is known about the validity of gene transfer and selection in cell lines with a mixed MHC class I phenotype. To address this issue we identified a C26 cell subline that consists of distinct populations of MHC class I (H-2D/K) positive and negative cells. Transient transfection experiments using liposome-based transfer showed a lower transgene expression in MHC class I negative cells. In addition, MHC class I negative cells were more sensitive to antibiotic selection. This led to the generation of fully MHC class I positive cell lines. In contrast to C26 cells, all transfectants were rejected in vivo and induced protection against the parental tumour cells in rechallenge experiments. Tumour cell specificity of the immune response was demonstrated in in vitro cytokine secretion and cytotoxicity assays. Transfectants expressing CD40 ligand and hygromycin phosphotransferase were not more immunogenic than cells expressing hygromycin resistance alone. We suggest that the MHC class I positive phenotype of the C26 transfectants had a bearing on their immunogenicity, because selected MHC class I positive cells were more immunogenic than parental C26 cells and could induce specific anti-tumour immune responses. These data demonstrate that the generation of tumour cell transfectants can lead to the selection of subpopulations that show an altered phenotype compared to the parental cell line and display altered immunogenicity independent of selection marker genes or other immune modulatory genes. Our results show the importance of monitoring gene transfer in the whole tumour cell population, especially for the evaluation of in vivo therapies targeted to heterogeneous tumour cell populations.

Apolipoprotein e4 Is Associated with More Rapid Decline in Odor Identification than in Odor Threshold or Dementia Rating Scale Scores

Science.gov (United States)

Calhoun-Haney, R.; Murphy, C.

2005-01-01

Individuals with the apolipoprotein E e4 genetic risk factor for Alzheimer's disease (AD) show deficits in olfactory function. The purpose of the present study was to examine longitudinally odor identification (odor ID), odor threshold, picture identification, and global cognitive status in allele positive (e4+) and negative (e4-) persons.…

CD4+ T cell-mediated cytotoxicity is associated with MHC class II expression on malignant CD19+ B cells in diffuse large B cell lymphoma.

Science.gov (United States)

Zhou, Yong; Zha, Jie; Lin, Zhijuan; Fang, Zhihong; Zeng, Hanyan; Zhao, Jintao; Luo, Yiming; Li, Zhifeng; Xu, Bing

2018-01-15

Diffuse large B cell lymphoma (DLBCL) is a common B cell malignancy with approximately 30% of patients present relapsed or refractory disease after first-line therapy. Research of further treatment options is needed. Cytotoxic CD4 + T cells express cytolytic molecules and have potential antitumor function. Here, we showed that the CD19 + cells from DLBCL patients presented significantly reduced expression of MHC II molecules than those from healthy controls. Three years after the first-line treatment, patients that presented relapsed disease had significantly lower MHC II expression on their CD19 + cells than patients who did not show recurrence. Examining cytotoxic CD4 + T cells show that DLBCL patients presented significantly elevated frequencies of granzyme A-, granzyme B-, and/or perforin-expressing cytotoxic CD4 + T cells. Also, frequency of cytotoxic CD4 + T cells in DLBCL patients was positively correlated with the MHC II expression level. Subsequently, the cytotoxic potential of CD4 + T cells against autologous CD19 + cells was investigated. We found that the cytotoxic potential of CD4 + T cells was highest in MHC II-high, intermediate in MHC II-mid, and lowest in MHC II-low patients. The percentage of MHC II-expressing viable CD19 + cells presented a significant reduction after longer incubation with cytotoxic CD4 + T cells, suggesting that cytotoxic CD4 + T cells preferentially eliminated MHC II-expressing CD19 + cells. Blocking MHC II on CD19 + cells significantly reduced the cytolytic capacity of CD4 + T cells. Despite these discoveries, the frequency of cytotoxic CD4 + T cells did not predict the clinical outcome of DLBCL patients. Together, these results demonstrated that cytotoxic CD4 + T cells presented an MHC II-dependent cytotoxic potential against autologous CD19 + cells and could potentially represent a future treatment option for DLBCL. Copyright © 2017 Elsevier Inc. All rights reserved.

Low MHC variation in the endangered Galápagos penguin (Spheniscus mendiculus).

Science.gov (United States)

Bollmer, Jennifer L; Vargas, F Hernán; Parker, Patricia G

2007-07-01

The major histocompatibility complex (MHC) is one of the most polymorphic regions of the genome, likely due to balancing selection acting to maintain alleles over time. Lack of MHC variability has been attributed to factors such as genetic drift in small populations and relaxed selection pressure. The Galápagos penguin (Spheniscus mendiculus), endemic to the Galápagos Islands, is the only penguin that occurs on the equator. It relies upon cold, nutrient-rich upwellings and experiences severe population declines when ocean temperatures rise during El Niño events. These bottlenecks, occurring in an already small population, have likely resulted in reduced genetic diversity in this species. In this study, we used MHC class II exon 2 sequence data from a DRB1-like gene to characterize the amount of genetic variation at the MHC in 30 Galápagos penguins, as well as one Magellanic penguin (S. magellanicus) and two king penguins (Aptenodytes patagonicus), and compared it to that in five other penguin species for which published data exist. We found that the Galápagos penguin had the lowest MHC diversity (as measured by number of polymorphic sites and average divergence among alleles) of the eight penguin species studied. A phylogenetic analysis showed that Galápagos penguin MHC sequences are most closely related to Humboldt penguin (Spheniscus humboldti) sequences, its putative sister species based on other loci. An excess of non-synonymous mutations and a pattern of trans-specific evolution in the neighbor-joining tree suggest that selection is acting on the penguin MHC.

Rapid encoding and perception of novel odors in the rat.

Directory of Open Access Journals (Sweden)

Daniel W Wesson

2008-04-01

Full Text Available To gain insight into which parameters of neural activity are important in shaping the perception of odors, we combined a behavioral measure of odor perception with optical imaging of odor representations at the level of receptor neuron input to the rat olfactory bulb. Instead of the typical test of an animal's ability to discriminate two familiar odorants by exhibiting an operant response, we used a spontaneously expressed response to a novel odorant-exploratory sniffing-as a measure of odor perception. This assay allowed us to measure the speed with which rats perform spontaneous odor discriminations. With this paradigm, rats discriminated and began responding to a novel odorant in as little as 140 ms. This time is comparable to that measured in earlier studies using operant behavioral readouts after extensive training. In a subset of these trials, we simultaneously imaged receptor neuron input to the dorsal olfactory bulb with near-millisecond temporal resolution as the animal sampled and then responded to the novel odorant. The imaging data revealed that the bulk of the discrimination time can be attributed to the peripheral events underlying odorant detection: receptor input arrives at the olfactory bulb 100-150 ms after inhalation begins, leaving only 50-100 ms for central processing and response initiation. In most trials, odor discrimination had occurred even before the initial barrage of receptor neuron firing had ceased and before spatial maps of activity across glomeruli had fully developed. These results suggest a coding strategy in which the earliest-activated glomeruli play a major role in the initial perception of odor quality, and place constraints on coding and processing schemes based on simple changes in spike rate.

Numerical simulation of airway dimension effects on airflow patterns and odorant deposition patterns in the rat nasal cavity.

Directory of Open Access Journals (Sweden)

Zehong Wei

Full Text Available The sense of smell is largely dependent on the airflow and odorant transport in the nasal cavity, which in turn depends on the anatomical structure of the nose. In order to evaluate the effect of airway dimension on rat nasal airflow patterns and odorant deposition patterns, we constructed two 3-dimensional, anatomically accurate models of the left nasal cavity of a Sprague-Dawley rat: one was based on high-resolution MRI images with relatively narrow airways and the other was based on artificially-widening airways of the MRI images by referencing the section images with relatively wide airways. Airflow and odorant transport, in the two models, were determined using the method of computational fluid dynamics with finite volume method. The results demonstrated that an increase of 34 µm in nasal airway dimension significantly decreased the average velocity in the whole nasal cavity by about 10% and in the olfactory region by about 12% and increased the volumetric flow into the olfactory region by about 3%. Odorant deposition was affected to a larger extent, especially in the olfactory region, where the maximum odorant deposition difference reached one order of magnitude. The results suggest that a more accurate nasal cavity model is necessary in order to more precisely study the olfactory function of the nose when using the rat.

Pan-specific prediction of peptide-MHC Class I complex stability, a correlate of T cell immunogenicity

DEFF Research Database (Denmark)

Rasmussen, Michael; Fenoy, Emilio; Harndahl, Mikkel

2016-01-01

Binding of peptides to MHC class I (MHC-I) molecules is the most selective event in the processing and presentation of Ags to CTL, and insights into the mechanisms that govern peptide-MHC-I binding should facilitate our understanding of CTL biology. Peptide-MHC-I interactions have traditionally b...

Male risk taking, female odors, and the role of estrogen receptors.

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Kavaliers, Martin; Clipperton-Allen, Amy; Cragg, Cheryl L; Gustafsson, Jan-Åke; Korach, Kenneth S; Muglia, Louis; Choleris, Elena

2012-12-05

Male risk-taking and decision making are affected by sex-related cues, with men making riskier choices and decisions after exposure to either women or stimuli associated with women. In non-human species females and, or their cues can also increase male risk taking. Under the ecologically relevant condition of predation threat, brief exposure of male mice to the odors of a sexually receptive novel female reduces the avoidance of, and aversive responses to, a predator. We briefly review evidence showing that estrogen receptors (ERs), ERα and ERβ, are associated with the mediation of these risk taking responses. We show that ERs influence the production of the female odors that affect male risk taking, with the odors of wild type (ERαWT, ERβWT), oxytocin (OT) wildtype (OTWT), gene-deleted 'knock-out' ERβ (ERβKO), but not ERαKO or oxytocin (OT) OTKO or ovariectomized (OVX) female mice reducing the avoidance responses of male mice to cat odor. We further show that administration of specific ERα and ERβ agonists to OVX females results in their odors increasing male risk taking and boldness towards a predator. We also review evidence that ERs are involved in the mediation of the responses of males to female cues, with ERα being associated with the sexual and both ERβ and ERα with the sexual and social mechanisms underlying the effects of female cues on male risk taking. The implications and relations of these findings with rodents to ERs and the regulation of human risk taking are briefly considered. Copyright © 2012 Elsevier Inc. All rights reserved.

One-pot, mix-and-read peptide-MHC tetramers

DEFF Research Database (Denmark)

Leisner, Christian Valdemar Vinge; Loeth, Nina; Lamberth, Kasper

2008-01-01

BACKGROUND: Cytotoxic T Lymphocytes (CTL) recognize complexes of peptide ligands and Major Histocompatibility Complex (MHC) class I molecules presented at the surface of Antigen Presenting Cells (APC). Detection and isolation of CTL's are of importance for research on CTL immunity, and development...... molecules can be refolded in vitro, tetramerized with streptavidin, and used for specific T cell staining-all in a one-pot reaction without any intervening purification steps. CONCLUSIONS/SIGNIFICANCE: We have developed an efficient "one-pot, mix-and-read" strategy for peptide-MHC tetramer generation...

Mass Spectrometry Reveals Changes in MHC I Antigen Presentation After Lentivector Expression of a Gene Regulation System

Directory of Open Access Journals (Sweden)

Roland Vogel

2013-01-01

Full Text Available The rapamycin-inducible gene regulation system was designed to minimize immune reactions in man and may thus be suited for gene therapy. We assessed whether this system indeed induces no immune responses. The protein components of the regulation system were produced in the human cell lines HEK 293T, D407, and HER 911 following lentiviral transfer of the corresponding genes. Stable cell lines were established, and the peptides presented by major histocompatibility complex class I (MHC I molecules on transduced and wild-type (wt cells were compared by differential mass spectrometry. In all cell lines examined, expression of the transgenes resulted in prominent changes in the repertoire of MHC I-presented self-peptides. No MHC I ligands originating from the transgenic proteins were detected. In vitro analysis of immunogenicity revealed that transduced D407 cells displayed slightly higher capacity than wt controls to promote proliferation of cytotoxic T cells. These results indicate that therapeutic manipulations within the genome of target cells may affect pathways involved in the processing of peptide antigens and their presentation by MHC I. This makes the genomic modifications visible to the immune system which may recognize these events and respond. Ultimately, the findings call attention to a possible immune risk.

Recognition of Bread Key Odorants by Using Polymer Coated QCMs

Science.gov (United States)

Nakai, Takashi; Kouno, Shinji; Hiruma, Naoya; Shuzo, Masaki; Delaunay, Jean-Jacques; Yamada, Ichiro

Polyisobutylene (PIB) polymer and methylphenylsiloxane (25%) diphenylsiloxane (75%) copolymer (OV25) were coated on Quartz Crystal Microbalance (QCM) sensors and used in recognition of bread key odorants. Representative compounds of key roasty odorants of bread were taken as 3-acetylpyridine and benzaldehyde, and representative key fatty odorants were hexanal and (E)-2-nonenal. Both OV25- and PIB-coated QCM fabricated sensors could detect concentration as low as 0.9 ppm of 3-acetylpyridine and 1.2 ppm of (E)-2-nonenal. The sensitivity to 3-acetylpyridine of the OV25-coated QCM was about 1000 times higher than that of ethanol, the major interference compound in bread key odorant analysis. Further, the OV25-coated QCM response was 5-6 times and 2-3 times larger than that of the PIB-coated QCM when exposed to roasty odorants and to fatty odorants, respectively. The difference in sensitivity of the OV25- and PIB-coated QCMs we fabricated made possible to discriminate roasty from fatty odorants as was evidenced by the odor recognition map representing the frequency shifts of the OV25-coated QCM against the frequency shift of the PIB-coated QCM. In conclusion, we found that the combination of an OV25-coated QCM and a PIB-coated QCM was successful in discriminating roasty odorants from fatty odorants at the ppm level.

Functional Neuronal Processing of Human Body Odors

OpenAIRE

Lundström, Johan N.; Olsson, Mats J.

2010-01-01

Body odors carry informational cues of great importance for individuals across a wide range of species, and signals hidden within the body odor cocktail are known to regulate several key behaviors in animals. For a long time, the notion that humans may be among these species has been dismissed. We now know, however, that each human has a unique odor signature that carries information related to his or her genetic makeup, as well as information about personal environmental variables, such as d...

What's that smell? An ecological approach to understanding preferences for familiar odors.

Science.gov (United States)

Schloss, Karen B; Goldberger, Carolyn S; Palmer, Stephen E; Levitan, Carmel A

2015-01-01

How do odor preferences arise? Following Palmer and Schloss's (2010, PNAS, 107, 8877-8882) ecological valence theory of color preferences, we propose that preference for an odor is determined by preferences for all objects and/or entities associated with that odor. The present results showed that preferences for familiar odors were strongly predicted by average preferences for all things associated with the odors (eg people liked the apple odor which was associated with mostly positive things, such as apples, soap, and candy, but disliked the fish odor, which was associated with mostly negative things, such as dead fish, trash, and vomit). The odor WAVEs (weighted affective valence estimates) performed significantly better than one based on preference for only the namesake object (eg predicting preference for the apple odor based on preference for apples). These results suggest that preferences for familiar odors are based on a summary statistic, coding the valence of previous odor-related experiences. We discuss how this account of odor preferences is consistent with the idea that odor preferences exist to guide organisms to approach beneficial objects and situations and avoid harmful ones.

Identification of the cognate peptide-MHC target of T cell receptors using molecular modeling and force field scoring

DEFF Research Database (Denmark)

Lanzarotti, Esteban; Marcatili, Paolo; Nielsen, Morten

2018-01-01

Interactions of T cell receptors (TCR) to peptides in complex with MHC (p:MHC) are key features that mediate cellular immune responses. While MHC binding is required for a peptide to be presented to T cells, not all MHC binders are immunogenic. The interaction of a TCR to the p:MHC complex holds...... terms. Building a benchmark of TCR:p:MHC complexes where epitopes and non-epitopes are modelled using state-of-the-art molecular modelling tools, scoring p:MHC to a given TCR using force-fields, optimized in a cross-validation setup to evaluate TCR inter atomic interactions involved with each p:MHC, we...... and model the TCR:p:MHC complex structure. In summary, we conclude that it is possible to identify the TCR cognate target among different candidate peptides by using a force-field based model, and believe this works could lay the foundation for future work within prediction of TCR:p:MHC interactions....

A “Misfit” Theory of Spontaneous Conscious Odor Perception (MITSCOP): reflections on the role and function of odor memory in everyday life

Science.gov (United States)

Köster, Egon P.; Møller, Per; Mojet, Jozina

2014-01-01

Our senses have developed as an answer to the world we live in (Gibson, 1966) and so have the forms of memory that accompany them. All senses serve different purposes and do so in different ways. In vision, where orientation and object recognition are important, memory is strongly linked to identification. In olfaction, the guardian of vital functions such as breathing and food ingestion, perhaps the most important (and least noticed and researched) role of odor memory is to help us not to notice the well-known odors or flavors in our everyday surroundings, but to react immediately to the unexpected ones. At the same time it provides us with a feeling of safety when our expectancies are met. All this happens without any smelling intention or conscious knowledge of our expectations. Identification by odor naming is not involved in this and people are notoriously bad at it. Odors are usually best identified via the episodic memory of the situation in which they once occurred. Spontaneous conscious odor perception normally only occurs in situations where attention is demanded, either because the inhaled air or the food smell is particularly good or particularly bad and people search for its source or because people want to actively enjoy the healthiness and pleasantness of their surroundings or food. Odor memory is concerned with novelty detection rather than with recollection of odors. In this paper, these points are illustrated with experimental results and their consequences for doing ecologically valid odor memory research are drawn. Furthermore, suggestions for ecologically valid research on everyday odor memory and some illustrative examples are given. PMID:24575059

Olfactory Imagination and Odor Processing: Three Same-Different Experiments

NARCIS (Netherlands)

Koster, E.P.; Stelt, van der O.; Nixdorf, R.R.; Linschoten, M.R.I.; Mojet, J.; Wijk, de R.A.

2014-01-01

Do people who claim to have olfactory imagination process odors more efficiently? In three same–different experiments, using all possible combinations of odors and odor names as primes and targets, selected high imagers (n¿=¿12) were faster (±230 ms; P¿

Effect of aging on hedonic appreciation of pleasant and unpleasant odors.

Directory of Open Access Journals (Sweden)

Pauline Joussain

Full Text Available Does hedonic appreciation evolve differently for pleasant odors and unpleasant odors during normal aging? To answer this question we combined psychophysics and electro-encephalographic recordings in young and old adults. A first study showed that pleasant odorants (but not unpleasant ones were rated as less pleasant by old adults. A second study validated this decrease in hedonic appreciation for agreeable odors and further showed that smelling these odorants decreased beta event-related synchronization in aged participants. In conclusion, the study offers new insights into the evolution of odor hedonic perception during normal aging, highlighting for the first time a change in processing pleasant odors.

Odors as triggering and worsening factors for migraine in men

Directory of Open Access Journals (Sweden)

A M Lima

2011-01-01

Full Text Available OBJECTIVE: To assess the role of odors in triggering or worsening migraine in men. METHOD: Ninety-eight male migraineurs from the general population were assessed individually through questionnaires. Environmental factors relating to their migraine were reported, with special focus on the role of odors. RESULTS: Odors were the second most frequent triggering factor for migraine attacks (48%, behind stressful situations (59%. Likewise, odors were the second most frequent worsening factor (73%, just behind excessive light (74%. Thirty-three individuals (33.4% stated that odors were both triggering and worsening factors for their migraine attacks. Perfume, cigarette smoke and cleaning products were the most frequent migraine-related odors reported by these male migraineurs. CONCLUSION: This was the first study to assess the role of odors in migraine exclusively in men. There was a high degree of odor-related migraine among these men, thus suggesting that patient education could alert such individuals to gender-related factors, since different triggering and worsening factors have been reported by males and females.

Programming of stress-related behavior and epigenetic neural gene regulation in mice offspring through maternal exposure to predator odor

Science.gov (United States)

St-Cyr, Sophie; McGowan, Patrick O.

2015-01-01

Perinatal stress mediated through the mother can lead to long-term alterations in stress-related phenotypes in offspring. The capacity for adaptation to adversity in early life depends in part on the life history of the animal. This study was designed to examine the behavioral and neural response in adult offspring to prenatal exposure to predator odor: an ethologically-relevant psychological stressor. Pregnant mice were exposed daily to predator odors or distilled water control over the second half of the pregnancy. Predator odor exposure lead to a transient decrease in maternal care in the mothers. As adults, the offspring of predator odor-exposed mothers showed increased anti-predator behavior, a predator-odor induced decrease in activity and, in female offspring, an increased corticosterone (CORT) response to predator odor exposure. We found a highly specific response among stress-related genes within limbic brain regions. Transcript abundance of Corticotropin-releasing hormone receptor 1 (CRHR1) was elevated in the amygdala in adult female offspring of predator odor-exposed mothers. In the hippocampus of adult female offspring, decreased Brain-derived neurotrophic factor (BDNF) transcript abundance was correlated with a site-specific decrease in DNA methylation in Bdnf exon IV, indicating the potential contribution of this epigenetic mechanism to maternal programming by maternal predator odor exposure. These data indicate that maternal predator odor exposure alone is sufficient to induce an altered stress-related phenotype in adulthood, with implications for anti-predator behavior in offspring. PMID:26082698

Predicted MHC peptide binding promiscuity explains MHC class I 'hotspots' of antigen presentation defined by mass spectrometry eluted ligand data.

Science.gov (United States)

Jappe, Emma Christine; Kringelum, Jens; Trolle, Thomas; Nielsen, Morten

2018-02-15

Peptides that bind to and are presented by MHC class I and class II molecules collectively make up the immunopeptidome. In the context of vaccine development, an understanding of the immunopeptidome is essential, and much effort has been dedicated to its accurate and cost-effective identification. Current state-of-the-art methods mainly comprise in silico tools for predicting MHC binding, which is strongly correlated with peptide immunogenicity. However, only a small proportion of the peptides that bind to MHC molecules are, in fact, immunogenic, and substantial work has been dedicated to uncovering additional determinants of peptide immunogenicity. In this context, and in light of recent advancements in mass spectrometry (MS), the existence of immunological hotspots has been given new life, inciting the hypothesis that hotspots are associated with MHC class I peptide immunogenicity. We here introduce a precise terminology for defining these hotspots and carry out a systematic analysis of MS and in silico predicted hotspots. We find that hotspots defined from MS data are largely captured by peptide binding predictions, enabling their replication in silico. This leads us to conclude that hotspots, to a great degree, are simply a result of promiscuous HLA binding, which disproves the hypothesis that the identification of hotspots provides novel information in the context of immunogenic peptide prediction. Furthermore, our analyses demonstrate that the signal of ligand processing, although present in the MS data, has very low predictive power to discriminate between MS and in silico defined hotspots. © 2018 John Wiley & Sons Ltd.

Brain-immune interaction accompanying odor-evoked autobiographic memory.

Science.gov (United States)

Matsunaga, Masahiro; Bai, Yu; Yamakawa, Kaori; Toyama, Asako; Kashiwagi, Mitsuyoshi; Fukuda, Kazuyuki; Oshida, Akiko; Sanada, Kazue; Fukuyama, Seisuke; Shinoda, Jun; Yamada, Jitsuhiro; Sadato, Norihiro; Ohira, Hideki

2013-01-01

The phenomenon in which a certain smell evokes a specific memory is known as the Proust phenomenon. Odor-evoked autobiographic memories are more emotional than those elicited by other sensory stimuli. The results of our previous study indicated that odor-evoked autobiographic memory accompanied by positive emotions has remarkable effects on various psychological and physiological activities, including the secretion of cytokines, which are immune-signaling molecules that modulate systemic inflammation. In this study, we aimed to clarify the neural substrates associated with the interaction between odor-evoked autobiographic memory and peripheral circulating cytokines. We recruited healthy male and female volunteers and investigated the association between brain responses and the concentration of several cytokines in the plasma by using positron emission tomography (PET) recordings when an autographic memory was evoked in participants by asking them to smell an odor that was nostalgic to them. Participants experienced positive emotions and autobiographic memories when nostalgic odors were presented to them. The levels of peripheral proinflammatory cytokines, such as the tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), were significantly reduced after experiencing odor-evoked autobiographic memory. Subtraction analysis of PET images indicated that the medial orbitofrontal cortex (mOFC) and precuneus/posterior cingulate cortex (PCC) were significantly activated during experiences of odor-evoked autobiographic memory. Furthermore, a correlation analysis indicated that activities of the mOFC and precuneus/PCC were negatively correlated with IFN-γ concentration. These results indicate that the neural networks including the precuneus/PCC and mOFC might regulate the secretion of peripheral proinflammatory cytokines during the experience of odor-evoked autobiographic memories accompanied with positive emotions.

Brain–Immune Interaction Accompanying Odor-Evoked Autobiographic Memory

Science.gov (United States)

Matsunaga, Masahiro; Bai, Yu; Yamakawa, Kaori; Toyama, Asako; Kashiwagi, Mitsuyoshi; Fukuda, Kazuyuki; Oshida, Akiko; Sanada, Kazue; Fukuyama, Seisuke; Shinoda, Jun; Yamada, Jitsuhiro; Sadato, Norihiro; Ohira, Hideki

2013-01-01

The phenomenon in which a certain smell evokes a specific memory is known as the Proust phenomenon. Odor-evoked autobiographic memories are more emotional than those elicited by other sensory stimuli. The results of our previous study indicated that odor-evoked autobiographic memory accompanied by positive emotions has remarkable effects on various psychological and physiological activities, including the secretion of cytokines, which are immune-signaling molecules that modulate systemic inflammation. In this study, we aimed to clarify the neural substrates associated with the interaction between odor-evoked autobiographic memory and peripheral circulating cytokines. We recruited healthy male and female volunteers and investigated the association between brain responses and the concentration of several cytokines in the plasma by using positron emission tomography (PET) recordings when an autographic memory was evoked in participants by asking them to smell an odor that was nostalgic to them. Participants experienced positive emotions and autobiographic memories when nostalgic odors were presented to them. The levels of peripheral proinflammatory cytokines, such as the tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), were significantly reduced after experiencing odor-evoked autobiographic memory. Subtraction analysis of PET images indicated that the medial orbitofrontal cortex (mOFC) and precuneus/posterior cingulate cortex (PCC) were significantly activated during experiences of odor-evoked autobiographic memory. Furthermore, a correlation analysis indicated that activities of the mOFC and precuneus/PCC were negatively correlated with IFN-γ concentration. These results indicate that the neural networks including the precuneus/PCC and mOFC might regulate the secretion of peripheral proinflammatory cytokines during the experience of odor-evoked autobiographic memories accompanied with positive emotions. PMID:23977312

Brain-immune interaction accompanying odor-evoked autobiographic memory.

Directory of Open Access Journals (Sweden)

Masahiro Matsunaga

Full Text Available The phenomenon in which a certain smell evokes a specific memory is known as the Proust phenomenon. Odor-evoked autobiographic memories are more emotional than those elicited by other sensory stimuli. The results of our previous study indicated that odor-evoked autobiographic memory accompanied by positive emotions has remarkable effects on various psychological and physiological activities, including the secretion of cytokines, which are immune-signaling molecules that modulate systemic inflammation. In this study, we aimed to clarify the neural substrates associated with the interaction between odor-evoked autobiographic memory and peripheral circulating cytokines. We recruited healthy male and female volunteers and investigated the association between brain responses and the concentration of several cytokines in the plasma by using positron emission tomography (PET recordings when an autographic memory was evoked in participants by asking them to smell an odor that was nostalgic to them. Participants experienced positive emotions and autobiographic memories when nostalgic odors were presented to them. The levels of peripheral proinflammatory cytokines, such as the tumor necrosis factor-α (TNF-α and interferon-γ (IFN-γ, were significantly reduced after experiencing odor-evoked autobiographic memory. Subtraction analysis of PET images indicated that the medial orbitofrontal cortex (mOFC and precuneus/posterior cingulate cortex (PCC were significantly activated during experiences of odor-evoked autobiographic memory. Furthermore, a correlation analysis indicated that activities of the mOFC and precuneus/PCC were negatively correlated with IFN-γ concentration. These results indicate that the neural networks including the precuneus/PCC and mOFC might regulate the secretion of peripheral proinflammatory cytokines during the experience of odor-evoked autobiographic memories accompanied with positive emotions.

Odor Classification using Agent Technology

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Sigeru OMATU

2014-03-01

Full Text Available In order to measure and classify odors, Quartz Crystal Microbalance (QCM can be used. In the present study, seven QCM sensors and three different odors are used. The system has been developed as a virtual organization of agents using an agent platform called PANGEA (Platform for Automatic coNstruction of orGanizations of intElligent Agents. This is a platform for developing open multi-agent systems, specifically those including organizational aspects. The main reason for the use of agents is the scalability of the platform, i.e. the way in which it models the services. The system models functionalities as services inside the agents, or as Service Oriented Approach (SOA architecture compliant services using Web Services. This way the adaptation of the odor classification systems with new algorithms, tools and classification techniques is allowed.

Cross-Cultural Color-Odor Associations

OpenAIRE

Levitan, Carmel A.; Ren, Jiana; Woods, Andy T.; Boesveldt, Sanne; Chan, Jason S.; McKenzie, Kirsten J.; Dodson, Michael; Levin, Jai A.; Leong, Christine X. R.; van den Bosch, Jasper J. F.

2014-01-01

Colors and odors are associated; for instance, people typically match the smell of strawberries to the color pink or red. These associations are forms of crossmodal correspondences. Recently, there has been discussion about the extent to which these correspondences arise for structural reasons (i.e., an inherent mapping between color and odor), statistical reasons (i.e., covariance in experience), and/or semantically-mediated reasons (i.e., stemming from language). The present study probed th...

Cross-cultural color-odor associations

OpenAIRE

Levitan, C.A.; Ren, J.; Boesveldt, S.; Chan, J.; McKenzie, K.J.; Levin, J.A.; Leong, C.X.; Bosch, van den, J.F.

2014-01-01

Colors and odors are associated; for instance, people typically match the smell of strawberries to the color pink or red. These associations are forms of crossmodal correspondences. Recently, there has been discussion about the extent to which these correspondences arise for structural reasons (i.e., an inherent mapping between color and odor), statistical reasons (i.e., covariance in experience), and/or semantically-mediated reasons (i.e., stemming from language). The present study probed th...

Testing odorants recovery from a novel metallized fluorinated ethylene propylene gas sampling bag.

Science.gov (United States)

Zhu, Wenda; Koziel, Jacek A; Cai, Lingshuang; Wright, Donald; Kuhrt, Fred

2015-12-01

Industry-standard Tedlar bags for odor sample collection from confined animal feeding operations (CAFOs) have been challenged by the evidence of volatile organic compound (VOC) losses and background interferences. Novel impermeable aluminum foil with a thin layer of fluorinated ethylene propylene (FEP) film on the surface that is in contact with a gas sample was developed to address this challenge. In this research, Tedlar and metallized FEP bags were compared for (a) recoveries of four characteristic CAFO odorous VOCs (ethyl mercaptan, butyric acid, isovaleric acid and p-cresol) after 30 min and 24 hr sample storage time and for (b) chemical background interferences. All air sampling and analyses were performed with solid-phase microextraction (SPME) followed by gas chromatography-mass spectroscopy (GC-MS). Mean target gas sample recoveries from metallized FEP bags were 25.9% and 28.0% higher than those in Tedlar bags, for 30 min and 24 hr, respectively. Metallized FEP bags demonstrated the highest p-cresol recoveries after 30-min and 24-hr storage, 96.1±44.5% and 44.8±10.2%, respectively, among different types of sampling bags reported in previous studies. However, a higher variability was observed for p-cresol recovery with metallized FEP bags. A 0% recovery of ethyl mercaptan was observed with Tedlar bags after 24-hr storage, whereas an 85.7±7.4% recovery was achieved with metallized FEP bags. Recoveries of butyric and isovaleric acids were similar for both bag types. Two major impurities in Tedlar bags' background were identified as N,N-dimethylacetamide and phenol, while backgrounds of metallized FEP bags were significantly cleaner. Reusability of metallized FEP bags was tested. Caution is advised when using polymeric materials for storage of livestock-relevant odorous volatile organic compounds. The odorants loss with storage time confirmed that long-term storage in whole-air form is ill advised. A focused short-term odor sample containment should be

Identification of character impact odorants of different soybean lecithins.

Science.gov (United States)

Stephan, A; Steinhart, H

1999-07-01

The potent odorants of standardized, enzymatically hydrolyzed, and deoiled soybean lecithins were characterized systematically by combined gas chromatography/mass spectrometry and olfactometry. Sixty-one odorants were identified; 53 of these odor-active compounds have not previously been reported as odorants of soybean lecithin flavor. By aroma extract dilution analysis and modified combined hedonic and response measurement the following odorants showed the highest flavor dilution factors and CHARM values: (E,E)-2, 4-decadienal (deep-fried), (E)-beta-damascenone (apple-like), 2, 3-diethyl-5-methylpyrazine (roasty, earthy), (E)-2-nonenal (cardboard-like), trans-4,5-epoxy-(E)-2-decenal (metallic), 1-nonen-3-one (mushroom-like), 2-ethyl-3,5-dimethylpyrazine (roasty, earthy), and 1-octen-3-one (mushroom-like). Enzymatic hydrolysis intensified especially the roasty sensation of 2, 3-diethyl-5-methylpyrazine, whereas deoiling effected a general significant decrease in olfactory perception on the nitrogen-containing compounds. In addition, sensory profiles of nasal and retronasal lecithin odor were performed.

A Wheat R2R3-type MYB Transcription Factor TaODORANT1 Positively Regulates Drought and Salt Stress Responses in Transgenic Tobacco Plants

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Qiuhui Wei

2017-08-01

Full Text Available MYB transcription factors play important roles in plant responses to biotic and abiotic stress. In this study, TaODORANT1, a R2R3-MYB gene, was cloned from wheat (Triticum aestivum L.. TaODORANT1 was localized in the nucleus and functioned as a transcriptional activator. TaODORANT1 was up-regulated in wheat under PEG6000, NaCl, ABA, and H2O2 treatments. TaODORANT1-overexpressing transgenic tobacco plants exhibited higher relative water content and lower water loss rate under drought stress, as well as lower Na+ accumulation in leaves under salt stress. The transgenic plants showed higher CAT activity but lower ion leakage, H2O2 and malondialdehyde contents under drought and salt stresses. Besides, the transgenic plants also exhibited higher SOD activity under drought stress. Our results also revealed that TaODORANT1 overexpression up-regulated the expression of several ROS- and stress-related genes in response to both drought and salt stresses, thus enhancing transgenic tobacco plants tolerance. Our studies demonstrate that TaODORANT1 positively regulates plant tolerance to drought and salt stresses.

Aversive learning of odor-heat associations in ants.

Science.gov (United States)

Desmedt, Lucie; Baracchi, David; Devaud, Jean-Marc; Giurfa, Martin; d'Ettorre, Patrizia

2017-12-15

Ants have recently emerged as useful models for the study of olfactory learning. In this framework, the development of a protocol for the appetitive conditioning of the maxilla-labium extension response (MaLER) provided the possibility of studying Pavlovian odor-food learning in a controlled environment. Here we extend these studies by introducing the first Pavlovian aversive learning protocol for harnessed ants in the laboratory. We worked with carpenter ants Camponotus aethiops and first determined the capacity of different temperatures applied to the body surface to elicit the typical aversive mandible opening response (MOR). We determined that 75°C is the optimal temperature to induce MOR and chose the hind legs as the stimulated body region because of their high sensitivity. We then studied the ability of ants to learn and remember odor-heat associations using 75°C as the unconditioned stimulus. We studied learning and short-term retention after absolute (one odor paired with heat) and differential conditioning (a punished odor versus an unpunished odor). Our results show that ants successfully learn the odor-heat association under a differential-conditioning regime and thus exhibit a conditioned MOR to the punished odor. Yet, their performance under an absolute-conditioning regime is poor. These results demonstrate that ants are capable of aversive learning and confirm previous findings about the different attentional resources solicited by differential and absolute conditioning in general. © 2017. Published by The Company of Biologists Ltd.

Effects of visual priming on taste-odor interaction.

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Marije van Beilen

Full Text Available Little is known about the influence of visual characteristics other than colour on flavor perception, and the complex interactions between more than two sensory modalities. This study focused on the effects of recognizability of visual (texture information on flavor perception of odorized sweet beverages. Participants rated the perceived sweetness of odorized sucrose solutions in the presence or absence of either a congruent or incongruent visual context. Odors were qualitatively reminiscent of sweet foods (strawberry and caramel or not (savoury. Visual context was either an image of the same sweet foods (figurative context or a visual texture derived from this product (non-figurative context. Textures were created using a texture synthesis method that preserved perceived food qualities while removing object information. Odor-taste combinations were rated sweeter within a figurative than a non-figurative context. This behaviour was exhibited for all odor-taste combinations, even in trials without images, indicating sustained priming by figurative visual context. A non-figurative context showed a transient sweetening effect. Sweetness was generally enhanced most by the strawberry odor. We conclude that the degree of recognizability of visual information (figurative versus non-figurative, influences flavor perception differently. Our results suggest that this visual context priming is mediated by separate sustained and transient processes that are differently evoked by figurative and non-figurative visual contexts. These components operate independent of the congruency of the image-odor-taste combinations.

Structural and Functional Characterization of a Single-chain Peptide-MHC Molecule that Modulates both Naive and Activated CD8plus T Cells

Energy Technology Data Exchange (ETDEWEB)

D Samanta; G Mukherjee; U Ramagopal; R Chaparro; S Nathenson; T DiLorenzo; S Almo

2011-12-31

Peptide-MHC (pMHC) multimers, in addition to being tools for tracking and quantifying antigen-specific T cells, can mediate downstream signaling after T-cell receptor engagement. In the absence of costimulation, this can lead to anergy or apoptosis of cognate T cells, a property that could be exploited in the setting of autoimmune disease. Most studies with class I pMHC multimers used noncovalently linked peptides, which can allow unwanted CD8{sup +} T-cell activation as a result of peptide transfer to cellular MHC molecules. To circumvent this problem, and given the role of self-reactive CD8{sup +} T cells in the development of type 1 diabetes, we designed a single-chain pMHC complex (scK{sup d}.IGRP) by using the class I MHC molecule H-2K{sup d} and a covalently linked peptide derived from islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP{sub 206-214}), a well established autoantigen in NOD mice. X-ray diffraction studies revealed that the peptide is presented in the groove of the MHC molecule in canonical fashion, and it was also demonstrated that scK{sup d}.IGRP tetramers bound specifically to cognate CD8{sup +} T cells. Tetramer binding induced death of naive T cells and in vitro- and in vivo-differentiated cytotoxic T lymphocytes, and tetramer-treated cytotoxic T lymphocytes showed a diminished IFN-{gamma} response to antigen stimulation. Tetramer accessibility to disease-relevant T cells in vivo was also demonstrated. Our study suggests the potential of single-chain pMHC tetramers as possible therapeutic agents in autoimmune disease. Their ability to affect the fate of naive and activated CD8{sup +} T cells makes them a potential intervention strategy in early and late stages of disease.

Autoimmunity and inflammation are independent of class II transactivator type PIV-dependent class II major histocompatibility complex expression in peripheral tissues during collagen-induced arthritis.

Science.gov (United States)

Waldburger, Jean-Marc; Palmer, Gaby; Seemayer, Christian; Lamacchia, Celine; Finckh, Axel; Christofilopoulos, Panayiotis; Baeten, Dominique; Reith, Walter; Gabay, Cem

2011-11-01

To determine the regulation of class II major histocompatibility complex (MHC) expression in fibroblast-like synoviocytes (FLS) in order to investigate their role as nonprofessional antigen-presenting cells in collagen-induced arthritis (CIA). Expression of class II MHC, class II MHC transactivator (CIITA), and Ciita isoforms PI, PIII, and PIV was examined by real-time quantitative polymerase chain reaction, immunohistochemistry, and flow cytometry in human synovial tissues, arthritic mouse joints, and human and murine FLS. CIA was induced in mice in which isoform PIV of Ciita was knocked out (PIV(-/-) ), in PIV(-/-) mice transgenic for CIITA in the thymus (K14 CIITA), and in their control littermates. HLA-DRA, total CIITA, and CIITA PIII messenger RNA levels were significantly increased in synovial tissue samples from patients with rheumatoid arthritis compared with the levels in tissue from patients with osteoarthritis. Human FLS expressed surface class II MHC via CIITA PIII and PIV, while class II MHC expression in murine FLS was entirely mediated by PIV. Mice with a targeted deletion of CIITA PIV lack CD4+ T cells and were protected against CIA. The expression of CIITA was restored in the thymus of PIV(-/-) K14 CIITA-transgenic mice, which had a normal CD4+ T cell repertoire and normal surface levels of class II MHC on professional antigen-presenting cells, but did not induce class II MHC on FLS. Synovial inflammation and immune responses against type II collagen were similar in PIV(-/-) K14 CIITA-transgenic mice and control mice with CIA, but bone erosion was significantly reduced in the absence of PIV. Overexpression of class II MHC is tightly correlated with CIITA expression in arthritic synovium and in FLS. Selective targeting of Ciita PIV in peripheral tissues abrogates class II MHC expression by murine FLS but does not protect against inflammation and autoimmune responses in CIA. Copyright © 2011 by the American College of Rheumatology.

Odor Discrimination in Drosophila: From Neural Population Codes to Behavior

Science.gov (United States)

Parnas, Moshe; Lin, Andrew C.; Huetteroth, Wolf; Miesenböck, Gero

2013-01-01

Summary Taking advantage of the well-characterized olfactory system of Drosophila, we derive a simple quantitative relationship between patterns of odorant receptor activation, the resulting internal representations of odors, and odor discrimination. Second-order excitatory and inhibitory projection neurons (ePNs and iPNs) convey olfactory information to the lateral horn, a brain region implicated in innate odor-driven behaviors. We show that the distance between ePN activity patterns is the main determinant of a fly’s spontaneous discrimination behavior. Manipulations that silence subsets of ePNs have graded behavioral consequences, and effect sizes are predicted by changes in ePN distances. ePN distances predict only innate, not learned, behavior because the latter engages the mushroom body, which enables differentiated responses to even very similar odors. Inhibition from iPNs, which scales with olfactory stimulus strength, enhances innate discrimination of closely related odors, by imposing a high-pass filter on transmitter release from ePN terminals that increases the distance between odor representations. PMID:24012006

Effects of 4-week continuous ingestion of champignon extract on halitosis and body and fecal odor

Directory of Open Access Journals (Sweden)

Jun Nishihira

2017-01-01

Full Text Available This was placebo-controlled double-blind parallel-group comparative clinical trial targeting 80 men and women aged 50–79 years with halitosis and body and fecal odor. We investigated whether daily champignon extract ingestion for 4 weeks improved these conditions. Subjects were divided into four groups: a placebo group and 50, 500, and 1000 mg/day ingestion groups. No severe adverse events or side effects were noted during the study period. Compared with the placebo group, all champignon extract ingestion groups showed improvement or tendency toward improvement in halitosis and body and fecal odor. Furthermore, our results suggested that the effectiveness of champignon extract in alleviating odors is dose-dependent, i.e., it increases with the dosage.

Odor identification: perceptual and semantic dimensions.

Science.gov (United States)

Cain, W S; de Wijk, R; Lulejian, C; Schiet, F; See, L C

1998-06-01

Five studies explored identification of odors as an aspect of semantic memory. All dealt in one way or another with the accessibility of acquired olfactory information. The first study examined stability and showed that, consistent with personal reports, people can fail to identify an odor one day yet succeed another. Failure turned more commonly to success than vice versa, and once success occurred it tended to recur. Confidence ratings implied that subjects generally knew the quality of their answers. Even incorrect names, though, often carried considerable information which sometimes reflected a semantic and sometimes a perceptual source of errors. The second study showed that profiling odors via the American Society of Testing and Materials list of attributes, an exercise in depth of processing, effected no increment in the identifiability/accessibility beyond an unelaborated second attempt at retrieval. The third study showed that subjects had only a weak ability to predict the relative recognizability of odors they had failed to identify. Whereas the strength of the feeling that they would 'know' an answer if offered choices did not associate significantly with performance for odors, it did for trivia questions. The fourth study demonstrated an association between ability to discriminate among one set of odors and to identify another, but this emerged only after subjects had received feedback about identity, which essentially changed the task to one of recognition and effectively stabilized access. The fifth study illustrated that feedback improves performance dramatically only for odors involved with it, but that mere retrieval leads to some improvement. The studies suggest a research agenda that could include supplemental use of confidence judgments both retrospectively and prospectively in the same subjects to indicate the amount of accessible semantic information; use of second and third guesses to examine subjects' simultaneously held hypotheses about

Biomimetic Sensors for the Senses: Towards Better Understanding of Taste and Odor Sensation.

Science.gov (United States)

Wu, Chunsheng; Du, Ya-Wen; Huang, Liquan; Ben-Shoshan Galeczki, Yaron; Dagan-Wiener, Ayana; Naim, Michael; Niv, Masha Y; Wang, Ping

2017-12-11

Taste and smell are very important chemical senses that provide indispensable information on food quality, potential mates and potential danger. In recent decades, much progress has been achieved regarding the underlying molecular and cellular mechanisms of taste and odor senses. Recently, biosensors have been developed for detecting odorants and tastants as well as for studying ligand-receptor interactions. This review summarizes the currently available biosensing approaches, which can be classified into two main categories: in vitro and in vivo approaches. The former is based on utilizing biological components such as taste and olfactory tissues, cells and receptors, as sensitive elements. The latter is dependent on signals recorded from animals' signaling pathways using implanted microelectrodes into living animals. Advantages and disadvantages of these two approaches, as well as differences in terms of sensing principles and applications are highlighted. The main current challenges, future trends and prospects of research in biomimetic taste and odor sensors are discussed.

Biomimetic Sensors for the Senses: Towards Better Understanding of Taste and Odor Sensation

Directory of Open Access Journals (Sweden)

Chunsheng Wu

2017-12-01

Full Text Available Taste and smell are very important chemical senses that provide indispensable information on food quality, potential mates and potential danger. In recent decades, much progress has been achieved regarding the underlying molecular and cellular mechanisms of taste and odor senses. Recently, biosensors have been developed for detecting odorants and tastants as well as for studying ligand-receptor interactions. This review summarizes the currently available biosensing approaches, which can be classified into two main categories: in vitro and in vivo approaches. The former is based on utilizing biological components such as taste and olfactory tissues, cells and receptors, as sensitive elements. The latter is dependent on signals recorded from animals’ signaling pathways using implanted microelectrodes into living animals. Advantages and disadvantages of these two approaches, as well as differences in terms of sensing principles and applications are highlighted. The main current challenges, future trends and prospects of research in biomimetic taste and odor sensors are discussed.

Gestão de odores: fundamentos do Nariz Eletrônico Odor management: fundamentals of Electronic Nose

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Henrique de Melo Lisboa

2009-03-01

Full Text Available Narizes Eletrônicos têm sido desenvolvidos para detecção automática e classificação de odores, vapores e gases. São instrumentos capazes de medir a concentração ou intensidade odorante de modo similar a um olfatômetro, mas sem as limitações inerentes ao uso de painéis humanos, o que é altamente desejável. Um Nariz Eletrônico é geralmente composto por um sistema de sensores químicos e um sistema eletrônico associado à inteligência artificial para reconhecimento. Têm sido aplicados em muitas áreas, tais como análise de alimentos, controles ambientais e diagnósticos médicos. Do ponto de vista ambiental, sistemas de Narizes Eletrônicos vêm sendo usados para monitorar a qualidade do ar, detectar fontes e quantificar emissões odorantes. Este artigo pretende apresentar os fundamentos dos Narizes Eletrônicos.Electronic noses have been developed for automatic detection and classification of odors, vapors and gases. They are instruments capable to identify odors as the human nose does, and measure the odor concentration or intensity according to similar metrics as an olfactometer, but without the inherent limitations of human panels. An Electronic Nose is generally composed of a matrix of chemical sensors and computer based system for odor recognition and classification. It has been applied in many areas, such as food quality analysis, explosives detection, environmental monitoring and medical diagnosis. In the ambient environment, systems of Electronic Noses have been used to monitor the quality of air and to detect and quantify odor sources and emissions. This article intends to present the fundamentals and main characteristics of Electronic Noses.

Odor Signals of Immune Activation and CNS Inflammation

Science.gov (United States)

2014-12-01

inflammation results in detectable alteration of body odor and that traumatic brain injury (TBI) might similarly produce volatile metabolites specific to...Because both LPS and TBI elicit inflammatory processes and LPS-induced inflammation induces body odor changes, we hypothesized that (1) TBI would...induce a distinct change in body odor and (2) this change would resemble the change induced by LPS. Mice receiving surgery and lateral fluid percussion

Circumvention of MHC class II restriction by genetic immunization.

Science.gov (United States)

Schuler, K; Lu, C; Chang, H D; Croft, M; Zanetti, M; Gerloni, M

2001-11-12

The fate of T cell responses to peptide-based vaccination is subject to constraints by the major histocompatibility complex (MHC), MHC restriction. Using as a model system of T and B cell epitopes from the circumsporozoite protein of Plasmodium falciparum malaria parasite, we show that vaccination by somatic transgene immunization readily primes Balb/c mice (H-2(d)) a strain previously reported to be non-responder to immunization with a synthetic peptide vaccine encompassing these epitopes. Following genetic vaccination Balb/c mice developed a primary T cell response comparable to that of the responder strain C57Bl/6 (H-2(b)). Following booster immunization on day 45 Balb/c mice responded with a typical T cell memory response. Priming induced the formation of specific antibodies, which rose sharply after booster immunization. These findings suggests that genetic immunization can circumvent MHC class II restriction.

Psychological and physiological responses to odor-evoked autobiographic memory.

Science.gov (United States)

Matsunaga, Masahiro; Isowa, Tokiko; Yamakawa, Kaori; Kawanishi, Yoko; Tsuboi, Hirohito; Kaneko, Hiroshi; Sadato, Norihiro; Oshida, Akiko; Katayama, Atsushi; Kashiwagi, Mitsuyoshi; Ohira, Hideki

2011-01-01

The "Proust phenomenon" occurs when a certain smell evokes a specific memory. Recent studies have demonstrated that odor-evoked autobiographic memories are more emotional than those elicited by other sensory stimuli because of the direct neural communication between the olfactory system and the amygdala. The amygdala is known to regulate various physiological activities including the endocrine and immune systems; therefore, odor-evoked autobiographic memory may trigger various psychological and physiological responses; however, the responses elicited by this memory remains obscure. In this study, we aimed to investigate the psychological and physiological responses accompanying odor-evoked autobiographic memory. We recruited healthy male and female volunteers and investigated changes in their mood states and autonomic nervous, endocrine, and immune activities when autobiographic memory was evoked in the participants by asking them to smell an odor(s) that was nostalgic to them. The autobiographic memories associated with positive emotion resulted in increased positive mood states, such as comfort and happiness, and decreased negative mood states, such as anxiety. Furthermore, heart rate was decreased, skin-conductance level was increased, and peripheral interleukin-2 level was decreased after smelling the nostalgic odor. These psychological and physiological responses were significantly correlated. The present study suggests that odor-evoked autobiographic memory along with a positive feeling induce various physiological responses, including the autonomic nervous and immune activities. To the best of our knowledge, the present study is the first to observe an interaction between odor-evoked autobiographic memories and immune function.

Gapped sequence alignment using artificial neural networks: application to the MHC class I system

DEFF Research Database (Denmark)

Andreatta, Massimo; Nielsen, Morten

2016-01-01

. On this relatively simple system, we developed a sequence alignment method based on artificial neural networks that allows insertions and deletions in the alignment. Results: We show that prediction methods based on alignments that include insertions and deletions have significantly higher performance than methods...... trained on peptides of single lengths. Also, we illustrate how the location of deletions can aid the interpretation of the modes of binding of the peptide-MHC, as in the case of long peptides bulging out of the MHC groove or protruding at either terminus. Finally, we demonstrate that the method can learn...... the length profile of different MHC molecules, and quantified the reduction of the experimental effort required to identify potential epitopes using our prediction algorithm. Availability and implementation: The NetMHC-4.0 method for the prediction of peptide-MHC class I binding affinity using gapped...

Odorant responsiveness of embryonic mouse olfactory sensory neurons expressing the odorant receptors S1 or MOR23.

Science.gov (United States)

Lam, Rebecca S; Mombaerts, Peter

2013-07-01

The mammalian olfactory system has developed some functionality by the time of birth. There is behavioral and limited electrophysiological evidence for prenatal olfaction in various mammalian species. However, there have been no reports, in any mammalian species, of recordings from prenatal olfactory sensory neurons (OSNs) that express a given odorant receptor (OR) gene. Here we have performed patch-clamp recordings from mouse OSNs that express the OR gene S1 or MOR23, using the odorous ligands 2-phenylethyl alcohol or lyral, respectively. We found that, out of a combined total of 20 OSNs from embryos of these two strains at embryonic day (E)16.5 or later, all responded to a cognate odorous ligand. By contrast, none of six OSNs responded to the ligand at E14.5 or E15.5. The kinetics of the odorant-evoked electrophysiological responses of prenatal OSNs are similar to those of postnatal OSNs. The S1 and MOR23 glomeruli in the olfactory bulb are formed postnatally, but the axon terminals of OSNs expressing these OR genes may be synaptically active in the olfactory bulb at embryonic stages. The upper limit of the acquisition of odorant responsiveness for S1 and MOR23 OSNs at E16.5 is consistent with the developmental expression patterns of components of the olfactory signaling pathway. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Modeling the generation and dispersion of odors from mushroom composting facilities

International Nuclear Information System (INIS)

Heinemann, P.; Wahanik, D.

1998-01-01

An odor source generation model and an odor dispersion model were developed to predict the local distribution of odors emanating from mushroom composting facilities. The odor source generation model allowed for simulation of various composting wharf configurations and odor source strengths. This model was linked to a Gaussian plume diffusion model that predicted odor dispersion. Dimethyl disulfide production at a rate of 1760 micrograms/h was simulated by the source generation model and six different atmospheric conditions were analyzed to demonstrate the effect of wind speed, atmospheric stability, and source generation on the dispersion of this odor producing compound. Detectable levels of dimethyl disulfide were predicted to range from less than 100 m from the source during very unstable conditions to almost 5000 m during very stable conditions

Crystal structure of a TAPBPR–MHC I complex reveals the mechanism of peptide editing in antigen presentation

Energy Technology Data Exchange (ETDEWEB)

Jiang, Jiansheng; Natarajan, Kannan; Boyd, Lisa F.; Morozov, Giora I.; Mage, Michael G.; Margulies, David H. (NIH); (Hebrew)

2017-10-12

Central to CD8+ T cell–mediated immunity is the recognition of peptide–major histocompatibility complex class I (p–MHC I) proteins displayed by antigen-presenting cells. Chaperone-mediated loading of high-affinity peptides onto MHC I is a key step in the MHC I antigen presentation pathway. However, the structure of MHC I with a chaperone that facilitates peptide loading has not been determined. We report the crystal structure of MHC I in complex with the peptide editor TAPBPR (TAP-binding protein–related), a tapasin homolog. TAPBPR remodels the peptide-binding groove of MHC I, resulting in the release of low-affinity peptide. Changes include groove relaxation, modifications of key binding pockets, and domain adjustments. This structure captures a peptide-receptive state of MHC I and provides insights into the mechanism of peptide editing by TAPBPR and, by analogy, tapasin.

The consequence of fetal ethanol exposure and adolescent odor re-exposure on the response to ethanol odor in adolescent and adult rats

Directory of Open Access Journals (Sweden)

Molina Juan C

2009-01-01

Full Text Available Abstract Background An epidemiologic predictive relationship exists between fetal ethanol exposure and the likelihood for adolescent use. Further, an inverse relationship exists between the age of first experience and the probability of adult abuse. Whether and how the combined effects of prenatal and adolescent ethanol experiences contribute to this progressive pattern remains unknown. Fetal ethanol exposure directly changes the odor attributes of ethanol important for both ethanol odor preference behavior and ethanol flavor perception. These effects persist only to adolescence. Here we tested whether adolescent ethanol odor re-exposure: (Experiment 1 augments the fetal effect on the adolescent behavioral response to ethanol odor; and/or (Experiment 2 perpetuates previously observed adolescent behavioral and neurophysiological responses into adulthood. Methods Pregnant rats received either an ethanol or control liquid diet. Progeny (observers experienced ethanol odor in adolescence via social interaction with a peer (demonstrators that received an intragastric infusion of either 1.5 g/kg ethanol or water. Social interactions were scored for the frequency that observers followed their demonstrator. Whole-body plethysmography evaluated the unconditioned behavioral response of observers to ethanol odor in adolescence (P37 or adulthood (P90. The olfactory epithelium of adults was also examined for its neural response to five odorants, including ethanol. Results Experiment 1: Relative to fetal or adolescent exposure alone, adolescent re-exposure enhanced the behavioral response to ethanol odor in P37 animals. Compared to animals with no ethanol experience, rats receiving a single experience (fetal or adolescent show an enhanced, yet equivalent, ethanol odor response. Fetal ethanol experience also increased olfactory-guided following of an intoxicated peer. Experiment 2: Combined exposure yielded persistence of the behavioral effects only in adult

Antibody Stabilization of Peptide–MHC Multimers Reveals Functional T Cells Bearing Extremely Low-Affinity TCRs

DEFF Research Database (Denmark)

Tungatt, Katie; Bianchi, Valentina; Crowther, Michael D

2015-01-01

Fluorochrome-conjugated peptide-MHC (pMHC) multimers are commonly used in combination with flow cytometry for direct ex vivo visualization and characterization of Ag-specific T cells, but these reagents can fail to stain cells when TCR affinity and/or TCR cell-surface density are low. pMHC multim...

Nanocellulose-Zeolite Composite Films for Odor Elimination.

Science.gov (United States)

Keshavarzi, Neda; Mashayekhy Rad, Farshid; Mace, Amber; Ansari, Farhan; Akhtar, Farid; Nilsson, Ulrika; Berglund, Lars; Bergström, Lennart

2015-07-08

Free standing and strong odor-removing composite films of cellulose nanofibrils (CNF) with a high content of nanoporous zeolite adsorbents have been colloidally processed. Thermogravimetric desorption analysis (TGA) and infrared spectroscopy combined with computational simulations showed that commercially available silicalite-1 and ZSM-5 have a high affinity and uptake of volatile odors like ethanethiol and propanethiol, also in the presence of water. The simulations showed that propanethiol has a higher affinity, up to 16%, to the two zeolites compared with ethanethiol. Highly flexible and strong free-standing zeolite-CNF films with an adsorbent loading of 89 w/w% have been produced by Ca-induced gelation and vacuum filtration. The CNF-network controls the strength of the composite films and 100 μm thick zeolite-CNF films with a CNF content of less than 10 vol % displayed a tensile strength approaching 10 MPa. Headspace solid phase microextraction (SPME) coupled to gas chromatography-mass spectroscopy (GC/MS) analysis showed that the CNF-zeolite films can eliminate the volatile thiol-based odors to concentrations below the detection ability of the human olfactory system. Odor removing zeolite-cellulose nanofibril films could enable improved transport and storage of fruits and vegetables rich in odors, for example, onion and the tasty but foul-smelling South-East Asian Durian fruit.

Polymorphisms in the F8 gene and MHC-II variants as risk factors for the development of inhibitory anti-factor VIII antibodies during the treatment of hemophilia a: a computational assessment.