Τετάρτη 9 Μαΐου 2018

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

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

Mamm Genome. 2018 May 08;:

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

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

PMID: 29737391 [PubMed - as supplied by publisher]



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Τρίτη 8 Μαΐου 2018

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

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

Hum Brain Mapp. 2018 May 07;:

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

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

PMID: 29736907 [PubMed - as supplied by publisher]



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

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

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

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

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

PMID: 29735652 [PubMed - as supplied by publisher]



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

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

J Pediatr. 2018 May 02;:

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

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

PMID: 29730147 [PubMed - as supplied by publisher]



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Δευτέρα 7 Μαΐου 2018

Olfactory fMRI: implications of stimulation length and repetition time.

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Olfactory fMRI: implications of stimulation length and repetition time.

Chem Senses. 2018 May 03;:

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

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

PMID: 29726890 [PubMed - as supplied by publisher]



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Τετάρτη 2 Μαΐου 2018

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

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

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

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

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

PMID: 29712850 [PubMed - as supplied by publisher]



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Τρίτη 1 Μαΐου 2018

Normal feline behaviour: … and why problem behaviours develop.

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Normal feline behaviour: … and why problem behaviours develop.

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

Authors: Bradshaw J

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

PMID: 29706092 [PubMed - in process]



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