Neuroscience

Hey Julie,I hope you've had a fun week. I saw a new in-press publication with your name on it - "Smelling more or less: Investigating the olfactory experience of the domestic dog" - looks like a really great study, and so timely after my last post about dogs and olfactory enrichment! Looking forward to reading it (and all those other cool Learning and Motivation articles) over the weekend. So did you do your homework? Did you watch this clip from the Sydney Opera House's Ship Song Project? I wanted you to watch this clip, and more importantly, LISTEN to it, because it features lots of different musical styles. I don't know about you, but I certainly have a different reaction to the different styles. Some appeal to me more than others. Some I find relaxing, while others make me want to nod my head to keep the beat or even hum along. I was talking about this clip recently with my friend Mark (from SARC, in my head that always runs together "Mark-from-SARC") and of course we shifted to talking about dogs and music. As you do. That's normal - right?! What kind of music do dogs prefer? As part of my PhD research into kennel enrichment, I looked into this very question. The research in this area has been conducted in two kennel environments. Headphones on dog = silly (they hear around x4 better than us!) sourceIn the first study, scientists played five different recordings to dogs housed in a shelter kennel: - a control (nothing) - human speech- classical music- pop music- heavy metal musicto the dogs and recorded the behaviours of the dogs using an ethogram. Then they looked at the differences in the behaviour of the dogs during each condition. The dogs were significantly more likely to run around barking when the heavy metal music was played; and lie down, apparently resting quietly, when the classical music was on. There was no difference to their behaviour when the control, human speech or pop music were played. The second study showed similar results, with classical music linked to more sleeping and heavy metal correlating with more body shaking.(source)It's probably worth noting that these changes in behaviour may not reflect dogs' actual PREFERENCE for music. To assess that, we'd need to set up a study design that offered dogs a choice of multiple sound environments. But it certainly suggests that if we want to encourage behaviours associated with relaxation, like lying down, not barking, and sleeping; we should be piping some gentle classical music to the environment our dogs are in. I reckon my dogs quite like Chopin's Nocturnes... Kogan Lori R., Schoenfeld-Tacher Regina, & Simon Allen A. (2012) Behavioral effects of auditory stimulation on kenneled dogs. Journal of Veterinary Behavior: Clinical Applications and Research, 7(5), 268-275. DOI: 10.1016/j.jveb.2011.11.002 Behavioral effects of auditory stimulation on kenneled dogs Wells D, Graham L, & Hepper P. (2002) The influence of auditory stimulation on the behaviour of dogs housed in a rescue shelter. Animal Welfare, 11(4), 385-393. http://www.ufaw.org.uk/v11main.php

by Vanessa Segura, Miguel Pérez-Aso, Fermí Montó, Elena Carceller, María Antonia Noguera, John Pediani, Graeme Milligan, Ian Christie McGrath, Pilar D’Ocon Aims To compare the constitutive and agonist-dependent endosomal trafficking of ?1A- and ?1B-adrenoceptors (ARs) and to establish if the internalization pattern determines the signaling pathways of each subtype. Methods Using CypHer5 technology and VSV-G epitope tagged ?1A- and ?1B-ARs stably and transiently expressed in HEK 293 cells, we analyzed by confocal microscopy the constitutive and agonist-induced internalization of each subtype, and the temporal relationship between agonist induced internalization and the increase in intracellular calcium (determined by FLUO-3 flouorescence), or the phosphorylation of ERK1/2 and p38 MAP kinases (determined by Western blot). Results and Conclusions Constitutive as well as agonist-induced trafficking of ?1A and ?1B ARs maintain two different endosomal pools of receptors: one located close to the plasma membrane and the other deeper into the cytosol. Each subtype exhibited specific characteristics of internalization and distribution between these pools that determines their signaling pathways: ?1A-ARs, when located in the plasma membrane, signal through calcium and ERK1/2 pathways but, when translocated to deeper endosomes, through a mechanism sensitive to ?-arrestin and concanavalin A, continue signaling through ERK1/2 and also activate the p38 pathway. ?1B-ARs signal through calcium and ERK1/2 only when located in the membrane and the signals disappear after endocytosis and by disruption of the membrane lipid rafts by methyl-?-cyclodextrin

by Li Yang, Dongxiao Liu, Song Liang, Renhua Guo, Zhihong Zhang, Hao Xu, Chao Yang, Yi Zhu Aim To evaluate the impact of the Janus kinase 2 single nucleotide polymorphisms (SNPs) on gastric cancer risk. Methods In this hospital-based, case–control study, the genotypes were identified by polymerase chain reaction–restriction fragment length polymorphism protocols in 661 individuals (359 gastric cancer patients and 302 age and sex matched cancer-free controls). Results Both the frequency of A allele in rs2230724 and G allele in rs1887427 were more frequent in patients with gastric cancer (P?=?0.013 and 0.001, respectively). Compared with the common genotype, subjects with the (AG+AA) genotypes of rs2230724 and the (AG+GG) genotypes of rs1887427 had a 59% and 98% increased risk of developing gastric cancer, respectively (P?=?0.010, adjusted OR?=?1.59, 95% CI?=?1.12–2.27; P56 years), males, nonsmokers and urban subjects, while the association between the risk and the rare genotypes of rs1887427 persisted in subgroups of younger individuals (?56 years), males, nonsmokers and both of rural and urban subjects. Conclusion The JAK2 gene rs2230724 and rs1887427 polymorphisms are associated with an increased risk of gastric cancer in a Chinese Han population.

by Jieun Koh, Jong Rak Choi, Kyung Hwa Han, Eun-Kyung Kim, Jung Hyun Yoon, Hee Jung Moon, Jin Young Kwak Background The aim of this study was to evaluate the proper indication of adjunctive BRAFV600E mutation analysis at the time of ultrasound-guided fine-needle aspiration in the diagnosis of thyroid nodules. Methods This study included 518 nodules in 479 patients who underwent ultrasound-guided fine-needle aspiration with BRAFV600E mutation. We calculated and compared the diagnostic performances of cytology and cytology with BRAFV600E mutation analysis to detect malignancy among thyroid nodules according to ultrasound features and size. Results Sensitivity, negative predictive value, and accuracy of cytology with BRAFV600E mutation analysis were significantly higher than those of cytology alone in thyroid nodules with suspicious ultrasound features, regardless of size. Diagnostic performances did not show significant differences between cytology and cytology with BRAFV600E mutation analysis in nodules without any suspicious ultrasound features, regardless of size. Conclusion The BRAFV600E mutation analysis was a useful adjunctive diagnostic tool in the diagnosis of thyroid nodules with suspicious ultrasound features regardless of size.

by Takayuki Hirai, Kenzo Uchida, Hideaki Nakajima, Alexander Rodriguez Guerrero, Naoto Takeura, Shuji Watanabe, Daisuke Sugita, Ai Yoshida, William E. B. Johnson, Hisatoshi Baba Background Cervical compressive myelopathy, e.g. due to spondylosis or ossification of the posterior longitudinal ligament is a common cause of spinal cord dysfunction. Although human pathological studies have reported neuronal loss and demyelination in the chronically compressed spinal cord, little is known about the mechanisms involved. In particular, the neuroinflammatory processes that are thought to underlie the condition are poorly understood. The present study assessed the localized prevalence of activated M1 and M2 microglia/macrophages in twy/twy mice that develop spontaneous cervical spinal cord compression, as a model of human disease. Methods Inflammatory cells and cytokines were assessed in compressed lesions of the spinal cords in 12-, 18- and 24-weeks old twy/twy mice by immunohistochemical, immunoblot and flow cytometric analysis. Computed tomography and standard histology confirmed a progressive spinal cord compression through the spontaneously development of an impinging calcified mass. Results The prevalence of CD11b-positive cells, in the compressed spinal cord increased over time with a concurrent decrease in neurons. The CD11b-positive cell population was initially formed of arginase-1- and CD206-positive M2 microglia/macrophages, which later shifted towards iNOS- and CD16/32-positive M1 microglia/macrophages. There was a transient increase in levels of T helper 2 (Th2) cytokines at 18 weeks, whereas levels of Th1 cytokines as well as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and macrophage antigen (Mac) ?2 progressively increased. Conclusions Spinal cord compression was associated with a temporal M2 microglia/macrophage response, which may act as a possible repair or neuroprotective mechanism. However, the persistence of the neural insult also associated with persistent expression of Th1 cytokines and increased prevalence of activated M1 microglia/macrophages, which may lead to neuronal loss and demyelination despite the presence of neurotrophic factors. This understanding of the aetiopathology of chronic spinal cord compression is of importance in the development of new treatment targets in human disease.

by Shweta Shah, Nathaniel M. Butler, David J. Hannapel, A. Gururaj Rao Polypyrimidine tract-binding (PTB) proteins are RNA-binding proteins that generally contain four RNA recognition motifs (RRMs). In potato, six cDNAs encoding full-length PTB proteins have been identified. In the present study Nova1-like protein, designated StNova1, was identified as a potential interacting partner of the StPTB proteins via yeast two-hybrid screening. Nova protein is a RNA-binding protein that contains three K-homology (KH) domains. In humans, these proteins are involved in regulation of neuronal RNA metabolism but the role of Nova-like proteins in plants is poorly understood. We have validated this interaction and mapped the protein binding region on StNova1 and StPTB1 and ?6 using a novel domain interaction phage display (DIPP) technique. The interaction between the two RNA-binding proteins StPTB1/6 and StNova1 is mediated through linker regions that are distinctly separated from the RRMs. Furthermore, using a random 21-mer phage-peptide library, we have identified a number of peptides with the consensus sequence motif [S/G][V/I][L/V]G that recognize the StPTB proteins. One over-represented peptide that recognizes StPTB6 contains the GVLGPWP sequence that is similar to the GIGGRYP sequence in the glycine-rich linker region between the KH2 and KH3 domains of StNova1. We show, through site-specific mutations, the importance of glycine and proline residues in StNova1-StPTB interactions.

by Julia Jaekel, Nicole Baumann, Dieter Wolke Objective Cognitive deficits have been inconsistently described for late or moderately preterm children but are consistently found in very preterm children. This study investigates the association between cognitive workload demands of tasks and cognitive performance in relation to gestational age at birth. Methods Data were collected as part of a prospective geographically defined whole-population study of neonatal at-risk children in Southern Bavaria. At 8;5 years, n?=?1326 children (gestation range: 23–41 weeks) were assessed with the K-ABC and a Mathematics Test. Results Cognitive scores of preterm children decreased as cognitive workload demands of tasks increased. The relationship between gestation and task workload was curvilinear and more pronounced the higher the cognitive workload: GA2 (quadratic term) on low cognitive workload: R2?=?.02, pR2?=?.09, pR2?=?.14, p Conclusions The cognitive workload model may help to explain variations of findings on the relationship of gestational age with cognitive performance in the literature. The findings have implications for routine cognitive follow-up, educational intervention, and basic research into neuro-plasticity and brain reorganization after preterm birth.

by Nikolai Hecker, Carsten Stephan, Hans-Joachim Mollenkopf, Klaus Jung, Robert Preissner, Hellmuth-A. Meyer Background MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. It has been proposed that miRNAs play an important role in cancer development and progression. Their ability to affect multiple gene pathways by targeting various mRNAs makes them an interesting class of regulators. Methodology/Principal Findings We have developed an algorithm, Classification based Analysis of Paired Expression data of RNA (CAPE RNA), which is capable of identifying altered miRNA-mRNA regulation between tissues samples that assigns interaction states to each sample without preexisting stratification of groups. The distribution of the assigned interaction states compared to given experimental groups is used to assess the quality of a predicted interaction. We demonstrate the applicability of our approach by analyzing urothelial carcinoma and normal bladder tissue samples derived from 24 patients. Using our approach, normal and tumor tissue samples as well as different stages of tumor progression were successfully stratified. Also, our results suggest interesting differentially regulated miRNA-mRNA interactions associated with bladder tumor progression. Conclusions/Significance The need for tools that allow an integrative analysis of microRNA and mRNA expression data has been addressed. With this study, we provide an algorithm that emphasizes on the distribution of samples to rank differentially regulated miRNA-mRNA interactions. This is a new point of view compared to current approaches. From bootstrapping analysis, our ranking yields features that build strong classifiers. Further analysis reveals genes identified as differentially regulated by miRNAs to be enriched in cancer pathways, thus suggesting biologically interesting interactions.

by Sheng-Ru Shiou, Yueyue Yu, Yuee Guo, Shu-Mei He, C. Haikaeli Mziray-Andrew, Jeanette Hoenig, Jun Sun, Elaine O. Petrof, Erika C. Claud Balance among the complex interactions of the gut microbial community is important for intestinal health. Probiotic bacteria can improve bacterial balance and have been used to treat gastrointestinal diseases. Neonatal necrotizing enterocolitis (NEC) is a life-threatening inflammatory bowel disorder primarily affecting premature infants. NEC is associated with extensive inflammatory NF-?B signaling activation as well as intestinal barrier disruption. Clinical studies have shown that probiotic administration may protect against NEC, however there are safety concerns associated with the ingestion of large bacterial loads in preterm infants. Bacteria-free conditioned media (CM) from certain probiotic organisms have been shown to retain bioactivity including anti-inflammatory and cytoprotective properties without the risks of live organisms. We hypothesized that the CM from Lactobacillus acidophilus (La), Bifidobacterium infantis (Bi), and Lactobacillus plantarum (Lp), used separately or together would protect against NEC. A rodent model with intestinal injury similar to NEC was used to study the effect of CM from Lp, La/Bi, and La/Bi/Lp on the pathophysiology of NEC. All the CM suppressed NF-?B activation via preserved I?B? expression and this protected I?B? was associated with decreased liver activity of the proteasome, which is the degrading machinery for I?B?. These CM effects also caused decreases in intestinal production of the pro-inflammatory cytokine TNF-?, a downstream target of the NF-?B pathway. Combined La/Bi and La/Bi/Lp CM in addition protected intestinal barrier function by maintaining tight junction protein ZO-1 levels and localization at the tight junction. Double combined La/Bi CM significantly reduced intestinal injury incidence from 43% to 28% and triple combined La/Bi/Lp CM further reduced intestinal injury incidence to 20%. Thus, this study demonstrates different protective mechanisms and synergistic bioactivity of the CM from different organisms in ameliorating NEC-like intestinal injury in an animal model.

by Stefan Wirtz, Manuel Seeger, Andreas Zell, Christian Wagner, Jean-Frank Wagner, Johannes B. Ries This study presents the comparison of experimental results with assumptions used in numerical models. The aim of the field experiments is to test the linear relationship between different hydraulic parameters and soil detachment. For example correlations between shear stress, unit length shear force, stream power, unit stream power and effective stream power and the detachment rate does not reveal a single parameter which consistently displays the best correlation. More importantly, the best fit does not only vary from one experiment to another, but even between distinct measurement points. Different processes in rill erosion are responsible for the changing correlations. However, not all these procedures are considered in soil erosion models. Hence, hydraulic parameters alone are not sufficient to predict detachment rates. They predict the fluvial incising in the rill's bottom, but the main sediment sources are not considered sufficiently in its equations. The results of this study show that there is still a lack of understanding of the physical processes underlying soil erosion. Exerted forces, soil stability and its expression, the abstraction of the detachment and transport processes in shallow flowing water remain still subject of unclear description and dependence.