Coding of odors in the anterior olfactory nucleus

Odorant molecules stimulate olfactory receptor neurons, and axons of these neurons project into the main olfactory bulb where they synapse onto mitral and tufted cells. These project to the primary olfactory cortex including the anterior olfactory nucleus (AON), the piriform cortex, amygdala, and the entorhinal cortex. The properties of mitral cells have been investigated extensively, but how odor information is processed in subsequent brain regions is less well known. In the present study, we recorded the electrical activity of AON neurons in anesthetized rats. Most AON cells fired in bursts of 2–10 spikes separated by very short intervals (<20 ms), in a period linked to the respiratory rhythm. Simultaneous recordings from adjacent neurons revealed that the rhythms of adjacent cells, while locked to the same underlying rhythm, showed marked differences in phase. We studied the responses of AON cells to brief high-frequency stimulation of the lateral olfactory tract, mimicking brief activation of mitral cells by odor. In different cells, such stimuli evoked transient or sustained bursts during stimulation or, more commonly, post-stimulation bursts after inhibition during stimulation. This suggests that, in AON cells, phase shifts occur as a result of post-inhibitory rebound firing, following inhibition by mitral cell input, and we discuss how this supports processing of odor information in the olfactory pathway. Cells were tested for their responsiveness to a social odor (the bedding of a strange male) among other simple and complex odors tested. In total, 11 cells responded strongly and repeatedly to bedding odor, and these responses were diverse, including excitation (transient or sustained), inhibition, and activation after odor presentation, indicating that AON neurons respond not only to the type of complex odor but also to temporal features of odor application.The Biotechnology and Biological Research Council (BB/J004723/1) and Medical Research Council (MR/M022838/1) (ML, GL), and fellowships from the Japanese Society for the Promotion of Science (TT, CT).http://wileyonlinelibrary.com/journal/phy2am2020Immunolog

Laryngotracheal separation for a type 4 laryngotracheoesophageal cleft with multiple significant malformations

AbstractLaryngotracheoesophageal cleft (LTEC) is an extremely rare congenital malformation that is difficult to treat. We present a female patient with type 4 LTEC associated with multiple significant malformations. She suffered from a severe asthma attack due to aspiration of saliva, and it was determined that she should undergo surgery for associated congenital heart disease as early as possible to ensure long-term survival. Therefore, we performed laryngotracheal separation with an end-tracheostomy to completely and immediately prevent aspiration. She was then able to undergo radical surgery for her congenital heart disease. She recovered well postoperatively, and long-term survival is expected

Carbon Monoxide Poisoning in a Psychiatric Patient Mistaken for Indefinite Complaints

Introduction: Carbon monoxide (CO) binds to haemoglobin with a much higher affinity than oxygen, forming carboxyhaemoglobin (COHb), which impairs oxygen transport and utilization. As CO concentrations can easily peak in closed environments, non-fire-related CO poisoning can also occur. However, because CO poisoning is often a nonspecific clinical finding, it can result in a diagnostic error. This report details the misdiagnosis of a 42-year-old male patient with psychiatric disorders.Case description: The patient presented to the hospital with dizziness, abdominal pain and nausea on multiple occasions. His symptoms were ascribed to his psychiatric conditions. On his fifth visit, we diagnosed the patient with CO poisoning. Discussion: It is apparent that this patient was misdiagnosed because of his medical history, and standard analysis was overlooked. When patients with psychiatric disorders have nonspecific symptoms, it is important to check for urgent underlying conditions during diagnosis

Titanium Immobilized with an Antimicrobial Peptide Derived from Histatin Accelerates the Differentiation of Osteoblastic Cell Line, MC3T3-E1

The objective of this study was to evaluate the effect of titanium immobilized with a cationic antimicrobial peptide (JH8194) derived from histatin on the biofilm formation of Porphyromonas gingivalis and differentiation of osteoblastic cells (MC3T3-E1). The titanium specimens (Ti) were immobilized with JH8194, according to the method previously described. The colonization of P. gingivalis on JH8194-Ti was significantly lower than that on control- and blocking-Ti. JH8194-Ti enhanced the mRNA expressions of Runx2 and OPN, and ALPase activity in the MC3T3-E1, as compared with those of control- and blocking-Ti. These results, taken together, suggested the possibility that JH8194-Ti may be a potential aid to shorten the period of acquiring osseointegration

Participatory art activities increase aalivary oxytocin secretion of ASD children

Autism spectrum disorder (ASD) occurs in 1 in 160 children worldwide. Individuals with ASD tend to be unique in the way that they comprehend themselves and others, as well as in the way that they interact and socialize, which can lead to challenges with social adaptation. There is currently no medication to improve the social deficit of children with ASD, and consequently, behavioral and complementary/alternative intervention plays an important role. In the present pilot study, we focused on the neuroendocrinological response to participatory art activities, which are known to have a positive effect on emotion, self-expression, sociability, and physical wellbeing. We collected saliva from 12 children with ASD and eight typically developed (TD) children before and after a visual art-based participatory art workshop to measure the levels of oxytocin, a neuropeptide involved in a wide range of social behaviors. We demonstrated that the rate of increase in salivary oxytocin following art activities in ASD children was significantly higher than that in TD children. In contrast, the change rate of salivary cortisol after participatory art activities was similar between the two groups. These results suggest that the beneficial effects of participatory art activities may be partially mediated by oxytocin release, and may have therapeutic potential for disorders involving social dysfunction

Split luciferase complementation assay to detect regulated protein-protein interactions in rice protoplasts in a large-scale format

© 2014 Fujikawa et al. Background: The rice interactome, in which a network of protein-protein interactions has been elucidated in rice, is a useful resource to identify functional modules of rice signal transduction pathways. Protein-protein interactions occur in cells in two ways, constitutive and regulative. While a yeast-based high-throughput method has been widely used to identify the constitutive interactions, a method to detect the regulated interactions is rarely developed for a large-scale analysis. Results: A split luciferase complementation assay was applied to detect the regulated interactions in rice. A transformation method of rice protoplasts in a 96-well plate was first established for a large-scale analysis. In addition, an antibody that specifically recognizes a carboxyl-terminal fragment of Renilla luciferase was newly developed. A pair of antibodies that recognize amino- and carboxyl- terminal fragments of Renilla luciferase, respectively, was then used to monitor quality and quantity of interacting recombinant-proteins accumulated in the cells. For a proof-of-concept, the method was applied to detect the gibberellin-dependent interaction between GIBBERELLIN INSENSITIVE DWARF1 and SLENDER RICE 1. Conclusions: A method to detect regulated protein-protein interactions was developed towards establishment of the rice interactome

Nectin-2 is a potential target for antibody therapy of breast and ovarian cancers

BACKGROUND: Nectin-2 is a Ca(2+)-independent cell-cell adhesion molecule that is one of the plasma membrane components of adherens junctions. However, little has been reported about the involvement of Nectin-2 in cancer. METHODS: To determine the expression of Nectin-2 in cancer tissues and cancer cell lines, we performed gene expression profile analysis, immunohistochemistry studies, and flow cytometry analysis. We also investigated the potential of this molecule as a target for antibody therapeutics to treat cancers by generating and characterizing an anti-Nectin-2 rabbit polyclonal antibody (poAb) and 256 fully human anti-Nectin-2 monoclonal antibodies (mAbs). In addition, we tested anti-Nectin-2 mAbs in several in vivo tumor growth inhibition models to investigate the primary mechanisms of action of the mAbs. RESULTS: In the present study, we found that Nectin-2 was over-expressed in clinical breast and ovarian cancer tissues by using gene expression profile analysis and immunohistochemistry studies. Nectin-2 was over-expressed in various cancer cell lines as well. Furthermore, the polyclonal antibody specific to Nectin-2 suppressed the in vitro proliferation of OV-90 ovarian cancer cells, which express endogenous Nectin-2 on the cell surface. The anti-Nectin-2 mAbs we generated were classified into 7 epitope bins. The anti-Nectin-2 mAbs demonstrated antibody-dependent cellular cytotoxicity (ADCC) and epitope bin-dependent features such as the inhibition of Nectin-2-Nectin-2 interaction, Nectin-2-Nectin-3 interaction, and in vitro cancer cell proliferation. A representative anti-Nectin-2 mAb in epitope bin VII, Y-443, showed anti-tumor effects against OV-90 cells and MDA-MB-231 breast cancer cells in mouse therapeutic models, and its main mechanism of action appeared to be ADCC. CONCLUSIONS: We observed the over-expression of Nectin-2 in breast and ovarian cancers and anti-tumor activity of anti-Nectin-2 mAbs via strong ADCC. These findings suggest that Nectin-2 is a potential target for antibody therapy against breast and ovarian cancers

Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: Novel insights into the regulation of Rev nuclear import

<p>Abstract</p> <p>Background</p> <p>The HIV-1 regulatory protein Rev, which is essential for viral replication, mediates the nuclear export of unspliced viral transcripts. Rev nuclear function requires active nucleocytoplasmic shuttling, and Rev nuclear import is mediated by the recognition of its Nuclear Localisation Signal (NLS) by multiple import factors, which include transportin and importin β. However, it remains unclear which nuclear import pathway(s) predominate <it>in vivo</it>, and the cellular environment that modulates Rev nucleocytoplasmic shuttling remains to be characterised.</p> <p>Results</p> <p>In our study, we have identified the cellular protein HIC (Human I-mfa domain-Containing protein) as a novel interactor of HIV-1 Rev. We demonstrate that HIC selectively interferes with Rev NLS interaction with importin β and impedes its nuclear import and function, but does not affect Rev nuclear import mediated by transportin. Hence, the molecular determinants mediating Rev-NLS recognition by importin β and transportin appear to be distinct. Furthermore, we have employed HIC and M9 M, a peptide specifically designed to inhibit the transportin-mediated nuclear import pathway, to characterise Rev nuclear import pathways within different cellular environments. Remarkably, we could show that in 293T, HeLa, COS7, Jurkat, U937, THP-1 and CEM cells, Rev nuclear import is cell type specific and alternatively mediated by transportin or importin β, in a mutually exclusive fashion.</p> <p>Conclusions</p> <p>Rev cytoplasmic sequestration by HIC may represent a novel mechanism for the control of Rev function. These studies highlight that the multivalent nature of the Rev NLS for different import receptors enables Rev to adapt its nuclear trafficking strategy.</p