Publications by authors named "Yoichi Seki"

34 Publications

Human CD36 monocytes induce Foxp3 CD25 T cells with regulatory functions from CD4 and CD8 subsets.

Immunology 2021 Feb 1. Epub 2021 Feb 1.

Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, 2160 South First Avenue, Maywood, IL, 60153, USA.

The fetal and neonatal immune systems are uniquely poised to generate tolerance to self, maternal, and environmental antigens encountered in the womb and shortly after birth. However, the tolerogenic nature of fetal and neonatal immunity can be detrimental in the context of pathogens, leading to overwhelming bacterial infections or chronic viral infections. A variety of mechanisms contribute to fetal and neonatal tolerance, including a propensity to generate Foxp3 regulatory T cells (Treg cells). However, the mechanism(s) of fetal Foxp3 T cell differentiation, the specific antigen-presenting cells required, and factors that inhibit Treg generation after the neonatal period are poorly understood. Here, we demonstrate that a subset of CD14 monocytes expressing the scavenger molecule, CD36, can generate CD4 and CD8 T cells that co-express Foxp3 and T-bet from both umbilical cord blood. These Foxp3 T-bet T cells potently suppress T cell proliferation and ameliorate xenogeneic graft versus host disease. CD14 CD36 monocytes provide known Treg-inducing signals: membrane-bound transforming growth factor-beta and retinoic acid. Unexpectedly, adult peripheral blood monocytes are also capable of inducing Foxp3 T cells from both cord blood and adult peripheral naïve T cells. The induction of Foxp3 T cells in umbilical cord blood by monocytes was inhibited by the lymphoid fraction of adult peripheral blood cells. These studies highlight a novel immunoregulatory role of monocytes and suggest that antigen presentation by CD36 monocytes may contribute to the peripheral development of Foxp3 T-bet T cells with regulatory functions in both neonates and adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/imm.13316DOI Listing
February 2021

Spectral response properties of higher visual neurons in Drosophila melanogaster.

J Comp Physiol A Neuroethol Sens Neural Behav Physiol 2020 03 13;206(2):217-232. Epub 2019 Dec 13.

Laboratory of Molecular Neuroscience and Neurology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.

The fruit fly Drosophila melanogaster can process chromatic information for true color vision and spectral preference. Spectral information is initially detected by a few distinct photoreceptor channels with different spectral sensitivities and is processed through the visual circuit. The neuroanatomical bases of the circuit are emerging. However, only little information is available in chromatic response properties of higher visual neurons from this important model organism. We used in vivo whole-cell patch-clamp recordings in response to monochromatic light stimuli ranging from 300 to 650 nm with 25-nm steps. We characterized the chromatic response of 33 higher visual neurons, including their general response type and their wavelength tuning. Color-opponent-type responses that had been typically observed in primates and bees were not identified. Instead, the majority of neurons showed excitatory responses to broadband wavelengths. The UV (300-375 nm) and middle wavelength (425-575 nm) ranges could be separated at the population level owing to neurons that preferentially responded to a specific wavelength range. Our results provide a first mapping of chromatic information processing in higher visual neurons of D. melanogaster that is a suitable model for exploring how color-opponent neural mechanisms are implemented in the visual circuits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00359-019-01391-9DOI Listing
March 2020

Alterations of mental defeat and cognitive flexibility during cognitive behavioral therapy in patients with major depressive disorder: a single-arm pilot study.

BMC Res Notes 2019 Nov 6;12(1):723. Epub 2019 Nov 6.

Research Center for Child Mental Development, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba, 260-8670, Japan.

Objective: Mental defeat affects the occurrence and chronicity of depression and cognitive flexibility. This study aimed to examine changes in mental defeat and cognitive flexibility scores after cognitive behavioral therapy including IR. In the intervention group, patients with depression (n = 18, mean age = 37.89 years) received 15 cognitive behavioral therapy sessions. Patients completed the Beck Depression Inventory-II; Mental Defeat Scale; Cognitive Flexibility Scale; EuroQol five dimensions questionnaire; Patient Health Questionnaire-9 and seven-item Generalized Anxiety Disorder Scale before the intervention, after six sessions, and post-intervention. The healthy control group (n = 33, mean age = 37.91) completed all scales once and did not receive treatment.

Results: Post-cognitive behavioral therapy, a significant decrease was observed in Beck Depression Inventory-II, Mental Defeat Scale, Cognitive Flexibility Scale, and Patient Health Questionnaire-9 scores. Although mental defeat and cognitive flexibility did not reach the level of the healthy control group, they demonstrated improvement. Therefore, when treating depression, mental defeat and cognitive flexibility should be measured in addition to depressive symptoms. Trial registration This study was registered retrospectively in the national UMIN Clinical Trials Registry on July 25, 2016 (registration ID: UMIN000023320).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13104-019-4758-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833291PMC
November 2019

Data on the effects of Charcot-Marie-Tooth disease type 2N-associated AARS missense mutation (Arg329-to-His) on the cell biological properties.

Data Brief 2019 Aug 24;25:104029. Epub 2019 May 24.

Laboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0355, Japan.

Charcot-Marie-Tooth (CMT) diseases are genetic neuropathies in the peripheral nervous system (PNS). Type 1 CMT diseases are neuropathies in Schwann cells, PNS myelinating glial cells, whereas type 2 CMT diseases are axonal neuropathies. In addition, there are other types of categories in CMT diseases. CMT diseases are associated with approximately 100 responsible genes. Taiwanese mutation (Asn71-to-Tyr) of alanyl-tRNA synthetase (AARS) in type 2N CMT disease has been reported to have several pathological effects on properties of AARS proteins themselves [1]. Also, some mutations in other responsible genes affect cell biological properties of their gene products [2,3]. Herein we provide the data regarding the effects of another type 2N CMT disease-associated AARS mutation (Arg329-to-His) in French family on the cellular properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dib.2019.104029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554220PMC
August 2019

Treatment Preferences for Internet-Based Cognitive Behavioral Therapy for Insomnia in Japan: Online Survey.

JMIR Form Res 2019 May 15;3(2):e12635. Epub 2019 May 15.

Department of Cognitive Behavioral Physiology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background: The internet has the potential to increase individuals' access to cognitive behavioral therapy (CBT) for insomnia at low cost. However, treatment preferences regarding internet-based computerized CBT for insomnia have not been fully examined.

Objective: The aim was to conduct an anonymous online survey to evaluate treatment preferences for insomnia among patients with insomnia and individuals without insomnia.

Methods: We developed an online survey to recruit a total of 600 participants living in the Kanto district in Japan. There were three subgroups: 200 medicated individuals with insomnia, 200 unmedicated individuals with insomnia, and 200 individuals without insomnia. The survey asked questions about the severity of the respondent's insomnia (using the Athens Insomnia Scale), the frequency of sleep medication use and the level of satisfaction with sleep medication use, the respondent's knowledge of CBT, his or her preference for CBT for insomnia before drug therapy, preference for CBT versus drug therapy, and preference for internet-based CBT versus face-to-face CBT.

Results: Of the 600 respondents, 47.7% (286/600) indicated that they received CBT before drug therapy, and 57.2% (343/600) preferred CBT for insomnia to drug therapy. In addition, 47.0% (282/600) preferred internet-based CBT for insomnia to face-to-face CBT. Although the respondents with insomnia who were taking an insomnia medication had a relatively lower preference for internet-based CBT (40.5%, 81/200), the respondents with insomnia who were not taking an insomnia medication had a relatively higher preference for internet-based CBT (55.5%, 111/200).

Conclusions: The results of our online survey suggest that approximately half of the people queried preferred CBT for insomnia to drug therapy, and half of the respondents preferred internet-based CBT for insomnia to face-to-face CBT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/12635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540872PMC
May 2019

Internet-Based Cognitive Behavioral Therapy With Real-Time Therapist Support via Videoconference for Patients With Obsessive-Compulsive Disorder, Panic Disorder, and Social Anxiety Disorder: Pilot Single-Arm Trial.

J Med Internet Res 2018 12 17;20(12):e12091. Epub 2018 Dec 17.

Research Center for Child Mental Development, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background: Cognitive behavioral therapy (CBT) is the first-line treatment for adults with obsessive-compulsive disorder (OCD), panic disorder (PD), and social anxiety disorder (SAD). Patients in rural areas can access CBT via the internet. The effectiveness of internet-delivered cognitive behavioral therapy (ICBT) has been consistently shown, but no clinical studies have demonstrated the feasibility of ICBT with real-time therapist support via videoconference for OCD, PD, and SAD at the same time.

Objectives: This study aimed to evaluate the feasibility of videoconference-delivered CBT for patients with OCD, PD, or SAD.

Methods: A total of 30 Japanese participants (mean age 35.4 years, SD 9.2) with OCD, SAD, or PD received 16 sessions of individualized videoconference-delivered CBT with real-time support of a therapist, using tablet personal computer (Apple iPad Mini 2). Treatment involved individualized CBT formulations specific to the presenting diagnosis; all sessions were provided by the same therapist. The primary outcomes were reduction in symptomatology, using the Yale-Brown obsessive-compulsive scale (Y-BOCS) for OCD, Panic Disorder Severity Scale (PDSS) for PD, and Liebowitz Social Anxiety Scale (LSAS) for SAD. The secondary outcomes included the EuroQol-5 Dimension (EQ-5D) for Quality of Life, the Patient Health Questionnaire (PHQ-9) for depression, the Generalized Anxiety Disorder (GAD-7) questionnaire for anxiety, and Working Alliance Inventory-Short Form (WAI-SF). All primary outcomes were assessed at baseline and at weeks 1 (baseline), 8 (midintervention), and 16 (postintervention) face-to-face during therapy. The occurrence of adverse events was observed after each session. For the primary analysis comparing between pre- and posttreatments, the participants' points and 95% CIs were estimated by the paired t tests with the change between pre- and posttreatment.

Results: A significant reduction in symptom of obsession-compulsion (Y-BOCS=-6.2; Cohen d=0.74; 95% CI -9.4 to -3.0, P=.002), panic (PDSS=-5.6; Cohen d=0.89; 95% CI -9.83 to -1.37; P=.02), social anxiety (LSAS=-33.6; Cohen d=1.10; 95% CI -59.62 to -7.49, P=.02) were observed. In addition, depression (PHQ-9=-1.72; Cohen d=0.27; 95% CI -3.26 to -0.19; P=.03) and general anxiety (GAD-7=-3.03; Cohen d=0.61; 95% CI -4.57 to -1.49, P<.001) were significantly improved. Although there were no significant changes at 16 weeks from baseline in EQ-5D (0.0336; Cohen d=-0.202; 95% CI -0.0198 to 0.00869; P=.21), there were high therapeutic alliance (ie, WAI-SF) scores (from 68.0 to 73.7) throughout treatment, which significantly increased (4.14; 95% CI 1.24 to 7.04; P=.007). Of the participants, 86% (25/29) were satisfied with videoconference-delivered CBT, and 83% (24/29) preferred videoconference-delivered CBT to face-to-face CBT. An adverse event occurred to a patient with SAD; the incidence was 3% (1/30).

Conclusions: Videoconference-delivered CBT for patients with OCD, SAD, and SAD may be feasible and acceptable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/12091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315259PMC
December 2018

Does cognitive behavioral therapy alter mental defeat and cognitive flexibility in patients with panic disorder?

BMC Res Notes 2018 Jan 12;11(1):23. Epub 2018 Jan 12.

Department of Cognitive Behavioral Physiology, Graduate School of Medicine, Chiba University, Chiba, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba, 260-8670, Japan.

Objective: Mental defeat and cognitive flexibility have been studied as explanatory factors for depression and posttraumatic stress disorder. This study examined mental defeat and cognitive flexibility scores in patients with panic disorder (PD) before and after cognitive behavioral therapy (CBT), and compared them to those of a gender- and age-matched healthy control group.

Results: Patients with PD (n = 15) received 16 weekly individual CBT sessions, and the control group (n = 35) received no treatment. Patients completed the Mental Defeat Scale and the Cognitive Flexibility Scale before the intervention, following eight CBT sessions, and following 16 CBT sessions, while the control group did so only prior to receiving CBT (baseline). The patients' pre-CBT Mental Defeat and Cognitive Flexibility Scale scores were significantly higher on the Mental Defeat Scale and lower on the Cognitive Flexibility Scale than those of the control group participants were. In addition, the average Mental Defeat Scale scores of the patients decreased significantly, from 22.2 to 12.4, while their average Cognitive Flexibility Scale scores increased significantly, from 42.8 to 49.5. These results suggest that CBT can reduce mental defeat and increase cognitive flexibility in patients with PD Trial registration The study was registered retrospectively in the national UMIN Clinical Trials Registry on June 10, 2016 (registration ID: UMIN000022693).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13104-018-3130-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767061PMC
January 2018

Exploratory study of imagery rescripting without focusing on early traumatic memories for major depressive disorder.

Psychol Psychother 2018 09 9;91(3):345-362. Epub 2017 Dec 9.

Department of Cognitive Behavioral Physiology, Graduate School of Medicine, Chiba University, Japan.

Background: Mental imagery has a more powerful impact on our emotions than thinking in words about the same material. Treating intrusive images with imagery rescripting (IR) has been reported for various disorders, including post-traumatic stress disorder, social anxiety disorder, and bipolar disorder. There has been less research about IR as a major depressive disorder (MDD).

Aims: We examined whether IR without focusing on early traumatic memories is effective in MDD.

Methods: We enrolled 19 participants with MDD, who received 15 weekly sessions of full CBT, including two sessions for IR of intrusive images and, separately, for memory rescripting. Before and after the IR intervention, participants were asked to rate the intrusive images they experienced against, an intrusion index that included difficulty (interference with daily life), uncontrollability, distress caused by the negative image, and vividness. We recorded the contents of each participant's negative and positive imagery to classify these.

Results: The intrusion index scores decreased after the IR sessions. Negative images experienced by the participants while in a depressive mood were categorized into three different types: blame, social exclusion, and loneliness. The rescripted positive images were categorized into good relations and worthy self (competent self).

Conclusions: These results suggest that IR of intrusive images without focusing on early traumatic memories may usefully be incorporated into routine CBT sessions for MDD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/papt.12164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175347PMC
September 2018

Data on the effect of knockout of cytohesin-1 in myelination-related protein kinase signaling.

Data Brief 2017 Dec 20;15:234-239. Epub 2017 Sep 20.

Laboratory of Molecular Neuroscience and Neurology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0355, Japan.

Cytohesin-1 is the guanine-nucleotide exchange factor of Arf6, a small GTPase of Arf family, and participates in cellular morphological changes. Knockout mice of cytohesin-1 exhibit decreased myelination of neuronal axons in the peripheral nervous system (PNS) "Phosphorylation of cytohesin-1 by Fyn is required for initiation of myelination and the extent of myelination during development (Yamauchi et al., 2012) [1]". Herein we provide the data regarding decreased phosphorylation levels of protein kinases involved in two major myelination-related kinase cascades in cytohesin-1 knockout mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dib.2017.09.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633161PMC
December 2017

Olfactory coding from the periphery to higher brain centers in the Drosophila brain.

BMC Biol 2017 06 30;15(1):56. Epub 2017 Jun 30.

Department of Evolutionary Neuroethology, Max Planck Institute for Chemical Ecology, Hans-Knöll-Strasse 8, 07745, Jena, Germany.

Background: Odor information is processed through multiple receptor-glomerular channels in the first order olfactory center, the antennal lobe (AL), then reformatted into higher brain centers and eventually perceived by the fly. To reveal the logic of olfaction, it is fundamental to map odor representations from the glomerular channels into higher brain centers.

Results: We characterize odor response profiles of AL projection neurons (PNs) originating from 31 glomeruli using whole cell patch-clamp recordings in Drosophila melanogaster. We reveal that odor representation from olfactory sensory neurons to PNs is generally conserved, while transformation of odor tuning curves is glomerulus-dependent. Reconstructions of PNs reveal that attractive and aversive odors are represented in different clusters of glomeruli in the AL. These separate representations are preserved into higher brain centers, where attractive and aversive odors are segregated into two regions in the lateral horn and partly separated in the mushroom body calyx.

Conclusions: Our study reveals spatial representation of odor valence coding from the AL to higher brain centers. These results provide a global picture of the olfactory circuit design underlying innate odor-guided behavior.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12915-017-0389-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493115PMC
June 2017

Data supporting the role of Fyn in embryonic sciatic nerve fasciculation.

Data Brief 2017 Apr 22;11:358-363. Epub 2017 Feb 22.

Laboratory of Molecular Neuroscience and Neurology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0355, Japan; Laboratory of Molecular Pharmacology, Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.

Fyn is the cytoplasmic tyrosine kinase that has critical roles in many aspects of biological functions. In the central [1] and peripheral nervous systems [2], [3], Fyn plays the key role in initiating myelination by myelin-forming glial cells (Schwann cells and oligodendrocytes). Herein we provide the data regarding the role of Fyn in fasciculation and branching of embryonic peripheral nerves.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dib.2017.02.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5329064PMC
April 2017

Data on the effect of hypomyelinating leukodystrophy 6 (HLD6)-associated mutations on the TUBB4A properties.

Data Brief 2017 Apr 16;11:284-289. Epub 2017 Feb 16.

Laboratory of Molecular Neuroscience and Neurology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0355, Japan; Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.

Hypomyelinating leukodystrophy (HLD) is genetic demyelinating or dysmyelinating disease and is associated with at least 13 responsible genes. The mutations seem likely cause the functional deficiency of their gene products. HLD4- and HLD5-associated HSPD1 and FAM126A mutations affect biochemical properties of the gene products (Miyamoto et al. (2015,2014) [[1], [2]]). Herein we provide the data regarding the effects of HLD6-associated tubulin beta 4A (TUBB4A) mutations on the properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dib.2017.02.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328720PMC
April 2017

Morphology and physiology of antennal lobe projection neurons in the hawkmoth Agrius convolvuli.

J Insect Physiol 2017 04 21;98:214-222. Epub 2017 Jan 21.

Agricultural and Environmental Biology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8567, Japan.

The neuronal pathways involved in the processing of sex pheromone information were investigated in the hawkmoth Agrius convolvuli (Lepidoptera: Sphingidae), which uses (E,E)-11,13-hexadecadienal (E11,E13-16:Ald) as the single sex pheromone component. We first clarified the anatomical organization of the antennal lobe of A. convolvuli. Subsequently, central neurons in the antennal lobe that responded to E11,E13-16:Ald were identified. The dendritic processes of these neurons were confined within a specific glomerulus (cumulus) in the antennal lobe. The axons of these neurons projected to the inferior lateral protocerebrum and mushroom body calyx. Although the anatomical organization and morphology of individual neurons in A. convolvuli were similar to other species in the superfamily Bombycoidea, the use of cumulus as the single pathway for sex pheromone information processing was characteristic to this species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinsphys.2017.01.010DOI Listing
April 2017

A feasibility study of the clinical effectiveness and cost-effectiveness of individual cognitive behavioral therapy for panic disorder in a Japanese clinical setting: an uncontrolled pilot study.

BMC Res Notes 2016 Oct 7;9(1):458. Epub 2016 Oct 7.

Research Center for Child Mental Development, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba, 260-8670, Japan.

Background: In Japan, cognitive behavioral therapy (CBT) for panic disorder (PD) is not well established. Therefore, a feasibility study of the clinical effectiveness and cost-effectiveness of CBT for PD in a Japanese clinical setting is urgently required. This was a pilot uncontrolled trial and the intervention consisted of a 16-week CBT program. The primary outcome was Panic Disorder Severity Scale (PDSS) scores. Quality of life was assessed using the EuroQol's EQ-5D questionnaire. Assessments were conducted at baseline, 8 weeks, and at the end of the study. Fifteen subjects completed outcome measures at all assessment points.

Results: At post-CBT, the mean reduction in PDSS scores from baseline was -6.6 (95 % CI 3.80 to -9.40, p < 0.001) with a Cohen's d = 1.77 (95 % CI 0.88-2.55). Ten (66.7 %) participants achieved a 40 % or greater reduction in PDSS. By calculating areas under the curve for EQ-5D index changes, we estimated that patients gained a minimum of 0.102 QALYs per 1 year due to the CBT.

Conclusions: This study demonstrated that individual CBT for PD may be useful in Japanese clinical settings but further randomized control trials are needed.

Trial Registration: UMIN-CTR UMIN000022693 (retrospectively registered).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13104-016-2262-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055685PMC
October 2016

Use of capillary electrophoresis with dual-opposite end injection for simultaneous analysis of small ions in saliva samples from wrestlers undergoing a weight training program.

J Chromatogr B Analyt Technol Biomed Life Sci 2016 Feb 24;1012-1013:178-85. Epub 2016 Jan 24.

Department of Clinical Laboratory Medicine, Gunma University and Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.

Capillary electrophoresis-capacitively coupled contactless conductivity detection (CE-C4D), conducted using an in-house-developed polyvinyl alcohol (PVA)-coated capillary system, was applied for the simultaneous analysis of small anions and cations in saliva samples from wrestlers undergoing a weight training program. Use of the PVA capillary for CE provided good reproducible ion separation with minimization of the electroosmotic flow and suppression of protein adsorption onto the capillary wall. Four cations and eight anions were separated in 12min, using a background electrolyte of 20mM MES/20mM histidine and 18-crown-6 ether (pH 6) at 20kV. The relative standard deviations (n=5) of the migration times and peak areas were <1% and <8%, respectively. The detection limit at a signal-to-noise ratio of 3 ranged from 1.6 to 10μM. Using the optimized CE-C4D system, we investigated the correlations between the concentrations of salivary ions and cortisol, which is commonly used as a stress marker. Analysis of saliva samples from ten wrestlers, who were attempting rapid weight loss before a competition, showed the following trends: (1) all ion concentrations, except for Ca(2+), Na(+), and Cl(-), increased between the first and last days of weight loss; (2) Mg(2+) increased to 166% (from 0.50mM to 1.4mM) between the first and last days of weight loss, being the highest increase of all the ions; and (3) K(+), Mg(2+), NO3(-), and SCN(-) levels were strongly correlated (P<0.05) with cortisol. The CE-C4D rapidly produced useful data on saliva ion contents, with good ion recovery as determined by the standard addition method (89-110%).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchromb.2016.01.037DOI Listing
February 2016

Drosophila Avoids Parasitoids by Sensing Their Semiochemicals via a Dedicated Olfactory Circuit.

PLoS Biol 2015 Dec 16;13(12):e1002318. Epub 2015 Dec 16.

Max Planck Institute for Chemical Ecology, Jena, Germany.

Detecting danger is one of the foremost tasks for a neural system. Larval parasitoids constitute clear danger to Drosophila, as up to 80% of fly larvae become parasitized in nature. We show that Drosophila melanogaster larvae and adults avoid sites smelling of the main parasitoid enemies, Leptopilina wasps. This avoidance is mediated via a highly specific olfactory sensory neuron (OSN) type. While the larval OSN expresses the olfactory receptor Or49a and is tuned to the Leptopilina odor iridomyrmecin, the adult expresses both Or49a and Or85f and in addition detects the wasp odors actinidine and nepetalactol. The information is transferred via projection neurons to a specific part of the lateral horn known to be involved in mediating avoidance. Drosophila has thus developed a dedicated circuit to detect a life-threatening enemy based on the smell of its semiochemicals. Such an enemy-detecting olfactory circuit has earlier only been characterized in mice and nematodes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pbio.1002318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687525PMC
December 2015

Interferon-γ constrains cytokine production of group 2 innate lymphoid cells.

Immunology 2016 Jan 25;147(1):21-9. Epub 2015 Oct 25.

Department of Immune Regulation, Research Centre for Hepatitis and Immunology, Research Institute, National Centre for Global Health and Medicine, Chiba, Japan.

Group 2 innate lymphoid cells (ILC2s) produce a significant amount of interleukin-5 (IL-5), which supports eosinophil responses in various tissues; they also produce IL-13, which induces mucus production and contributes to tissue repair or fibrosis. The ILC2s are activated by alarmins, such as IL-33 released from epithelia, macrophages and natural killer T (NKT) cells in response to infection and allergen exposure, leading to epithelial injury. We examined gene expression in lung ILC2s and found that ILC2s expressed Ifngr1, the receptor for interferon-γ (IFN-γ). Interferon-γ severely inhibited IL-5 and IL-13 production by lung and kidney ILC2s. To evaluate the effects in vivo, we used α-galactosylceramide (α-GalCer) to induce NKT cells to produce IL-33 and IFN-γ. Intraperitoneal injection of α-GalCer in mice induced NKT cell activation resulting in IL-5 and IL-13 production by ILC2s. Administration of anti-IFN-γ together with α-GalCer significantly enhanced the production of IL-5 and IL-13 by ILC2s in lung and kidney. Conversely, cytokine production from ILC2s was markedly suppressed after injection of exogenous IL-33 in Il33(-/-) mice pre-treated with α-GalCer. Hence, IFN-γ induced or already present in tissues can impact downstream pleiotropic functions mediated by ILC2s, such as inflammation and tissue repair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/imm.12537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693881PMC
January 2016

Noise-robust recognition of wide-field motion direction and the underlying neural mechanisms in Drosophila melanogaster.

Sci Rep 2015 May 14;5:10253. Epub 2015 May 14.

School of Life Sciences; Tokyo University of Pharmacy and Life Sciences, Hachio-ji, Tokyo, 192-0392, Japan.

Appropriate and robust behavioral control in a noisy environment is important for the survival of most organisms. Understanding such robust behavioral control has been an attractive subject in neuroscience research. Here, we investigated the processing of wide-field motion with random dot noise at both the behavioral and neuronal level in Drosophila melanogaster. We measured the head yaw optomotor response (OMR) and the activity of motion-sensitive neurons, horizontal system (HS) cells, with in vivo whole-cell patch clamp recordings at various levels of noise intensity. We found that flies had a robust sensation of motion direction under noisy conditions, while membrane potential changes of HS cells were not correlated with behavioral responses. By applying signal classification theory to the distributions of HS cell responses, however, we found that motion direction under noise can be clearly discriminated by HS cells, and that this discrimination performance was quantitatively similar to that of OMR. Furthermore, we successfully reproduced HS cell activity in response to noisy motion stimuli with a local motion detector model including a spatial filter and threshold function. This study provides evidence for the physiological basis of noise-robust behavior in a tiny insect brain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep10253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431354PMC
May 2015

Lnk/Sh2b3 controls the production and function of dendritic cells and regulates the induction of IFN-γ-producing T cells.

J Immunol 2014 Aug 14;193(4):1728-36. Epub 2014 Jul 14.

Department of Immune Regulation, Research Institute, National Center for Global Health and Medicine, Chiba 272-8516, Japan;

Dendritic cells (DCs) are proficient APCs that play crucial roles in the immune responses to various Ags and pathogens and polarize Th cell immune responses. Lnk/SH2B adaptor protein 3 (Sh2b3) is an intracellular adaptor protein that regulates B lymphopoiesis, megakaryopoiesis, and expansion of hematopoietic stem cells by constraining cytokine signals. Recent genome-wide association studies have revealed a link between polymorphism in this adaptor protein and autoimmune diseases, including type 1 diabetes and celiac disease. We found that Lnk/Sh2b3 was also expressed in DCs and investigated its role in the production and function of DC lineage cells. In Lnk(-/-) mice, DC numbers were increased in the spleen and lymph nodes, and growth responses of bone marrow-derived DCs to GM-CSF were augmented. Mature DCs from Lnk(-/-) mice were hypersensitive and showed enhanced responses to IL-15 and GM-CSF. Compared to normal DCs, Lnk(-/-) DCs had enhanced abilities to support the differentiation of IFN-γ-producing Th1 cells from naive CD4(+) T cells. This was due to their elevated expression of IL-12Rβ1 and increased production of IFN-γ. Lnk(-/-) DCs supported the appearance of IFN-γ-producing T cells even under conditions in which normal DCs supported induction of regulatory T cells. These results indicated that Lnk/Sh2b3 plays a regulatory role in the expansion of DCs and might influence inflammatory immune responses in peripheral lymphoid tissues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.1303243DOI Listing
August 2014

Lnk prevents inflammatory CD8⁺ T-cell proliferation and contributes to intestinal homeostasis.

Eur J Immunol 2014 Jun 2;44(6):1622-32. Epub 2014 May 2.

Department of Immune Regulation, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.

The intracellular adaptor Lnk (also known as SH2B3) regulates cytokine signals that control lymphohematopoiesis, and Lnk(-/-) mice have expanded B-cell, megakaryocyte, and hematopoietic stem-cell populations. Moreover, mutations in the LNK gene are found in patients with myeloproliferative disease, whereas LNK polymorphisms have recently been associated with inflammatory and autoimmune diseases, including celiac disease. Here, we describe a previously unrecognized function of Lnk in the control of inflammatory CD8(+) T-cell proliferation and in intestinal homeostasis. Mature T cells from newly generated Lnk-Venus reporter mice had low but substantial expression of Lnk, whereas Lnk expression was downregulated during homeostatic T-cell proliferation under lymphopenic conditions. The numbers of CD44(hi) IFN-γ(+) CD8(+) effector or memory T cells were found to be increased in Lnk(-/-) mice, which also exhibited shortening of villi in the small intestine. Lnk(-/-) CD8(+) T cells survived longer in response to stimulation with IL-15 and proliferated even in nonlymphopenic hosts. Transfer of Lnk(-/-) CD8(+) T cells together with WT CD4(+) T cells into Rag2-deficient mice recapitulated a sign of villous abnormality. Our results reveal a link between Lnk and immune cell-mediated intestinal tissue destruction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/eji.201343883DOI Listing
June 2014

Ontogeny and localization of the cells produce IL-2 in healthy animals.

Cytokine 2013 Mar 16;61(3):831-41. Epub 2013 Jan 16.

Department of Microbiology and Immunology, Loyola University Chicago, 2160 South First Ave., Maywood, IL 60153, USA.

IL-2 is a growth factor for activated T cells and is required for maintenance of naturally arising regulatory T cells (nTregs). Mice defective in IL-2/IL-2 receptor signaling pathways have impaired nTregs and suffer from lymphoproliferative disorders, suggesting that IL-2 is present and functional in healthy animals. However, the cellular source of IL-2 is currently unknown. To determine which cells produce IL-2 in healthy animals, we established mice carrying cre gene knock in at the il-2 locus (termed IL-2(cre)). When IL-2(cre) mice were crossed with EGFP reporter mice, EGFP was exclusively expressed by a fraction of CD4 T cells present in both lymphoid and non-lymphoid tissues. Live imaging of IL-2(cre) mice that carry the luciferase reporter showed concentrated localization of luciferase(+) cells in Peyer's patches. These cells were not observed in new born mice but appeared within 3days after birth. Reduction of antigen receptor repertoire by transgene expression reduced their number, indicating that recognition of environmental antigens is necessary for generation of these IL-2 producers in healthy animals. A substantial fraction of EGFP(+) cells also produce IL-10 and IFN-γ, a characteristic profile of type 1 regulatory T cells (Tr1). The data suggest that a group of Tr1 cells have addition roles in immune homeostasis by producing IL-2 along with other cytokines and help maintaining Tregs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cyto.2012.11.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595346PMC
March 2013

A conserved dedicated olfactory circuit for detecting harmful microbes in Drosophila.

Cell 2012 Dec;151(6):1345-57

Department of Evolutionary Neuroethology, Max Planck Institute for Chemical Ecology, Hans-Knöll-Strasse 8, 07745 Jena, Germany.

Flies, like all animals, need to find suitable and safe food. Because the principal food source for Drosophila melanogaster is yeast growing on fermenting fruit, flies need to distinguish fruit with safe yeast from yeast covered with toxic microbes. We identify a functionally segregated olfactory circuit in flies that is activated exclusively by geosmin. This microbial odorant constitutes an ecologically relevant stimulus that alerts flies to the presence of harmful microbes. Geosmin activates only a single class of sensory neurons expressing the olfactory receptor Or56a. These neurons target the DA2 glomerulus and connect to projection neurons that respond exclusively to geosmin. Activation of DA2 is sufficient and necessary for aversion, overrides input from other olfactory pathways, and inhibits positive chemotaxis, oviposition, and feeding. The geosmin detection system is a conserved feature in the genus Drosophila that provides flies with a sensitive, specific means of identifying unsuitable feeding and breeding sites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2012.09.046DOI Listing
December 2012

Concentric zones for pheromone components in the mushroom body calyx of the moth brain.

J Comp Neurol 2013 Apr;521(5):1073-92

Intelligent Cooperative Systems Laboratory, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo 153-8904, Japan.

The spatial distribution of input and output neurons in the mushroom body (MB) calyx was investigated in the silkmoth Bombyx mori. In Lepidoptera, the brain has a specialized system for processing sex pheromones. How individual pheromone components are represented in the MB has not yet been elucidated. Toward this end, we first compared the distribution of the presynaptic boutons of antennal lobe projection neurons (PNs), which transfer odor information from the antennal lobe to the MB calyx. The axons of PNs that innervate pheromonal glomeruli were confined to a relatively small area within the calyx. In contrast, the axons of PNs that innervate nonpheromonal glomeruli were more widely distributed. PN axons for the minor pheromone component covered a larger area than those for the major pheromone component and partially overlapped with those innervating nonpheromonal glomeruli, suggesting the integration of the minor pheromone component with plant odors. Overall, we found that PN axons innervating pheromonal and nonpheromonal glomeruli were organized into concentric zones. We then analyzed the dendritic fields of Kenyon cells (KCs), which receive inputs from PNs. Despite the strong regional localization of axons of different PN classes, the dendrites of KCs were less well classified. Finally, we estimated the connectivity between PNs and KCs and suggest that the dendritic field may be organized to receive different amounts of pheromonal and nonpheromonal inputs. PNs for multiple pheromone components and plant odors enter the calyx in a concentric fashion, and they are read out by the elaborate dendritic field of KCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cne.23219DOI Listing
April 2013

Cellular basis of tissue regeneration by omentum.

PLoS One 2012 6;7(6):e38368. Epub 2012 Jun 6.

Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Chicago, Illinois, United States of America.

The omentum is a sheet-like tissue attached to the greater curvature of the stomach and contains secondary lymphoid organs called milky spots. The omentum has been used for its healing potential for over 100 years by transposing the omental pedicle to injured organs (omental transposition), but the mechanism by which omentum helps the healing process of damaged tissues is not well understood. Omental transposition promotes expansion of pancreatic islets, hepatocytes, embryonic kidney, and neurons. Omental cells (OCs) can be activated by foreign bodies in vivo. Once activated, they become a rich source for growth factors and express pluripotent stem cell markers. Moreover, OCs become engrafted in injured tissues suggesting that they might function as stem cells.Omentum consists of a variety of phenotypically and functionally distinctive cells. To understand the mechanism of tissue repair support by the omentum in more detail, we analyzed the cell subsets derived from the omentum on immune and inflammatory responses. Our data demonstrate that the omentum contains at least two groups of cells that support tissue repair, immunomodulatory myeloid derived suppressor cells and omnipotent stem cells that are indistinguishable from mesenchymal stem cells. Based on these data, we propose that the omentum is a designated organ for tissue repair and healing in response to foreign invasion and tissue damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0038368PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368844PMC
November 2012

Physiological and morphological characterization of local interneurons in the Drosophila antennal lobe.

J Neurophysiol 2010 Aug 26;104(2):1007-19. Epub 2010 May 26.

Max Planck Institute for Chemical Ecology, Department of Evolutionary Neuroethology, Jena, Germany.

The Drosophila antennal lobe (AL) has become an excellent model for studying early olfactory processing mechanisms. Local interneurons (LNs) connect a large number of glomeruli and are ideally positioned to increase computational capabilities of odor information processing in the AL. Although the neural circuit of the Drosophila AL has been intensively studied at both the input and the output level, the internal circuit is not yet well understood. An unambiguous characterization of LNs is essential to remedy this lack of knowledge. We used whole cell patch-clamp recordings and characterized four classes of LNs in detail using electrophysiological and morphological properties at the single neuron level. Each class of LN displayed unique characteristics in intrinsic electrophysiological properties, showing differences in firing patterns, degree of spike adaptation, and amplitude of spike afterhyperpolarization. Notably, one class of LNs had characteristic burst firing properties, whereas the others were tonically active. Morphologically, neurons from three classes innervated almost all glomeruli, while LNs from one class innervated a specific subpopulation of glomeruli. Three-dimensional reconstruction analyses revealed general characteristics of LN morphology and further differences in dendritic density and distribution within specific glomeruli between the different classes of LNs. Additionally, we found that LNs labeled by a specific enhancer trap line (GAL4-Krasavietz), which had previously been reported as cholinergic LNs, were mostly GABAergic. The current study provides a systematic characterization of olfactory LNs in Drosophila and demonstrates that a variety of inhibitory LNs, characterized by class-specific electrophysiological and morphological properties, construct the neural circuit of the AL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/jn.00249.2010DOI Listing
August 2010

CD4(+)CD25(+) regulatory T cells resist a novel form of CD28- and Fas-dependent p53-induced T cell apoptosis.

J Immunol 2010 Jan 30;184(1):94-104. Epub 2009 Nov 30.

Immunotherapy Center, Medical College of Georgia, Augusta, GA 30912, USA.

Ag receptor stimulation of preactivated T cells causes rapid cell death in an IL-2- and Fas-dependent manner. This phenomenon, known as activation-induced cell death (AICD), plays a pivotal role in the removal of Ag-reactive T cells after initial expansion. In this study, we report a novel form of T cell apoptosis that is distinct from classic AICD. When peripheral T cells were activated with anti-CD3 and anti-CD28 Abs precoated onto plastic plates, CD4(+)CD25(-) and CD8 T cells initially expanded but underwent massive apoptosis after 4 d. Unlike classic AICD, this type of T cell apoptosis pathway requires engagement of CD28 and expression of p53, a tumor-suppressor gene. The most striking feature of this form of apoptosis was regulatory T cell resistance. Under the same stimulating conditions, CD4(+)CD25(+) T cells grew continuously beyond 4 d. Consequently, when the entire CD4 population was cultured with plate-bound anti-CD3 plus anti-CD28 Ab, CD4(+)CD25(+)FoxP3(+) regulatory T cells outgrew nonregulatory T cells and expanded >7000-fold after 11 d. The data presented herein demonstrate a novel process of Ag-induced T cell death by sustained TCR and CD28 engagement and represent a simple and efficient procedure for the expansion of regulatory T cells in vitro.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.0900753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436589PMC
January 2010

Effects of mild calorie restriction and high-intensity interval walking in middle-aged and older overweight Japanese.

Exp Gerontol 2009 Oct 26;44(10):666-75. Epub 2009 Jul 26.

Departments of Aging Biology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto, Japan.

We investigated whether a combination of mild calorie restriction (MCR) and high-intensity interval walking (HIW) improved physical fitness more than HIW alone in middle-aged and older overweight Japanese (40-69years old, BMI23.6kg/m(2)). Forty-seven women and 16 men were divided into MCR+HIW and HIW groups. All subjects performed HIW: 5 sets of 3-min low-intensity walking (40% peak aerobic capacity for walking, VO(2peak)) and 3-min high-intensity walking (70% VO(2peak)) per day, 4days per week, for 16weeks while energy expenditure was monitored with a tri-axial accelerometer. The MCR+HIW group consumed meal replacement formula (240kcal): a mixture of low-carbohydrates and -fat and high-protein, for either lunch or dinner everyday and therefore, had approximately 87% of the energy intake of the HIW group during the intervention period. Although the HIW group showed improvements in BMI, blood pressure, and several blood chemicals, the MCR+HIW group had greater improvement. Moreover, the medical expenditure for the 6months including the intervention period was 59% lower in the MCR+HIW group than in the HIW group. Our strategy of a short-term combination of MCR and HIW may thus prevent lifestyle-associated diseases and improve health in middle-aged and older overweight Japanese.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.exger.2009.07.007DOI Listing
October 2009

Comprehensive morphological identification and GABA immunocytochemistry of antennal lobe local interneurons in Bombyx mori.

J Comp Neurol 2008 Jan;506(1):93-107

Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan.

The insect antennal lobe (AL) is the structural and functional analog of the olfactory bulb of mammals, in which odor information is spatially and/or temporally represented by functional glomerular units. Local interneurons (LNs) play critical roles through intra- and interglomerular communication to shape the output from the AL to higher brain centers; however, the function and even the components of LNs are unclear. We have used morphological and immunocytochemical approaches to examine LNs in the silkworm moth, Bombyx mori. First, we comprehensively analyzed the morphological variation of LNs. One hundred fifty-three AL LNs were intracellularly stained, analyzed in three dimensions with a confocal microscope, and subdivided into five morphological types based on differences in the arborization region in the AL and dendritic profiles within the glomeruli. Two global multiglomerular types arborized in the macroglomerular complex (MGC) and in most ordinary glomeruli, and the other three oligoglomerular types innervated some ordinary glomeruli with or without the MGC. Second, we performed double-labeling of Lucifer Yellow staining of a single LN combined with gamma-aminobutyric acid (GABA) immunocytochemistry. The two global multiglomerular types and two of the oligoglomerular types were GABA-immunoreactive, but the third oligoglomerular type, which innervates the MGC and some ordinary glomeruli, included some GABA-immunonegative neurons, suggesting the existence of a non-GABAergic subtype. These results suggest that the complex neural circuits of the AL are composed of several morphologically different types of LNs, most of which are inhibitory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cne.21528DOI Listing
January 2008

Role of CD28 in fatal autoimmune disorder in scurfy mice.

Blood 2007 Aug 26;110(4):1199-206. Epub 2007 Apr 26.

Immunotherapy Center, Medical College of Georgia, Augusta, USA.

Scurfy mice develop CD4 T-cell-mediated lymphoproliferative disease leading to death within 4 weeks of age. The scurfy mutation causes loss of function of the foxp3 gene (foxp3(sf)), which is essential for development and maintenance of naturally occurring regulatory CD4 T cells (nTregs). In humans, mutations of the foxp3 gene cause immune dysregulation, polyendocrinopathy, enteropathy, and X-linked syndrome (IPEX). In most patients with IPEX and also in scurfy mice, T cells show hyperreactivity and levels of Th1- and Th2-associated cytokines are substantially elevated. We report that removal of CD28 expression rescued scurfy mice from early death. Longer-term surviving CD28-deficient scurfy mice still had lymphoproliferative disorder, but their CD4 T cells showed decreased interferon-gamma and no sign of interleukin-4 or interleukin-10 hyperproduction. Furthermore, injection of CTLA4-Ig to block CD28-B7 interactions substantially improved the survival of scurfy mice by blocking effector T-cell differentiation. These data support the hypothesis that CD28-B7 interactions play a critical role in the etiology of lethal autoimmune disease in scurfy mice by stimulating the differentiation of antigen-activated naive T cells into effector T cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2006-10-054585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1939901PMC
August 2007