Increased complexity of mushroom body Kenyon cell subtypes in the brain is associated with behavioral evolution in hymenopteran insects

In insect brains, the mushroom bodies (MBs) are a higher-order center for sensory integration and memory. Honeybee (Apis mellifera L.) MBs comprise four Kenyon cell (KC) subtypes: class I large-, middle-, and small-type, and class II KCs, which are distinguished by the size and location of somata, and gene expression profiles. Although these subtypes have only been reported in the honeybee, the time of their acquisition during evolution remains unknown. Here we performed in situ hybridization of tachykinin-related peptide, which is differentially expressed among KC subtypes in the honeybee MBs, in four hymenopteran species to analyze whether the complexity of KC subtypes is associated with their behavioral traits. Three class I KC subtypes were detected in the MBs of the eusocial hornet Vespa mandarinia and the nidificating scoliid wasp Campsomeris prismatica, like in A. mellifera, whereas only two class I KC subtypes were detected in the parasitic wasp Ascogaster reticulata. In contrast, we were unable to detect class I KC subtype in the primitive and phytophagous sawfly Arge similis. Our findings suggest that the number of class I KC subtypes increased at least twice – first with the evolution of the parasitic lifestyle and then with the evolution of nidification

Kenyon Cell Subtypes/Populations in the Honeybee Mushroom Bodies: Possible Function Based on Their Gene Expression Profiles, Differentiation, Possible Evolution, and Application of Genome Editing

Mushroom bodies (MBs), a higher-order center in the honeybee brain, comprise some subtypes/populations of interneurons termed as Kenyon cells (KCs), which are distinguished by their cell body size and location in the MBs, as well as their gene expression profiles. Although the role of MBs in learning ability has been studied extensively in the honeybee, the roles of each KC subtype and their evolution in hymenopteran insects remain mostly unknown. This mini-review describes recent progress in the analysis of gene/protein expression profiles and possible functions of KC subtypes/populations in the honeybee. Especially, the discovery of novel KC subtypes/populations, the “middle-type KCs” and “KC population expressing FoxP,” necessitated a redefinition of the KC subtype/population. Analysis of the effects of inhibiting gene function in a KC subtype-preferential manner revealed the function of the gene product as well as of the KC subtype where it is expressed. Genes expressed in a KC subtype/population-preferential manner can be used to trace the differentiation of KC subtypes during the honeybee ontogeny and the possible evolution of KC subtypes in hymenopteran insects. Current findings suggest that the three KC subtypes are unique characteristics to the aculeate hymenopteran insects. Finally, prospects regarding future application of genome editing for the study of KC subtype functions in the honeybee are described. Genes expressed in a KC subtype-preferential manner can be good candidate target genes for genome editing, because they are likely related to highly advanced brain functions and some of them are dispensable for normal development and sexual maturation in honeybees

Loxoprofen Sodium, a Non-Selective NSAID, Reduces Atherosclerosis in Mice by Reducing Inflammation

Recently, it is suggested that the use of nonsteroidal anti-inflammatory drugs (NSAID) may contribute to the occurrence of cardiovascular events, while the formation of atherosclerotic lesions is related to inflammation. Loxoprofen sodium, a non-selective NSAID, becomes active after metabolism in the body and inhibits the activation of cyclooxygenase. We fed apoE−/− mice a western diet from 8 to 16 weeks of age and administered loxoprofen sodium. We measured atherosclerotic lesions at the aortic root. We examined serum levels of cholesterol and triglycerides with HPLC, platelet aggregation, and urinary prostaglandin metabolites with enzyme immune assay. Atherosclerotic lesion formation was reduced to 63.5% and 41.5% as compared to the control in male and female apoE−/− mice treated with loxoprofen sodium respectively. Urinary metabolites of prostaglandin E2, F1α, and thromboxane B2, and platelet aggregation were decreased in mice treated with loxoprofen sodium. Serum levels of cholesterol and triglycerides were not changed. We conclude that loxoprofen sodium reduced the formation of early to intermediate atherosclerotic lesions at the proximal aorta in mice mediated by an anti-inflammatory effect

Case-based similar image retrieval for weakly annotated large histopathological images of malignant lymphoma using deep metric learning

In the present study, we propose a novel case-based similar image retrieval (SIR) method for hematoxylin and eosin (H&E)-stained histopathological images of malignant lymphoma. When a whole slide image (WSI) is used as an input query, it is desirable to be able to retrieve similar cases by focusing on image patches in pathologically important regions such as tumor cells. To address this problem, we employ attention-based multiple instance learning, which enables us to focus on tumor-specific regions when the similarity between cases is computed. Moreover, we employ contrastive distance metric learning to incorporate immunohistochemical (IHC) staining patterns as useful supervised information for defining appropriate similarity between heterogeneous malignant lymphoma cases. In the experiment with 249 malignant lymphoma patients, we confirmed that the proposed method exhibited higher evaluation measures than the baseline case-based SIR methods. Furthermore, the subjective evaluation by pathologists revealed that our similarity measure using IHC staining patterns is appropriate for representing the similarity of H&E-stained tissue images for malignant lymphoma

Exceptionally high incidence of symptomatic grade 2–5 radiation pneumonitis after stereotactic radiation therapy for lung tumors

<p>Abstract</p> <p>Background</p> <p>To determine the usefulness of dose volume histogram (DVH) factors for predicting the occurrence of radiation pneumonitis (RP) after application of stereotactic radiation therapy (SRT) for lung tumors, DVH factors were measured before irradiation.</p> <p>Methods</p> <p>From May 2004 to April 2006, 25 patients were treated with SRT at the University of Tokyo Hospital. Eighteen patients had primary lung cancer and seven had metastatic lung cancer. SRT was given in 6–7 fields with an isocenter dose of 48 Gy in four fractions over 5–8 days by linear accelerator.</p> <p>Results</p> <p>Seven of the 25 patients suffered from RP of symptomatic grade 2–5 according to the NCI-CTC version 3.0. The overall incidence rate of RP grade2 or more was 29% at 18 months after completing SRT and three patients died from RP. RP occurred at significantly increased frequencies in patients with higher conformity index (CI) (p = 0.0394). Mean lung dose (MLD) showed a significant correlation with V₅–V₂₀(irradiated lung volume) (p < 0.001) but showed no correlation with CI. RP did not statistically correlate with MLD. MLD had the strongest correlation with V₅.</p> <p>Conclusion</p> <p>Even in SRT, when large volumes of lung parenchyma are irradiated to such high doses as the minimum dose within planning target volume, the incidence of lung toxicity can become high.</p

Circulating KCNH2 Current-Activating Factor in Patients with Heart Failure and Ventricular Tachyarrhythmia

It is estimated that approximately half of the deaths in patients with HF are sudden and that the most likely causes of sudden death are lethal ventricular tachyarrhythmias such as ventricular tachycardia (VT) or fibrillation (VF). However, the precise mechanism of ventricular tachyarrhythmias remains unknown. The KCNH2 channel conducting the delayed rectifier K(+) current (I(Kr)) is recognized as the most susceptible channel in acquired long QT syndrome. Recent findings have revealed that not only suppression but also enhancement of I(Kr) increase vulnerability to major arrhythmic events, as seen in short QT syndrome. Therefore, we investigated the existence of a circulating KCNH2 current-modifying factor in patients with HF.We examined the effects of serum of HF patients on recombinant I(Kr) recorded from HEK 293 cells stably expressing KCNH2 by using the whole-cell patch-clamp technique. Study subjects were 14 patients with non-ischemic HF and 6 normal controls. Seven patients had a history of documented ventricular tachyarrhythmias (VT: 7 and VF: 1). Overnight treatment with 2% serum obtained from HF patients with ventricular arrhythmia resulted in a significant enhancement in the peaks of I(Kr) tail currents compared to the serum from normal controls and HF patients without ventricular arrhythmia.Here we provide the first evidence for the presence of a circulating KCNH2 channel activator in patients with HF and ventricular tachyarrhythmias. This factor may be responsible for arhythmogenesis in patients with HF

Active gas features in three HSC-SSP CAMIRA clusters revealed by high angular resolution analysis of MUSTANG-2 SZE and XXL X-ray observations

International audienceWe present results from simultaneous modelling of high angular resolution GBT/MUSTANG-2 90 GHz Sunyaev–Zel’dovich effect (SZE) measurements and XMM-XXL X-ray images of three rich galaxy clusters selected from the HSC-SSP Survey. The combination of high angular resolution SZE and X-ray imaging enables a spatially resolved multicomponent analysis, which is crucial to understand complex distributions of cluster gas properties. The targeted clusters have similar optical richnesses and redshifts, but exhibit different dynamical states in their member galaxy distributions: a single-peaked cluster, a double-peaked cluster, and a cluster belonging to a supercluster. A large-scale residual pattern in both regular Compton-parameter y and X-ray surface brightness distributions is found in the single-peaked cluster, indicating a sloshing mode. The double-peaked cluster shows an X-ray remnant cool core between two SZE peaks associated with galaxy concentrations. The temperatures of the two peaks reach ∼20–30 keV in contrast to the cool core component of ∼2 keV, indicating a violent merger. The main SZE signal for the supercluster is elongated along a direction perpendicular to the major axis of the X-ray core, suggesting a minor merger before core passage. The and y distributions are thus perturbed at some level, regardless of the optical properties. We find that the integrated Compton y parameter and the temperature for the major merger are boosted from those expected by the weak-lensing mass and those for the other two clusters show no significant deviations, which is consistent with predictions of numerical simulations

LPS変異体であるRe-LPSはリウマチ滑膜細胞培養におけるLPS混入の検出に有用である

内容の要約広島大学(Hiroshima University)博士(医学)Doctor of Philosophy in Medical Sciencedoctora

Oscillation Characteristics of an Artificial Cochlear Sensory Epithelium Optimized for a Micrometer-Scale Curved Structure

Based on the modern microelectromechanical systems technology, we present a revolutionary miniaturized artificial cochlear sensory epithelium for future implantation tests on guinea pigs. The device was curved to fit the spiral structure of the cochlea and miniaturized to a maximum dimension of <1 mm to be implanted in the cochlea. First, the effect of the curved configuration on the oscillation characteristics of a trapezoidal membrane was evaluated using the relatively larger devices, which had a trapezoidal and a comparable curved shape designed for high-precision in vitro measurements. Both experimental and numerical analyses were used to determine the resonance frequencies and positions, and multiple oscillation modes were clearly observed. Because the maximum oscillation amplitude positions, i.e., the resonance positions, differed depending on the resonance frequencies in both trapezoidal and curved membrane devices, the sound frequency was determined based on the resonance position, thus reproducing the frequency selectivity of the basilar membrane in the organ of Corti. Furthermore, the resonance frequencies and positions of these two devices with different configurations were determined to be quantitatively consistent and similar in terms of mechanical dynamics. This result shows that despite a curved angle of 50–60°, the effect of the curved shape on oscillation characteristics was negligible. Second, the nanometer-scale oscillation of the miniaturized device was successfully measured, and the local resonance frequency in air was varied from 157 to 277 kHz using an experimental system that could measure the amplitude distribution in a two-dimensional (2D) plane with a high accuracy and reproducibility at a high speed. The miniaturized device developed in this study was shown to have frequency selectivity, and when the device was implanted in the cochlea, it was expected to discriminate frequencies in the same manner as the basilar membrane in the biological system. This study established methods for fabricating and evaluating the miniaturized device, and the proposed miniaturized device in a curved shape demonstrated the feasibility of next-generation cochlear implants