Evolution, morphology and paleobiology of the pareiasauria and their relatives

Parareptilien stellen ein artenreiches Monophylum paläozoischer und früh-mesozoischer Amnioten dar; sie bilden innerhalb der Reptilien die Schwestergruppe zu den Eureptilien. Pareiasaurier, eine Untergruppe der Parareptilien, sind eine bedeutende Komponente spät-permischer …kosysteme. Jüngst wurde ein Schwestergruppenverhältnis zu den Nycyeroletern entdeckt, mit welchen sie die "Pareiasauromorpha" bilden. Diese Arbeit befasst sich mit der Beschreibung einiger dieser bisher schlecht untersuchten Parareptilien und deren Verwandtschaftsverhältnisse.Der Pareiasaurier Deltavjatia vjatkensis und der Nycteroleter Emeroleter levis aus der russischen Lokalität Kotel''nich werden mithilfe neu entdeckten Materials im Detail beschrieben. Das gut erhaltene Deltavjatja Materials umfasst mehrere Grössenstadien und erlaubt eine Analyse der Wachstumsraten. Eine geometrisch-morphometrische Analyse des Schädeldachs lässt eine allometrische Zunahme von Schnauzenlänge und Postorbitalregion erkennen. Auch wird der historisch erste Pareiasaurier, Parasaurus geinitzi, aus dem oberpermischen Kupferschiefer von Deutschland neu beschrieben. Zudem ergibt eine Neuanalyse der russischen Nycteroleter eine Synonymie von Tokosaurus perforatus und Macroleter poezicus. Eine phylogenetische Analyse unter Verwendung von Parsimonie und bayesischen Methoden ergibt eine basale Stellung von Parasaurus und eine Monophylie der Nycteroleter; letztere wird aber nur durch die Parsimonie unterstützt. Alle phylogenetischen Methoden ergeben jedoch eine Monophylie der Pareiasauromorpha. Eine strato-kladistische Analyse zeigt zudem eine ähnliche Topologie. Eine biogeographische Analyse der Pareiasauromorpha ergibt mehrfache Verbreitungsereignisse nach Russland und China. Diese stimmen überein mit denen anderer oberpermischer Gruppen, jedoch werden nur wenige dieser Ereignisse komplett bei allen Taxa gefunden.Parareptilia is a diverse, yet enigmatic clade of fossil amniotes, sister-group to Eureptilia within Reptilia. Pareiasauria, a widely distributed and speciose parareptile group, was a prominent part of Late Permian ecosystems, yet few taxa have been examined in detail. This work describes some poorly known parareptiles, using this data to assess interrelationships and evaluate evolutionary trends within the clade. A reassessment of a group of derived parareptiles, the Russian ''nycteroleters'', results in the synonymy of Tokosaurus perforatus with Macroleter poezicus. A phylogenetic analysis of parareptilian relationships recovers a ''nycteroleter'' monophyly in the parsimony analysis, but not with Bayesian, with the genus Bashkyroleter paraphyletic in both. A monophyletic clade consisting of the nycteroleters and pareiasaurs, termed Pareiasauromorpha, is supported by all methods. Parasaurus geinitzi von Mayer, 1857 is redescribed and confirmed to be a pareiasaur based on the anatomy of the type specimens and fragmentary material that has subsequently been assigned to the taxon. Well-preserved cranial and postcranial material of the pareiasaur Deltavjatia vjatkensis from Kotel''nich, Russia, is described in detail for the first time, including specimens of radically different size classes. The first geometric morphometric analysis of a parareptile reveals an allometric increase in snout length along with an increase in postorbital length. A reassessment of the relationships of Pareiasauromorpha using different methods of phylogenetic inference recovers similar results. The topologies are not well supported, but are relatively consistent with the stratigraphic record. Biogeographic analysis of pareiasauromorph taxa recovers complex and reticulated patterns of dispersal and vicariance, including multiple dispersal events into both Russia and China; patterns that are consistent with those seen in other Late Permian groups, though few events are shared by all clades

FILTERING SOFTWARE IN JAPANESE PUBLIC LIBRARIES AND THEIR PERFORMANCE

Introduction: This study clarifies the current status of implementing filtering software in Japanese public libraries and their performance.Method: 253 municipal libraries and 47 prefectural libraries that provide Internet terminals to their users were chosen as the target, and a mail survey was conducted from November 2007 to January 2008. We received usable responses from a total of 155 libraries. As for the performance of filtering software, we manually checked 4,640 web pages by using PCs on which i-FILTER and InterSafe were installed. We determined whether they blocked content that “should be blocked" and, conversely, whether they excessively blocked content that should not be blocked.Result: We found that 85.3% of prefectural and 76.9% of municipal libraries installed filtering software. The most chosen software applications were i-FILTER, InterSafe, and CYBERsitter. Among the complaints from users, some mentioned that they could not access the pages of online bookstores, which are considered useful to library users. The survey revealed a trade-off relationship between i-FILTER and InterSafe regarding the blocking rate for harmful pages and the incorrect blocking rate for non-harmful pages. Moreover, block leaks are common for relatively new concepts such as 学校裏サイト (student run school site).Conclusion: Filtering software is now common among public libraries, but vendors’ offerings perform differently. Public libraries should select and set up their software in correspondence with their own information supply policies

Sh3bp2 Gain-Of-Function Mutation Ameliorates Lupus Phenotypes in B6.MRL-Faslpr Mice

SH3 domain-binding protein 2 (SH3BP2) is an adaptor protein that is predominantly expressed in immune cells, and it regulates intracellular signaling. We had previously reported that a gain-of-function mutation in SH3BP2 exacerbates inflammation and bone loss in murine arthritis models. Here, we explored the involvement of SH3BP2 in a lupus model. Sh3bp2 gain-of-function (P416R knock-in; Sh3bp2KI/+) mice and lupus-prone B6.MRL-Faslpr mice were crossed to yield double-mutant (Sh3bp2KI/+Faslpr/lpr) mice. We monitored survival rates and proteinuria up to 48 weeks of age and assessed renal damage and serum anti-double-stranded DNA antibody levels. Additionally, we analyzed B and T cell subsets in lymphoid tissues by flow cytometry and determined the expression of apoptosis-related molecules in lymph nodes. Sh3bp2 gain-of-function mutation alleviated the poor survival rate, proteinuria, and glomerulosclerosis and significantly reduced serum anti-dsDNA antibody levels in Sh3bp2KI/+Faslpr/lpr mice. Additionally, B220+CD4-CD8- T cell population in lymph nodes was decreased in Sh3bp2KI/+Faslpr/lpr mice, which is possibly associated with the observed increase in cleaved caspase-3 and tumor necrosis factor levels. Sh3bp2 gain-of-function mutation ameliorated clinical and immunological phenotypes in lupus-prone mice. Our findings offer better insight into the unique immunopathological roles of SH3BP2 in autoimmune diseases

Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury

Podocyte injury is an independent risk factor for the progression of renal diseases. Semaphorin3A (SEMA3A), expressed in podocytes and tubular cells in the mammalian adult kidneys, has been reported to regulate diverse biological functions and be associated with renal diseases. Here, we investigated pathological roles of SEMA3A signaling on podocyte injury using a doxorubicin (Dox)-induced mouse model and examined the therapeutic effect of SEMA3A-inhibitor (SEMA3A-I). We demonstrated that Dox caused massive albuminuria and podocyte apoptosis as well as an increase of SEMA3A expression in podocytes, all of which were ameliorated with SEMA3A-I treatment. In addition, c-Jun N-terminal kinase (JNK), known as a downstream of SEMA3A signaling, was activated in Dox-injected mouse podocytes while SEMA3A-I treatment partially blocked the activation. In vitro, SEMA3A-I protected against Dox-induced podocyte apoptosis and recombinant SEMA3A caused podocyte apoptosis with activation of JNK signaling. JNK inhibitor, SP600125, attenuated SEMA3A-induced podocyte apoptosis, indicating that the JNK pathway would be involved in SEMA3A-induced podocyte apoptosis. Furthermore, the analysis of human data revealed a positive correlation between levels of urinary SEMA3A and protein, suggesting that SEMA3A is associated with podocyte injury. In conclusion, SEMA3A has essential roles in podocyte injury and it would be the therapeutic target for protecting from podocyte injury

Simulation-based medical education in clinical skills laboratory

Clinical skills laboratories have been established in medical institutions as facilities for simulation-based medical education (SBME). SBME is believed to be superior to the traditional style of medical education from the viewpoint of the active and adult learning theories. SBME can provide a learning cycle of debriefing and feedback for learners as well as evaluation of procedures and competency. SBME offers both learners and patients a safe environment for practice and error. In a full-environment simulation, learners can obtain not only technical skills but also non-technical skills, such as leadership, team work, communication, situation awareness, decision-making, and awareness of personal limitations. SBME is also effective for integration of clinical medicine and basic medicine. In addition, technology-enhanced simulation training is associated with beneficial effects for outcomes of knowledge, skills, behaviors, and patient-related outcomes. To perform SBME, effectively, not only simulators including high-fidelity mannequin-type simulators or virtual-reality simulators but also full-time faculties and instructors as professionals of SBME are essential in a clinical skills laboratory for SBME. Clinical skills laboratory is expected to become an integrated medical education center to achieve continuing professional development, integrated learning of basic and clinical medicine, and citizens’ participation and cooperation in medical education

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

Suppressive effects of transforming growth factor-beta1 produced by hepatocellular carcinoma cell lines on interferon-gamma production by peripheral blood mononuclear cells.

Transforming growth factor-beta1 (TGF-beta1) exerts potent immunosuppressive effects. In this study, we investigated the potential role of TGF-beta1 produced by hepatocellular carcinoma (HCC) cell lines in immunosuppression mechanisms. Using the Mv1Lu cell-growth inhibition assay and an enzyme-linked immunosorbent assay (ELISA), we detected optimal levels of TGF-beta1 in the culture supernatants conditioned by the HCC cell lines PLC/PRF/5, Hep3B, and HepG2. To determine the biological activity of TGF-beta1 in the supernatants, we examined the effects of the culture supernatants on the production of interferon (IFN)-gamma induced during the culture of peripheral blood mononuclear cells (PBMCs) stimulated with interleukin (IL)-12. IFN-gamma production of IL-12-stimulated PBMCs in the 1:1 dilution of the acid-activated conditioned medium of PLC/PRF/5, Hep3B, and HepG2 reduced to 14.7 +/- 0.8, 17.3 +/- 9.0, and 35.9 +/- 14.6%, respectively, compared with the value in the culture with control medium (complete culture medium). These results suggest that HCC cells producing TGF-beta1 may reduce the generation or activation of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, and thus could enhance their ability to escape immune-mediated surveillance.</p

Comparison of Anti-Inflammatory Analgesics for Mechanical Stress-induced Inflammation in a Human Synovial Sarcoma Cell Line

Osteoarthritis is a complicated clinical condition affected by age, mechanical stress, cartilage hypertrophy, cytokines, and genetic predisposition. In this study, we compared the effects of various anti-inflammatory analgesics on mechanical stress-induced inflammation in a synovial sarcoma cell line （SW982 cells）. SW982 cells exposed to mechanical stress by shaking with hydroxyapatite-simulating bone chips were treated with acetaminophen, ketoprofen, triamcinolone acetonide, celecoxib, or neurotrophin for 48hr. The expression of integrin α5β1 receptor, observed in fibroblasts and synovium, was evaluated. Levels of the transcription factor, nuclear factor-κB, the inflammatory cytokine, tumor necrosis factor-α, the proteolytic enzyme, matrix metalloproteinase-3, and prostaglandin E2, which is associated with pain and arachidonate cascade product levels, were measured by ELISA. The expression of integrin α5β1 was significantly increased by mechanical stress. Activation of nuclear factor-κB by mechanical stress was significantly suppressed by celecoxib only. Mechanical stress-induced increases in tumor necrosis factor-α and matrix metalloproteinase-3 levels were significantly suppressed by acetaminophen, triamcinolone acetonide, and neurotrophin. The mechanical stress-induced increase in prostaglandin E2 levels was significantly suppressed by acetaminophen, ketoprofen, and celecoxib. SW982 exposed to mechanical stress is proposed as a model for arthritis, and indeed, the expression of integrin α5β1, a membrane receptor protein that binds to fibronectin and the extracellular matrix, and is involved in cell proliferation, differentiation, and neovascularization in osteoarthritis, was significantly upregulated. Following evaluation using this model, acetaminophen was found to possess anti-inflammatory, analgesic, and joint-destruction suppression properties. This drug may, therefore, have applications in the treatment of mechanical stress-induced inflammation

Vaginal Lymphoma with Immune Thrombocytopenic Purpura: An Unusual Case Report

The female genital tract is rarely the initial site of presentation in lymphoma or leukemia. We report a case of non-Hodgkin's lymphoma (NHL) presenting initially in the vagina. The patient, a 75-year-old woman, had a history of immune thrombocytopenic purpura (ITP). She presented with a chief complaint of genital bleeding and introital pain. On transvaginal ultrasonography, a vaginal tumor with an irregular wall was detected, and the internal echo showed a hypoechoic and echogenic pattern. Ultrasonography and magnetic resonance imaging (MRI) suggested that the vaginal tumor was likely to be a hematoma or a hemorrhagic tumor arising from ITP. Incision and resection for a hematoma or a hemorrhagic tumor were carried out in response to genital bleeding, introital pain, and pathological diagnosis. Postoperative microscopic examination confirmed that the tumor was a vaginal NHL. The final diagnosis using the Ann Arbor staging system was high-stage (stage IV) NHL. The patient received chemotherapy, and she remains in remission for 42 months after treatment