Heparan sulfate proteoglycan is an important attachment factor for cell entry of Akabane and Schmallenberg viruses

Akabane (AKAV) and Schmallenberg (SBV) viruses are Orthobunyavirus transmitted by arthropod vectors with a broad cellular tropism in vitro as well as in vivo Both AKAV and SBV cause arthrogryposis-hydranencephaly syndrome in ruminants. The main cellular receptor and attachment factor for entry of these orthobunyaviruses are unknown. Here, we found that AKAV and SBV infections were inhibited by the addition of heparin or enzymatic removal of cell surface heparan sulfates. To confirm this finding, we prepared heparan sulfate proteoglycan (HSPG)-knockout (KO) cells by using a CRISPR/Cas9 system and measured the binding quantities of these viruses to cell surfaces. We observed a substantial reduction in AKAV and SBV binding to cells, limiting the infections by these viruses. These data demonstrate that HSPGs are important cellular attachment factors for AKAV and SBV, at least in vitro, to promote virus replication in susceptive cells. Importance: AKAV and SBV are the etiological agents of arthrogryposis-hydranencephaly syndrome in ruminants, which causes considerable economic losses in the livestock industry. Here, we identified heparan sulfate proteoglycan as a major cellular attachment factor for the entry of AKAV and SBV. Moreover, we found that heparin is a strong inhibitor of AKAV and SBV infections. Revealing the molecular mechanisms of virus-host interactions is critical in order to understand virus biology and develop novel live attenuated vaccines

Network evaluation from the consistency of the graph structure with the measured data

<p>Abstract</p> <p>Background</p> <p>A knowledge-based network, which is constructed by extracting as many relationships identified by experimental studies as possible and then superimposing them, is one of the promising approaches to investigate the associations between biological molecules. However, the molecular relationships change dynamically, depending on the conditions in a living cell, which suggests implicitly that all of the relationships in the knowledge-based network do not always exist. Here, we propose a novel method to estimate the consistency of a given network with the measured data: i) the network is quantified into a log-likelihood from the measured data, based on the Gaussian network, and ii) the probability of the likelihood corresponding to the measured data, named the graph consistency probability (<it>GCP</it>), is estimated based on the generalized extreme value distribution.</p> <p>Results</p> <p>The plausibility and the performance of the present procedure are illustrated by various graphs with simulated data, and with two types of actual gene regulatory networks in <it>Escherichia coli</it>: the SOS DNA repair system with the corresponding data measured by fluorescence, and a set of 29 networks with data measured under anaerobic conditions by microarray. In the simulation study, the procedure for estimating <it>GCP </it>is illustrated by a simple network, and the robustness of the method is scrutinized in terms of various aspects: dimensions of sampling data, parameters in the simulation study, magnitudes of data noise, and variations of network structures.</p> <p>In the actual networks, the former example revealed that our method operates well for an actual network with a size similar to those of the simulated networks, and the latter example illustrated that our method can select the activated network candidates consistent with the actual data measured under specific conditions, among the many network candidates.</p> <p>Conclusion</p> <p>The present method shows the possibility of bridging between the static network from the literature and the corresponding measurements, and thus will shed light on the network structure variations in terms of the changes in molecular interaction mechanisms that occur in response to the environment in a living cell.</p

Study on Learning in Movement Which Demanding Construction of Public Hall : Focusing on the Case of the Construction Movement for “Children’s Culture Hall” of “Kawasaki Oyako Gekijou”

The purpose of this study is to examine the learning function of public hall through focusing on movement of community residents demanding construction of public hall. In this study I picked up the movement for “Children’s Culture Hall” of “Kawasaki Oyako Gekijou”. Through analysis of the documents, activities of “Kawasaki Oyako Gekijou” can be organized into (1) learning and research on the environment and cultural situations in which children are placed, (2) learning on facilities with public halls, (3) appealing to Kawasaki City administration and citizens. The public hall which was targeted was regarded as a base for activities aiming at creation, development and improvement of child culture for residents. As residents worked on the theme of “construction of public hall”, residents turned their eyes from the public hall to the culture and the environment of Kawasaki City. In addition, that brought the expansion of local cultural activities

Mizoribine Inhibits the Proliferation of Renal Stem/Progenitor Cells by G1/S Arrest during Renal Regeneration

Immunosuppressive agents are generally administered to treat kidney diseases. However, it is unclear whether renal stem/progenitor cells are directly affected by the immunosuppressive agents. We used normal rat kidney cells, ureteric bud cells and rat kidney stem/progenitor cells in this study. Mizoribine (MZR), cyclophosphamide (CPA) and cyclosporine (CyA) were added to the culture media of these cells. We evaluated the effects of these immunosuppressive agents on cell proliferation using an electrical cell-substrate impedance sensing system (ECIS) and their effects on the process of renal regeneration using the ischemia-reperfusion (I/R) injury rat model. The ECIS data showed that proliferation of each of the 3 types of cells was significantly suppressed by MZR. MZR treatment enhanced renal tubular injury in ischemia-reperfusion (I/R) injured rats, and significantly decreased levels of M-phase cells and Nestin-positive cells. These results suggested that MZR inhibits the cell cycle of renal stem/progenitor cells;thus, physicians should take note that MZR might affect not only inflammation but also renal regeneration

Sobreposição de esclerose sistêmica e artrite reumatoide: uma entidade clínica distinta?

ResumoIntroduçãoA esclerose sistêmica (ES) é uma enfermidade do tecido conjuntivo de caráter autoimune caracterizada pela tríade de injúria vascular, autoimunidade (celular e humoral) e fibrose tecidual. Estima‐se que a dor musculoesquelética seja uma queixa frequente dos pacientes com ES, que oscila entre 40% e 80%, e principalmente em pacientes com doença difusa precoce. A artrite, clinicamente observada, pode ser uma característica observada na apresentação da ES, frequentemente leva a erros diagnósticos iniciais com artrite reumatoide (AR). No curso da enfermidade, a artrite é observada em 24% a 97% dos pacientes com ES.ObjetivosCorrelacionar a ocorrência ou não de artrite em pacientes com ES da região Centro‐Oeste do Brasil com possíveis manifestações clínicas e laboratoriais distintas observadas em três grupos de pacientes. Relatar a frequência de verdadeira associação entre esclerose sistêmica e artrite reumatoide em pacientes com sinovite clínica e radiologicamente observada.MétodosForam avaliados 61 pacientes portadores de ES subsequentemente a cada três meses durante um ano, para fins de se constatar clinicamente a ocorrência de sinovite e padrões de evolução. Os pacientes foram divididos em três grupos: 41 com ES sem artrite, 16 com ES com artrite e quatro com sobreposição entre ES e AR. Todos os pacientes foram submetidos a exame radiológicos das mãos no fim do estudo.ResultadosDentre todos os pacientes avaliados, encontrou‐se predomínio feminino (98,7%), idade média de 50,94 anos, cor branca (49,2%), forma limitada da doença (47,6%), tempo de diagnóstico entre cinco e 10 anos (47,6%) e tempo de evolução da doença de 8,30 anos. Entre todos os pacientes, 14 (22,9%) apresentavam fator reumatoide (FR) positivo, embora entre aqueles com FR positivo apenas 10 apresentaram artrite durante o seguimento de um ano. O anticorpo anticitrulina (anti‐ CCP) foi feito em 24 pacientes, com positividade em quatro deles (16,7%), observada somente nos pacientes com sobreposição ES/AR. Na comparação das manifestações clínicas entre os grupos de pacientes, observou‐se a maior ocorrência de gastrite e valvulopatia cardíaca em pacientes com ES e artrite, mas não nos demais grupos. No grupo de pacientes com overlap ES/AR e nos pacientes com ES e artrite observou‐se redução importante de qualidade de vida, medida pelo índice HAQ, sobretudo nos pacientes com artrite presente no momento da avaliação clínica. Encontramos alterações radiográficas em 42,6% dos pacientes com ES. Contudo, nos pacientes com sinovite, encontraram‐se alterações radiológicas compatíveis com artrite reumatoide em 50%.ConclusõesEnquanto a frequência de artrite clínica observada em pacientes com esclerose sistêmica foi de 32,8%, a verdadeira sobreposição entre ES e AR foi de 6,6% neste estudo. Observou‐se ainda a frequência de anti‐CCP positivo em 20% dos pacientes com artrite contra nenhum paciente com ES sem artrite.AbstractIntroductionSystemic sclerosis (SSc) is an autoimmune disease of the connective tissue characterized by the triad of vascular injury, autoimmunity (cellular and humoral) and tissue fibrosis. It is estimated that musculoskeletal pain is a common complaint of patients with SSc, ranging from 40 to 80%, and mainly in patients with early diffuse disease. Arthritis, clinically observed, may be a feature seen in the presentation of SSc, often leading to early diagnostic errors with rheumatoid arthritis (RA). In the course of the disease, arthritis is observed in 24 to 97% of patients with SSc.ObjectivesTo correlate the occurrence or nonoccurrence of arthritis in patients with SSc of the Midwest region of Brazil with possible distinct clinical and laboratory manifestations observed in three groups of patients. To report the frequency of true association between systemic sclerosis and rheumatoid arthritis in patients with clinically and radiologically observed synovitis.MethodsSixty‐one SSc patients were subsequently assessed every 3 months within 1 year, in order to clinically observe the occurrence of synovitis and its patterns of progression. Patients were divided into 3 groups: 41 patients with SSc without arthritis, 16 SSc patients with arthritis and 4 patients with overlap of SSc and RA. All patients underwent a radiological examination of the hands at the end of the study.ResultsAmong all patients evaluated, we found a female predominance (98.7%), mean age of 50.94 years, white color (49.2%), limited form of the disease (47.6%), time of diagnosis between 5 to 10 years (47.6%) and duration of the disease of 8.30 years. Among all patients, 14 (22.9%) had positive rheumatoid factor (RF), while among those with positive RF, only 10 patients had arthritis during one‐year follow‐up. The antibody anticitrulline (anti‐CCP) test was performed in 24 patients, being positive in 4 of them (16.7%), with positivity being observed only in patients with SSc/RA overlap. Comparing the clinical manifestations among the groups of patients, there was a higher incidence of gastritis and cardiac valvulopathy in patients with SSc and arthritis, but not in the others. In the group of patients with SSc/RA overlap and in patients with SSc and arthritis a significant reduction in quality of life was observed, measured by HAQ index, especially in patients with arthritis present during clinical evaluation. We found radiographic changes in 42.6% of patients with SSc. However, in patients with synovitis, radiological changes consistent with rheumatoid arthritis were found in 50% of patients.ConclusionsWhile the frequency of clinical arthritis observed in patients with systemic sclerosis was 32.8%, the true overlap between of SSc and RA was 6.6% in this study. We also observed the frequency of positive anti‐CCP in 20% of patients with arthritis versus no patients with SSc without arthritis

Fresh-marketable tomato yields enhanced by moderate weed control and suppressed fruit dehiscence with woodchip mulching

The use of plastic film imposes various environmental risks in agroecosystems. The replacement of plastics with organic materials for mulching has been suggested to enhance the sustainability of agroecosystems. However, whether woodchip mulch can be used for annual crops needs to be verified. We examined the effects of mulberry woodchip mulches on tomato-fruit yields over two successive years. Mulberry is the unique food plant of silkworms, and it will be better if its pruned shoots can be recycled rather than incinerated as waste. Setting three treatments, including woodchip mulch, weed-free and weedy (i.e., unweeded) treatments, we compared the amounts of fresh-marketable and unmarketable tomato fruits. The yields of fresh-marketable tomato fruits in the woodchip mulch treatment were significantly 16–57% higher than those in the weed-free treatment and comparable to those in the weedy treatment. The yields of unmarketable dehiscent tomato fruits in the weed-free treatment were significantly 46–86% higher than those of the other two treatments. The woodchip mulches extensively suppressed the weed density, while the grown weeds became large, preventing strong sunlight exposure and dehiscence of tomato fruits. Current results suggest that woodchips could be a possible alternative to plastics, facilitating climate change mitigation with agroforestry practices

Cardiac Sarcoidosis Culminating in Severe Biventricular Failure

A 59-year-old woman with a history of lung sarcoidosis developed general edema and exertional dyspnea. An electrocardiogram showed first-degree atrioventricular block with complete right bundle branch block. Chest X-ray showed cardiomegaly. Echocardiography showed diffuse and severe hypokinesis of the left ventricle (LV) and biventricular enlargement with severe tricuspid regurgitation. Myocardial scintigraphy disclosed a perfusion defect at the ventricular septum and hypoperfusion at the posterior wall and the apex. On cardiac catheterization, pulmonary capillary wedge pressure, right ventricular, and right atrial pressures were elevated. Coronary angiograms were normal. Myocardial biopsy of the right ventricle histologically revealed epithelioid cell granuloma with infiltration of fibrous cells. The patient's symptom and LV function were improved with conventional medical therapy for heart failure. This is a rare case of cardiac sarcoidosis resulting in biventricular failure

A Case of Cystic Basal Cell Carcinoma Which Shows a Homogenous Blue/Black Area under Dermatoscopy

Basal cell carcinoma (BCC) is the most common skin tumor and contains several different histopathological types. Here, we report a case of cystic basal cell carcinoma, which is relatively rare and might be clinically misdiagnosed. A dermatoscopic examination of the case revealed a homogenous blue/black area usually not seen in BCC. We reviewed 102 BCC cases resected and diagnosed at Sapporo Medical University Hospital between April 2005 and March 2010. Among them, only three were the cystic type