Selection of Color-Changing and Intensity-Increasing Fluorogenic Probe as Protein-Specific Indicator Obtained via the 10BASEd-T

To obtain a molecular probe for specific protein detection, we have synthesized fluorogenic probe library of vastdiversity on bacteriophage T7 via the gp10 based-thioetherificaion (10BASEd-T). A remarkable color-changing and turning-on probewas selected from the library, and its physicochemical properties upon target-specific binding were obtained. Combination analysesof fluorescence emission titration, isothermal titration calorimetry (ITC), and quantitative saturation-transfer difference (STD) NMRmeasurements followed by in silico docking simulation, rationalized most plausible geometry of the ligand-protein interaction

Küttner's tumor of the sub-mandibular gland associated with fibrosclerosis and follicular hyperplasia of regional lymph nodes: a case report

<p>Abstract</p> <p>Introduction</p> <p>Küttner's tumor is characterized through histology by peri-ductal fibrosis, dense lymphocytic infiltration with lymphoid follicles, loss of acini, and occasional marked sclerosis of the salivary gland. On occasion, Küttner's tumor can be difficult to distinguish from malignant neoplasm.</p> <p>Case presentation</p> <p>A 58-year-old Japanese man was referred to our hospital with a three-month history of a painless swollen mass in the right sub-mandibular region. Histological findings revealed both lymphoid follicles with reactive germinal centers and variously sized lymphoid follicle-like nodules without definitive germinal centers or mantle zones. B-cells of similar size and shape occupied the lymphoid follicle-like nodules and stained positive for B-cell lymphoma. These cells were detected in the polyclonal B-cells by flow cytometric analysis and tested negative for CD10. Unusual B-cell proliferation was observed, but as there was no definitive evidence of B-cell lymphoma, the lesion was diagnosed as Küttner's tumor.</p> <p>Conclusion</p> <p>We report on a rare case of Küttner's tumor associated with fibrosclerosis and atypical lymphoid hyperplasia in both the sub-mandibular gland and regional lymph nodes. Although more cases need to be investigated, our findings might be helpful to further studies seeking to clarify the etiology of idiopathic sclerosing lesions arising in the organs and regional lymph nodes.</p

Validation of radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas: Japanese Orthopaedic Association Committee on Musculoskeletal Tumors Cooperative Study

AbstractBackgroundThe radiographic evaluation of the response to preoperative chemotherapy for bone and soft tissue sarcomas is based mostly on the change in primary tumor size before and after chemotherapy, as is done for many solid cancers. Its prognostic correlation, however, has hardly been validated.MethodsWe conducted a retrospective validation study of the Japanese Orthopaedic Association (JOA) radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas as a JOA Committee on Musculoskeletal Tumors cooperative study. A total of 125 consecutive patients with high-grade bone (n = 77) and soft tissue (n = 48) sarcomas treated with neoadjuvant chemotherapy and definitive surgery in 25 tertiary referral hospitals were selected for the study. We investigated the correlation between the tumor size-based radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas provided by the JOA Committee on Musculoskeletal Tumors (hereafter called the JOA criteria) and the patients’ overall survival using the Kaplan-Meier method and the log-rank test.ResultsThe JOA criteria correlated relatively well with survival for malignant bone tumors (mostly comprising osteosarcoma and Ewing’s sarcoma) but not for soft tissue sarcomas, suggesting that the tumor size-based radiographic evaluation criteria for the response to preoperative chemotherapy in patients with soft tissue sarcomas is invalid.ConclusionsThe JOA criteria, based on the change in primary tumor size, is valid for malignant bone tumors but invalid for soft tissue sarcomas. Other new evaluation modalities of the response to preoperative chemotherapy using innovative functional imaging techniques are needed for soft tissue sarcomas

フィリピン・ルソン島地震の高密度震度分布調査

1990年7月16日午後4時26分(現地時間)にフィリピン・ルソン島の中央部に発生したフィリピン地震(M= 7.8) は，内陸部に発生した最大級の地震であり，延長約120km，水平平均ずれ量約5.0mに及ぶ左横ずれ断層が出現した。震度地は，首都マニラの北北東約110kmのDigdig断層上で，震度の深さは約25kmとされている。本地震において，多数の建物が被災し約2000名の死者と3500名の負傷者が発生し，全壊建物約22000棟，被災者約160万人に及び被害が発生した。この地震による被害は，地震断層に沿った広範囲の地域に発生したが，被害が比較的集中的に発生した地域は，震央近傍の地域より，むしろ上記地震断層の北西方向の末端部の西側に位置している地域に多数の被害建物が認められた。また，Lingayen湾に面した沿岸地域の沖積軟弱地盤地帯においては，顕著な液状化現象が発生し，多数の構造物に被害が認められた。しかし，残念ながら本地震の被災地域における強震観測記録は得られていない。本研究の目的は，アンケートによる震度推定法を用いて本地震の震源域を中心とする広い範囲の地域における震度(MM震度)を可能な限り高密度に推定し，強震記録に代わる情報のひとつとして各地の地震動の強さとその分布状況を推定することである。また，被害地域といえども，ごく狭い地域でさえ被害程度に大きな差を生じることは過去の地震において確認され，今回の地震においてもまた同様の傾向がみられた。そこで，可能な限り高密度の震度分布を推定し，被害分布などともにいわゆるサイミックマイクロゾーニングマップを作成することを最終的な目的としている。本報告は，これまでに分析ができた各地の震度分布の結果を示したのである。その結果，調査地域内の主要都市の推定震度では， La Union 州のAgoo町が最も大きく平均震度(MM震度)で10.7となり，次いでAringay町で9.8，Baguio市で8.8となるO 以下，Dagupan市で8.7，Cabanatuan市で7.8，San Carlos市で7.7，首都Manilaの北側に隣接するQuezon市で6.5と推定された。また，各州や主要都市における震度分布も明かとなっている。本調査により，1990年フィリピン地震の震源域における震度分布がほぼ明かとなり，震度分布は被害分布とよく対応し，地震動の強さを推測する上で重要な情報を提供するものと考えられる

A prospective compound screening contest identified broader inhibitors for Sirtuin 1

Potential inhibitors of a target biomolecule, NAD-dependent deacetylase Sirtuin 1, were identified by a contest-based approach, in which participants were asked to propose a prioritized list of 400 compounds from a designated compound library containing 2.5 million compounds using in silico methods and scoring. Our aim was to identify target enzyme inhibitors and to benchmark computer-aided drug discovery methods under the same experimental conditions. Collecting compound lists derived from various methods is advantageous for aggregating compounds with structurally diversified properties compared with the use of a single method. The inhibitory action on Sirtuin 1 of approximately half of the proposed compounds was experimentally accessed. Ultimately, seven structurally diverse compounds were identified

Unc-51/ATG1 Controls Axonal and Dendritic Development via Kinesin-Mediated Vesicle Transport in the Drosophila Brain

Background:Members of the evolutionary conserved Ser/Thr kinase Unc-51 family are key regulatory proteins that control neural development in both vertebrates and invertebrates. Previous studies have suggested diverse functions for the Unc-51 protein, including axonal elongation, growth cone guidance, and synaptic vesicle transport.Methodology/Principal Findings:In this work, we have investigated the functional significance of Unc-51-mediated vesicle transport in the development of complex brain structures in Drosophila. We show that Unc-51 preferentially accumulates in newly elongating axons of the mushroom body, a center of olfactory learning in flies. Mutations in unc-51 cause disintegration of the core of the developing mushroom body, with mislocalization of Fasciclin II (Fas II), an IgG-family cell adhesion molecule important for axonal guidance and fasciculation. In unc-51 mutants, Fas II accumulates in the cell bodies, calyx, and the proximal peduncle. Furthermore, we show that mutations in unc-51 cause aberrant overshooting of dendrites in the mushroom body and the antennal lobe. Loss of unc-51 function leads to marked accumulation of Rab5 and Golgi components, whereas the localization of dendrite-specific proteins, such as Down syndrome cell adhesion molecule (DSCAM) and No distributive disjunction (Nod), remains unaltered. Genetic analyses of kinesin light chain (Klc) and unc-51 double heterozygotes suggest the importance of kinesin-mediated membrane transport for axonal and dendritic development. Moreover, our data demonstrate that loss of Klc activity causes similar axonal and dendritic defects in mushroom body neurons, recapitulating the salient feature of the developmental abnormalities caused by unc-51 mutations.Conclusions/Significance:Unc-51 plays pivotal roles in the axonal and dendritic development of the Drosophila brain. Unc-51-mediated membrane vesicle transport is important in targeted localization of guidance molecules and organelles that regulate elongation and compartmentalization of developing neurons