Science News | June 3(3), 2008

独立行政法人理化学研究所オミックス基盤研究領域
　# つまり、両方とも理研GSCから長が出たことになるわけね

アルツハイマー病の原因となる酵素の活性調節機構を解明 | 独立行政法人理化学研究所プレスリリース

Crystal Structure of an Active Form of BACE1, an Enzyme Responsible for Amyloid β Protein Production.
Hideaki Shimizu, Asako Tosaki, Kumi Kaneko, Tamao Hisano, Takashi Sakurai, Nobuyuki Nukina.
Mol. Cell. Biol. 28, 3663-3671 (2008) | doi:10.1128/MCB.02185-07

BACE1 (β-secretase) is a transmembrane aspartic protease that cleaves the β-amyloid precursor protein and generates the amyloid β peptide (Aβ). BACE1 cycles between the cell surface and the endosomal system many times and becomes activated interconvertibly during its cellular trafficking, leading to the production of Aβ. Here we report the crystal structure of the catalytically active form of BACE1. The active form has novel structural features involving the conformation of the flap and subsites that promote substrate binding. The functionally essential residues and water molecules are well defined and play a key role in the iterative activation of BACE1. We further describe the crystal structure of the dehydrated form of BACE1, showing that BACE1 activity is dependent on the dynamics of a catalytically required Asp-bound water molecule, which directly affects its catalytic properties. These findings provide insight into a novel regulation of BACE1 activity and elucidate how BACE1 modulates its activity during cellular trafficking.

結晶化ってpHをそんなに厳密に反映させられるんだ…

飲酒と肺がんの発生率との関係について　-- 概要 --

Alcohol and risk of lung cancer among Japanese men: data from a large-scale population-based cohort study, the JPHC study.
Taichi Shimazu, Manami Inoue, Shizuka Sasazuki, Motoki Iwasaki, Norie Kurahashi, Taiki Yamaji, Shoichiro Tsugane, The JPHC Study Group.
Cancer Causes and Control, Online First | DOI:10.1007/s10552-008-9173-2

Objective Although large-scale studies, including meta-analyses, on the association between alcohol consumption and lung cancer have been reported, the risk of lung cancer in extremely high consumption groups (≥450 g ethanol/week) in both current smokers and nonsmokers remains unclear. Here, we investigated the association between alcohol consumption and lung cancer incidence.
Methods We conducted a population-based prospective cohort study in 46,347 Japanese men aged 40–69 years with no history of cancer at baseline in 1990–1994. We used Cox proportional hazards regression analysis to estimate the hazard ratio (HR) and 95% confidence interval (CI) of lung cancer incidence according to alcohol consumption.
Results During the 14-year follow-up period, we documented 651 cases of lung cancer. We found a positive association between alcohol consumption and lung cancer risk confined to current smokers. Compared with occasional drinkers, the multivariate HRs (95% CI) in the highest category (≥450 g ethanol/week) were 1.31 (0.89–1.94) among total participants, 0.58 (0.26–1.30) (p for trend = 0.49) among nonsmokers, and 1.69 (1.05–2.72) (p for trend = 0.02) among current smokers.
Conclusions Among this population with a large variation in alcohol consumption, alcohol consumption was not an independent risk factor for lung cancer except for current smokers.

　# 喫煙者にのみ飲酒と肺ガンの相関が見られたそうです…

脳腫瘍の治療にヘルペスウイルス用のワクチンを利用 | WIRED VISION

Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma.
Duane A. Mitchell, Weihua Xie, Robert Schmittling, Chris Learn, Allan Friedman, Roger E. McLendon, John H. Sampson.
Neuro Oncol 10, 10-18 (2008) | DOI:10.1215/15228517-2007-035

Human cytomegalovirus (HCMV) has been described to be associated with several human malignancies, though the frequency of detection remains controversial. It is unclear whether HCMV plays an active role in malignant tumor progression or becomes reactivated under pathologic conditions that result in chronic inflammation or immunosuppression. In this study, we report on the investigation of detecting HCMV in the tumors and peripheral blood of patients with newly diagnosed glioblastoma multiforme (GBM). Using immunohistochemistry, in situ hybridization, and polymerase chain reaction amplification of viral DNA, the detection of HCMV was investigated in tumor and blood specimens from patients with GBM as well as in the peripheral blood of normal volunteers and patients undergoing craniotomy for diagnoses other than GBM. We found that a high percentage (>90%) of GBM tumors, not surrounding normal brain, are associated with HCMV nucleic acids and proteins. Furthermore, a significant proportion of patients (80%) with newly diagnosed GBM have detectable HCMV DNA in their peripheral blood, while seropositive normal donors and other surgical patients did not exhibit detectable virus, suggesting either a systemic reactivation of HCMV within patients with GBM or shedding of viral DNA from infected tumor cells into the periphery. These results confirm the association of HCMV with malignant gliomas and demonstrate that subclinical HCMV viremia (presence of viral DNA in blood without clinical symptoms of infection) is a previously unrecognized disease spectrum in patients with GBM.

　# 子宮頸ガンの主要因がHPVというのは聞いたことがあったが、多形性膠芽腫にサイトメガロウィルスが関係しているとは知らんかった…

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Masaca's Blog 2

独り言・日記・愚痴・戯言・備忘録・・・。なんとでもお呼び下され(笑)。

Science News | June 3(3), 2008