Protein Domain Boundary Predictions: A Structural Biology Perspective

One of the important fields to apply computational tools for domain boundaries prediction is structural biology. They can be used to design protein constructs that must be expressed in a stable and functional form and must produce diffraction-quality crystals. However, prediction of protein domain boundaries on the basis of amino acid sequences is still very problematical. In present study the performance of several computational approaches are compared. It is observed that the statistical significance of most of the predictions is rather poor. Nevertheless, when the right number of domains is correctly predicted, domain boundaries are predicted within very few residues from their real location. It can be concluded that prediction methods cannot be used yet as routine tools in structural biology, though some of them are rather promising

Airway Expression of Smad7, a TGF-β-inducible Inhibitory Molecule of TGF-β Signaling, Decreases after Repeated Airway Antigen Challenges

Transforming growth factor-β (TGF-β) is a profibrogenic cytokine that is involved in airway remodeling largely associated with chronic asthma. Accordingly, regulators of TGF-β activity could also play some role in airway remodeling in asthma. In this study, we investigated expression of Smad 7, a major intracellular inhibitor of TGF-β signaling, in the airways of mouse models of acute and chronic asthma. Sensitized, repeatedly (14 days) ovalbumin (OVA)-inhaled BALB/c mice exhibited evidence of airway remodeling including prominent subepithelial fibrosis associated with airway hyperresponsiveness (AHR) and airway inflammation (chronic asthma model) whereas sensitized, shortly OVA-inhaled BALB/c mice showed only AHR and airway inflammation (acute asthma model). Immunohistochemical analysis showed that Smad 7 immunoreactivity in the airways was increased after the development of acute and chronic asthma models and mainly detected in bronchial epithelial cells. Interestingly, Smad 7 immunoreactivity was significantly less in the airways of chronic asthma model than in those of acute asthma model, which was also confirmed by real-time PCR analysis of Smad 7. In consistent with decreased Smad 7 expression in the airways of chronic asthma model, phosphorylation of Smad 2, a marker of active TGF-β signaling, was increased in bronchial epithelial cells of chronic asthma model when compared with acute asthma model. These results suggest that decreased Smad 7 expression and Smad 2 upregulation in bronchial epithelial cells might result in increased TGF-β activity and contribute to the development of airway remodeling seen in chronic asthma

シンニュウセイ オ タイショウ トシタ キツエン ボウシ キョウイク シコウ ガ タバコ ニ タイスル イシキ ニ アタエル エイキョウ ノ ケントウ

大学入学早期からの喫煙防止教育の大切さがこれまでに指摘されていたが,喫煙防止教育の効果に関してほとんど検討されていない.本研究は,大学新入学時に喫煙防止教育を施行し,その前後の喫煙に対する態度や喫煙防止教育を行う意欲や自信の変化等を検討することを目的とした.2008 年4 月に,新入生74 名(男子54 名,女子20 名)を対象に喫煙防止教育を施行し,教育の直前とその一週間後に同一アンケート調査を行い,PASW Statistics 18.0 for Windows を使用し,c 2 検定及びt 検定を行った.喫煙防止教育後の喫煙者の禁煙に対する関心度や非喫煙者の喫煙に対する関心度には,有意差は見られなかった.さらに,喫煙防止教育を受けた経験が十分あるかという質問に関しては,「タバコの害」と「タバコの依存性」では教育前と有意差は無く,「禁煙指導の方法」に関してのみ,有意に上昇した.しかし,喫煙行動に対する態度に関しては,「医療施設の全面禁煙化」以外の全項目で有意に上昇した.さらに,タバコに関する社会の動きに対する関心度が有意に高まり,喫煙防止教育に対する意欲や自信も有意に上昇した.本研究は長期的な教育効果を検討するには不十分であるが,喫煙防止教育として新入生の意識向上に良い影響を与えた.Several studies have discussed the importance of educatingstudents on smoking prevention during the initial yearsof university education. In this study we examined thechanging perceptions of smoking behavior among freshmenin university just before and after 1 week of education onthe health hazards due to smoking.In April, 2008, 74 freshmen (54 boys and 20 girls) of aparamedical university were provided health education onthe hazards caused by smoking, and the changes in the perceptionsregarding the smoking behavior were examinedby the basis of a questionnaire that was answered by thestudents before and after the education;the same questionnairewas filled both the times. For statistical examination,c 2 test and t test were performed using IBM SPSS(PASW Statistics 18.0) for Windows.Even after educating the students on smoking prevention,there was no significant difference in the attitude ofsmokers toward smoking cessation and that of non-smokerstoward smoking. Although the awareness among thestudents with regard to the health hazards of smoking wasnot significantly different before and after this education,their awareness of the methods to quit smoking had increasedsignificantly. Moreover, the mean values of the differentopinions on the smoking behavior increased significantly.However, one exception was the opinions in themedical institutions that had tobacco-free environments.The mean values that increased the highest after this education,were "Implementation of non-smoking in the entireuniversity" and "The need for effective education that assistsin quitting smoking." Further, after this education, thescore of interest in social activities against smoking increased.Education on anti-smoking is vital for freshmenafter enrollment in a university

PointCloudExplore 2: Visual exploration of 3D gene expression

To better understand how developmental regulatory networks are defined inthe genome sequence, the Berkeley Drosophila Transcription Network Project (BDNTP)has developed a suite of methods to describe 3D gene expression data, i.e.,the output of the network at cellular resolution for multiple time points. To allow researchersto explore these novel data sets we have developed PointCloudXplore (PCX).In PCX we have linked physical and information visualization views via the concept ofbrushing (cell selection). For each view dedicated operations for performing selectionof cells are available. In PCX, all cell selections are stored in a central managementsystem. Cells selected in one view can in this way be highlighted in any view allowingfurther cell subset properties to be determined. Complex cell queries can be definedby combining different cell selections using logical operations such as AND, OR, andNOT. Here we are going to provide an overview of PointCloudXplore 2 (PCX2), thelatest publicly available version of PCX. PCX2 has shown to be an effective tool forvisual exploration of 3D gene expression data. We discuss (i) all views available inPCX2, (ii) different strategies to perform cell selection, (iii) the basic architecture ofPCX2., and (iv) illustrate the usefulness of PCX2 using selected examples

BRCA1-BARD1 associate with the synaptonemal complex and pro-crossover factors and influence RAD-51 dynamics during Caenorhabditis elegans meiosis

During meiosis, the maternal and paternal homologous chromosomes must align along their entire length and recombine to achieve faithful segregation in the gametes. Meiotic recombination is accomplished through the formation of DNA double-strand breaks, a subset of which can mature into crossovers to link the parental homologous chromosomes and promote their segregation. Breast and ovarian cancer susceptibility protein BRCA1 and its heterodimeric partner BARD1 play a pivotal role in DNA repair in mitotic cells; however, their functions in gametogenesis are less well understood. Here we show that localization of BRC-1 and BRD-1 (Caenorhabditis elegans orthologues of BRCA1 and BARD1) is dynamic during meiotic prophase I; they ultimately becoming concentrated at regions surrounding the presumptive crossover sites, co-localizing with the pro-crossover factors COSA-1, MSH-5 and ZHP-3. The synaptonemal complex and PLK-2 activity are essential for recruitment of BRC-1 to chromosomes and its subsequent redistribution towards the short arm of the bivalent. BRC-1 and BRD-1 form in vivo complexes with the synaptonemal complex component SYP-3 and the crossover-promoting factor MSH-5. Furthermore, BRC-1 is essential for efficient stage-specific recruitment/stabilization of the RAD-51 recombinase to DNA damage sites when synapsis is impaired and upon induction of exogenous damage. Taken together, our data provide new insights into the localization and meiotic function of the BRC-1–BRD-1 complex and highlight its essential role in DNA double-strand break repair during gametogenesis.© 2018 Janisiw et a