MRN complex is an essential effector of DNA damage repair

Genome stability can be threatened by both endogenous and exogenous agents.Organisms have evolved numerous mechanisms to repair DNA damage,including homologous recombination(HR)and non-homologous end joining(NHEJ).Among the factors associated with DNA repair,the MRE11-RAD50-NBS1(MRN)complex(MRE11-RAD50-XRS2 in Saccharomyces cerevisiae)plays important roles not only in DNA damage recognition and signaling but also in subsequent HR or NHEJ repair.Upon detecting DNA damage,the MRN complex activates signaling molecules,such as the protein kinase ataxia-telangiectasia mutated(ATM),to trigger a broad DNA damage response,including cell cycle arrest.The nuclease activity of the MRN complex is responsible for DNA end resection,which guides DNA repair to HR in the presence of sister chromatids.The MRN complex is also involved in NHEJ,and has a species-specific role in hairpin repair.This review focuses on the structure of the MRN complex and its function in DNA damage repair.     

Detection of human papillomavirus in oropharyngeal squamous cell carcinoma

Worldwide there has been a significant increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) etiologically attributed to oncogenic human papillomavirus (HPV). Reliable and accurate identification and detection tools are important as the incidence of HPV-related cancer is on the rise. Several HPV detection methods for OPSCC have been developed and each has its own advantages and disadvantages in regard to sensitivity, specificity, and technical difficulty. This review summarizes our current knowledge of molecular methods for detecting HPV in OPSCC, including HPV DNA/RNA polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), p16 immunohistochemistry (IHC), and DNA/RNA in situ hybridization (ISH) assays. This summary may facilitate the selection of a suitable method for detecting HPV infection, and therefore may help in the early diagnosis of HPV-related carcinoma to reduce its mortality, incidence, and morbidity.     

‘Is it like one of those infectious kind of things?’ The importance of educating young people about HPV and HPV vaccination at school

Abstract

The National Human Papillomavirus (HPV) Vaccination Program in Australia commenced in 2007 for girls and in 2013 for boys, using the quadrivalent HPV [4vHPV] vaccine. In Australia, students are primarily vaccinated en masse, on school grounds, after parental/guardian consent is obtained. Students most often receive little, or no, education at school about HPV or HPV vaccination prior to immunisation. There is also some uncertainty about where young people can and should obtain reliable information about the vaccine, outside of school. We conducted a cluster randomised controlled trial of a complex intervention in schools. This study aimed to improve: (1) student knowledge about HPV vaccination; (2) psycho-social outcomes and (3) vaccination uptake. In this paper, we briefly outline our educational intervention and discuss its implementation by educators including facilitators and barriers. We also discuss the study findings pertaining to student knowledge about HPV and HPV vaccination and their attitudes to vaccination across control and intervention schools. Study results showed students in intervention schools demonstrate greater knowledge and understanding of HPV and HPV vaccination. Greater knowledge and understanding of HPV and HPV vaccination appeared to promote positive attitudes towards vaccination and supported confidence with vaccination.     

Role of deubiquitinating enzymes in DNA double-strand break repair

DNA is the hereditary material in humans and almost all other organisms. It is essential for maintaining accurate transmission of genetic information. In the life cycle, DNA replication, cell division, or genome damage, including that caused by endogenous and exogenous agents, may cause DNA aberrations. Of all forms of DNA damage, DNA double-strand breaks(DSBs) are the most serious. If the repair function is defective, DNA damage may cause gene mutation, genome instability, and cell chromosome loss, which in turn can even lead to tumorigenesis. DNA damage can be repaired through multiple mechanisms. Homologous recombination(HR) and non-homologous end joining(NHEJ) are the two main repair mechanisms for DNA DSBs. Increasing amounts of evidence reveal that protein modifications play an essential role in DNA damage repair.Protein deubiquitination is a vital post-translational modification which removes ubiquitin molecules or polyubiquitinated chains from substrates in order to reverse the ubiquitination reaction. This review discusses the role of deubiquitinating enzymes(DUBs) in repairing DNA DSBs. Exploring the molecular mechanisms of DUB regulation in DSB repair will provide new insights to combat human diseases and develop novel therapeutic approaches.     

拓扑异构酶Ⅰ抑制剂介导的DNA损伤、修复和检验点应答

拓扑异构酶Ⅰ在DNA翻译和转录过程中催化单链DNA的断裂和连接,从而松弛DNA超螺旋,促进复制与转录的进行．拓扑异构酶Ⅰ抑制剂能够阻断DNA链的再连接,结果导致TopⅠ断裂复合物的积累,抑制复制和转录,造成DNA损伤,从而激活DNA损伤检验点,抑制细胞生长和诱发凋亡。喜树碱是最早发现、也是最重要和最广泛使用的拓扑异构酶Ⅰ抑制剂．细胞周期中DNA损伤、修复和检验点应答的分子机制是目前生命科学研究热点,而喜树碱已成为进行相关研究的重要的药理学工具．     

Predictors of Information Seeking about the HPV Vaccine From Parents and Doctors Among Young College Women

This study applied the theory of motivated information management (TMIM) to predict young women's intentions to seek information about the HPV vaccine from their doctors and parents. A sample of 215 women aged 18–25 who have not yet received their HPV vaccinations completed a survey measuring their HPV and cervical cancer risk perceptions, TMIM-related variables (i.e., uncertainty discrepancy, anxiety, outcome expectancy, efficacy, information-seeking intent), and HPV vaccination intentions. Results indicate that positive outcome expectancies, anxiety about uncertainty discrepancy, and HPV risk perception were significant predictors of HPV vaccine information-seeking intent, which in turn predicted HPV vaccination intent.     

Identifying Health Beliefs Influencing Hispanic College Men's Willingness to Vaccinate against HPV

This study identifies health beliefs influencing Hispanic college men's human papillomavirus (HPV) vaccine uptake decision making processes. Hispanic college men were interviewed about their HPV vaccine knowledge, and information seeking behaviors. Overall, participants did not view HPV infection or vaccination as an immediate concern or priority; belief that it was a virus that only affected women, and a sense of invulnerability informed their positions. Despite these issues, most men were willing to consider getting the HPV vaccine if they received more education from health care providers, and cost concerns were addressed. These findings pointed to gaps in our understandings of Hispanic college men's HPV vaccination beliefs and provided insight into the importance of integrating this population's unique beliefs into campus health providers efforts aimed at increasing vaccination rates.     

无党派代表人士的代表性问题研究

无党派代表人士是中国政治生活中的一支重要力量。作为代为表达者,应当具有表率性、代理性和表达性。通过对H市和S县政协委员的个案研究,可以看到无党派委员正在发挥越来越大的参政议政作用,但也存在代理性不足和表达性不够的问题,总体上属于象征代理,而不是实质代理。如何使无党派代表人士从象征代理转变为实质代理,以发挥更大作用,这是摆在我们面前的一个重大课题。     

Perception of teacher education and professional identity among novice teachers

This study examines student teachers’ perceptions of teacher education and its contribution to their professional life, when they become novice teachers during their internship period. The sample comprised 97 student teachers in their fourth year of studies for a BEd degree. Data were collected through questionnaires which included both a structured and an open‐ended part, with regard to five aspects of the teaching profession and teacher education: motivation for teaching, conceptions of teaching–learning, roles of teachers, components of teacher education, and agents of training. Prominent among the findings regarding the motivational aspects of teaching, is a perception of the profession as granting intrinsic rewards. Teaching is perceived as according self‐realisation, providing a sense of purpose and mission, and enabling lifelong development. The component perceived as most important to the teacher’s role is delivering universal values. Findings regarding perception of learning–teaching processes reveal a preference for a constructivist approach.     

DNA-damage response network at the crossroads of cell-cycle checkpoints,cellular senescence and apoptosis

Tissue homeostasis requires a carefully-orchestrated balance between cell proliferation, cellular senescence and cell death. Cells proliferate through a cell cycle that is tightly regulated by cyclin-dependent kinase activities. Cellular senescence is a safeguard program limiting the proliferative competence of cells in living organisms. Apoptosis eliminates unwanted cells by the coordinated activity of gene products that regulate and effect cell death. The intimate link between the cell cycle, cellular senescence, apoptosis regulation, cancer development and tumor responses to cancer treatment has become eminently apparent. Extensive research on tumor suppressor genes, oncogenes, the cell cycle and apoptosis regulatory genes has revealed how the DNA damage-sensing and -signaling pathways, referred to as the DNA-damage response network, are tied to cell proliferation, cell-cycle arrest, cellular senescence and apoptosis. DNA-damage responses are complex, involving ＂sensor＂ proteins that sense the damage, and transmit signals to ＂transducer＂ proteins, which, in turn, convey the signals to numerous ＂effector＂ proteins implicated in specific cellular pathways, including DNA repair mechanisms, cell-cycle checkpoints, cellular senescence and apoptosis. The Bcl-2 family of proteins stands among ＂the mos＂t crucial regula＂tors of apop＂tosis and performs vi＂tal func＂tions in deciding whether a cell will live or die after cancer chemotherapy and irradiation. In addition, several studies have now revealed that members of the Bcl-2 family also interface with the cell cycle, DNA repair/recombination and cellular senescence, effects that are generally distinct from their function in apoptosis. In this review, we report progress in understanding the molecular networks that regulate cell-cycle checkpoints, cellular senescence and apoptosis after DNA damage, and discuss the influence of some Bcl-2 family members on cell-cycle checkpoint regulation.     

‘I connected so well with it’: a teen mother talks about reading

In this paper, one 19‐year‐old married mother who was sexually abused when younger discusses the painful and important role reading has played in her life. By using narrative discourse analysis, I parse the young mother’s spoken narrative and illuminate the emotions that cluster around her reading experiences. I discover that she has used reading as a way to make sense of the traumatic experiences of her childhood. I discover as well that, though she evidences immaturity, her moral thinking – refined through her roles as daughter, mother, and wife – is more nuanced than are the texts she is able to read. The questions I ask about her relationship to these books can be generalized to many non‐traditional students going to high schools, or reading in book clubs, today.     

Roles of assessment in secondary education: Participant perspectives

Performance pressure at both the institutional and individual level of secondary education has been identified as a pressure that is acknowledged all over Europe and raises questions about the extent to which agents in lower and upper secondary education interpret assessment in terms of either control or learning, or perhaps both. Drawing on empirical findings from two case studies in Denmark, the article focuses on the social roles of educational evaluation and assessment, and discusses the ways in which the local level interpretations of policy demands influence teaching and learning in secondary education. To enable an analysis of the understanding of different agents in the field, the article combines important sociological thinking with the basic distinction between assessment of programmes and assessment of individuals. Presuming that assessment practices bear the traces of the social structure that they both express and reproduce, the aim of this paper is to interrogate how the agents view and interpret such practices.     

高危型人乳头瘤病毒在宫颈病变筛查中的临床价值

目的探讨高危型人乳头瘤病毒（HPV）在宫颈病变筛查中的临床价值。方法利用宫颈液基细胞学（TCT）检测4类宫颈病变病人，包括ASC-US，LSIL，ASC-H和HSIL，运用DNA基因捕获技术（HC2）检测上述4类病人的HPV值，并分析HPV值与各类宫颈病变病人的关系。结果4类宫颈病变病人中，HPV阳性检出率平均为38％，其中HSIL病人中，HPV阳性检出率最高，同时HPV阳性值最高。结论宫颈液基细胞学联合HPV—DNA检测在宫颈癌癌前病变筛查中具有重要的临床应用价值。     

CDC25在细胞周期运行和细胞周期检验点应答中的作用和调控机制

细胞分裂周期运行和不同时相的转换通过CDC25磷酸酶去磷酸化和激活周期蛋白依赖性激酶(CDK)复合物来调控.在哺乳动物中发现3种CDC25同工物:CDC25A、CDC25B和CDC25C.早期认为在特定的细胞周期时相CDC25的3个同工物间没有功能上的重叠,然而最近发现多个CDC25同工物协同调节每个细胞周期转换过程.CDC25的活性通过多种在某种程度上重叠的机制严格调控,包括细胞内含量、亚细胞定位和磷酸化状态.CDC25也是细胞周期检验点应答中的关键调节因子,而CDC25B在检验点诱导的G2-M阻滞的恢复中起作用.未来对CDC25调控机制的阐明,将有助于发展出以CDC25为靶目标的、更为有效的抗肿瘤药物.     

Herding cats or getting heard: The SENCo–teacher dynamic and its impact on teachers' classroom practice

This article is based on two key findings of doctoral research into the impact that Special Educational Needs Coordinators (SENCos) in England have on teachers' skills when addressing the needs of children with SEN in mainstream primary schools. I use data from questionnaires and interviews with SENCos, teachers and headteachers to argue that key indicators for successful teaching of children with SEN include SENCos skilling teachers in their roles as ‘agents of change’ in relation to SENCos' views of their teaching colleagues, as well as the evolving nature of their own professional identity.     

ATM技术的最新研究进展及其应用

介绍了ATM的交换原理、ATM的应用及其最新研究进展。其未来的发展趋势是采用IP overATM技术方案及多协议标记交换MPLS等技术,挖掘纯ATM的潜力,大力降低成本。     

用例驱动需求建模过程的探讨

需求分析是软件生命周期中的一个重要阶段。用例是一种描述系统需求的方法。用例建模主要是分离出系统活动的参与者和用例,用例模型易于被不同的角色所理解。通过一个ATM系统的实例说明了如何寻找用例,如何构建用例模型以及用例规约,通过“提款”的活动图实现了对用例的进一步求精,展现了用例驱动需求建模的全过程,明确了用例建模的过程要避免功能分解和数据流建模;用例分析技术是一种合成技术;用例建模的核心是用例描述;不要描述系统之外的情况。     

Coping with difficult teachers

Conclusion In conclusion, this article has briefly reviewed the findings of the media management survey and has examined coping strategies. While it is true that the major obstacle to your fulfillment and feeling of well-being and excitement at work may or may not be difficult teachers, work is an evolving interaction between yourself and others. It is probably one of the most important roles in your life. An analysis of your management style and personality traits, along with a caring, understanding attitude toward staff and teachers, can go a long way in facilitating teamwork and an effective school media services program.     

Family counseling in the Netherlands for Turkish-origin parents of deaf children with a cochlear implant

Cultural elements such as language, beliefs about health, and family context play important roles in the uptake of rehabilitation and treatment of deafness. Because of cultural issues, minority groups often do not receive optimal care. Focusing on the Netherlands, the researchers explored how the rehabilitation and counseling of deaf children of Turkish-origin parents can be improved. The most important findings were that (a) most parents initially did not believe their child was deaf and regretted later that they did not start hearing rehabilitation earlier; (b) parents had little confidence in the Dutch health care system and sought a second opinion from a medical doctor of their own national origin; (c) parents did not know how to be actively involved in the care of their deaf child. Implications for practice aimed at improving rehabilitation and counseling for these children are described.