抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , کتابخانه مرکزی دانشگاه علوم پزشکی تهران

WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues

Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.

Inflammation and cancer

Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets

The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

P.I.3 Recent advances in defective prelamin A associated syndromes

Protease genes are involved in multiple steps of cancer progression, including cell growth, migration and angiogenesis. These genes are valuable as prognostic and/or diagnostic markers of disease and are potential therapeutic targets.

We used TaqMan® real-time quantitative PCR to conduct the first detailed quantitative expression profiling of the entire family of metalloprotease and serine protease genes and their inhibitors in breast cancer (over 380 genes). Using a bank of 60 samples (50 cancer and 10 normal mammary tissue) collected at the Norfolk and Norwich University Hospital [1] we have identified a number of genes that show significant disregulation in tumour samples compared with normal breast tissue. Expression correlates either positively or negatively with tumour grade in many genes.

A further cohort of 229 Dutch patients with more extensive clinical history [2] was profiled in a subset of the metalloproteinase genes. Among the genes that showed significant aberrant expression, Matrix metalloproteinase-8 (MMP8) emerged as a candidate to play a protective role during tumour progression. MMP8 was found to have significant prognostic value and was strongly correlated with prolonged survival. MMP8 is prognostic as a continuous variable for relapse-free survival (hazard ratio = 0.76, P = 0.045) and for overall survival (hazard ratio = 0.69, P = 0.025). Expression of MMP8 also correlated with lymph node involvement, reduced expression equating to greater nodal spread (P = 0.001). Expression of MMP8 was independent of tumour grade. These data show that MMP8 is prognostic in breast cancer, and suggest that the function of MMP8 antagonizes metastasis.

/pdf/matrix-metalloproteinase-8-is-a-regulator-of-the-clinical-4u0joijs30.pdf

Matrix metalloproteinase-8 is a regulator of the clinical aggressiveness of mammary tumours

Risk Factors Associated with Chronic Lymphocytic Leukaemia in a Spanish Case Control Study (MCC Spain) Y. Benavente, D. Casabonne, C. Robles, L. Costas, M. Aymerich, R. Peiro-Perez, I. GomezAcebo, A. Lopez Guillermo, A. Tardon, A. Salar, M. Pollan, M. Kogevinas, C. LopezOtin, E. Campo, S. denome Pe Sanjose for the MCC Spain and ICGC CLL Genome Project Consortium Unit of Infections and Cancer (UNIC), Cancer Epidemiology Research Programme, Institut Catala d’Oncologia, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain; CIBER de Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain; Hematopathology Section, Department of Pathology, Hospital Clinic, Institut d’Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Barcelona, Spain; Public Health Research Centre (CSISP), Valencia, Spain; Preventive Medicine and Public Health Department, Faculty of Medicine, University of Cantabria, Santander, Spain; Department of Hematology, Hospital Clinic, University of Barcelona, Barcelona, Spain; Molecular Epidemiology Cancer Unit, University Institute of Oncology, University of Oviedo, Oviedo, Spain; Department of Clinical Hematology, Hospital Universitari del Mar, Barcelona, Spain; Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain; Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; IMIM (Hospital del Mar Research Institute), Barcelona, Spain; National School of Public Health, Athens, Greece; Instituto Universitario de Oncologia, Department of Biochemistry and Molecular Biology, Oviedo University, Oviedo, Spain

https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)00369-7/pdf

3.10 Risk Factors Associated with Chronic Lymphocytic Leukaemia in a Spanish Case−Control Study (MCC−Spain)

Chapter 412 – Cathepsin O

Background Personalized precision medicine represents a paradigm shift and a new reality for the health care system in Spain, with training being fundamental for its full implementation and application in clinical practice. In this sense, health care professionals face educational challenges related to the acquisition of competencies to perform their professional practice optimally and efficiently in this new environment. The definition of competencies for health care professionals provides a clear guide on the level of knowledge, skills, and attitudes required to adequately carry out their professional practice. In this context, this acquisition of competencies by health care professionals can be defined as a dynamic and longitudinal process by which they use knowledge, skills, attitudes, and good judgment associated with their profession to develop it effectively in all situations corresponding to their field of practice. Objective This report aims to define a proposal of essential knowledge domains and common competencies for all health care professionals, which are necessary to optimally develop their professional practice within the field of personalized precision medicine as a fundamental part of the medicine of the future. Methods Based on a benchmark analysis and the input and expertise provided by a multidisciplinary group of experts through interviews and workshops, a new competency framework that would guarantee the optimal performance of health care professionals was defined. As a basis for the development of this report, the most relevant national and international competency frameworks and training programs were analyzed to identify aspects that are having an impact on the application of personalized precision medicine and will be considered when developing professional competencies in the future. Results This report defines a framework made up of 58 competencies structured into 5 essential domains: determinants of health, biomedical informatics, practical applications, participatory health, and bioethics, along with a cross-cutting domain that impacts the overall performance of the competencies linked to each of the above domains. Likewise, 6 professional profiles to which this proposal of a competency framework is addressed were identified according to the area where they carry out their professional activity: health care, laboratory, digital health, community health, research, and management and planning. In addition, a classification is proposed by progressive levels of training that would be advisable to acquire for each competency according to the professional profile. Conclusions This competency framework characterizes the knowledge, skills, and attitudes required by health care professionals for the practice of personalized precision medicine. Additionally, a classification by progressive levels of training is proposed for the 6 professional profiles identified according to their professional roles.

Carlos López-Otín

Papers

P.I.3 Recent advances in defective prelamin A associated syndromes

Matrix metalloproteinase-8 is a regulator of the clinical aggressiveness of mammary tumours

3.10 Risk Factors Associated with Chronic Lymphocytic Leukaemia in a Spanish Case−Control Study (MCC−Spain)

Chapter 412 – Cathepsin O

Personalized Precision Medicine for Health Care Professionals: Development of a Competency Framework