Bringing systems biology to cancer,immunology and infectious disease

A report on the seventh annual ‘International Conference on Systems Biology of Human Disease’ held in Boston, Massachusetts, USA, 17–19 June, 2014.     

Understanding the contribution of synonymous mutations to human disease

Synonymous mutations - sometimes called 'silent' mutations - are now widely acknowledged to be able to cause changes in protein expression, conformation and function. The recent increase in knowledge about the association of genetic variants with disease, particularly through genome-wide association studies, has revealed a substantial contribution of synonymous SNPs to human disease risk and other complex traits. Here we review current understanding of the extent to which synonymous mutations influence disease, the various molecular mechanisms that underlie these effects and the implications for future research and biomedical applications.     

117例医院真菌感染分析及预防

目的 了解佛山市南海人民医院真菌感染的分布,探讨有效预防和控制真菌感染的措施。方法 对该院117例真菌感染病例作回顾性分析。结果 3583例送检标本中真菌检出率为3．27％（117／3583）,医院内真菌感染率为2．95％（106／3583）。分离出真菌以白色念珠菌为主（70／117．59．8％）、热带念珠菌次之（17／117,14．5％）、霉菌居第3位（9／117．7．69％）。药敏显示：5-氟胞嘧啶、两性霉素B和制霉素敏感率较高,分别为92．4％、93．3％和92．5％,咪康唑、酮康唑和益康唑敏感率较低．为52．0％、49．0％和36．0％。结论 医院内真菌感染占真菌感染绝大部分,感染真菌以白色念珠菌为主。感染部位以呼吸道为主;临床规范、合理使用广谱抗生素,加强消毒护理工作。是预防控制真菌感染发生的最有效措施。     

The clinical immunology of human Chagas disease

Human infection with the protozoan parasite Trypanosoma cruzi leads to Chagas disease, which affects approximately 17 million people in Latin America. A significant percentage of the infected population will develop clinical symptoms or present changes in laboratory and/or image evaluation. The existence of a large spectrum of clinical manifestations--with patients ranging from asymptomatic to severe cardiac involvement--emphasizes the need to use standardized and well-defined clinical criteria among different research groups. In this article, we carry out a systematic review of the immunology in human Chagas disease, discussing recent findings in the context of a clinical perspective.     

From fundamental immunology to development of vaccinology

In the last ten years research in vaccinology has been developed in the world to conceive new vaccine approaches against infections like HIV/AIDS. Jean-Gérard Guillet is a pioneer in the development of new vaccine strategies. From the first results he obtained in the late 80's on the presentation of antigenic peptides to T cells, he axed his work on the study of induction mechanisms of T cell mediated immune responses. The selection of antigenic peptides and the search to enhance antigen immunogenicity led him to elaborate lipopeptides as new vaccine formulae. The efficacy of these preparations was tested in animal models (mouse, macaque) and, thereafter, in humans with clinical trials promoted by the French National Agency for AIDS and viral hepatitis (ANRS). The study of T-cell induced responses in vaccinated volunteers was implemented following the creation of two facilities, an immuno-monitoring platform and the Clinical Investigation Centre Cochin-Pasteur, a structure specialized in vaccinology.     

The contribution of dormant origins to genome stability: From cell biology to human genetics

The ability of a eukaryotic cell to precisely and accurately replicate its DNA is crucial to maintain genome stability. Here we describe our current understanding of the process by which origins are licensed for DNA replication and review recent work suggesting that fork stalling has exerted a strong selective pressure on the positioning of licensed origins. In light of this, we discuss the complex and disparate phenotypes observed in mouse models and humans patients that arise due to defects in replication licensing proteins.     

The contribution of immunology to the rational design of novel antibacterial vaccines

In most cases, a successful vaccine must induce an immune response that is better than the response invoked by natural infection. Vaccines are still unavailable for several bacterial infections and vaccines to prevent such infections will be best developed on the basis of our increasing insights into the immune response. Knowledge of the signals that determine the best possible acquired immune response against a given pathogen - comprising a profound T- and B-cell memory response as well as long-lived plasma cells - will provide the scientific framework for the rational design of novel antibacterial vaccines.     

Anthropogenic biomes: a key contribution to earth-system science

Human activities now dominate most of the ice-free terrestrial surface. A recent article presents a classification and global map of human-influenced biomes of the world that provides a novel and potentially appropriate framework for projecting changes in earth-system dynamics.     

Pond conservation: from science to practice

In Europe, ponds are an exceptionally numerous and widely distributed landscape feature forming a major part of the continental freshwater resource and contributing significantly to freshwater biodiversity conservation. This has been reflected by a growing scientific concern over the first few years of the twenty-first century and is evidenced by an increasing number of academic publications on pond related topics, particularly those relating to biodiversity. It is essential, however, that this expanding scientific knowledge is widely disseminated to those involved with pond management and is then rapidly translated into action. Inevitably, the task of transferring science to practice remains a significant challenge. As a first step towards meeting this challenge the European Pond Conservation Network (EPCN), at its biennial meeting in 2008 in Valencia (Spain), made this the main theme of the conference together with two special workshops further encouraging exchanges between scientists, practitioners and policy makers. The papers selected for this special issue of Hydrobiologia (from over 120 communications presented) are all from the conference. They represent a diverse collection of themes from across the continent and North Africa and present new and original insights into topics as wide ranging as: pond biodiversity; human disturbance; landscape ecology; ecological assessment and monitoring; practical management measures; ecological restoration; hydrology and climate change; invasive species and threatened species. In all cases, the papers demonstrate an overriding need for the development of a tight link between scientific knowledge and management. Furthermore, scientific advances have to be beneficial for on the ground management and, vitally, have to be disseminated, communicated and implemented into local, national and international policy. As such, national and international networks (such as the EPCN) have a central role to play and have to develop a robust information and communication strategy which will enable the dissemination of best practice materials and advice across the continent and beyond. The work contained in this volume represents a step in the right direction and will help to ensure that ponds remain a characteristic and highly visible feature of the European landscape in the twenty-first century. Guest editors: B. Oertli, R. Céréghino, A. Hull & R. Miracle Pond Conservation: From Science to Practice. 3rd Conference of the European Pond Conservation Network, Valencia, Spain, 14–16 May 2008     

Macaque models of human infectious disease

Macaques have served as models for more than 70 human infectious diseases of diverse etiologies, including a multitude of agents-bacteria, viruses, fungi, parasites, prions. The remarkable diversity of human infectious diseases that have been modeled in the macaque includes global, childhood, and tropical diseases as well as newly emergent, sexually transmitted, oncogenic, degenerative neurologic, potential bioterrorism, and miscellaneous other diseases. Historically, macaques played a major role in establishing the etiology of yellow fever, polio, and prion diseases. With rare exceptions (Chagas disease, bartonellosis), all of the infectious diseases in this review are of Old World origin. Perhaps most surprising is the large number of tropical (16), newly emergent (7), and bioterrorism diseases (9) that have been modeled in macaques. Many of these human diseases (e.g., AIDS, hepatitis E, bartonellosis) are a consequence of zoonotic infection. However, infectious agents of certain diseases, including measles and tuberculosis, can sometimes go both ways, and thus several human pathogens are threats to nonhuman primates including macaques. Through experimental studies in macaques, researchers have gained insight into pathogenic mechanisms and novel treatment and vaccine approaches for many human infectious diseases, most notably acquired immunodeficiency syndrome (AIDS), which is caused by infection with human immunodeficiency virus (HIV). Other infectious agents for which macaques have been a uniquely valuable resource for biomedical research, and particularly vaccinology, include influenza virus, paramyxoviruses, flaviviruses, arenaviruses, hepatitis E virus, papillomavirus, smallpox virus, Mycobacteria, Bacillus anthracis, Helicobacter pylori, Yersinia pestis, and Plasmodium species. This review summarizes the extensive past and present research on macaque models of human infectious disease.