Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Crossing Boundaries with Teamwork and Economics for Water Management

The Water Team used teamwork and economics to transcend water boundaries. Recommendations implemented and physical improvements extended the irrigation season by 16 days in 2008, increased potential farm profits, and increased water conservation. The Team is now poised to cross more boundaries, assembling data and coordinated plans for watershed management and groundwater recharge for larger geographic areas, watersheds, and organizations

Acylated homoserine lactones in the environment: chameleons of bioactivity

Over the last 15 years, it has become increasingly apparent that a single class of compounds, the acylated homoserine lactones (AHLs), elicit effects on many levels of biological and ecological organization. Despite the fact that the distribution of AHL production in the prokaryotic phylogenetic tree is restricted to a small set of genera, representatives of these genera are abundant in the environment and are responsible for processes of much interest to humans. As well as driving interactions between clones, AHLs have been shown to mediate interactions between different species of bacteria and between bacteria and higher organisms, either through the phenotypes they regulate or directly through their own chemical behaviour. Understanding the biological activity of AHLs and the ecological consequences of these activities may provide us with an opportunity to manipulate the composition and function of complex biological assemblages. Ultimately, this broadens the biotechnological focus of AHL-based research beyond the attenuation of virulence in humans and plant pathogens

Service users' views of self-help strategies and research in the UK

Background: Self-help approaches for mental health problems are a research and service development priority within the UK. Aim: To engage service users in the research process through a consultation exercise, seek their views on the strategies they use to manage their lives and priorities for research into self-help. Method: Service users were involved in planning and conducting a consultation event and in analysing, interpreting and disseminating the findings. Forty nine service users attended the consultation event. Notes and key points from focus groups discussions were analysed to identify main themes. Results: Five themes for service user self-help strategies were identified; managing and structuring the day; empowerment; engaging others to help yourself; physical health and well being; and spirituality. Four research priority areas in self-help were identified: the importance of user-led research; research into self-help strategies to improve physical health and well being; mapping of available services and self-help approaches; and what works and why. Conclusions: Self-help research and developments should take account of these service users' views of research priorities and the strategies they use to manage their lives. Declaration of interest: The project was initiated by Psychological Therapies Network North (PsyReNN). Funding for the venue and service user expenses was provided by the NIMHE Regional Development Centre, North East, Yorkshire and Humberside and by the Tees and North East Yorkshire Mental Health and Learning Disabilities NHS Trust

Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia.

Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms1. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21)2, 3. We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes

Climate, Ticks and Disease

This book brings together expert opinions from scientists to consider the evidence for climate change and its impacts on ticks and tick-borne infections. It considers what is meant by 'climate change', how effective climate models are in relation to ecosystems, and provides predictions for changes in climate at global, regional and local scales relevant for ticks and tick-borne infections. It examines changes to tick distribution and the evidence that climate change is responsible. The effect of climate on the physiology and behaviour of ticks is stressed, including potentially critical impacts on the tick microbiome. Given that the notoriety of ticks derives from pathogens they transmit, the book considers whether changes in climate affect vector capacity. Ticks transmit a remarkable range of micro- and macro-parasites many of which are pathogens of humans and domesticated animals. The intimacy between a tick-borne agent and a tick vector means that any impacts of climate on a tick vector will impact tick-borne pathogens. Most obviously, such impacts will be apparent as changes in disease incidence and prevalence. The evidence that climate change is affecting diseases caused by tick-borne pathogens is considered, along with the potential to make robust predictions of future events. This book contains: Expert opinions and predictions. Global coverage of trends in ticks and disease. In-depth examination of climate change and tick distribution links.This book is suitable for researchers and students studying zoology, biological sciences, medical entomology, animal health, veterinary medicine, epidemiology, parasitology, and climate change impacts; and for those concerned with public health planning or livestock management where ticks and tick-borne pathogens pose a threat