DNA sequence and analysis of human chromosome 8

The International Human Genome Sequencing Consortium (IHGSC) recently completed a sequence of the human genome. As part of this project, we have focused on chromosome 8. Although some chromosomes exhibit extreme characteristics in terms of length, gene content, repeat content and fraction segmentally duplicated, chromosome 8 is distinctly typical in character, being very close to the genome median in each of these aspects. This work describes a finished sequence and gene catalogue for the chromosome, which represents just over 5% of the euchromatic human genome. A unique feature of the chromosome is a vast region of approximately 15 megabases on distal 8p that appears to have a strikingly high mutation rate, which has accelerated in the hominids relative to other sequenced mammals. This fast-evolving region contains a number of genes related to innate immunity and the nervous system, including loci that appear to be under positive selection--these include the major defensin (DEF) gene cluster and MCPH1, a gene that may have contributed to the evolution of expanded brain size in the great apes. The data from chromosome 8 should allow a better understanding of both normal and disease biology and genome evolution.     

Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice

Minocycline mediates neuroprotection in experimental models of neurodegeneration. It inhibits the activity of caspase-1, caspase-3, inducible form of nitric oxide synthetase (iNOS) and p38 mitogen-activated protein kinase (MAPK). Although minocycline does not directly inhibit these enzymes, the effects may result from interference with upstream mechanisms resulting in their secondary activation. Because the above-mentioned factors are important in amyotrophic lateral sclerosis (ALS), we tested minocycline in mice with ALS. Here we report that minocycline delays disease onset and extends survival in ALS mice. Given the broad efficacy of minocycline, understanding its mechanisms of action is of great importance. We find that minocycline inhibits mitochondrial permeability-transition-mediated cytochrome c release. Minocycline-mediated inhibition of cytochrome c release is demonstrated in vivo, in cells, and in isolated mitochondria. Understanding the mechanism of action of minocycline will assist in the development and testing of more powerful and effective analogues. Because of the safety record of minocycline, and its ability to penetrate the blood-brain barrier, this drug may be a novel therapy for ALS.     

First documentation of Salmincola californiensis in Lake Tahoe, CA–NV, USA

Salmincola californiensis is a parasitic copepod in the Lernaeopodidae family that commonly parasitizes salmonid fishes ( Oncorhynchus spp.) by attaching near the fins and on gill filaments. Historically their distribution was limited to streams that emptied into the Pacific Ocean. During the summer of 2006, several rainbow trout ( Oncorhynchus mykiss ) captured in Lake Tahoe were infested with S. californiensis . This is the first known record of S. californiensis in Lake Tahoe.     

Geography of exotic plants adjacent to campgrounds, Yellowstone National Park, USA

Eleven campgrounds in Yellowstone National Park were studied to determine the geography of 10 specific exotic plant species adjacent to campgrounds. Exotics were found in only 6 campgrounds. Six species were found at Mammoth campground, a low-elevation, dry site with year-round use. Only 2 species were found in the other 5 campgrounds. Exotics decreased with distance from Mammoth campground out to 6 m and then increased, suggesting a spread in their distribution. Significant associations were found between exotic presence and both open and closed canopies and low levels of disturbance. Generally, exotics decreased with an increase in cover of other vegetation forms. Five species were found most frequently in big sagebrush habitat types.     

Thymic cortical epithelial cells can present self-antigens in vivo

Antigens present during neonatal life are recognized as self and individuals are tolerant to these antigens. In normal individuals T cells are tolerant to most self proteins but we still know little of the mechanism(s) by which tolerance is established. A requisite part of the current negative selection model of self tolerance is the expression of self proteins complexed with major histocompatibility complex molecules in the thymus. As MHC proteins bind antigens and present them to the receptor on the antigen-specific T cell, then for tolerance to self to occur, it is possible that each self protein must be processed and presented by an MHC molecule. As a result of the development of a unique T-cell hybrid reactive to the self protein murine haemoglobin, we have shown that in normal animals this self protein is continuously processed and potentially presented in an MHC-restricted manner. Here we show that self haemoglobin is being processed and presented by thymic antigen-presenting cells as early as gestational day 14. We also demonstrate that three types of thymic stromal cells, namely macrophages, dendritic cells and cortical epithelial cells, can present the haemoglobin self antigen in vivo. This surprising presentation of a self antigen by thymic cortical epithelial cells implies that they could be involved in T-cell development and negative selection.     

Warming experiments underpredict plant phenological responses to climate change

Warming experiments are increasingly relied on to estimate plant responses to global climate change. For experiments to provide meaningful predictions of future responses, they should reflect the empirical record of responses to temperature variability and recent warming, including advances in the timing of flowering and leafing. We compared phenology (the timing of recurring life history events) in observational studies and warming experiments spanning four continents and 1,634 plant species using a common measure of temperature sensitivity (change in days per degree Celsius). We show that warming experiments underpredict advances in the timing of flowering and leafing by 8.5-fold and 4.0-fold, respectively, compared with long-term observations. For species that were common to both study types, the experimental results did not match the observational data in sign or magnitude. The observational data also showed that species that flower earliest in the spring have the highest temperature sensitivities, but this trend was not reflected in the experimental data. These significant mismatches seem to be unrelated to the study length or to the degree of manipulated warming in experiments. The discrepancy between experiments and observations, however, could arise from complex interactions among multiple drivers in the observational data, or it could arise from remediable artefacts in the experiments that result in lower irradiance and drier soils, thus dampening the phenological responses to manipulated warming. Our results introduce uncertainty into ecosystem models that are informed solely by experiments and suggest that responses to climate change that are predicted using such models should be re-evaluated.