Sequence space coverage, entropy of genomes and the potential to detect non-human DNA in human samples

Background: Genomes store information for building and maintaining organisms. Complete sequencing of many genomes provides the opportunity to study and compare global information properties of those genomes. Results: We have analyzed aspects of the information content of Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, Saccharomyces cerevisiae, and Escherichia coli (K-12) genomes. Virtually all possible (\u3e 98%) 12 bp oligomers appear in vertebrate genomes while \u3c 2% of 19 bp oligomers are present. Other species showed different ranges of \u3e 98% to \u3c 2% of possible oligomers in D. melanogaster (12-17 bp), C. elegans (11-17 bp), A. thaliana (11-17 bp), S. cerevisiae (10-16 bp) and E. coli (9-15 bp). Frequencies of unique oligomers in the genomes follow similar patterns. We identified a set of 2.6 M 15-mers that are more than 1 nucleotide different from all 15-mers in the human genome and so could be used as probes to detect microbes in human samples. In a human sample, these probes would detect 100% of the 433 currently fully sequenced prokaryotes and 75% of the 3065 fully sequenced viruses. The human genome is significantly more compact in sequence space than a random genome. We identified the most frequent 5- to 20-mers in the human genome, which may prove useful as PCR primers. We also identified a bacterium, Anaeromyxobacter dehalogenans, which has an exceptionally low diversity of oligomers given the size of its genome and its GC content. The entropy of coding regions in the human genome is significantly higher than non-coding regions and chromosomes. However chromosomes 1, 2, 9, 12 and 14 have a relatively high proportion of coding DNA without high entropy, and chromosome 20 is the opposite with a low frequency of coding regions but relatively high entropy. Conclusion: Measures of the frequency of oligomers are useful for designing PCR assays and for identifying chromosomes and organisms with hidden structure that had not been previously recognized. This information may be used to detect novel microbes in human tissues

Leaching of a low-grade, copper-nickel sulfide ore. 1. Key parameters impacting on Cu recovery during column bioleaching

This study was prompted by the disparate recoveries of nickel (>70%) and copper (<20%) from a test heap of copper-nickel sulfide ore after about 200 days of leaching. Variables tested in bioleaching columns charged with a pyrrhotite-rich, chalcopyrite and pentlandite ore were acid pre-conditioning, inoculation and aeration. The results indicated that the rapid reaction of pyrrhotite with acid created conditions that impacted directly and/or indirectly on copper recovery. Important reactions were hydrogen sulfide formation, high soluble iron concentrations and the formation of large amounts of elemental sulfur. It was hypothesized that copper loss, evidenced by copper re-distribution during passage through the ore, was mainly the result of reaction with hydrogen sulfide to form covellite, although this could not be confirmed by XRD analysis of leached residues. A layer of iron-oxy-hydroxy-sulfate 'scale' on particle surfaces encapsulated sulfide grains as well as elemental sulfur formed by the oxidation of pyrrhotite and was of sufficient depth and integrity to have hindered but not prevented leaching and bioleaching. Lack of aeration (oxygen, carbon dioxide) impacted on ferrous ion biooxidation and probably sulfur biooxidation. More extensive sulfur biooxidation to form acid might have lowered the solution pH and reduced the amount of scale formation, resulting in higher ferric ion concentrations and better chalcopyrite oxidation

Animal Cell Differentiation Patterns Suppress Somatic Evolution

Cell differentiation in multicellular organisms has the obvious function during development of creating new cell types. However, in long-lived organisms with extensive cell turnover, cell differentiation often continues after new cell types are no longer needed or produced. Here, we address the question of why this is true. It is believed that multicellular organisms could not have arisen or been evolutionarily stable without possessing mechanisms to suppress somatic selection among cells within organisms, which would otherwise disrupt organismal integrity. Here, we propose that one such mechanism is a specific pattern of ongoing cell differentiation commonly found in metazoans with cell turnover, which we call “serial differentiation.” This pattern involves a sequence of differentiation stages, starting with self-renewing somatic stem cells and proceeding through several (non–self-renewing) transient amplifying cell stages before ending with terminally differentiated cells. To test the hypothesis that serial differentiation can suppress somatic evolution, we used an agent-based computer simulation of cell population dynamics and evolution within tissues. The results indicate that, relative to other, simpler patterns, tissues organized into serial differentiation experience lower rates of detrimental cell-level evolution. Self-renewing cell populations are susceptible to somatic evolution, while those that are not self-renewing are not. We find that a mutation disrupting differentiation can create a new self-renewing cell population that is vulnerable to somatic evolution. These results are relevant not only to understanding the evolutionary origins of multicellularity, but also the causes of pathologies such as cancer and senescence in extant metazoans, including humans

Validation of a multiplex-tandem RT-PCR for the detection of bovine respiratory disease complex using Scottish bovine lung samples

The welfare and economic impact of bovine respiratory disease complex (BRDC), and its associated antibiotic usage, are major challenges to cattle rearing and beef cattle finishing industries. Accurate pathogen diagnosis is important to undertake appropriate treatment and long-term management strategies, such as vaccine selection. Conventional diagnostic approaches have several limitations including high costs, long turnaround times and difficulty in test interpretation, which could delay treatment decisions and lead to unnecessary animal losses. We describe the validation of a multiplex-tandem (MT) reverse transcription-polymerase chain reaction (RT-PCR) for the detection of seven common pathogens associated with BRDC. This test has the potential to advance pathogen identification and to overcome many of the limitations of current testing methods. It requires a single sample and results are obtained quickly and not influenced by prior antimicrobial therapy or overgrowth of contaminating organisms. We demonstrated a test specificity of 100% and sensitivity ranging from 93.5% to 100% for these seven common pathogens. This test will be a useful addition to advance BRDC investigation and diagnosis.</p

The evolution of biodiversity : a simulation approach

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1998.Vita.Includes bibliographical references (p. 186-195).by Carlo C. Maley.Ph.D

Optical Properties of Crystals with Spatial Dispersion: Josephson Plasma Resonance in Layered Superconductors

We derive the transmission coefficient, $T(\omega)$, for grazing incidence of crystals with spatial dispersion accounting for the excitation of multiple modes with different wave vectors ${\bf k}$ for a given frequency $\omega$. The generalization of the Fresnel formulas contains the refraction indices of these modes as determined by the dielectric function $\epsilon(\omega,{\bf k})$. Near frequencies $\omega_e$, where the group velocity vanishes, $T(\omega)$ depends also on an additional parameter determined by the crystal microstructure. The transmission $T$ is significantly suppressed, if one of the excited modes is decaying into the crystal. We derive these features microscopically for the Josephson plasma resonance in layered superconductors.Comment: 4 pages, 2 figures, epl.cls style file, minor change

Chromosomal instability and copy number alterations in Barrett’s esophagus and esophageal adenocarcinoma

Purpose: Chromosomal instability, as assessed by many techniques, including DNA content aneuploidy, LOH, and comparative genomic hybridization, has consistently been reported to be common in cancer and rare in normal tissues. Recently, a panel of chromosome instability biomarkers, including LOH and DNA content, has been reported to identify patients at high and low risk of progression from Barrett’s esophagus (BE) to esophageal adenocarcinoma (EA), but required multiple platforms for implementation. Although chromosomal instability involving amplifications and deletions of chromosome regions have been observed in nearly all cancers, copy number alterations (CNAs) in premalignant tissues have not been well characterized or evaluated in cohort studies as biomarkers of cancer risk. Experimental Design: We examined CNAs in 98 patients having either BE or EA using BAC array CGH to characterize CNAs at different stages of progression ranging from early BE to advanced EA. Results: CNAs were rare in early stages (<HGD) but were progressively more frequent and larger in later stages (HGD and EA), including high level amplifications. The number of CNAs correlated highly with DNA content aneuploidy. Patients whose biopsies contained CNAs involving more than 70 Mbp were at increased risk of progression to DNA content abnormalities or EA (HR=4.9, 95% CI 1.6-14.8, p=0.0047), and the risk increased as more of the genome was affected. Conclusions: Genome wide analysis of CNAs provides a common platform for evaluation of chromosome instability for cancer risk assessment as well as identification of common regions of alteration that can be further studied for biomarker discovery