205158145
Using galaxy to perform large-scale interactive data analyses.
While most experimental biologists know where to download genomic data, few have a concrete plan on how to analyze it. This situation can be corrected by: (1) providing unified portals serving genomic data and (2) building Web applications to allow flexible retrieval and on-the-fly analyses of the data. Powerful resources, such as the UCSC Genome Browser already address the first issue. The second issue, however, remains open. For example, how to find human protein-coding exons with the highest density of single nucleotide polymorphisms (SNPs) and extract orthologous sequences from all sequenced mammals? Indeed, one can access all relevant data from the UCSC Genome Browser. But once the data is downloaded how would one deal with millions of SNPs and gigabytes of alignments? Galaxy (http://g2.bx.psu.edu) is designed specifically for that purpose. It amplifies the strengths of existing resources (such as UCSC Genome Browser) by allowing the user to access and, most importantly, analyze data within a single interface in an unprecedented number of ways.
19711359
Clues to function in gene deserts.
Recent work by Ivan Ovcharenko and colleagues has shed new light on the functional importance of gene deserts. They demonstrate that sequence conservation levels separate gene deserts into stable (more conserved) and variable classes. Both classes exhibit characteristics suggestive of function. The stable deserts in particular show features suggesting a role in the complex regulation of core vertebrate genes.
14002416
Strong and weak male mutation bias at different sites in the primate genomes: insights from the human-chimpanzee comparison.
Male mutation bias is a higher mutation rate in males than in females thought to result from the greater number of germ line cell divisions in males. If errors in DNA replication cause most mutations, then the magnitude of male mutation bias, measured as the male-to-female mutation rate ratio (alpha), should reflect the relative excess of male versus female germ line cell divisions. Evolutionary rates averaged among all sites in a sequence and compared between mammalian sex chromosomes were shown to be indeed higher in males than in females. However, it is presently unknown whether individual classes of substitutions exhibit such bias. To address this issue, we investigated male mutation bias separately at non-CpG and CpG sites using human-chimpanzee whole-genome alignments. We observed strong male mutation bias at non-CpG sites: alpha in the X-autosome comparison was approximately 6-7, which was similar to the male-to-female ratio in the number of germ line cell divisions. In contrast, mutations at CpG sites exhibited weak male mutation bias: alpha in the X-autosome comparison was only approximately 2-3. This is consistent with the methylation-induced and replication-independent mechanism of CpG transitions, which constitute the majority of mutations at CpG sites. Interestingly, our study also indicated weak male mutation bias for transversions at CpG sites, implying a spontaneous mechanism largely not associated with replication. Male mutation bias was equally strong at CpG and non-CpG sites located within unmethylated "CpG islands," suggesting the replication-dependent origin of these mutations. Thus, we found that the strength of male mutation bias is nonuniform in the primate genomes. Importantly, we discovered that male mutation bias depends on the proportion of CpG sites in the loci compared. This might explain the differences in the magnitude of primate male mutation bias observed among studies.
13468480
ESPERR: learning strong and weak signals in genomic sequence alignments to identify functional elements.
Genomic sequence signals - such as base composition, presence of particular motifs, or evolutionary constraint - have been used effectively to identify functional elements. However, approaches based only on specific signals known to correlate with function can be quite limiting. When training data are available, application of computational learning algorithms to multispecies alignments has the potential to capture broader and more informative sequence and evolutionary patterns that better characterize a class of elements. However, effective exploitation of patterns in multispecies alignments is impeded by the vast number of possible alignment columns and by a limited understanding of which particular strings of columns may characterize a given class. We have developed a computational method, called ESPERR (evolutionary and sequence pattern extraction through reduced representations), which uses training examples to learn encodings of multispecies alignments into reduced forms tailored for the prediction of chosen classes of functional elements. ESPERR produces a greatly improved Regulatory Potential score, which can discriminate regulatory regions from neutral sites with excellent accuracy ( approximately 94%). This score captures strong signals (GC content and conservation), as well as subtler signals (with small contributions from many different alignment patterns) that characterize the regulatory elements in our training set. ESPERR is also effective for predicting other classes of functional elements, as we show for DNaseI hypersensitive sites and highly conserved regions with developmental enhancer activity. Our software, training data, and genome-wide predictions are available from our Web site (http://www.bx.psu.edu/projects/esperr).
32957442
Approach to sustainable primary health care service delivery for rural and remote South Australia.
We describe the operation of four University Teaching Practices established by the South Australian Centre for Rural and Remote Health (SACRRH) and the Adelaide University Department of General Practice. These practices were established in response to the acknowledged difficulty in recruiting and retaining GPs in rural South Australia. The practices are co-located with a hospital or accident and emergency service and community based nurses and allied health professionals. They provide integrated health care and multidisciplinary health care student placements in a learning environment where students experience rural multidisciplinary practice and country life. The study found that although the sites differed in significant ways, they all provided integrated care and effective placements for students. This style of health care delivery is flexible and broadly applicable. Sustainability is achieved through financially viability, attracting and retaining health care professionals and the development of electronic information systems, to support integrated practice.
44845847
Human hepatitis delta virus: an agent with similarities to certain satellite RNAs of plants.
One of the most intriguing aspects of hepatitis delta virus (HDV) is that, even though it is a naturally occurring infectious agent of human beings, it nevertheless shows a number of remarkable similarities to viroids, the subviral agents of plants that are considered elsewhere in this volume. The recognition and exploitation of this analogy has been a major contributor to studies of HDV genome replication. This review will concentrate on the structure of the HDV genome and the mechanism by which the genome is replicated, with special emphasis on similarities to the viroids. The review will not consider in any depth other important aspects of HDV, such as the assembly of genomes into virus particles, experimental transmission, host responses, or epidemiology. For such information the reader is directed to other more extensive reviews (Lai 1995; Purcell and Gerin 1996; Hadziyannis 1997; Margolis et al. 1997). However, to put this review in perspective, we will present a limited amount of background material.
24529809
Multiple-electrode nerve cuffs for low-velocity and velocity-selective neural recording
In the paper, a method using multiple-electrode nerve cuffs is presented that enables electroneurographic signals (ENG) to be recorded selectively by action potential velocity. The theory uses a one-dimensional model of the electrodes in the cuff. Using this model, the transfer function for a single tripole is derived, and it is shown that more than one tripole signal can be recorded from within a cuff. When many tripole signals are available and are temporally aligned by artificial delays and summed, there is a significant increase in the amplitude of the recorded action potential, depending on the cuff length and the action potential velocity, with the greatest gain occurring for low velocities. For example, a cuff was considered that was constrained by surgical considerations to 30 mm between the end electrodes. For action potentials with a velocity of 120 ms−1, it was shown that, as the number of tripoles increased from one, the peak energy spectral density of the recorded output increased by a factor of about 1.6 with three tripoles, whereas, for 20 ms−1, the increase was about 19, with ten tripoles. The time delays and summation act as a velocity-selective filter. With consideration of the energy spectral densities at frequencies where are maximum (to give the best signal-to-noise ratio), the tuning curves are presented for these velocity-selective filters and show that useful velocity resolution is possible using this method. For a 30 mm cuff with nine tripoles, it is demonstrated that it is possible to resolve at least five distinct velocity bands in the range 20–120 ms−1.
8789806
SmartStretch™ technology VI. The impact of SmartStretch™ technology on the meat quality of hot-boned beef striploin (m. longissimus lumborum).
The impact of SmartStretch™ technology and ageing (0 or 14 days ageing) on the meat quality traits of m. longissimus lumborum hot-boned from adult cull cattle was assessed. Tenderness, as reflected in reduced shear force measurement, was significantly (P<0.05) improved in 0 day aged stretched samples over the non stretched samples. After 14 days ageing there was no longer any difference in the tenderness between stretched and non stretched samples and the aged meat was significantly tenderer than either the SmartStretch™ treated or non stretched meat aged for 0 days. Sarcomere length was unchanged by stretching. Presentation traits such as purge loss and fresh colour were unaffected by the stretch treatment, whilst cooking loss was significantly (P<0.05) increased by stretching and ageing for 14 days.
11817035
Restriction enzyme sites on the avian RNA tumor virus genome.
Full-size single-stranded DNA transcripts of the avian RNA tumor virus genome were isolated from the products of the endogenous reaction of detergent-disrupted avian sarcoma virus particles. These transcripts were converted with Escherichia coli DNA polymerase I and 32P-labeled nucleoside triphosphates into labeled double-stranded DNA. The latter DNA was used to map the sites of action of seven restriction enzymes (Pvu I, Hpa I, Kpn I, Xba I, EcoRI, HindIII, and Xho I) on the genome of three strains of avian sarcoma virus (Prague B, Prague C, and Bratislava 77).