MsatAllele_1.0: An R package to visualize the binning of microsatellite Alleles

MsatAllele is a computer package built on R to visualize and bin the raw microsatellite allele size distributions. The method is based on the creation of an R database with exported files from the open-source electropherogram peak-reading program STRAND. Contrary to other binning programs, in this program, the bin limits are not fixed and are automatically defined by the data stored in the database. Data manipulation and graphical functions allow to 1) visualize raw allele size variation, allowing the detection of potential scoring errors, strange bin distributions, and unexpected spacing between the bins; 2) bin raw fragment sizes and write bin summary statistics for each locus; and 3) export genotype files with the resulting binned data.Fundacao para a Ciencia e Tecnologia [SFRH/BPD/14945/2004]; MEGIKELP [PTDC/MAR/65461/2006]info:eu-repo/semantics/publishedVersio

Quality control of the sheep bacterial artificial chromosome library, CHORI-243

<p>Abstract</p> <p>Background</p> <p>The sheep CHORI-243 bacterial artificial chromosome (BAC) library is being used in the construction of the virtual sheep genome, the sequencing and construction of the actual sheep genome assembly and as a source of DNA for regions of the genome of biological interest. The objective of our study is to assess the integrity of the clones and plates which make up the CHORI-243 library using the virtual sheep genome.</p> <p>Findings</p> <p>A series of analyses were undertaken based on the mapping the sheep BAC-end sequences (BESs) to the virtual sheep genome. Overall, very few plate specific biases were identified, with only three of the 528 plates in the library significantly affected. The analysis of the number of tail-to-tail (concordant) BACs on the plates identified a number of plates with lower than average numbers of such BACs. For plates 198 and 213 a partial swap of the BESs determined with one of the two primers appear to have occurred. A third plate, 341, also with a significant deficit in tail-to-tail BACs, appeared to contain a substantial number of sequences determined from contaminating eubacterial 16 S rRNA DNA. Additionally a small number of eubacterial 16 S rRNA DNA sequences were present on two other plates, 111 and 338, in the library.</p> <p>Conclusions</p> <p>The comparative genomic approach can be used to assess BAC library integrity in the absence of fingerprinting. The sequences of the sheep CHORI-243 library BACs have high integrity, especially with the corrections detailed above. The library represents a high quality resource for use by the sheep genomics community.</p

Structural and thermodynamic characterization of the adrenodoxin-like domain of the electron-transfer protein Etp1 from Schizosaccharomyces pombe

The protein Etp1 of Schizosaccharomyces pombe consists of an amino-terminal COX15-like domain and a carboxy-terminal ferredoxin-like domain, Etp1(fd), which is cleaved off after mitochondrial import. The physiological function of Etp1(fd) is supposed to lie in the participation in the assembly of iron-sulfur clusters and the synthesis of heme A. In addition, the protein was shown to be the first microbial ferredoxin being able to support electron transfer in mitochondrial steroid hydroxylating cytochrome P450 systems in vivo and in vitro, replacing thereby the native redox partner, adrenodoxin. Despite a sequence similarity of 39% and the fact that fission yeast is a mesophilic organism, thermodynamic studies revealed that Etp1(fd) has a melting temperature more than 20°C higher than adrenodoxin. The three-dimensional structure of Etp1(fd) has been determined by crystallography. To the best of our knowledge it represents the first three-dimensional structure of a yeast ferredoxin. The structure-based sequence alignment of Etp1(fd) with adrenodoxin yields a rational explanation for their observed mutual exchangeability in the cytochrome P450 system. Analysis of the electron exchange with the S. pombe redox partner Arh1 revealed differences between Etp1(fd) and adrenodoxin, which might be linked to their different physiological functions in the mitochondria of mammals and yeast

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Identification of Movement Strategies during the Sit-to-Walk Movement in Patients with Knee Osteoarthritis

Patients with osteoarthritis (OA) of the knee commonly alter their movement to compensate for deficiencies. This study presents a new numerical procedure for classifying sit-to-walk (STW) movement strategies. Ten control and twelve OA participants performed the STW task in a motion capture laboratory. A full body biomechanical model was used. Participants were instructed to sit in a comfortable self-selected position on a stool height adjusted to 100% of their knee height and then stand and pick up an object from a table in front of them. Three matrices were constructed defining the progression of the torso, feet and hands in the sagittal plane along with a fourth expressing the location of the hands relative to the knees. Hierarchical clustering (HC) was used to identify different strategies. Trials were also classified as to whether the left (L) and right (R) extremities used a matching strategy (bilateral) or not (asymmetrical). Fisher’s exact test was used to compare this between groups. Clustering of the torso matrix dichotomised the trials in two major clusters; subjects leaning forward (LF) or not. The feet and hands matrices revealed sliding the foot backward (FB) and moving an arm forward (AF) strategies respectively. Trials not belonging in the AF cluster were submitted to the last HC of the fourth matrix exposing three additional strategies, the arm pushing through chair (PC), arm pushing through knee (PK) and arm not used (NA). The control participants used the LF+FBR+PK combination most frequently whereas the OA participants used the AFR+PCL. OA patients used significantly more asymmetrical arm strategies, p=0.034. The results demonstrated that control and OA participants favour different STW strategies. The OA patients asymmetrical arm behaviour possibly indicates compensating for weakness of the affected leg. These strategy definitions may be useful to assess post-operative outcomes and rehabilitation progress

Quantifying the Impoverishing Effects of Purchasing Medicines: A Cross-Country Comparison of the Affordability of Medicines in the Developing World

Laurens Niëns and colleagues estimate the impoverishing effects of four medicines in 16 low- and middle-income countries using the impoverishment method as a metric of affordability and show that medicine purchases could impoverish large numbers of people

An integrated 4249 marker FISH/RH map of the canine genome

BACKGROUND: The 156 breeds of dog recognized by the American Kennel Club offer a unique opportunity to map genes important in genetic variation. Each breed features a defining constellation of morphological and behavioral traits, often generated by deliberate crossing of closely related individuals, leading to a high rate of genetic disease in many breeds. Understanding the genetic basis of both phenotypic variation and disease susceptibility in the dog provides new ways in which to dissect the genetics of human health and biology. RESULTS: To facilitate both genetic mapping and cloning efforts, we have constructed an integrated canine genome map that is both dense and accurate. The resulting resource encompasses 4249 markers, and was constructed using the RHDF5000-2 whole genome radiation hybrid panel. The radiation hybrid (RH) map features a density of one marker every 900 Kb and contains 1760 bacterial artificial chromosome clones (BACs) localized to 1423 unique positions, 851 of which have also been mapped by fluorescence in situ hybridization (FISH). The two data sets show excellent concordance. Excluding the Y chromosome, the map features an RH/FISH mapped BAC every 3.5 Mb and an RH mapped BAC-end, on average, every 2 Mb. For 2233 markers, the orthologous human genes have been established, allowing the identification of 79 conserved segments (CS) between the dog and human genomes, dramatically extending the length of most previously described CS. CONCLUSIONS: These results provide a necessary resource for the canine genome mapping community to undertake positional cloning experiments and provide new insights into the comparative canine-human genome maps

Nanoscale friction of biomimetic hair surfaces

We investigate the nanoscale friction between biomimetic hair surfaces using chemical colloidal probe atomic force microscopy experiments and nonequilibrium molecular dynamics simulations. In the experiments, friction is measured between water-lubricated silica surfaces functionalised with monolayers formed from either octadecyl or sulfonate groups, which are representative of the surfaces of virgin and ultimately bleached hair, respectively. In the simulations, friction is monitored between coarse-grained model hair surfaces with different levels of chemical damage, where a specified amount of grafted octadecyl groups are randomly replaced with sulfonate groups. The sliding velocity dependence of friction in the simulations can be described using an extended stress-augmented thermally activation model. As the damage level increases in the simulations, the friction coefficient generally increases, but its sliding velocity-dependence decreases. At low sliding velocities, which are closer to those encountered experimentally and physiologically, we observe a monotonic increase of the friction coefficient with damage ratio, which is consistent with our new experiments using biomimetic surfaces and previous ones using real hair. This observation demonstrates that modified surface chemistry, rather than roughness changes or subsurface damage, control the increase in nanoscale friction of bleached or chemically damaged hair. We expect the methods and biomimetic surfaces proposed here to be useful to screen the tribological performance of hair care formulations both experimentally and computationally

Cloning of the Canine \u3cem\u3eABCA4\u3c/em\u3e Gene and Evaluation in Canine Cone-Rod Dystrophies and Progressive Retinal Atrophies

PURPOSE: To characterize a novel early onset canine retinal disease, and evaluate the ATP-binding cassette transporter gene ABCA4 as a potential candidate gene in this and other canine retinal degenerations. METHODS: Retinal disease was characterized ophthalmoscopically and electroretinographically in two pit bull terrier dogs and their purpose-bred descendants. All 50 exons of the canine ABCA4 gene were amplified, cloned and sequenced from retinal mRNA of a normal, a carrier and an affected animal, and polymorphisms identified. The latter were used to search for association between ABCA4 and retinal disease both within the study pedigrees and in additional canine breeds segregating retinal degenerations. RESULTS: The disease derived from either founder is distinguished by early, severe, and rapidly progressive loss of cone function accompanied by progressive rod loss that is only relatively slower. Cloning and comparative sequencing of ABCA4 identified six point mutations, none of which were obviously pathogenic. Crossbreeding studies revealed that the diseases in the two founders, although similar, are nonallelic. Pedigree analysis of segregating polymorphisms revealed dissociation between ABCA4 and both retinal phenotypes. CONCLUSIONS: The early, severe cone dysfunction in these diseases distinguish them from other forms of canine Progressive Retinal Atrophy. The development of a research population segregating these diseases presents two large animal models for the heterogenous human diseases termed cone-rod dystrophies. Analysis of the canine ABCA4 homolog gene documented its sequence and identified a set of point mutations that were used to exclude this gene as causal to these canine cone-rod dystrophies