Integrating heterogeneous sequence information for transcriptome-wide microarray design; a Zebrafish example

BACKGROUND: A complete gene-expression microarray should preferably detect all genomic sequences that can be expressed as RNA in an organism, i.e. the transcriptome. However, our knowledge of a transcriptome of any organism still is incomplete and transcriptome information is continuously being updated. Here, we present a strategy to integrate heterogeneous sequence information that can be used as input for an up-to-date microarray design. FINDINGS: Our algorithm consists of four steps. In the first step transcripts from different resources are grouped into Transcription Clusters (TCs) by looking at the similarity of all transcripts. TCs are groups of transcripts with a similar length. If a transcript is much smaller than a TC to which it is highly similar, it will be annotated as a subsequence of that TC and is used for probe design only if the probe designed for the TC does not query the subsequence. Secondly, all TCs are mapped to a genome assembly and gene information is added to the design. Thirdly TC members are ranked according to their trustworthiness and the most reliable sequence is used for the probe design. The last step is the actual array design. We have used this strategy to build an up-to-date zebrafish microarray. CONCLUSIONS: With our strategy and the software developed, it is possible to use a set of heterogeneous transcript resources for microarray design, reduce the number of candidate target sequences on which the design is based and reduce redundancy. By changing the parameters in the procedure it is possible to control the similarity within the TCs and thus the amount of candidate sequences for the design. The annotation of the microarray is carried out simultaneously with the design

Low geographic and subspecific variation in the loud call of the widespread and phenotypically cryptic northern lesser galago (Galago senegalensis) suggests taxonomic uniformity

Like other nocturnal primates, many species of galago (Galagidae) are phenotypically cryptic, making their taxonomic status difficult to resolve. Recent taxonomic work has disentangled some of the confusion. This has resulted in an increase in the number of recognised galago species. The most widespread galago species, and indeed the most widespread nocturnal primate, is the northern lesser galago (Galago senegalensis) whose geographic range stretches >7,000 km across Africa. Based on morphology, 4 subspecies are currently recognised: G. s. senegalensis, G. s. braccatus, G. s. sotikae and G. s. dunni. We explore geographic and subspecific acoustic variation in G. senegalensis, testing three hypotheses: isolation by distance, genetic basis, and isolation by barrier. There is statistical support for isolation by distance for 2 of 4 call parameters (fundamental frequency and unit length). Geographic distance explains a moderate amount of the acoustic variation. Discriminant function analysis provides some degree of separation of geographic regions and subspecies, but the percentage of misdesignation is high. Despite having (putative) parapatric geographic ranges, the most pronounced acoustic differences are between G. s. senegalensis and G. s. dunni. The findings suggest that the Eastern Rift Valley and Niger River are significant barriers for G. senegalensis. The acoustic structures of the loud calls of 121 individuals from 28 widespread sites are not significantly different. Although this makes it unlikely that additional unrecognised species occur within G. senegalensis at the sites sampled, vast areas of the geographic range remain unsampled. We show that wide-ranging species do not necessarily exhibit large amounts of variation in their vocal repertoire. This pattern may also be present in nocturnal primates with smaller geographic ranges

Toward Reliable Uptake Metrics in Large Vessel Vasculitis Studies

The aim of this study is to investigate the influence of sex, age, fat mass, fasting blood glucose level (FBGL), and estimated glomerular filtration rate (eGFR) on blood pool activity in patients with large vessel vasculitis (LVV). Blood pool activity was measured in the superior caval vein using mean, maximum, and peak standardized uptake values corrected for body weight (SUVs) and lean body mass (SULs) in 41 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans of LVV patients. Sex influence on the blood pool activity was assessed with t-tests, while linear correlation analyses were used for age, fat mass, FBGL, and eGFR. Significantly higher SUVs were found in women compared with men, whereas SULs were similar between sexes. In addition, higher fat mass was associated with increased SUVs (r = 0.56 to 0.65; all p p > 0.05). Lower eGFR was associated with a higher FDG blood pool activity for all uptake values. In FDG-PET/CT studies with LVV patients, we recommend using SUL over SUV, while caution is advised in interpreting SUV and SUL measures when patients have impaired kidney function

Unfocused Extracorporeal Shock Waves Induce Anabolic Effects in Rat Bone

Abstract. BACKGROUND: Extracorporeal shock waves are known to stimulate the differentiation of mesenchymal stem cells toward osteoprogenitors and induce the expression of osteogenic-related growth hormones. The aim of this study was to investigate if and how extracorporeal shock waves affected new bone formation, bone microarchitecture, and the mechanical properties of bone in a healthy rat model, in order to evaluate whether extracorporeal shock wave therapy might be a potential treatment for osteoporosis. METHODS: Thirteen rats received 1000 electrohydraulically generated unfocused extracorporeal shock waves to the right tibia. The contralateral, left tibia was not treated and served as a control. At two, seven, twenty-one, and forty-nine days after administration of the shock waves, in vivo single-photon-emission computed tomography (SPECT) scanning was performed to measure new bone formation on the basis of uptake of technetium-labeled methylene diphosphonate ((99m)Tc-MDP) (n = 6). Prior to and forty-nine days after the extracorporeal shock wave therapy, micro-computed tomography (micro-CT) scans were made to examine the architectural bone changes. In addition, mechanical testing, microcrack, and histological analyses were performed. RESULTS: Extracorporeal shock waves induced a strong increase in (99m)Tc-MDP uptake in the treated tibia compared with the uptake in the untreated, control tibia. Micro-CT analysis showed that extracorporeal shock waves stimulated increases in both trabecular and cortical volume, which resulted in higher bone stiffness compared with that of the contro