Transcriptional responses consistent with perturbation in dermo-epidermal homeostasis in septic sole ulceration.

The aim of this study was to evaluate transcriptional changes in sole epidermis and dermis of bovine claws with septic sole ulceration of the lateral claw. Assessment included changes in transcripts orchestrating epidermal homeostatic processes including epidermal proliferation, differentiation, inflammation, and cell signaling. Sole epidermis and dermis was removed from region 4 of lesion-bearing lateral and lesion-free medial claws of pelvic limbs in multiparous, lactating Holstein cows. Control sole epidermis and dermis was obtained from region 4 of lateral claws of normal pelvic limbs. Transcript abundances were evaluated by real-time QPCR and relative expression analyzed by ANOVA. Relative to normal lateral claws, sole epidermis and dermis in ulcer-bearing claws exhibited downregulation of genes associated with growth factors, growth factor receptors, activator protein 1 (AP-1) and proto-oncogene (CMYC) transcription components, cell cycle elements, lateral cell-to-cell signaling elements and structures of early and late keratinocyte differentiation. These changes were accompanied by upregulation of pro-inflammatory transcripts interleukin 1 α (IL1A), interleukin1 ß (IL1B), interleukin 1 receptor 1 (IL1R1), inducible nitric oxide synthase (NOS2), the inflammasome components NOD like receptor protein 3 (NLRP3), pyrin and caspase recruitment domain (PYCARD), and caspase-1 interleukin converting enzyme (CASPASE), the matrix metalloproteinases (MMP2 and MMP9), and anti-inflammatory genes interleukin 1 receptor antagonist (IL1RN) and interleukin1 receptor 2 (IL1R2). Transcript abundance varied across epidermis and dermis from the ulcer center, margin and epidermis and dermis adjacent to the lesion. Sole epidermis and dermis of lesion-free medial claws exhibited changes paralleling those in the adjacent lateral claws in an environment lacking inflammatory transcripts and downregulated IL1A, interleukin 18 (IL18), tumor necrosis factor α (TNFA) and NOS2. These data imply perturbations in signal pathways driving epidermal proliferation and differentiation are associated with, but not inevitably linked to epidermis and dermis inflammation. Further work is warranted to better define the role of crushing tissue injury, sepsis, metalloproteinase activity, and inflammation in sole ulceration.

Evaluation of an environmentally sustainable UV-assisted water treatment system for the removal of Bacillus globigii spores in water.

Development of greener water treatment technologies is important for the production of safe drinking water and water security applications, such as decontamination. Chlorine assisted disinfection is common and economical, but can generate disinfection byproducts (DBPs) that may be of health concern. DBPs are formed due to the reaction of chlorine with naturally occurring organic and inorganic substances in water. Currently, various innovative technologies are being developed as alternative approaches for preventing DBPs during water treatment. In this study, we evaluated the effectiveness of a novel combination of high efficiency flow filtration and UV disinfection treatment system for the removal of Bacillus globigii (B. globigii) spores in water. The filtration system consists of a charged membrane filter (CMF) that not only helps to remove suspended particles but also reduces the impact of other impurities including bio organisms. In order to get most performance details, the CMF was evaluated at clean, half-life, and end of life (EOL) conditions along with 100% UV transmittance (UVT). In addition, the effectiveness of the UV system was evaluated as a stand alone system at 100% and 70% EOL intensity. The study was conducted at the US EPA's Test and Evaluation (T&E) Facility in Cincinnati, OH, using B. globigii, a surrogate for B. anthracis spores. This non-chemical environmentally-friendly CMF/UV combination system and the stand alone UV unit showed greater than 6.0 log removal of B. globigii during the tests.

A computational model of cardiac fibroblast signaling predicts context-dependent drivers of myofibroblast differentiation.

Cardiac fibroblasts support heart function, and aberrant fibroblast signaling can lead to fibrosis and cardiac dysfunction. Yet how signaling molecules drive myofibroblast differentiation and fibrosis in the complex signaling environment of cardiac injury remains unclear. We developed a large-scale computational model of cardiac fibroblast signaling in order to identify regulators of fibrosis under diverse signaling contexts. The model network integrates 10 signaling pathways, including 91 nodes and 134 reactions, and it correctly predicted 80% of independent previous experiments. The model predicted key fibrotic signaling regulators (e.g. reactive oxygen species, tissue growth factor ß (TGFß) receptor), whose function varied depending on the extracellular environment. We characterized how network structure relates to function, identified functional modules, and predicted cross-talk between TGFß and mechanical signaling, which was validated experimentally in adult cardiac fibroblasts. This study provides a systems framework for predicting key regulators of fibroblast signaling across diverse signaling contexts.

CBioC: beyond a prototype for collaborative annotation of molecular interactions from the literature.

In molecular biology research, looking for information on a particular entity such as a gene or a protein may lead to thousands of articles, making it impossible for a researcher to individually read these articles and even just their abstracts. Thus, there is a need to curate the literature to get various nuggets of knowledge, such as an interaction between two proteins, and store them in a database. However the body of existing biomedical articles is growing at a very fast rate, making it impossible to curate them manually. An alternative approach of using computers for automatic extraction has problem with accuracy. We propose to leverage the advantages of both techniques, extracting binary relationships between biological entities automatically from the biomedical literature and providing a platform that allows community collaboration in the annotation of the extracted relationships. Thus, the community of researchers that writes and reads the biomedical texts can use the server for searching our database of extracted facts, and as an easy-to-use web platform to annotate facts relevant to them. We presented a preliminary prototype as a proof of concept earlier(1). This paper presents the working implementation available for download at http://www.cbioc.org as a browser-plug in for both Internet Explorer and FireFox. This current version has been available since June of 2006, and has over 160 registered users from around the world. Aside from its use as an annotation tool, data from CBioC has also been used in computational methods with encouraging results.

Identification, tissue specific expression, and chromosomal localisation of several human dynein heavy chain genes.

Sliding between adjacent microtubules within the axonema gives rise to the motility of cilia and flagella. The driving force is produced by dynein complexes which are mainly composed of the axonemal dynein heavy chains. We used cells of human respiratory epithelium after in vitro ciliogenesis to clone cDNA fragments of nine dynein heavy chain genes, one of which had never been identified before. Dynein heavy chains are highly conserved from protozoa to human and the evolutionary ancestry of these dynein heavy chain cDNA fragments was deduced by phylogenetic analysis. These dynein heavy chain cDNAs are highly transcribed in human tissues containing axonema such as trachea, testis and brain, but not in adult heart or placenta. PAC clones containing dynein heavy chains were obtained and used to determine by FISH their chromosomal position in the human genome. They were mapped to 2p12-p11, 2q33, 3p21.2-p21.1, 13q14, 16p12 and 17p12. The chromosomal assignment of these dynein heavy chain genes which was confirmed by GeneBridge 4 radiation hybrid screening, will be extremely useful for linkage analysis efforts in patients with primary ciliary dyskinesia (PCD).

Respiratory infection complicating long-term tracheostomy. The implication of persistent gram-negative tracheobronchial colonization.

Colonization of the lower respiratory tract by enteric Gram-negative bacilli (EGNB) has been a frequent finding in patients with long-term tracheostomies; however, the association of hospitalization and certain features of serious illness with this phenomenon has not been clearly established. Because such factors can render the oropharynx more susceptible to EGNB colonization, we sought to discover whether they can also have this effect on the tracheobronchial tree and its microflora. Thus, we collected serial paired culture samples from these two mucosal sites in 15 subjects with long-term tracheostomies and examined patterns and rates of colonization and related these findings to clinical parameters. In 49 sets of cultures, we found that EGNB (especially Pseudomonas species) were present in significantly fewer upper-airway cultures (36.7 percent) than lower-airway cultures (75.5 percent) (p = 0.009). At the tracheobronchial site, seven subjects had persistent EGNB colonization, all with Pseudomonas species, while only one subject had this finding at the oropharyngeal site (p = 0.015). Patients with persistent tracheobronchial colonization were more ill than those without this finding. They were treated with higher doses of prednisone (p = 0.06), received antibiotics more often, and developed purulent tracheobronchitis more often (100 percent vs 25 percent) than patients without persistent colonization. In addition, in the month following the culture survey, four subjects developed pneumonia, and three of these had previous persistent tracheobronchial colonization.(ABSTRACT TRUNCATED AT 250 WORDS)