Dynamic Changes in Protein Functional Linkage Networks Revealed by Integration with Gene Expression Data

Response of cells to changing environmental conditions is governed by the dynamics of intricate biomolecular interactions. It may be reasonable to assume, proteins being the dominant macromolecules that carry out routine cellular functions, that understanding the dynamics of protein∶protein interactions might yield useful insights into the cellular responses. The large-scale protein interaction data sets are, however, unable to capture the changes in the profile of protein∶protein interactions. In order to understand how these interactions change dynamically, we have constructed conditional protein linkages for Escherichia coli by integrating functional linkages and gene expression information. As a case study, we have chosen to analyze UV exposure in wild-type and SOS deficient E. coli at 20 minutes post irradiation. The conditional networks exhibit similar topological properties. Although the global topological properties of the networks are similar, many subtle local changes are observed, which are suggestive of the cellular response to the perturbations. Some such changes correspond to differences in the path lengths among the nodes of carbohydrate metabolism correlating with its loss in efficiency in the UV treated cells. Similarly, expression of hubs under unique conditions reflects the importance of these genes. Various centrality measures applied to the networks indicate increased importance for replication, repair, and other stress proteins for the cells under UV treatment, as anticipated. We thus propose a novel approach for studying an organism at the systems level by integrating genome-wide functional linkages and the gene expression data

Understanding Communication Signals during Mycobacterial Latency through Predicted Genome-Wide Protein Interactions and Boolean Modeling

About 90% of the people infected with Mycobacterium tuberculosis carry latent bacteria that are believed to get activated upon immune suppression. One of the fundamental challenges in the control of tuberculosis is therefore to understand molecular mechanisms involved in the onset of latency and/or reactivation. We have attempted to address this problem at the systems level by a combination of predicted functional protein∶protein interactions, integration of functional interactions with large scale gene expression studies, predicted transcription regulatory network and finally simulations with a Boolean model of the network. Initially a prediction for genome-wide protein functional linkages was obtained based on genome-context methods using a Support Vector Machine. This set of protein functional linkages along with gene expression data of the available models of latency was employed to identify proteins involved in mediating switch signals during dormancy. We show that genes that are up and down regulated during dormancy are not only coordinately regulated under dormancy-like conditions but also under a variety of other experimental conditions. Their synchronized regulation indicates that they form a tightly regulated gene cluster and might form a latency-regulon. Conservation of these genes across bacterial species suggests a unique evolutionary history that might be associated with M. tuberculosis dormancy. Finally, simulations with a Boolean model based on the regulatory network with logical relationships derived from gene expression data reveals a bistable switch suggesting alternating latent and actively growing states. Our analysis based on the interaction network therefore reveals a potential model of M. tuberculosis latency

Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass

Left ventricular mass (LVM) and cardiac gene expression are complex traits regulated by factors both intrinsic and extrinsic to the heart. To dissect the major determinants of LVM, we combined expression quantitative trait locus1 and quantitative trait transcript (QTT) analyses of the cardiac transcriptome in the rat. Using these methods and in vitro functional assays, we identified osteoglycin (Ogn) as a major candidate regulator of rat LVM, with increased Ogn protein expression associated with elevated LVM. We also applied genome-wide QTT analysis to the human heart and observed that, out of 22,000 transcripts, OGN transcript abundance had the highest correlation with LVM. We further confirmed a role for Ogn in the in vivo regulation of LVM in Ogn knockout mice. Taken together, these data implicate Ogn as a key regulator of LVM in rats, mice and humans, and suggest that Ogn modifies the hypertrophic response to extrinsic factors such as hypertension and aortic stenosi

A Theoretical Analysis of the Geography of Schistosomiasis in Burkina Faso Highlights the Roles of Human Mobility and Water Resources Development in Disease Transmission

We study the geography of schistosomiasis across Burkina Faso by means of a spatially explicit model of water-based disease dynamics. The model quantitatively addresses the geographic stratification of disease burden in a novel framework by explicitly accounting for drivers and controls of the disease, including spatial information on the distributions of population and infrastructure, jointly with a general description of human mobility and climatic/ecological drivers. Spatial patterns of disease are analysed by the extraction and the mapping of suitable eigenvectors of the Jacobian matrix subsuming the stability of the disease-free equilibrium. The relevance of the work lies in the novel mapping of disease burden, a byproduct of the parametrization induced by regional upscaling, by model-guided field validations and in the predictive scenarios allowed by exploiting the range of possible parameters and processes. Human mobility is found to be a primary control at regional scales both for pathogen invasion success and the overall distribution of disease burden. The effects of water resources development highlighted by systematic reviews are accounted for by the average distances of human settlements from water bodies that are habitats for the parasite's intermediate host. Our results confirm the empirical findings about the role of water resources development on disease spread into regions previously nearly disease-free also by inspection of empirical prevalence patterns. We conclude that while the model still needs refinements based on field and epidemiological evidence, the proposed framework provides a powerful tool for large-scale public health planning and schistosomiasis management

The bii4africa dataset of faunal and floral population intactness estimates across Africa’s major land uses

Sub-Saharan Africa is under-represented in global biodiversity datasets, particularly regarding the impact of land use on species’ population abundances. Drawing on recent advances in expert elicitation to ensure data consistency, 200 experts were convened using a modified-Delphi process to estimate ‘intactness scores’: the remaining proportion of an ‘intact’ reference population of a species group in a particular land use, on a scale from 0 (no remaining individuals) to 1 (same abundance as the reference) and, in rare cases, to 2 (populations that thrive in human-modified landscapes). The resulting bii4africa dataset contains intactness scores representing terrestrial vertebrates (tetrapods: ±5,400 amphibians, reptiles, birds, mammals) and vascular plants (±45,000 forbs, graminoids, trees, shrubs) in sub-Saharan Africa across the region’s major land uses (urban, cropland, rangeland, plantation, protected, etc.) and intensities (e.g., large-scale vs smallholder cropland). This dataset was co-produced as part of the Biodiversity Intactness Index for Africa Project. Additional uses include assessing ecosystem condition; rectifying geographic/ taxonomic biases in global biodiversity indicators and maps; and informing the Red List of Ecosystems

Microbial Profile and Antimicrobial Susceptibility of Isolates From Dogs with Otitis Externa in Kenya

Exudates from 78 dogs with clinical signs of otitis externa in the period 1991 to 2000 were submitted for culture and antimicrobial susceptibility testing. The microbial isolates recovered were Staphylococcus aureus, 40/78 (51.3 %), Streptococcus spp 11/78 (14. 1 %), Pseudomonas spp 11/78 (14.1 %), Proteus spp 8/78 (10.2 %), Escherichia coli 2/78 (2.6 %), Corynebacterium spp 1/78 (1.3 %) and yeasts 3/78 (3.8 %) were infrequently isolated. No organisms were isolated from 2/78 (2.6 %) of samples submitted. Otic cytology is useful in demonstrating yeasts from dogs with otitis externa. These isolates were resistant to tetracyclines, sulphonamides, kanamycin and streptomycin, hence the drugs may not be effective in treating bacterial otitis externa in dogs. However, good sensitivity was observed with gentamycin, chloramphenicol, ampicillin and penicillin. This study has characterized microbial isolates and antimicrobial susceptibility from dogs with otitis externa, information that can be used to provide appropriate antibiotic therapy to affected dogs. The Kenya Veterinarian Vol. 29 2005: pp. 40-44

An overview of the role of Veterinary Schools in emergency and disaster management

Recent events in Kenya (El Nino and La nina phenomena) and effects of civil unrest in the region have brought into focus the veterinarians' role in emergence and disaster management. there is need, therefore for veterinary schools to in the region to take a leadership role in providing the moral, professional and physical support to the veterinarians and communities in preparing for, anticipating and managing emergencies and disasters. This paper is a summary of the overview of how veterinary schools can provide this noble service. The Kenya Veterinarian Vol. 22 2001: pp. 66-6

Transmissible Venereal Tumor with Subcutaneous and Bone Metastasis in a Dog

A five year old entire mixed breed dog was admitted to the University of Nairobi's small animal clinic with a 5-months history of subcutaneous masses. Physical examination revealed firm and mobile masses in the subcuticular tissues, on the mandible and the transverse processes of the lumbar vertebrae. Visual inspection of the prepuce also revealed a timorous mass. Surgical excision of the subcutaneous masses and the mass on the prepuce was performed while the dog was under surgical anesthesia. Microscopic examination of the subcutaneous masses revealed features consistent with canine transmissible venereal tumor. This paper provides a detailed account of the clinical findings, surgical procedure and outcomes of managing the case. The Kenya Veterinarian Vol. 30 (1) 2006: pp. 11-1