An ontology-based search engine for protein-protein interactions

<p>Abstract</p> <p>Background</p> <p>Keyword matching or ID matching is the most common searching method in a large database of protein-protein interactions. They are purely syntactic methods, and retrieve the records in the database that contain a keyword or ID specified in a query. Such syntactic search methods often retrieve too few search results or no results despite many potential matches present in the database.</p> <p>Results</p> <p>We have developed a new method for representing protein-protein interactions and the Gene Ontology (GO) using modified Gödel numbers. This representation is hidden from users but enables a search engine using the representation to efficiently search protein-protein interactions in a biologically meaningful way. Given a query protein with optional search conditions expressed in one or more GO terms, the search engine finds all the interaction partners of the query protein by unique prime factorization of the modified Gödel numbers representing the query protein and the search conditions.</p> <p>Conclusion</p> <p>Representing the biological relations of proteins and their GO annotations by modified Gödel numbers makes a search engine efficiently find all protein-protein interactions by prime factorization of the numbers. Keyword matching or ID matching search methods often miss the interactions involving a protein that has no explicit annotations matching the search condition, but our search engine retrieves such interactions as well if they satisfy the search condition with a more specific term in the ontology.</p

Personal radio use and cancer risks among 48,518 British police officers and staff from the Airwave Health Monitoring Study

Background: Radiofrequency electromagnetic fields (RF-EMF) from mobile phones have been classified as potentially carcinogenic. No study has investigated use of Terrestrial Trunked Radio (TETRA), a source of RF-EMF with wide occupational use, and cancer risks. Methods: We investigated association of monthly personal radio use and risk of cancer using Cox proportional hazards regression among 48,518 police officers and staff of the Airwave Health Monitoring Study in Great Britain. Results: During median follow-up of 5.9 years, 716 incident cancer cases were identified. Among users, the median of the average monthly duration of use in the year prior to enrolment was 30.5 min (inter-quartile range 8.1, 68.1). Overall, there was no association between personal radio use and risk of all cancers (hazard ratio [HR] = 0.98, 95% confidence interval [CI]: 0.93, 1.03). For head and neck cancers HR = 0.72 (95% CI: 0.30, 1.70) among personal radio users vs non-users, and among users it was 1.06 (95% CI: 0.91, 1.23) per doubling of minutes of personal radio use. Conclusions: With the limited follow-up to date, we found no evidence of association of personal radio use with cancer risk. Continued follow-up of the cohort is warranted

Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background

The evolution of drug-resistance in pathogens is a major global health threat. Elucidating the molecular basis of pathogen drug-resistance has been the focus of many studies but rarely is it known whether a drug-resistance mechanism identified is universal for the studied pathogen; it has seldom been clarified whether drug-resistance mechanisms vary with the pathogen's genotype. Nevertheless this is of critical importance in gaining an understanding of the complexity of this global threat and in underpinning epidemiological surveillance of pathogen drug resistance in the field. This study aimed to assess the molecular and phenotypic heterogeneity that emerges in natural parasite populations under drug treatment pressure. We studied lines of the protozoan parasite Leishmania (L.) donovani with differential susceptibility to antimonial drugs; the lines being derived from clinical isolates belonging to two distinct genetic populations that circulate in the leishmaniasis endemic region of Nepal. Parasite pathways known to be affected by antimonial drugs were characterised on five experimental levels in the lines of the two populations. Characterisation of DNA sequence, gene expression, protein expression and thiol levels revealed a number of molecular features that mark antimonial-resistant parasites in only one of the two populations studied. A final series of in vitro stress phenotyping experiments confirmed this heterogeneity amongst drug-resistant parasites from the two populations. These data provide evidence that the molecular changes associated with antimonial-resistance in natural Leishmania populations depend on the genetic background of the Leishmania population, which has resulted in a divergent set of resistance markers in the Leishmania populations. This heterogeneity of parasite adaptations provides severe challenges for the control of drug resistance in the field and the design of molecular surveillance tools for widespread applicability

History of climate modeling

The history of climate modeling begins with conceptual models, followed in the 19th century by mathematical models of energy balance and radiative transfer, as well as simple analog models. Since the 1950s, the principal tools of climate science have been computer simulation models of the global general circulation. From the 1990s to the present, a trend toward increasingly comprehensive coupled models of the entire climate system has dominated the field. Climate model evaluation and intercomparison is changing modeling into a more standardized, modular process, presenting the potential for unifying research and operational aspects of climate science. WIREs Clim Change 2011 2 128–139 DOI: 10.1002/wcc.95 For further resources related to this article, please visit the WIREs websitePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79438/1/95_ftp.pd

Regulation of immunity during visceral Leishmania infection

Unicellular eukaryotes of the genus Leishmania are collectively responsible for a heterogeneous group of diseases known as leishmaniasis. The visceral form of leishmaniasis, caused by L. donovani or L. infantum, is a devastating condition, claiming 20,000 to 40,000 lives annually, with particular incidence in some of the poorest regions of the world. Immunity to Leishmania depends on the development of protective type I immune responses capable of activating infected phagocytes to kill intracellular amastigotes. However, despite the induction of protective responses, disease progresses due to a multitude of factors that impede an optimal response. These include the action of suppressive cytokines, exhaustion of specific T cells, loss of lymphoid tissue architecture and a defective humoral response. We will review how these responses are orchestrated during the course of infection, including both early and chronic stages, focusing on the spleen and the liver, which are the main target organs of visceral Leishmania in the host. A comprehensive understanding of the immune events that occur during visceral Leishmania infection is crucial for the implementation of immunotherapeutic approaches that complement the current anti-Leishmania chemotherapy and the development of effective vaccines to prevent disease.The research leading to these results has received funding from the European Community’s Seventh Framework Programme under grant agreement No.602773 (Project KINDRED). VR is supported by a post-doctoral fellowship granted by the KINDReD consortium. RS thanks the Foundation for Science and Technology (FCT) for an Investigator Grant (IF/00021/2014). This work was supported by grants to JE from ANR (LEISH-APO, France), Partenariat Hubert Curien (PHC) (program Volubilis, MA/11/262). JE acknowledges the support of the Canada Research Chair Program

Assessment of trace metal contamination in a historical freshwater canal (Buckingham Canal), Chennai, India

The present study was done to assess the sources and the major processes controlling the trace metal distribution in sediments of Buckingham Canal. Based on the observed geochemical variations, the sediments are grouped as South Buckingham Canal and North Buckingham Canal sediments (SBC and NBC, respectively). SBC sediments show enrichment in Fe, Ti, Mn, Cr, V, Mo, and As concentrations, while NBC sediments show enrichment in Sn, Cu, Pb, Zn, Ni, and Hg. The calculated Chemical Index of Alteration and Chemical Index of Weathering values for all the sediments are relatively higher than the North American Shale Composite and Upper Continental Crust but similar to Post-Archaean Average Shale, and suggest a source area with moderate weathering. Overall, SBC sediments are highly enriched in Mo, Zn, Cu, and Hg (geoaccumulation index (Igeo) class 4– 6), whereas NBC sediments are enriched in Sn, Cu,Zn, and Hg (Igeo class 4–6). Cu, Ni, and Cr show higher than Effects-Range Median values and hence the biological adverse effect of these metals is 20%; Zn, which accounts for 50%, in the NBC sediments, has a more biological adverse effect than other metalsfound in these sediments. The calculated Igeo, Enrichment Factor, and Contamination Factor values indicate that Mo, Hg, Sn, Cu, and Zn are highly enriched in the Buckingham Canal sediments, suggesting the rapid urban and industrial development of Chennai MetropolitanCity have negatively influenced on the surrounding aquatic ecosystem

The Acute Liver Injury in Mice Caused by Nano-Anatase TiO2

Although it is known that nano-TiO2or other nanoparticles can induce liver toxicities, the mechanisms and the molecular pathogenesis are still unclear. In this study, nano-anatase TiO2(5 nm) was injected into the abdominal cavity of ICR mice for consecutive 14 days, and the inflammatory responses of liver of mice was investigated. The results showed the obvious titanium accumulation in liver DNA, histopathological changes and hepatocytes apoptosis of mice liver, and the liver function damaged by higher doses nano-anatase TiO2. The real-time quantitative RT-PCR and ELISA analyses showed that nano-anatase TiO2can significantly alter the mRNA and protein expressions of several inflammatory cytokines, including nucleic factor-κB, macrophage migration inhibitory factor, tumor necrosis factor-α, interleukin-6, interleukin-1β, cross-reaction protein, interleukin-4, and interleukin-10. Our results also implied that the inflammatory responses and liver injury may be involved in nano-anatase TiO2-induced liver toxicity

Dimeric SecA Couples the Preprotein Translocation in an Asymmetric Manner

The Sec translocase mediates the post-translational translocation of a number of preproteins through the inner membrane in bacteria. In the initiatory translocation step, SecB targets the preprotein to the translocase by specific interaction with its receptor SecA. The latter is the ATPase of Sec translocase which mediates the post-translational translocation of preprotein through the protein-conducting channel SecYEG in the bacterial inner membrane. We examined the structures of Escherichia coli Sec intermediates in solution as visualized by negatively stained electron microscopy in order to probe the oligomeric states of SecA during this process. The symmetric interaction pattern between the SecA dimer and SecB becomes asymmetric in the presence of proOmpA, and one of the SecA protomers predominantly binds to SecB/proOmpA. Our results suggest that during preprotein translocation, the two SecA protomers are different in structure and may play different roles

Effect of MWCNTs on Gastric Emptying in Mice

After making model of gastric functional disorder (FD), part of model mice were injected intravenously (i.v.) with oxide multi-walled carbon nanotubes (oMWCNTs) to investigate effect of carbon nanotubes on gastric emptying. The results showed that NO content in stomach, compared with model group, was decreased significantly and close to normal level post-injection with oMWCNTs (500 and 800 μg/mouse). In contrast to FD or normal groups, the content of acetylcholine (Ach) in stomach was increased obviously in injection group with 500 or 800 μg/mouse of oMWCNTs. The kinetic curve of emptying was fitted to calculate gastric motility factor k; the results showed that the k of injection group was much higher than FD and normal. In other words, the gastric motility of FD mice was enhanced via injection with oMWCNTs. In certain dosage, oMWCNTs could improve gastric emptying and motility