Pathway analysis for intracellular Porphyromonas gingivalis using a strain ATCC 33277 specific database

<p>Abstract</p> <p>Background</p> <p><it>Porphyromonas gingivalis </it>is a Gram-negative intracellular pathogen associated with periodontal disease. We have previously reported on whole-cell quantitative proteomic analyses to investigate the differential expression of virulence factors as the organism transitions from an extracellular to intracellular lifestyle. The original results with the invasive strain <it>P. gingivalis </it>ATCC 33277 were obtained using the genome sequence available at the time, strain W83 [GenBank: <ext-link ext-link-id="AE015924" ext-link-type="gen">AE015924</ext-link>]. We present here a re-processed dataset using the recently published genome annotation specific for strain ATCC 33277 [GenBank: <ext-link ext-link-id="AP009380" ext-link-type="gen">AP009380</ext-link>] and an analysis of differential abundance based on metabolic pathways rather than individual proteins.</p> <p>Results</p> <p>Qualitative detection was observed for 1266 proteins using the strain ATCC 33277 annotation for 18 hour internalized <it>P. gingivalis </it>within human gingival epithelial cells and controls exposed to gingival cell culture medium, an improvement of 7% over the W83 annotation. Internalized cells showed increased abundance of proteins in the energy pathway from asparagine/aspartate amino acids to ATP. The pathway producing one short chain fatty acid, propionate, showed increased abundance, while that of another, butyrate, trended towards decreased abundance. The translational machinery, including ribosomal proteins and tRNA synthetases, showed a significant increase in protein relative abundance, as did proteins responsible for transcription.</p> <p>Conclusion</p> <p>Use of the ATCC 33277 specific genome annotation resulted in improved proteome coverage with respect to the number of proteins observed both qualitatively in terms of protein identifications and quantitatively in terms of the number of calculated abundance ratios. Pathway analysis showed a significant increase in overall protein synthetic and transcriptional machinery in the absence of significant growth. These results suggest that the interior of host cells provides a more energy rich environment compared to the extracellular milieu. Shifts in the production of cytotoxic fatty acids by intracellular <it>P. gingivalis </it>may play a role in virulence. Moreover, despite extensive genomic re-arrangements between strains W83 and 33277, there is sufficient sequence similarity at the peptide level for proteomic abundance trends to be largely accurate when using the heterologous strain annotated genome as the reference for database searching.</p

Quantitative proteomics of nutrient limitation in the hydrogenotrophic methanogen Methanococcus maripaludis

<p>Abstract</p> <p>Background</p> <p>Methanogenic Archaea play key metabolic roles in anaerobic ecosystems, where they use H₂and other substrates to produce methane. <it>Methanococcus maripaludis </it>is a model for studies of the global response to nutrient limitations.</p> <p>Results</p> <p>We used high-coverage quantitative proteomics to determine the response of <it>M. maripaludis </it>to growth-limiting levels of H₂, nitrogen, and phosphate. Six to ten percent of the proteome changed significantly with each nutrient limitation. H₂limitation increased the abundance of a wide variety of proteins involved in methanogenesis. However, one protein involved in methanogenesis decreased: a low-affinity [Fe] hydrogenase, which may dominate over a higher-affinity mechanism when H₂is abundant. Nitrogen limitation increased known nitrogen assimilation proteins. In addition, the increased abundance of molybdate transport proteins suggested they function for nitrogen fixation. An apparent regulon governed by the euryarchaeal nitrogen regulator NrpR is discussed. Phosphate limitation increased the abundance of three different sets of proteins, suggesting that all three function in phosphate transport.</p> <p>Conclusion</p> <p>The global proteomic response of <it>M. maripaludis </it>to each nutrient limitation suggests a wider response than previously appreciated. The results give new insight into the function of several proteins, as well as providing information that should contribute to the formulation of a regulatory network model.</p

Identifying Occupational Therapy Research Priorities in Trinidad and Tobago: A Group Concept Mapping Study

In Trinidad and Tobago, occupational therapy is an emerging profession with limitations in the number of practitioners and the scope of practice. With the development of a new Master of Science Occupational Therapy programme in the country, the profession is continuously growing. There has been an increased demand for culturally relevant research to build the occupational therapy evidence base locally. However, the narrow range of occupational therapy literature in the country makes it difficult to highlight research gaps and decipher what research areas should be prioritised to best impact occupational therapy practice at present. This group concept mapping study is aimed at identifying priority areas for occupational therapy research in Trinidad and Tobago from the perspectives of occupational therapy students and practitioners. Participants brainstormed and contributed specific research ideas they would like to see developed in the country. Individually, participants sorted these ideas into themes and rated each idea based on perceived importance and feasibility. Using the GroupWisdom™ software, multidimensional scaling and hierarchical cluster analyses were applied to the sort data to create idea clusters within a concept map. Rating values were analysed to determine priority research themes within the concept map. The resulting concept map illustrated seven research priorities: Contextualising Practitioner Development, The Realities of Emerging OT Practice, Localising Mental Health OT, Occupation and Participation of Children and Youth, School-based OT in the Local Context, OT with Special Populations, and OT Contributions to the Public Health Sector. These findings represent the research needs of the occupational therapy profession in Trinidad and Tobago and will help to focus future researchers’ efforts to expand the local evidence base

A Metapopulation Model for Chikungunya Including Populations Mobility on a Large-Scale Network

In this work we study the influence of populations mobility on the spread of a vector-borne disease. We focus on the chikungunya epidemic event that occurred in 2005-2006 on the R\'eunion Island, Indian Ocean, France, and validate our models with real epidemic data from the event. We propose a metapopulation model to represent both a high-resolution patch model of the island with realistic population densities and also mobility models for humans (based on real-motion data) and mosquitoes. In this metapopulation network, two models are coupled: one for the dynamics of the mosquito population and one for the transmission of the disease. A high-resolution numerical model is created out from real geographical, demographical and mobility data. The Island is modeled with an 18 000-nodes metapopulation network. Numerical results show the impact of the geographical environment and populations' mobility on the spread of the disease. The model is finally validated against real epidemic data from the R\'eunion event.Comment: Accepted in Journal of Theoretical biolog

BMP-7 Does Not Protect against Bleomycin-Induced Lung or Skin Fibrosis

Bone morphogenic protein (BMP)-7 is a member of the BMP family which are structurally and functionally related, and part of the TGFβ super family of growth factors. BMP-7 has been reported to inhibit renal fibrosis and TGFβ1-induced epithelial-mesenchymal transition (EMT), in part through negative interactions with TGFβ1 induced Smad 2/3 activation. We utilized in vivo bleomycin-induced fibrosis models in the skin and lung to determine the potential therapeutic effect of BMP-7. We then determined the effect of BMP-7 on TGFβ1-induced EMT in lung epithelial cells and collagen production by human lung fibroblasts. We show that BMP-7 did not affect bleomycin-induced fibrosis in either the lung or skin in vivo; had no effect on expression of pro-fibrotic genes by human lung fibroblasts, either at rest or following exposure to TGFβ1; and did not modulate TGFβ1 -induced EMT in human lung epithelial cells. Taken together our data indicates that BMP-7 has no anti-fibrotic effect in lung or skin fibrosis either in vivo or in vitro. This suggests that the therapeutic options for BMP-7 may be confined to the renal compartment

Measuring diet in primary school children aged 8-11 years: validation of the Child and Diet Evaluation Tool (CADET) with an emphasis on fruit and vegetable intake.

Background/Objectives:The Child And Diet Evaluation Tool (CADET) is a 24-h food diary that measures the nutrition intake of children aged 3-7 years, with a focus on fruit and vegetable consumption. Until now CADET has not been used to measure nutrient intake of children aged 8-11 years. To ensure that newly assigned portion sizes for this older age group were valid, participants were asked to complete the CADET diary (the school and home food diary) concurrently with a 1-day weighed record. Subjects/Methods:A total of 67 children with a mean age of 9.3 years (s.d.: ± 1.4, 51% girls) participated in the study. Total fruit and vegetable intake in grams and other nutrients were extracted to compare the mean intakes from the CADET diary and Weighed record using t-tests and Pearson's r correlations. Bland-Altman analysis was also conducted to assess the agreement between the two methods. Results: Correlations comparing the CADET diary to the weighed record were high for fruit, vegetables and combined fruit and vegetables (r=0.7). The results from the Bland-Altman plots revealed a mean difference of 54 g (95% confidence interval: -88, 152) for combined fruit and vegetables intake. CADET is the only tool recommended by the National Obesity Observatory that has been validated in a UK population and provides nutrient level data on children's diets. Conclusions:The results from this study conclude that CADET can provide high-quality nutrient data suitable for evaluating intervention studies now for children aged 3-11 years with a focus on fruit and vegetable intake

Neuropsychiatric outcomes of stroke

The most common neuropsychiatric outcomes of stroke are depression, anxiety, fatigue, and apathy, which each occur in at least 30% of patients and have substantial overlap of prevalence and symptoms. Emotional lability, personality changes, psychosis, and mania are less common but equally distressing symptoms that are also challenging to manage. The cause of these syndromes is not known, and there is no clear relation to location of brain lesion. There are important gaps in knowledge about how to manage these disorders, even for depression, which is the most studied syndrome. Further research is needed to identify causes and interventions to prevent and treat these disorders

Incorporating scale dependence in disease burden estimates:the case of human African trypanosomiasis in Uganda

The WHO has established the disability-adjusted life year (DALY) as a metric for measuring the burden of human disease and injury globally. However, most DALY estimates have been calculated as national totals. We mapped spatial variation in the burden of human African trypanosomiasis (HAT) in Uganda for the years 2000-2009. This represents the first geographically delimited estimation of HAT disease burden at the sub-country scale.Disability-adjusted life-year (DALY) totals for HAT were estimated based on modelled age and mortality distributions, mapped using Geographic Information Systems (GIS) software, and summarised by parish and district. While the national total burden of HAT is low relative to other conditions, high-impact districts in Uganda had DALY rates comparable to the national burden rates for major infectious diseases. The calculated average national DALY rate for 2000-2009 was 486.3 DALYs/100 000 persons/year, whereas three districts afflicted by rhodesiense HAT in southeastern Uganda had burden rates above 5000 DALYs/100 000 persons/year, comparable to national GBD 2004 average burden rates for malaria and HIV/AIDS.These results provide updated and improved estimates of HAT burden across Uganda, taking into account sensitivity to under-reporting. Our results highlight the critical importance of spatial scale in disease burden analyses. National aggregations of disease burden have resulted in an implied bias against highly focal diseases for which geographically targeted interventions may be feasible and cost-effective. This has significant implications for the use of DALY estimates to prioritize disease interventions and inform cost-benefit analyses

Identification of Birds through DNA Barcodes

Short DNA sequences from a standardized region of the genome provide a DNA barcode for identifying species. Compiling a public library of DNA barcodes linked to named specimens could provide a new master key for identifying species, one whose power will rise with increased taxon coverage and with faster, cheaper sequencing. Recent work suggests that sequence diversity in a 648-bp region of the mitochondrial gene, cytochrome c oxidase I (COI), might serve as a DNA barcode for the identification of animal species. This study tested the effectiveness of a COI barcode in discriminating bird species, one of the largest and best-studied vertebrate groups. We determined COI barcodes for 260 species of North American birds and found that distinguishing species was generally straightforward. All species had a different COI barcode(s), and the differences between closely related species were, on average, 18 times higher than the differences within species. Our results identified four probable new species of North American birds, suggesting that a global survey will lead to the recognition of many additional bird species. The finding of large COI sequence differences between, as compared to small differences within, species confirms the effectiveness of COI barcodes for the identification of bird species. This result plus those from other groups of animals imply that a standard screening threshold of sequence difference (10× average intraspecific difference) could speed the discovery of new animal species. The growing evidence for the effectiveness of DNA barcodes as a basis for species identification supports an international exercise that has recently begun to assemble a comprehensive library of COI sequences linked to named specimens