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Journal Cover   F1000Research
  [SJR: 0.219]   [H-I: 3]   [5 followers]  Follow
    
  This is an Open Access Journal Open Access journal
   ISSN (Online) 2046-1402
   Published by Faculty of 1000 Homepage  [1 journal]
  • Follow-up: Prospective compound design using the ‘SAR Matrix’
           method and matrix-derived conditional probabilities of activity [v2;
           indexed, http://f1000r.es/59v]

    • Authors: Disha Gupta-Ostermann, Yoichiro Hirose, Takenao Odagami, Hiroyuki Kouji, Jürgen Bajorath
      Abstract: In a previous Method Article, we have presented the ‘Structure-Activity Relationship (SAR) Matrix’ (SARM) approach. The SARM methodology is designed to systematically extract structurally related compound series from screening or chemical optimization data and organize these series and associated SAR information in matrices reminiscent of R-group tables. SARM calculations also yield many virtual candidate compounds that form a “chemical space envelope” around related series. To further extend the SARM approach, different methods are developed to predict the activity of virtual compounds. In this follow-up contribution, we describe an activity prediction method that derives conditional probabilities of activity from SARMs and report representative results of first prospective applications of this approach.
      PubDate: 2015-04-15T14:15:29Z
      DOI: 10.12688/f1000research.6271.2
      Issue No: Vol. 4 (2015)
       
  • Adherence to Artemisinin Combination Therapy for the treatment of
           uncomplicated malaria in the Democratic Republic of the Congo [v2;
           indexed, http://f1000r.es/596]

    • Authors: M. Ruby Siddiqui, Andrew Willis, Karla Bil, Jatinder Singh, Eric Mukomena Sompwe, Cono Ariti
      Abstract: Between 2011 and 2013 the number of recorded malaria cases had more than doubled, and between 2009 and 2013 had increased almost 4-fold in MSF-OCA (Médecins sans Frontières – Operational Centre Amsterdam) programmes in the Democratic Republic of the Congo (DRC). The reasons for this rise are unclear. Incorrect intake of Artemisinin Combination Therapy (ACT) could result in failure to treat the infection and potential recurrence. An adherence study was carried out to assess whether patients were completing the full course of ACT. One hundred and eight malaria patients in Shamwana, Katanga province, DRC were visited in their households the day after ACT was supposed to be completed. They were asked a series of questions about ACT administration and the blister pack was observed (if available). Sixty seven (62.0%) patients were considered probably adherent. This did not take into account the patients that vomited or spat their pills or took them at the incorrect time of day, in which case adherence dropped to 46 (42.6%). The most common reason that patients gave for incomplete/incorrect intake was that they were vomiting or felt unwell (10 patients (24.4%), although the reasons were not recorded for 22 (53.7%) patients). This indicates that there may be poor understanding of the importance of completing the treatment or that the side effects of ACT were significant enough to over-ride the pharmacy instructions. Adherence to ACT was poor in this setting. Health education messages emphasising the need to complete ACT even if patients vomit doses, feel unwell or their health conditions improve should be promoted.
      PubDate: 2015-04-08T09:16:34Z
      DOI: 10.12688/f1000research.6122.2
      Issue No: Vol. 4 (2015)
       
  • Weak and contradictory effects of self-medication with nectar nicotine by
           parasitized bumblebees [v1; indexed, http://f1000r.es/56l]

    • Authors: David Baracchi, Mark J. F. Brown, Lars Chittka
      Abstract: The presence of antimicrobial secondary metabolites in nectar suggests that pollinators, which are threatened globally by emergent disease, may benefit from the consumption of nectars rich in these metabolites. We tested whether nicotine, a nectar secondary metabolite common in Solenaceae and Tilia species, is used by parasitized bumblebees as a source of self-medication, using a series of toxicological, microbiological and behavioural experiments. Caged bees infected with Crithidia bombi [TI1] had a slight preference for sucrose solution laced with the alkaloid and behavioural tests showed that the parasite infection induced an increased consumption of nicotine during foraging activity. When ingested, nicotine delayed the progression of a gut infection in bumblebees by a few days, but dietary nicotine did not clear the infection, and after 10 days the parasite load approached that of control bees. Moreover, when pathogens were exposed to the alkaloid prior to host ingestion the protozoan’s viability was not directly affected, suggesting that anti-parasite effects were relatively weak. Nicotine consumption in a single dose did not impose any cost even in food-stressed bees (starved) but the alkaloid had detrimental effects on healthy bees if consistently consumed for weeks. These toxic effects disappeared in infected bees suggesting that detoxification costs might have been counterbalanced by the advantages in slowing the progression of the infection. Nonetheless we did not find a benefit of nicotine consumption in terms of life expectancy of infected bees, making these findings difficult to interpret. Our results indicate that caution is warranted in interpreting impacts of plant metabolites on insect parasites and suggest that the conditions under which nicotine consumption provides benefits to either bees or plants remain to be identified. The contention that secondary metabolites in nectar may be under selection from pollinators, or used by plants to enhance their own reproductive success, remains to be confirmed.
      PubDate: 2015-03-19T15:38:04Z
      DOI: 10.12688/f1000research.6262.1
      Issue No: Vol. 4 (2015)
       
  • The culture of scientific research [v1; indexed, http://f1000r.es/53j]

    • Authors: Catherine Joynson, Ottoline Leyser
      Abstract: In 2014, the UK-based Nuffield Council on Bioethics carried out a series of engagement activities, including an online survey to which 970 people responded, and 15 discussion events at universities around the UK to explore the culture of research in the UK and its effect on ethical conduct in science and the quality of research. The findings of the project were published in December 2014 and the main points are summarised here. We found that scientists are motivated in their work to find out more about the world and to benefit society, and that they believe collaboration, multidisciplinarity, openness and creativity are important for the production of high quality science. However, in some cases, our findings suggest, the culture of research in higher education institutions does not support or encourage these goals or activities. For example, high levels of competition and perceptions about how scientists are assessed for jobs and funding are reportedly contributing to a loss of creativity in science, less collaboration and poor research practices. The project led to suggestions for action for funding bodies, research institutions, publishers and editors, professional bodies and individual researchers.
      PubDate: 2015-03-13T10:08:14Z
      DOI: 10.12688/f1000research.6163.1
      Issue No: Vol. 4 (2015)
       
  • Effects of mutations on the molecular dynamics of oxygen escape from the
           dimeric hemoglobin of Scapharca inaequivalvis [v1; indexed,
           http://f1000r.es/52d]

    • Authors: Kevin Trujillo, Tasso Papagiannopoulos, Kenneth W. Olsen
      Abstract: Like many hemoglobins, the structure of the dimeric hemoglobin from the clam Scapharca inaequivalvis is a “closed bottle” since there is no direct tunnel from the oxygen binding site on the heme to the solvent.  The proximal histidine faces the dimer interface, which consists of the E and F helicies.  This is significantly different from tetrameric vertebrate hemoglobins and brings the heme groups near the subunit interface. The subunit interface is also characterized by an immobile, hydrogen-bonded network of water molecules.  Although there is data which is consistent with the histidine gate pathway for ligand escape, these aspects of the structure would seem to make that pathway less likely. Locally enhanced sampling molecular dynamics are used here to suggest alternative pathways in the wild-type and six mutant proteins. In most cases the point mutations change the selection of exit routes observed in the simulations. Exit via the histidine gate is rarely seem although oxygen molecules do occasionally cross over the interface from one subunit to the other. The results suggest that changes in flexibility and, in some cases, creation of new cavities can explain the effects of the mutations on ligand exit paths.
      PubDate: 2015-03-13T09:42:28Z
      DOI: 10.12688/f1000research.6127.1
      Issue No: Vol. 4 (2015)
       
  • Military-specific application of nutritional supplements: a brief overview
           [v1; indexed, http://f1000r.es/548]

    • Authors: Kyle Hoedebecke, Will Brink
      Abstract: The Soldiers of America's military endure numerous physical and mental challenges that demand strict physical fitness regimens, extreme mental agility, and a perpetual readiness to deploy at a moment's notice. The chronicity of these stressors has the potential to dramatically reduce performance - both directly and indirectly.  Because of this risk, many Soldiers turn to nutritional supplements with hopes of optimizing performance. Increasing amounts of research have demonstrated that various supplements may enhance overall physical prowess, health, and offer quicker recovery in the face of corporal or psychological extremes. Most individuals, including many medical and nutrition professionals, possess only an elementary comprehension of nutritional supplements and their effect on Soldiers in training or combat environments. Nevertheless, a grasp of these details is required for safety and optimal benefits. Various compounds have been evaluated - to include evidence within the military setting - and found to augment endurance, increase cognitive function, decrease knee pain, or offer hearing or lung protection in the face of high-energy impulses. These efficacious outcomes may serve to augment the health and longevity of these Soldiers; however, continued research is needed for efficacy and long-term safety within specific environments.
      PubDate: 2015-03-10T14:34:43Z
      DOI: 10.12688/f1000research.6187.1
      Issue No: Vol. 4 (2015)
       
  • Fused embryos and pre-metamorphic conjoined larvae in a broadcast spawning
           reef coral [v2; indexed, http://f1000r.es/54p]

    • Authors: Lei Jiang, Xin-Ming Lei, Sheng Liu, Hui Huang
      Abstract: Fusion of embryos or larvae prior to metamorphosis is rarely known to date in colonial marine organisms. Here, we document for the first time that the embryos of the broadcast spawning coral Platygyra daedalea could fuse during blastulation and further develop into conjoined larvae, and the settlement of conjoined larvae immediately resulted in inborn juvenile colonies. Fusion of embryos might be an adaptive strategy to form pre-metamorphic chimeric larvae and larger recruits, thereby promoting early survival. However, future studies are needed to explore whether and to what extent fusion of coral embryos occurs in the field, and fully evaluate its implications.
      PubDate: 2015-03-05T16:51:05Z
      DOI: 10.12688/f1000research.6136.2
      Issue No: Vol. 4 (2015)
       
  • Digital teaching tools and global learning communities [v1; indexed,
           http://f1000r.es/533]

    • Authors: Mary Williams, Patti Lockhart, Cathie Martin
      Abstract: In 2009, we started a project to support the teaching and learning of university-level plant sciences, called Teaching Tools in Plant Biology. Articles in this series are published by the plant science journal, The Plant Cell (published by the American Society of Plant Biologists). Five years on, we investigated how the published materials are being used through an analysis of the Google Analytics pageviews distribution and through a user survey. Our results suggest that this project has had a broad, global impact in supporting higher education, and also that the materials are used differently by individuals in terms of their role (instructor, independent learner, student) and geographical location. We also report on our ongoing efforts to develop a global learning community that encourages discussion and resource sharing.
      PubDate: 2015-03-05T11:11:40Z
      DOI: 10.12688/f1000research.6150.1
      Issue No: Vol. 4 (2015)
       
  • Finding small molecules for the ‘next Ebola’ [v1; indexed,
           http://f1000r.es/542]

    • Authors: Sean Ekins, Christopher Southan, Megan Coffee
      Abstract: The current Ebola virus epidemic may provide some suggestions of how we can better prepare for the next pathogen outbreak. We propose several cost effective steps that could be taken that would impact the discovery and use of small molecule therapeutics including: 1. text mine the literature, 2. patent assignees and/or inventors should openly declare their relevant filings, 3. reagents and assays could be commoditized, 4. using manual curation to enhance database links, 5. engage database and curation teams, 6. consider open science approaches, 7. adapt the “box” model for shareable reference compounds, and 8. involve the physician’s perspective.
      PubDate: 2015-02-27T15:21:16Z
      DOI: 10.12688/f1000research.6181.1
      Issue No: Vol. 4 (2015)
       
  • In vitro retention of a new thermoplastic titratable mandibular
           advancement device [v1; indexed, http://f1000r.es/509]

    • Authors: Marc Braem
      Abstract: Oral appliance (OA) therapy with a mandibular advancement device (OAm) is a non-invasive, alternative approach to maintaining upper airway patency. The main requirement for an OAm to be effective is the adequate retention on the teeth while the patient is asleep. We evaluated the retentive forces of a new low-cost, customizable, titratable, thermoplastic OAm (BluePro®; BlueSom, France). Dental impressions and casts were made for one patient with complete upper and lower dental arches including the third molars and class II bite proportions. A setup based on Frasaco ANA-4 models was also used. Two protrusive positions of the mandible were investigated: 3 mm and 8 mm, representing respectively 25% and 65% of the maximal protrusion. The forces required to remove the BluePro® device from the carriers were recorded continuously over 730 cycles (=365 days, twice a day) to simulate 1 year of clinical use. At 8 mm protrusion the BluePro® device showed retentive forces of ~27N. There was a slight but non-significant decrease in retentive forces in the tests on the epoxified carriers which was not found on the ANA-4 carriers. There were no significant differences between the carriers as a function of protrusion. The BluePro® device tested in the present study possesses sufficient retention forces to resist initial jaw opening forces and full mouth opening forces estimated to be ~20N. It could therefore broaden the indications for use of thermoplastic OAms. It could provide a temporary OAm while a custom-made OAm is being manufactured or repaired. Patients could be provided with a low-cost try-out device capable of reliable titration, providing an indication of effectiveness and of patient acceptance of an OAm, although the effect of device shape and size on therapeutic outcome is not yet known. Finally it could provide an affordable OAm solution in resource-restricted healthcare settings.
      PubDate: 2015-02-26T15:48:32Z
      DOI: 10.12688/f1000research.6061.1
      Issue No: Vol. 4 (2015)
       
  • A brief review of recent Charcot-Marie-Tooth research and priorities [v1;
           indexed, http://f1000r.es/53g]

    • Authors: Sean Ekins, Nadia K. Litterman, Renée J.G. Arnold, Robert W. Burgess, Joel S. Freundlich, Steven J. Gray, Joseph J. Higgins, Brett Langley, Dianna E. Willis, Lucia Notterpek, David Pleasure, Michael W. Sereda, Allison Moore
      Abstract: This brief review of current research progress on Charcot-Marie-Tooth (CMT) disease is a summary of discussions initiated at the Hereditary Neuropathy Foundation (HNF) scientific advisory board meeting on November 7, 2014. It covers recent published and unpublished in vitro and in vivo research. We discuss recent promising preclinical work for CMT1A, the development of new biomarkers, the characterization of different animal models, and the analysis of the frequency of gene mutations in patients with CMT. We also describe how progress in related fields may benefit CMT therapeutic development, including the potential of gene therapy and stem cell research. We also discuss the potential to assess and improve the quality of life of CMT patients. This summary of CMT research identifies some of the gaps which may have an impact on upcoming clinical trials. We provide some priorities for CMT research and areas which HNF can support. The goal of this review is to inform the scientific community about ongoing research and to avoid unnecessary overlap, while also highlighting areas ripe for further investigation. The general collaborative approach we have taken may be useful for other rare neurological diseases.
      PubDate: 2015-02-26T14:48:23Z
      DOI: 10.12688/f1000research.6160.1
      Issue No: Vol. 4 (2015)
       
  • Regulation of ryanodine receptor RyR2 by protein-protein interactions:
           prediction of a PKA binding site on the N-terminal domain of RyR2 and its
           

    • Authors: Belinda Nazan Walpoth, Burak Erman
      Abstract: Protein-protein interactions are the key processes responsible for signaling and function in complex networks. Determining the correct binding partners and predicting the ligand binding sites in the absence of experimental data require predictive models. Hybrid models that combine quantitative atomistic calculations with statistical thermodynamics formulations are valuable tools for bioinformatics predictions. We present a hybrid prediction and analysis model for determining putative binding partners and interpreting the resulting correlations in the yet functionally uncharacterized interactions of the ryanodine RyR2 N-terminal domain. Using extensive docking calculations and libraries of hexameric peptides generated from regulator proteins of the RyR2 channel, we show that the residues 318-323 of protein kinase A, PKA, have a very high affinity for the N-terminal of RyR2. Using a coarse grained Elastic Net Model, we show that the binding site lies at the end of a pathway of evolutionarily conserved residues in RyR2. The two disease causing mutations are also on this path. The program for the prediction of the energetically responsive residues by the Elastic Net Model is freely available on request from the corresponding author.
      PubDate: 2015-01-28T16:56:32Z
      DOI: 10.12688/f1000research.5858.1
      Issue No: Vol. 4 (2015)
       
  • Long read nanopore sequencing for detection of HLA and CYP2D6 variants and
           haplotypes [v1; indexed, http://f1000r.es/4zj]

    • Authors: Ron Ammar, Tara A. Paton, Dax Torti, Adam Shlien, Gary D. Bader
      Abstract: Haplotypes are often critical for the interpretation of genetic laboratory observations into medically actionable findings. Current massively parallel DNA sequencing technologies produce short sequence reads that are often unable to resolve haplotype information. Phasing short read data typically requires supplemental statistical phasing based on known haplotype structure in the population or parental genotypic data. Here we demonstrate that the MinION nanopore sequencer is capable of producing very long reads to resolve both variants and haplotypes of HLA-A, HLA-B and CYP2D6 genes important in determining patient drug response in sample NA12878 of CEPH/UTAH pedigree 1463, without the need for statistical phasing. Long read data from a single 24-hour nanopore sequencing run was used to reconstruct haplotypes, which were confirmed by HapMap data and statistically phased Complete Genomics and Sequenom genotypes. Our results demonstrate that nanopore sequencing is an emerging standalone technology with potential utility in a clinical environment to aid in medical decision-making.
      PubDate: 2015-01-21T15:08:42Z
      DOI: 10.12688/f1000research.6037.1
      Issue No: Vol. 4 (2015)
       
  • Development of an image-based screening system for inhibitors of the
           plastidial MEP pathway and of protein geranylgeranylation [v1; indexed,
           http://f1000r.es/4vt]

    • Authors: Michael Hartmann, Elisabet Gas-Pascual, Andrea Hemmerlin, Michel Rohmer, Thomas J. Bach
      Abstract: We have recently established an in vivo visualization system for the geranylgeranylation of proteins in a stably transformed tobacco BY-2 cell line, which involves expressing a dexamethasone-inducible GFP fused to the prenylable, carboxy-terminal basic domain of the rice calmodulin CaM61, which naturally bears a CaaL geranylgeranylation motif (GFP-BD-CVIL). By using pathway-specific inhibitors it was demonstrated that inhibition of the methylerythritol phosphate (MEP) pathway with oxoclomazone and fosmidomycin, as well as inhibition of protein geranylgeranyl transferase type 1 (PGGT-1), shifted the localization of the GFP-BD-CVIL protein from the membrane to the nucleus. In contrast, the inhibition of the mevalonate (MVA) pathway with mevinolin did not affect this localization. Furthermore, complementation assays with pathway-specific intermediates confirmed that the precursors for the cytosolic isoprenylation of this fusion protein are predominantly provided by the MEP pathway. In order to optimize this visualization system from a more qualitative assay to a statistically trustable medium or a high-throughput screening system, we established new conditions that permit culture and analysis in 96-well microtiter plates, followed by fluorescence microscopy. For further refinement, the existing GFP-BD-CVIL cell line was transformed with an estradiol-inducible vector driving the expression of a RFP protein, C-terminally fused to a nuclear localization signal (NLS-RFP). We are thus able to quantify the total number of viable cells versus the number of inhibited cells after various treatments. This approach also includes a semi-automatic counting system, based on the freely available image processing software. As a result, the time of image analysis as well as the risk of user-generated bias is reduced to a minimum. Moreover, there is no cross-induction of gene expression by dexamethasone and estradiol, which is an important prerequisite for this test system.
      PubDate: 2015-01-16T14:57:47Z
      DOI: 10.12688/f1000research.5923.1
      Issue No: Vol. 4 (2015)
       
  • Student perception about working in rural United States/Canada after
           graduation: a study in an offshore Caribbean medical school [v2; indexed,
           http://f1000r.es/5ac]

    • Authors: P Ravi Shankar, Arun K Dubey, Atanu Nandy, Burton L Herz, Brian W Little
      Abstract: Introduction: Rural residents of the United States (US) and Canada face problems in accessing healthcare. International medical graduates (IMGs) play an important role in delivering rural healthcare. IMGs from Caribbean medical schools have the highest proportion of physicians in primary care.  Xavier University School of Medicines admits students from the US, Canada and other countries to the undergraduate medical (MD) course and also offers a premedical program. The present study was conducted to obtain student perception about working in rural US/Canada after graduation.   Methods: The study was conducted among premedical and preclinical undergraduate medical (MD) students during October 2014. The questionnaire used was modified from a previous study. Semester of study, gender, nationality, place of residence and occupation of parents were noted. Information about whether students plan to work in rural US/Canada after graduation, possible reasons why doctors are reluctant to work in rural areas, how the government can encourage rural practice, possible problems respondents anticipate while working in rural areas were among the topics studied. Results: Ninety nine of the 108 students (91.7%) participated. Forty respondents were in favor of working in rural US/Canada after graduation. Respondents mentioned good housing, regular electricity, water supply, telecommunication facilities, and schools for education of children as important conditions to be fulfilled. The government should provide higher salaries to rural doctors, help with loan repayment, and provide opportunities for professional growth.  Potential problems mentioned were difficulty in being accepted by the rural community, problems in convincing patients to follow medical advice, lack of exposure to rural life among the respondents, and cultural issues. Conclusions: About 40% of respondents would consider working in rural US/Canada. Conditions required to be fulfilled have been mentioned above. Graduates from Caribbean medical schools have a role in addressing rural physician shortage. Similar studies in other offshore Caribbean medical schools are required as Caribbean IMGs make an important contribution to the rural US and Canadian health workforce.
      PubDate: 2015-04-23T11:19:47Z
      DOI: 10.12688/f1000research.5927.2
      Issue No: Vol. 3 (2015)
       
  • Malignant pleural effusions and the role of talc poudrage and talc slurry:
           a systematic review and meta-analysis [v2; indexed,
           http://f1000r.es/52v]

    • Authors: Srinivas Mummadi, Anusha Kumbam, Peter Y. Hahn
      Abstract: Background: Malignant Pleural Effusion (MPE) is common with advanced malignancy. Palliative care with minimal adverse events is the cornerstone of management. Although talc pleurodesis plays an important role in treatment, the best modality of talc application remains controversial.   Objective: To compare rates of successful pleurodesis, rates of respiratory and non-respiratory complications between thoracoscopic talc insufflation/poudrage (TTI) and talc slurry (TS).  Data sources and study selection: MEDLINE (PubMed, OVID),  EBM Reviews (Cochrane database of Systematic Reviews, ACP Journal Club, DARE, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, Health Technology Assessment and NHS Economic Evaluation Database), EMBASE and Scopus. Randomized controlled trials published between 01/01/1980 - 10/1/2014 and comparing the two strategies were selected.  Results: Twenty-eight potential studies were identified of which 24 studies were further excluded, leaving four studies. No statistically significant difference in the probability of successful pleurodesis was observed between TS and TTI groups (RR 1.06; 95 % CI 0.99-1.14; Q statistic, 4.84). There was a higher risk of post procedural respiratory complications in the TTI group compared to the TS group (RR 1.91, 95% CI= 1.24-2.93, Q statistic 3.15). No statistically significant difference in the incidence of non-respiratory complications between the TTI group and the TS group was observed (RR 0.88, 95% CI= 0.72-1.07, Q statistic 4.61). Conclusions: There is no difference in success rates of pleurodesis based on patient centered outcomes between talc poudrage and talc slurry treatments.  Respiratory complications are more common with talc poudrage via thoracoscopy.
      PubDate: 2015-02-17T14:03:19Z
      DOI: 10.12688/f1000research.5538.2
      Issue No: Vol. 3 (2015)
       
  • A critical evaluation of science outreach via social media: its role and
           impact on scientists [v1; indexed, http://f1000r.es/4vm]

    • Authors: Craig McClain, Liz Neeley
      Abstract: The role of scientists in social media and its impact on their careers are not fully explored.  While policies and best practices are still fluid, it is concerning that discourse is often based on little to no data, and some arguments directly contradict the available data.  Here, we consider the relevant but subjective questions about social media for science outreach (SOSM), specifically: (1) Does a public relations nightmare exist for science?; (2) Why (or why aren’t) scientists engaging in social media?; (3) Are scientists using social media well?; and (4) Will social media benefit a scientist’s career? We call for the scientific community to create tangible plans that value, measure, and help manage scientists’ social media engagement.
      PubDate: 2014-12-09T17:00:28Z
      DOI: 10.12688/f1000research.5918.1
      Issue No: Vol. 3 (2014)
       
  • Characterization of vaccine antigens of meningococcal serogroup W isolates
           from Ghana and Burkina Faso from 2003 to 2009 [v1; indexed,
           http://f1000r.es/37h]

    • Authors: Emma Ispasanie, Gerd Pluschke, Abraham Hodgson, Ali Sie, Calman MacLennan, Oliver Koeberling
      Abstract: Neisseria meningitidis is a major cause of bacterial meningitis and a considerable health problem in the 25 countries of the ‘African Meningitis Belt’ that extends from Senegal in West Africa to Ethiopia in the East. Approximately 80% of cases of meningococcal meningitis in Africa have been caused by strains belonging to capsular serogroup A. After the introduction of a serogroup A conjugate polysaccharide vaccine, MenAfriVac™, that began in December 2010, the incidence of meningitis due to serogroup A has markedly declined in this region. Currently, serogroup W of N. meningitidis accounts for the majority of cases. Vaccines based on sub-capsular antigens, such as Generalized Modules for Membrane Antigens (GMMA), are under investigation for use in Africa. To analyse the antigenic properties of a serogroup W wave of colonisation and disease, we investigated the molecular diversity of the protein vaccine antigens PorA, Neisserial Adhesin A (NadA), Neisserial heparin-binding antigen (NHBA) and factor H binding protein (fHbp) of 31 invasive and carriage serogroup W isolates collected as part of a longitudinal study from Ghana and Burkina Faso between 2003 and 2009. We found that the isolates all expressed fHbp variant 2 ID 22 or 23, differing from each other by only one amino acid, and a single PorA subtype of P1.5,2. Of the isolates, 49% had a functional nhbA gene and 100% had the nadA allele 3, which contained the insertion sequence IS1301 in five isolates. Of the W isolates tested, 41% had high fHbp expression when compared with a reference serogroup B strain, known to be a high expresser of fHbp variant 2. Our results indicate that in this collection of serogroup W isolates, there is limited antigenic diversification over time of vaccine candidate outer membrane proteins (OMP), thus making them promising candidates for inclusion in a protein-based vaccine against meningococcal meningitis for Africa.
      PubDate: 2014-11-03T15:44:10Z
      DOI: 10.12688/f1000research.3881.1
      Issue No: Vol. 3 (2014)
       
  • Visualisation of BioPAX Networks using BioLayout Express3D [v1; indexed,
           http://f1000r.es/4j1]

    • Authors: Derek W. Wright, Tim Angus, Anton J. Enright, Tom C. Freeman
      Abstract: BioLayout Express3D is a network analysis tool designed for the visualisation and analysis of graphs derived from biological data. It has proved to be powerful in the analysis of gene expression data, biological pathways and in a range of other applications. In version 3.2 of the tool we have introduced the ability to import, merge and display pathways and protein interaction networks available in the BioPAX Level 3 standard exchange format. A graphical interface allows users to search for pathways or interaction data stored in the Pathway Commons database. Queries using either gene/protein or pathway names are made via the cPath2 client and users can also define the source and/or species of information that they wish to examine. Data matching a query are listed and individual records may be viewed in isolation or merged using an ‘Advanced’ query tab. A visualisation scheme has been defined by mapping BioPAX entity types to a range of glyphs. Graphs of these data can be viewed and explored within BioLayout as 2D or 3D graph layouts, where they can be edited and/or exported for visualisation and editing within other tools.
      PubDate: 2014-10-20T13:43:39Z
      DOI: 10.12688/f1000research.5499.1
      Issue No: Vol. 3 (2014)
       
 
 
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