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Journal Cover   F1000Research
  [SJR: 0.219]   [H-I: 3]   [3 followers]  Follow
  This is an Open Access Journal Open Access journal
   ISSN (Online) 2046-1402
   Published by Faculty of 1000 Homepage  [1 journal]
  • Cytochrome P450 enzymes: understanding the biochemical hieroglyphs [v1;

    • Authors: John T. Groves
      Abstract: Cytochrome P450 (CYP) enzymes are the primary proteins of drug metabolism and steroid biosynthesis. These crucial proteins have long been known to harbor a cysteine thiolate bound to the heme iron. Recent advances in the field have illuminated the nature of reactive intermediates in the reaction cycle. Similar intermediates have been observed and characterized in novel heme-thiolate proteins of fungal origin. Insights from these discoveries have begun to solve the riddle of how enzyme biocatalyst design can afford a protein that can transform substrates that are more difficult to oxidize than the surrounding protein architecture.
      PubDate: 2015-07-01T14:23:06Z
      DOI: 10.12688/f1000research.6314.1
      Issue No: Vol. 4 (2015)
  • Drosophila's contribution to stem cell research [v1; indexed,

    • Authors: Gyanesh Singh
      Abstract: The discovery of Drosophila stem cells with striking similarities to mammalian stem cells has brought new hope for stem cell research. A recent development in Drosophila stem cell research is bringing wider opportunities for contemporary stem cell biologists. In this regard, Drosophila germ cells are becoming a popular model of stem cell research. In several cases, genes that controlled Drosophila stem cells were later discovered to have functional homologs in mammalian stem cells. Like mammals, Drosophila germline stem cells (GSCs) are controlled by both intrinsic as well as external signals. Inside the Drosophila testes, germline and somatic stem cells form a cluster of cells (the hub). Hub cells depend on JAK-STAT signaling, and, in absence of this signal, they do not self-renew. In Drosophila, significant changes occur within the stem cell niche that contributes to a decline in stem cell number over time. In case of aging Drosophila, somatic niche cells show reduced DE-cadherin and unpaired (Upd) proteins. Unpaired proteins are known to directly decrease stem cell number within the niches, and, overexpression of upd within niche cells restored GSCs in older males also . Stem cells in the midgut of Drosophila are also very promising. Reduced Notch signaling was found to increase the number of midgut progenitor cells. On the other hand, activation of the Notch pathway decreased proliferation of these cells. Further research in this area should lead to the discovery of additional factors that regulate stem and progenitor cells in Drosophila.
      PubDate: 2015-06-18T15:32:28Z
      DOI: 10.12688/f1000research.6611.1
      Issue No: Vol. 4 (2015)
  • 1-Octen-3-ol – the attractant that repels [v1; indexed,

    • Authors: Pingxi Xu, Fen Zhu, Garrison K. Buss, Walter S. Leal
      Abstract: Since the discovery in the early 1980s that 1-octen-3-ol, isolated from oxen breath, attracts tsetse fly, there has been growing interest in exploring the use of this semiochemical as a possible generic lure for trapping host-seeking mosquitoes. Intriguingly, traps baited with 1-octen-3-ol captured significantly more females of the malaria mosquito, Anopheles gambiae, and the yellow fever mosquito, Aedes aegypti, than control traps, but failed to attract the southern house mosquito, Culex quinquefasciatus. Additionally, it has been demonstrated that this attractant is detected with enantioselective odorant receptors (ORs) expressed only in maxillary palps. On the basis of indoor behavioral assays it has even been suggested that 1-octen-3-ol might be a repellent to the southern house mosquito. Our approach was two-prong, i.e., to isolate 1-octen-3-ol-sensitive ORs expressed in maxillary palps and antennae of southern house female mosquito, and test the hypothesis that this semiochemical is a repellent. An OR with high transcript levels in maxillary palps, CquiOR118b, showed remarkable selectivity towards (R)-1-octen-3-ol, whereas an OR expressed in antennae, CquiOR114b, showed higher preference for (S)-1-octen-3-ol than its antipode. Repellency by a surface landing and feeding assay showed that not only racemic, but enantiopure (R)- and (S)-1-octen-3-ol are repellents at 1% dose thus suggesting the occurrence of other (S)-1-octen-3-ol-sensitive OR(s). Female mosquitoes with ablated maxillary palps were repelled by 1-octen-3-ol, which implies that in addition to OR(s) in the maxillary palps, antennal OR(s) are essential for repellency activity.
      PubDate: 2015-06-18T14:12:45Z
      DOI: 10.12688/f1000research.6646.1
      Issue No: Vol. 4 (2015)
  • Personal attributes of authors and reviewers, social bias and the outcomes
           of peer review: a case study [v2; indexed,]

    • Authors: Richard Walker, Beatriz Barros, Ricardo Conejo, Konrad Neumann, Martin Telefont
      Abstract: Peer review is the "gold standard" for evaluating journal and conference papers, research proposals, on-going projects and university departments. However, it is widely believed that current systems are expensive, conservative and prone to various forms of bias. One form of bias identified in the literature is “social bias” linked to the personal attributes of authors and reviewers. To quantify the importance of this form of bias in modern peer review, we analyze three datasets providing information on the attributes of authors and reviewers and review outcomes: one from Frontiers - an open access publishing house with a novel interactive review process, and two from Spanish and international computer science conferences, which use traditional peer review. We use a random intercept model in which review outcome is the dependent variable, author and reviewer attributes are the independent variables and bias is defined by the interaction between author and reviewer attributes. We find no evidence of bias in terms of gender, or the language or prestige of author and reviewer institutions in any of the three datasets, but some weak evidence of regional bias in all three. Reviewer gender and the language and prestige of reviewer institutions appear to have little effect on review outcomes, but author gender, and the characteristics of author institutions have moderate to large effects. The methodology used cannot determine whether these are due to objective differences in scientific merit or entrenched biases shared by all reviewers.
      PubDate: 2015-06-10T15:35:15Z
      DOI: 10.12688/f1000research.6012.2
      Issue No: Vol. 4 (2015)
  • Longitudinal variations of brain functional connectivity: A case report
           study based on a mouse model of epilepsy [v1; indexed,

    • Authors: A. Erramuzpe, J. M. Encinas, A. Sierra, M. Maletic-Savatic, A.L. Brewster, Anne E. Anderson, S. Stramaglia, Jesus M. Cortes
      Abstract: Brain Functional Connectivity (FC) quantifies statistical dependencies between areas of the brain. FC has been widely used to address altered function of brain circuits in control conditions compared to different pathological states, including epilepsy, a major neurological disorder. However, FC also has the as yet unexplored potential to help us understand the pathological transformation of the brain circuitry. Our hypothesis is that FC can differentiate global brain interactions across a time-scale of days. To this end, we present a case report study based on a mouse model for epilepsy and analyze longitudinal intracranial electroencephalography data of epilepsy to calculate FC across three stages:   1, the initial insult (status epilepticus); 2, the latent period, when epileptogenic networks emerge; and 3, chronic epilepsy, when unprovoked seizures occur as spontaneous events. We found that the overall network FC at low frequency bands decreased immediately after status epilepticus was provoked, and increased monotonously later on during the latent period. Overall, our results demonstrate the capacity  of FC to address longitudinal variations of brain connectivity across the establishment of pathological states.
      PubDate: 2015-06-05T15:00:00Z
      DOI: 10.12688/f1000research.6570.1
      Issue No: Vol. 4 (2015)
  • Targeting metastatic breast cancer: problems and potential [v1; indexed,

    • Authors: Sarah Deasy, Karol Szczepanek, Kent Hunter
      Abstract: Breast cancer is one of the leading causes of cancer-related mortality of women in the United States. Since the majority of cancer deaths are due to metastases rather than the primary tumor, a better understanding of the biological mechanisms that lead to metastatic disease is critical to reduce breast cancer associated mortality. Current adjuvant therapies use the same broadly cytotoxic and targeted strategies against metastases as are used against the primary tumor. However, resistance to chemotherapy due to the cellular dormancy, high genotypic and phenotypic heterogeneity between primary tumor and metastases as well as among individual metastases, and the limitations in detection of disseminated tumor cells and micrometastases significantly hinder the efficiency of currently available therapies. While it is crucial to directly address the issue of metastatic dormancy and evaluate for anti-metastatic therapy the relevance of molecular targets chosen based on primary tumor profiling, it is also imperative to address metastasis-specific mechanisms of growth and survival that are likely to be distinct from those of the primary tumor. We believe that a three-pronged approach to therapy will be necessary to deal with progressive disease: blocking of further dissemination after diagnosis; eradication of disseminated tumor cells and prevention of the dormant-to-proliferative switch of those remaining; and elimination of established metastatic tumors. The implementation of this strategy requires a greater depth of knowledge of metastasis driver and maintenance genes and suggests the need for a “Metastasis Genome Atlas” project to complement the current investigations into cancer genomic landscapes.
      PubDate: 2015-06-04T14:45:03Z
      DOI: 10.12688/f1000research.6151.1
      Issue No: Vol. 4 (2015)
  • Prediction of multi-drug resistance transporters using a novel sequence
           analysis method [v2; indexed,]

    • Authors: Jason E. McDermott, Paul Bruillard, Christopher C. Overall, Luke Gosink, Stephen R. Lindemann
      Abstract: There are many examples of groups of proteins that have similar function, but the determinants of functional specificity may be hidden by lack of sequence similarity, or by large groups of similar sequences with different functions. Transporters are one such protein group in that the general function, transport, can be easily inferred from the sequence, but the substrate specificity can be impossible to predict from sequence with current methods. In this paper we describe a linguistic-based approach to identify functional patterns from groups of unaligned protein sequences and its application to predict multi-drug resistance transporters (MDRs) from bacteria. We first show that our method can recreate known patterns from PROSITE for several motifs from unaligned sequences. We then show that the method, MDRpred, can predict MDRs with greater accuracy and positive predictive value than a collection of currently available family-based models from the Pfam database. Finally, we apply MDRpred to a large collection of protein sequences from an environmental microbiome study to make novel predictions about drug resistance in a potential environmental reservoir.
      PubDate: 2015-05-29T15:34:10Z
      DOI: 10.12688/f1000research.6200.2
      Issue No: Vol. 4 (2015)
  • The Resource Identification Initiative: A cultural shift in publishing
           [v1; indexed,]

    • Authors: Anita Bandrowski, Matthew Brush, Jeffery S. Grethe, Melissa A. Haendel, David N. Kennedy, Sean Hill, Patrick R. Hof, Maryann E. Martone, Maaike Pols, Serena Tan, Nicole Washington, Elena Zudilova-Seinstra, Nicole Vasilevsky, Resource Identification Initiative Members are listed here:
      Abstract: A central tenet in support of research reproducibility is the ability to uniquely identify research resources, i.e., reagents, tools, and materials that are used to perform experiments. However, current reporting practices for research resources are insufficient to allow humans and algorithms to identify the exact resources that are reported or answer basic questions such as “What other studies used resource X'” To address this issue, the Resource Identification Initiative was launched as a pilot project to improve the reporting standards for research resources in the methods sections of papers and thereby improve identifiability and reproducibility. The pilot engaged over 25 biomedical journal editors from most major publishers, as well as scientists and funding officials.
      Authors were asked to include Research Resource Identifiers (RRIDs) in their manuscripts prior to publication for three resource types: antibodies, model organisms, and tools (including software and databases). RRIDs represent accession numbers assigned by an authoritative database, e.g., the model organism databases, for each type of resource. To make it easier for authors to obtain RRIDs, resources were aggregated from the appropriate databases and their RRIDs made available in a central web portal ( RRIDs meet three key criteria: they are machine readable, free to generate and access, and are consistent across publishers and journals. The pilot was launched in February of 2014 and over 300 papers have appeared that report RRIDs. The number of journals participating has expanded from the original 25 to more than 40. Here, we present an overview of the pilot project and its outcomes to date. We show that authors are generally accurate in performing the task of identifying resources and supportive of the goals of the project. We also show that identifiability of the resources pre- and post-pilot showed a dramatic improvement for all three resource types, suggesting that the project has had a significant impact on reproducibility relating to research resources.
      PubDate: 2015-05-29T10:42:09Z
      DOI: 10.12688/f1000research.6555.1
      Issue No: Vol. 4 (2015)
  • Transgenic supplementation of SIRT1 fails to alleviate acute loss of
           nigrostriatal dopamine neurons and gliosis in a mouse model of
           MPTP-induced parkinsonism [v1; indexed,]

    • Authors: Yasuko Kitao, Natsumi Ageta-Ishihara, Ryosuke Takahashi, Makoto Kinoshita, Osamu Hori
      Abstract: Background Dopamine (DA) neuron-selective uptake and toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes parkinsonism in humans. Loss of DA neurons via mitochondrial damage and oxidative stress is reproduced by systemic injection of MPTP in animals, which serves as models of parkinsonism and Parkinson’s disease (PD). This study aimed to test whether pan-neural supplementation of the longevity-related, pleiotropic deacetylase SIRT1, which confers partial tolerance to at least three models of stroke and neurodegeneration, could also alleviate MPTP-induced acute pathological changes in nigrostriatal DA neurons and neighboring glia. Results We employed a line of prion promoter-driven Sirt1-transgenic (Sirt1Tg) mice that chronically overexpress murine SIRT1 in the brain and spinal cord. Sirt1Tg and wild-type (WT) male littermates (3‒4 months old) were subjected to intraperitoneal injection of MPTP. Acute histopathological changes in the midbrain and striatum (caudoputamen) were assessed with serial coronal sections triply labeled for tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), and nuclear DNA. In the substantia nigra pars compacta (SNpc) of the midbrain, the number of TH-positive neurons and the reactive gliosis were comparable between the Sirt1Tg and WT littermates. In the striatum, the relative fluorescence intensity of TH-positive nerve terminals and the level of gliosis did not differ by the genotypes. Conclusions Sirt1Tg and WT littermate mice exhibited comparable acute histopathological reactions to the systemic injection of MPTP, loss of TH-positive neurons and reactive gliosis. Thus, the genetic supplementation of SIRT1 does not confer histologically recognizable protection on nigrostriatal DA neurons against acute toxicity of MPTP.
      PubDate: 2015-05-27T15:00:15Z
      DOI: 10.12688/f1000research.6386.1
      Issue No: Vol. 4 (2015)
  • Developmental biology teaching - the importance of a practical approach
           [v1; indexed,]

    • Authors: John F Mulley
      Abstract: The huge growth in knowledge in many areas of biological sciences over the past few decades has created a major dilemma for those of us in higher education, for not only must we adequately and efficiently convey these new facts and concepts to our students, we must also ensure that they understand and appreciate them. The field of developmental biology has witnessed such a massive growth in knowledge since the mid-1980s, driven mainly by advances in cell and molecular biology, and the development of new imaging techniques and tools. Ensuring that students fully appreciate the four-dimensional nature of embryonic development and morphogenesis is a particular issue, and one that I argue can only be properly learned via direct exposure to embryos via laboratory practicals.
      PubDate: 2015-05-26T10:01:32Z
      DOI: 10.12688/f1000research.6559.1
      Issue No: Vol. 4 (2015)
  • Unexpected lack of specificity of a rabbit polyclonal TAP-L (ABCB9)
           antibody [v1; indexed,]

    • Authors: Peter van Endert, Myriam Lawand
      Abstract: In this article, we describe the surprising non-specific reactivity in immunoblots of a rabbit polyclonal antibody (ref. Abcam 86222) expected to recognize the transporter associated with antigen processing like (TAP-L, ABCB9) protein. Although this antibody, according to company documentation, recognizes a band with the expected molecular weight of 84 kDa in HeLa, 293T and mouse NIH3T3 whole-cell lysates, we found that this band is also present in immunoblots of TAP-L deficient bone marrow-derived dendritic cell (BMDC) whole-cell lysates in three independent replicates. We performed extensive verification by multiple PCR tests to confirm the complete absence of the ABCB9 gene in our TAP-L deficient mice. We conclude that the antibody tested cross-reacts with an unidentified protein present in TAP-L knockout cells, which coincidentally runs at the same molecular weight as TAP-L. These findings underline the pitfalls of antibody specificity testing in the absence of cells lacking expression of the target protein.
      PubDate: 2015-05-22T16:06:26Z
      DOI: 10.12688/f1000research.6535.1
      Issue No: Vol. 4 (2015)
  • A reanalysis of mouse ENCODE comparative gene expression data [v1;

    • Authors: Yoav Gilad, Orna Mizrahi-Man
      Abstract: Recently, the Mouse ENCODE Consortium reported that comparative gene expression data from human and mouse tend to cluster more by species rather than by tissue. This observation was surprising, as it contradicted much of the comparative gene regulatory data collected previously, as well as the common notion that major developmental pathways are highly conserved across a wide range of species, in particular across mammals. Here we show that the Mouse ENCODE gene expression data were collected using a flawed study design, which confounded sequencing batch (namely, the assignment of samples to sequencing flowcells and lanes) with species. When we account for the batch effect, the corrected comparative gene expression data from human and mouse tend to cluster by tissue, not by species.
      PubDate: 2015-05-19T13:23:16Z
      DOI: 10.12688/f1000research.6536.1
      Issue No: Vol. 4 (2015)
  • In silico analysis suggests repurposing of ibuprofen for prevention and
           treatment of EBOLA virus disease [v1; indexed,]

    • Authors: Veljko Veljkovic, Marco Goeijenbier, Sanja Glisic, Nevena Veljkovic, Vladimir R. Perovic, Milan Sencanski, Donald R. Branch, Slobodan Paessler
      Abstract: The large 2014/2015 Ebola virus outbreak in West Africa points out the urgent need to develop new preventive and therapeutic approaches that are effective against Ebola viruses and  can be rapidly utilized. Recently, a simple theoretical criterion for the virtual screening of molecular libraries for candidate inhibitors of Ebola virus infection was proposed. Using this method the ‘drug space’ was screened and 267 approved and 382 experimental drugs as candidates for treatment of the Ebola virus disease (EVD) have been selected. Detailed analysis of these drugs revealed the non-steroidal anti-inflammatory drug ibuprofen as an inexpensive, widely accessible and minimally toxic candidate for prevention and treatment of EVD. Furthermore, the molecular mechanism underlying this possible protective effect of ibuprofen against EVD is suggested in this article.
      PubDate: 2015-05-01T12:59:28Z
      DOI: 10.12688/f1000research.6436.1
      Issue No: Vol. 4 (2015)
  • Linking patient outcome to high throughput protein expression data
           identifies novel regulators of colorectal adenocarcinoma aggressiveness
           [v1; indexed,]

    • Authors: Christi L. French, Fei Ye, Frank Revetta, Bing Zhang, Robert J. Coffey, M. Kay Washington, Natasha G. Deane, R. Daniel Beauchamp, Alissa M. Weaver
      Abstract: A key question in cancer systems biology is how to use molecular data to predict the biological behavior of tumors from individual patients. While genomics data have been heavily used, protein signaling data are more directly connected to biological phenotype and might predict cancer phenotypes such as invasion, metastasis, and patient survival. In this study, we mined publicly available data for colorectal adenocarcinoma from the Cancer Genome Atlas and identified protein expression and signaling changes that are statistically associated with patient outcome. Our analysis identified a number of known and potentially new regulators of colorectal cancer. High levels of insulin growth factor binding protein 2 (IGFBP2) were associated with both recurrence and death, and this was validated by immunohistochemical staining of a tissue microarray for a secondary patient dataset. Interestingly, GATA binding protein 3 (GATA3) was the protein most frequently associated with death in our analysis, and GATA3 expression was significantly decreased in tumor samples from stage I-II deceased patients. Experimental studies using engineered colon cancer cell lines show that exogenous expression of GATA3 decreases three-dimensional colony growth and invasiveness of colon cancer cells but does not affect two-dimensional proliferation. These findings suggest that protein data are useful for biomarker discovery and identify GATA3 as a regulator of colorectal cancer  aggressiveness.
      PubDate: 2015-04-24T14:10:29Z
      DOI: 10.12688/f1000research.6388.1
      Issue No: Vol. 4 (2015)
  • Algorithm for the anesthetic management of cesarean delivery in patients
           with unsatisfactory labor epidural analgesia [v1; indexed,

    • Authors: Sonia Vaida, Davide Cattano, Debra Hurwitz, Berend Mets
      Abstract: The management of a patient presenting with unsatisfactory labor epidural analgesia poses a severe challenge for the anesthetist wanting to provide safe anesthetic care for a cesarean delivery. Early recognition of unsatisfactory labor analgesia allows for replacement of the epidural catheter. The decision to convert labor epidural analgesia to anesthesia for cesarean delivery is based on the urgency of the cesarean delivery, airway examination, and the existence of a residual sensory and motor block.  We suggest an algorithm which is implemented in our department, based on the urgency of the cesarean delivery.
      PubDate: 2015-04-24T10:28:46Z
      DOI: 10.12688/f1000research.6381.1
      Issue No: Vol. 4 (2015)
  • Case Report: Primary dural based diffuse large B-Cell lymphoma in a 14
           year-old boy [v1; indexed,]

    • Authors: Sunil Munakomi, Binod Bhattarai, Balaji Srinivas, Iype Cherian
      Abstract: Primary dural lymphoma is a subentity of primary leptomeningeal lymphoma which represents 0.1% of all non-Hodgkin’s lymphomas. Only five cases have been reported so far. We report a very rare case of primary dural-based lymphoma in a 14 year-old boy presenting with mass effect. The patient was managed with excision of the lesion and removal of the involved bone. Post-operatively, the patient showed good recovery. He was then referred to the oncology unit for further chemo- and radiation therapy. A high index of suspicion should therefore be kept in order to diagnose the condition in a timely fashion and then plan for appropriate management since diffuse large cell lymphoma has a relatively benign clinical prognosis.
      PubDate: 2015-03-25T10:41:12Z
      DOI: 10.12688/f1000research.6269.1
      Issue No: Vol. 4 (2015)
  • Resources, challenges and way forward in rare mitochondrial diseases
           research [v1; indexed,]

    • Authors: Anshu Bhardwaj, Neeraj Kumar Rajput, Vipin Singh
      Abstract: Over 300 million people are affected by about 7000 rare diseases globally. There are tremendous resource limitations and challenges in driving research and drug development for rare diseases. Hence, innovative approaches are needed to identify potential solutions. This review focuses on the resources developed over the past years for analysis of genome data towards understanding disease biology especially in the context of mitochondrial diseases, given that mitochondria are central to major cellular pathways and their dysfunction leads to a broad spectrum of diseases. Platforms for collaboration of research groups, clinicians and patients and the advantages of community collaborative efforts in addressing rare diseases are also discussed. The review also describes crowdsourcing and crowdfunding efforts in rare diseases research and how the upcoming initiatives for understanding disease biology including analyses of large number of genomes are also applicable to rare diseases.
      PubDate: 2015-03-16T17:29:15Z
      DOI: 10.12688/f1000research.6208.1
      Issue No: Vol. 4 (2015)
  • Interactive lectures: Clickers or personal devices' [v1; indexed,

    • Authors: Lesley J. Morrell, Domino A. Joyce
      Abstract: Audience response systems (‘clickers’) are frequently used to promote participation in large lecture classes, and evidence suggests that they convey a number of benefits to students, including improved academic performance and student satisfaction. The limitations of these systems (such as limited access and cost) can be overcome using students’ personal electronic devices, such as mobile phones, tablets and laptops together with text message, web- or app-based polling systems. Using questionnaires, we compare student perceptions of clicker and smartphone based polling systems. We find that students prefer interactive lectures generally, but those that used their own device preferred those lectures over lectures using clickers. However, device users were more likely to report using their devices for other purposes (checking email, social media etc.) when they were available to answer polling questions. These students did not feel that this distracted them from the lecture, instead, concerns over the use of smartphones centred around increased battery usage and inclusivity for students without access to suitable technology. Our results suggest that students generally preferred to use their own devices over clickers, and that this may be a sensible way to overcome some of the limitations associated with clickers, although issues surrounding levels of distraction and the implications for retention and recall of information need further investigation.
      PubDate: 2015-03-12T10:38:25Z
      DOI: 10.12688/f1000research.6207.1
      Issue No: Vol. 4 (2015)
  • Structure and dynamics of the membrane attaching nitric oxide transporter
           nitrophorin 7 [v1; indexed,]

    • Authors: Markus Knipp, Hideaki Ogata, Giancarlo Soavi, Giulio Cerullo, Alessandro Allegri, Stefania Abbruzzetti, Stefano Bruno, Cristiano Viappiani, Axel Bidon-Chanal, F. Javier Luque
      Abstract: Nitrophorins represent a unique class of heme proteins that are able to perform the delicate transportation and release of the free-radical gaseous messenger nitric oxide (NO) in a pH-triggered manner. Besides its ability to bind to phospholipid membranes, the N-terminus contains an additional Leu-Pro-Gly stretch, which is a unique sequence trait, and the heme cavity is significantly altered with respect to other nitrophorins. These distinctive features encouraged us to solve the X-ray crystallographic structures of NP7 at low and high pH and bound with different heme ligands (nitric oxide, histamine, imidazole). The overall fold of the lipocalin motif is well preserved in the different X-ray structures and resembles the fold of other nitrophorins. However, a chain-like arrangement in the crystal lattice due to a number of head-to-tail electrostatic stabilizing interactions is found in NP7. Furthermore, the X-ray structures also reveal ligand-dependent changes in the orientation of the heme, as well as in specific interactions between the A-B and G-H loops, which are considered to be relevant for the biological function of nitrophorins. Fast and ultrafast laser triggered ligand rebinding experiments demonstrate the pH-dependent ligand migration within the cavities and the exit route. Finally, the topological distribution of pockets located around the heme as well as from inner cavities present at the rear of the protein provides a distinctive feature in NP7, so that while a loop gated exit mechanism to the solvent has been proposed for most nitrophorins, a more complex mechanism that involves several interconnected gas hosting cavities is proposed for NP7.
      PubDate: 2015-02-13T15:40:27Z
      DOI: 10.12688/f1000research.6060.1
      Issue No: Vol. 4 (2015)
  • AGA: Interactive pipeline for reproducible genomics analyses [v1; indexed,

    • Authors: Michael Considine, Hilary Parker, Yingying Wei, Xaio Xia, Leslie Cope, Michael Ochs, Elana Fertig
      Abstract: Automated Genomics Analysis (AGA) is an interactive program to analyze high-throughput genomic data sets on a variety of platforms. An easy to use, point and click, guided pipeline is implemented to combine, define, and compare datasets, and customize their outputs. In contrast to other automated programs, AGA enables flexible selection of sample groups for comparison from complex sample annotations. Batch correction techniques are also included to further enable the combination of datasets from diverse studies in this comparison. AGA also allows users to save plots, tables and data, and log files containing key portions of the R script run for reproducible analyses. The link between the interface and R supports collaborative research, enabling advanced R users to extend preliminary analyses generated from bioinformatics novices.
      PubDate: 2015-01-28T16:54:54Z
      DOI: 10.12688/f1000research.6030.1
      Issue No: Vol. 4 (2015)
  • Reliability and reproducibility of spectral and time domain optical
           coherence tomography images before and after correction for patients with
           age-related macular degeneration [v2; indexed,]

    • Authors: Mohammad A. Sadiq, Aymen Rashid, Roomasa Channa, Elham Hatef, Diana V Do, Quan Dong Nguyen, Yasir J Sepah
      Abstract: Purpose: To evaluate the reproducibility and reliability of optical coherence tomography scans obtained using the time domain (TD-OCT) StratusTM OCT, and the Spectral Domain (SD-OCT) SpectralisTM and CirrusTM OCT devices before and after manual correction in eyes with either Neovascular (NV-AMD) or Non-Neovascular (NNV-AMD) age-related macular degeneration. Design: Prospective observational study. Methods: Setting: University-based retina practice. Patients: Thirty-six patients (50 eyes) with NV-AMD or NNV-AMD. Procedure: OCT scans were taken simultaneously using one TD-OCT and two SD-OCT devices. Main Outcome Measures: Macular thickness measurements were assessed before and after correction of the algorithm by constructing Bland-Altman plots for agreement and calculating intraclass correlation coefficients (ICCs) and coefficients of repeatability (COR) to evaluate intraclass repeatability. Results: Spectralis had the highest number of images needing manual correction.  All machines had high ICCs, with Spectralis having the highest.  Also, Bland-Altman plots indicated that there was low agreement between Cirrus™ and Stratus™, Spectralis™ and Stratus™, while there was good agreement between the Cirrus™ and Spectralis™.  The CORs were lowest for SpectralisTM and similar and higher for CirrusTM and StratusTM.  Agreement, CORs, and ICCs generally improved after manual correction, but only minimally.  Conclusion: Agreement is low between devices, except between both SD-OCT machines.  Manual correction tends to improve results.
      PubDate: 2015-03-05T14:45:10Z
      DOI: 10.12688/f1000research.2-131.v2
      Issue No: Vol. 2 (2015)
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