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Journal Cover   F1000Research
  [SJR: 0.219]   [H-I: 3]   [4 followers]  Follow
    
  This is an Open Access Journal Open Access journal
   ISSN (Online) 2046-1402
   Published by Faculty of 1000 Homepage  [1 journal]
  • Advances in understanding cartilage remodeling [v1; indexed,
           http://f1000r.es/5e6]

    • Authors: Yefu Li, Lin Xu
      Abstract: Cartilage remodeling is currently among the most popular topics in osteoarthritis research. Remodeling includes removal of the existing cartilage and replacement by neo-cartilage. As a loss of balance between removal and replacement of articular cartilage develops (particularly, the rate of removal surpasses the rate of replacement), joints will begin to degrade. In the last few years, significant progress in molecular understanding of the cartilage remodeling process has been made. In this brief review, we focus on the discussion of some current “controversial” observations in articular cartilage degeneration: (1) the biological effect of transforming growth factor-beta 1 on developing and mature articular cartilages, (2) the question of whether aggrecanase 1 (ADAMTS4) and aggrecanase 2 (ADAMTS5) are key enzymes in articular cartilage destruction, and (3) chondrocytes versus chondron in the development of osteoarthritis. It is hoped that continued discussion and investigation will follow to better clarify these topics. Clarification will be critical for those in search of novel therapeutic targets for the treatment of osteoarthritis.
      PubDate: 2015-08-28T14:02:52Z
      DOI: 10.12688/f1000research.6514.1
      Issue No: Vol. 4 (2015)
       
  • Computer-aided drug discovery [v1; indexed, http://f1000r.es/5ij]

    • Abstract: Computational approaches are an integral part of interdisciplinary drug discovery research. Understanding the science behind computational tools, their opportunities, and limitations is essential to make a true impact on drug discovery at different levels. If applied in a scientifically meaningful way, computational methods improve the ability to identify and evaluate potential drug molecules, but there remain weaknesses in the methods that preclude naïve applications. Herein, current trends in computer-aided drug discovery are reviewed, and selected computational areas are discussed. Approaches are highlighted that aid in the identification and optimization of new drug candidates. Emphasis is put on the presentation and discussion of computational concepts and methods, rather than case studies or application examples. As such, this contribution aims to provide an overview of the current methodological spectrum of computational drug discovery for a broad audience.
      PubDate: 2015-08-26T13:19:56Z
      DOI: 10.12688/f1000research.6653.1
      Issue No: Vol. 4 (2015)
       
  • Sevoflurane [v1; indexed, http://f1000r.es/57c]

    • Authors: Stefan De Hert, Anneliese Moerman
      Abstract: Sevoflurane has been available for clinical practice for about 20 years. Nowadays, its pharmacodynamic and pharmacokinetic properties together with its absence of major adverse side effects on the different organ systems have made this drug accepted worldwide as a safe and reliable anesthetic agent for clinical practice in various settings.
      PubDate: 2015-08-25T14:11:00Z
      DOI: 10.12688/f1000research.6288.1
      Issue No: Vol. 4 (2015)
       
  • Congenital Adrenal Hyperplasia [v1; indexed, http://f1000r.es/5f6]

    • Authors: Phyllis W. Speiser
      Abstract: Congenital adrenal hyperplasia associated with deficiency of steroid 21-hydroxylase is the most common inborn error in adrenal function and the most common cause of adrenal insufficiency in the pediatric age group. As patients now survive into adulthood, adult health-care providers must also be familiar with this condition. Over the past several years, F1000 has published numerous commentaries updating research and practical guidelines for this condition. The purposes of this review are to summarize basic information defining congenital adrenal hyperplasia and to highlight current knowledge and controversies in management.
      PubDate: 2015-08-20T16:02:24Z
      DOI: 10.12688/f1000research.6543.1
      Issue No: Vol. 4 (2015)
       
  • Recent advances in understanding/managing eosinophilic esophagitis in
           adults [v1; indexed, http://f1000r.es/5rn]

    • Authors: David A. Katzka
      Abstract: It is an exciting time for research in eosinophilic esophagitis (EoE). As a new and increasingly prevalent disease, it is receiving considerable attention in the medical world, resulting in a flood of new insights. Clearly, a genetic predisposition seems likely with the identification of abnormalities in thymic stromal lymphopoietin (TSLP), calpain14, and eotaxin-3 genes. There are also well-defined abnormalities described in esophageal epithelial barrier function in these patients. The relationship between gastroesophageal reflux disease (GERD) and EoE remains unclear, but emerging data suggest that the concept of proton pump inhibitor responsive esophageal eosinophilia (PPIREE) may retain less importance, as this subset of patients becomes a likely subset of EoE in general. Finally, we approach the looming issue of long-term maintenance therapy. Although we lack adequate specific data on how to provide long-term pharmacologic treatment, studies clearly show that for most patients, this is a progressive disease that warrants such consideration.
      PubDate: 2015-08-20T14:38:21Z
      DOI: 10.12688/f1000research.6942.1
      Issue No: Vol. 4 (2015)
       
  • Androgenetic alopecia: new insights into the pathogenesis and mechanism of
           hair loss [v1; indexed, http://f1000r.es/5ar]

    • Authors: Rodney Sinclair, Niloufar Torkamani, Leslie Jones
      Abstract: The hair follicle is a complete mini-organ that lends itself as a model for investigation of a variety of complex biological phenomena, including stem cell biology, organ regeneration and cloning.  The arrector pili muscle inserts into the hair follicle at the level of the bulge- the epithelial stem cell niche.  The arrector pili muscle has been previously thought to be merely a bystander and not to have an active role in hair disease. Computer generated 3D reconstructions of the arrector pili muscle have helped explain why women with androgenetic alopecia (AGA) experience diffuse hair loss rather than the patterned baldness seen in men.  Loss of attachment between the bulge stem cell population and the arrector pili muscle also explains why miniaturization is irreversible in AGA but not alopecia areata. A new model for the progression of AGA is presented.
      PubDate: 2015-08-19T15:19:05Z
      DOI: 10.12688/f1000research.6401.1
      Issue No: Vol. 4 (2015)
       
  • Cadherin signaling: keeping cells in touch [v1; indexed,
           http://f1000r.es/5c4]

    • Authors: Olga Klezovitch, Valeri Vasioukhin
      Abstract: Cadherin-catenin complexes are critical for the assembly of cell-cell adhesion structures known as adherens junctions. In addition to the mechanical linkage of neighboring cells to each other, these cell-cell adhesion protein complexes have recently emerged as important sensors and transmitters of the extracellular cues inside the cell body and into the nucleus. In the past few years, multiple studies have identified a connection between the cadherin-catenin protein complexes and major intracellular signaling pathways. Those studies are the main focus of this review.
      PubDate: 2015-08-12T10:45:05Z
      DOI: 10.12688/f1000research.6445.1
      Issue No: Vol. 4 (2015)
       
  • Novel Insights and Therapeutics in Multiple Sclerosis [v1; indexed,
           http://f1000r.es/59z]

    • Authors: Catriona A. Wagner, Joan M. Goverman
      Abstract: The last twelve years have witnessed the development of new therapies for relapsing-remitting multiple sclerosis that demonstrate increased efficacy relative to previous therapies. Many of these new drugs target the inflammatory phase of disease by manipulating different aspects of the immune system. While these new treatments are promising, the development of therapies for patients with progressive multiple sclerosis remains a significant challenge. We discuss the distinct mechanisms that may contribute to these two types of multiple sclerosis and the implications of these differences in the development of new therapeutic targets for this debilitating disease.
      PubDate: 2015-08-07T15:18:41Z
      DOI: 10.12688/f1000research.6378.1
      Issue No: Vol. 4 (2015)
       
  • Membrane manipulations by the ESCRT machinery [v1; indexed,
           http://f1000r.es/588]

    • Authors: Greg Odorizzi
      Abstract: The endosomal sorting complexes required for transport (ESCRTs) collectively comprise a machinery that was first known for its function in the degradation of transmembrane proteins in the endocytic pathway of eukaryotic cells. Since their discovery, however, ESCRTs have been recognized as playing important roles at the plasma membrane, which appears to be the original site of function for the ESCRT machinery. This article reviews some of the major research findings that have shaped our current understanding of how the ESCRT machinery controls membrane dynamics and considers new roles for the ESCRT machinery that might be driven by these mechanisms.
      PubDate: 2015-08-07T14:56:43Z
      DOI: 10.12688/f1000research.6319.1
      Issue No: Vol. 4 (2015)
       
  • Understanding the direct and indirect costs of patients with schizophrenia
           [v2; indexed, http://f1000r.es/5ow]

    • Abstract: Background: Schizophrenia is a disabling mental disorder with high prevalence and that usually  requires long-term follow-up and expensive lifelong treatment. The cost of schizophrenia treatment consumes a significant amount of the health services' budget in western countries. Objective: The aim of the study was to find out about the costs related to schizophrenia across different european countries and compare them. Results: Schizophrenia treatment costs an estimated 18 billion euros annually worldwide. The direct costs associated with medical help are only part of the total expenditure. The indirect costs are an equally (or even more)important part of the total cost. These expenses are related to the lack of productivity of schizophrenic patients and the cost that relatives have to bear as a result of taking care of their affected relatives. Conclusions: Although data on the cost of schizophrenia may vary slightly between different european countries, the general conclusion that can be drawn is that schizophrenia is a very costly disorder. Not only because of direct costs related to medical procedures, but also due to the non-medical (indirect) costs. Together this suggests the need to investigate cost-efficient strategies that could provide a better outcome for schizophrenic patients, as well as the people who care for them.
      PubDate: 2015-08-06T14:04:57Z
      DOI: 10.12688/f1000research.6699.2
      Issue No: Vol. 4 (2015)
       
  • CyREST: Turbocharging Cytoscape Access for External Tools via a RESTful
           API [v1; indexed, http://f1000r.es/5ly]

    • Authors: Keiichiro Ono, Tanja Muetze, Georgi Kolishovski, Paul Shannon, Barry Demchak
      Abstract: As bioinformatic workflows become increasingly complex and involve multiple specialized tools, so does the difficulty of reliably reproducing those workflows. Cytoscape is a critical workflow component for executing network visualization, analysis, and publishing tasks, but it can be operated only manually via a point-and-click user interface. Consequently, Cytoscape-oriented tasks are laborious and often error prone, especially with multistep protocols involving many networks. In this paper, we present the new cyREST Cytoscape app and accompanying harmonization libraries. Together, they improve workflow reproducibility and researcher productivity by enabling popular languages (e.g., Python and R, JavaScript, and C#) and tools (e.g., IPython/Jupyter Notebook and RStudio) to directly define and query networks, and perform network analysis, layouts and renderings. We describe cyREST’s API and overall construction, and present Python- and R-based examples that illustrate how Cytoscape can be integrated into large scale data analysis pipelines. cyREST is available in the Cytoscape app store (http://apps.cytoscape.org) where it has been downloaded over 1900 times since its release in late 2014.
      PubDate: 2015-08-05T14:19:13Z
      DOI: 10.12688/f1000research.6767.1
      Issue No: Vol. 4 (2015)
       
  • A Case Study of the Impediments to the Commercialization of Research at
           the University of Kentucky [v2; indexed, http://f1000r.es/5pi]

    • Authors: Nathan L. Vanderford, Elizabeth Marcinkowski
      Abstract: The commercialization of university-based research occurs to varying degrees between academic institutions. Previous studies have found that multiple barriers can impede the effectiveness and efficiency by which academic research is commercialized. This case study was designed to better understand the impediments to research commercialization at the University of Kentucky via a survey and interview with three successful academic entrepreneurs. The study also garnered insight from the individuals as to how the commercialization process could be improved. Issues with commercialization infrastructure; a lack of emphasis, at the university level, on the importance of research commercialization; a void in an entrepreneurial culture on campus; inhibitory commercialization policies; and a lack of business and commercialization knowledge among faculty were highlighted as the most significant barriers. The research subjects also suggested that commercialization activity may generally increase if a number of factors were mitigated. Such insight can be communicated to the administrative leadership of the commercialization process at the University of Kentucky. Long term, improving university-based research commercialization will allow academic researchers to be more active and successful entrepreneurs such that intellectual property will progress more freely to the marketplace for the benefit of inventors, universities and society.
      PubDate: 2015-08-04T14:58:11Z
      DOI: 10.12688/f1000research.6487.2
      Issue No: Vol. 4 (2015)
       
  • Creating 3D visualizations of MRI data: A brief guide [v1; indexed,
           http://f1000r.es/5o8]

    • Authors: Christopher R. Madan
      Abstract: While magnetic resonance imaging (MRI) data is itself 3D, it is often difficult to adequately present the results papers and slides in 3D. As a result, findings of MRI studies are often presented in 2D instead. A solution is to create figures that include perspective and can convey 3D information; such figures can sometimes be produced by standard functional magnetic resonance imaging (fMRI) analysis packages and related specialty programs. However, many options cannot provide functionality such as visualizing activation clusters that are both cortical and subcortical (i.e., a 3D glass brain), the production of several statistical maps with an identical perspective in the 3D rendering, or animated renderings. Here I detail an approach for creating 3D visualizations of MRI data that satisfies all of these criteria. Though a 3D ‘glass brain’ rendering can sometimes be difficult to interpret, they are useful in showing a more overall representation of the results, whereas the traditional slices show a more local view. Combined, presenting both 2D and 3D representations of MR images can provide a more comprehensive view of the study’s findings.
      PubDate: 2015-08-04T11:02:20Z
      DOI: 10.12688/f1000research.6838.1
      Issue No: Vol. 4 (2015)
       
  • Case Report: Whole exome sequencing helps in accurate molecular diagnosis
           in siblings with a rare co-occurrence of paternally inherited 22q12
           duplication and autosomal recessive non-syndromic ichthyosis. [v1;
           indexed, http://f1000r.es/5mb]

    • Authors: Aayush Gupta, Yugal Sharma, Kirti Deo, Shamsudheen Vellarikkal, Rijith Jayarajan, Vishal Dixit, Ankit Verma, Vinod Scaria, Sridhar Sivasubbu
      Abstract: Lamellar ichthyosis (LI), considered an autosomal recessive monogenic genodermatosis, has an incidence of approximately 1 in 250,000. Usually associated with mutations in the transglutaminase gene (TGM1), mutations in six other genes have, less frequently, been shown to be causative. Two siblings, born in a collodion membrane, presented with fish like scales all over the body. Karyotyping revealed duplication of the chromosome arm on 22q12+ in the father and two siblings. Whole exome sequencing revealed a homozygous p.Gly218Ser variation in TGM1; a variation reported earlier in an isolated Finnish population in association with autosomal recessive non-syndromic ichthyosis. This concurrence of a potentially benign 22q12+ duplication and LI, both rare individually, is reported here likely for the first time.
      PubDate: 2015-07-31T14:45:01Z
      DOI: 10.12688/f1000research.6779.1
      Issue No: Vol. 4 (2015)
       
  • Villain of Molecular Biology: Why are we not reproducible in research'
           [v1; indexed, http://f1000r.es/5ou]

    • Authors: Vikash Bhardwaj
      Abstract: Worldwide, there is an issue of irreproducibility in life science research. In the USA alone $28 billion per year spent on preclinical research is not reproducible. Within this opinion article, I provide a brief historical account of the discovery of the Watson-Crick DNA model and introduce another neglected model of DNA. This negligence may be one of the fundamental reasons behind irreproducibility in molecular biology research.
      PubDate: 2015-07-30T13:58:40Z
      DOI: 10.12688/f1000research.6854.1
      Issue No: Vol. 4 (2015)
       
  • What’s in a Name? Exploring the Nomenclature of Science
           Communication in the UK [v1; indexed, http://f1000r.es/5p0]

    • Authors: Sam Illingworth, James Redfern, Steve Millington, Sam Gray
      Abstract: This study, via a consideration of the literature, and a survey of science communicators, presents concise and workable definitions for science outreach, public engagement, widening participation, and knowledge exchange, in a UK context.   Sixty-six per cent of participants agreed that their definitions of outreach, public engagement, and widening participation aligned with those of their colleagues, whilst 64% felt that their personal definitions matched those of their institute. However, closer inspection of the open-ended questions found the respondents often differed in the use of the nomenclature. In particular, the respondents found it difficult to define knowledge exchange in this context.
      PubDate: 2015-07-28T15:08:11Z
      DOI: 10.12688/f1000research.6858.1
      Issue No: Vol. 4 (2015)
       
  • Emergence of spatial behavioral function and associated mossy fiber
           connectivity and c-Fos labeling patterns in the hippocampus of rats [v1;
           indexed, http://f1000r.es/5nr]

    • Authors: Rachel Comba, Nicole Gervais, Dave Mumby, Matthew Holahan
      Abstract: Improvement on spatial tasks is observed during a late, postnatal developmental period (PND18 – PND24).  The purpose of the current work was 1) to determine whether the emergence of spatial-behavioral function was based on the ability to generate appropriate behavioral output; 2) to assess whether mossy fiber connectivity patterns preceded the emergence of spatial-behavioral function; 3) to explore functional changes in the hippocampus to determine whether activity in hippocampal networks occurred in a training-dependent or developmentally-dependent fashion.  To these ends, male, Long Evans rats were trained on a spatial water or dry maze task for one day (PND16, PND18 or PND20) then euthanized.  Training on these 2 tasks with opposing behavioral demands (swimming versus exploration) was hypothesized to control for behavioral topology.  Only at PND20 was there evidence of spatial-behavioral function for both tasks.  Examination of synaptophysin staining in the CA3 region (i.e., mossy fiber projections) revealed enhanced connectivity patterns that preceded the emergence of spatial behavior.  Analysis of c-Fos labeling (functional changes) revealed developmentally-dependent increases in c-Fos positive cells in the dentate gyrus, CA3 and CA1 regions whereas training-dependent increases were noted in the CA3 and CA1 regions for the water-maze trained groups.  Results suggest that changes in mossy fiber connectivity in association with enhanced hippocampal functioning precede the emergence of spatial behavior observed at PND20.  The combination of neuroanatomical and behavioural results confirms the hypothesis that this time represents a sensitive period for hippocampal development and modification and the emergence of spatial/ cognitive function.
      PubDate: 2015-07-27T10:36:43Z
      DOI: 10.12688/f1000research.6822.1
      Issue No: Vol. 4 (2015)
       
  • Intracellular Dynamics of the Ubiquitin-Proteasome-System [v1; indexed,
           http://f1000r.es/5o5]

    • Authors: Maisha Chowdhury, Cordula Enenkel
      Abstract: The ubiquitin-proteasome system is the major degradation pathway for short-lived proteins in eukaryotic cells. Targets of the ubiquitin-proteasome-system are proteins regulating a broad range of cellular processes including cell cycle progression, gene expression, the quality control of proteostasis and the response to geno- and proteotoxic stress. Prior to degradation, the proteasomal substrate is marked with a poly-ubiquitin chain. The key protease of the ubiquitin system is the proteasome. In dividing cells, proteasomes exist as holo-enzymes composed of regulatory and core particles. The regulatory complex confers ubiquitin-recognition and ATP dependence on proteasomal protein degradation. The catalytic sites are located in the proteasome core particle. Proteasome holo-enzymes are predominantly nuclear suggesting a major requirement for proteasomal proteolysis in the nucleus. In cell cycle arrested mammalian or quiescent yeast cells, proteasomes deplete from the nucleus and accumulate in granules at the nuclear envelope (NE) / endoplasmic reticulum (ER) membranes. In prolonged quiescence, proteasome granules drop off the NE / ER membranes and migrate as stable organelles throughout the cytoplasm, as thoroughly investigated in yeast. When quiescence yeast cells are allowed to resume growth, proteasome granules clear and proteasomes are rapidly imported into the nucleus. Here, we summarize our knowledge about the enigmatic structure of proteasome storage granules and the trafficking of proteasomes and their substrates between the cyto- and nucleoplasm. Most of our current knowledge is based on studies in yeast. Their translation to mammalian cells promises to provide keen insight into protein degradation in non-dividing cells which comprise the majority of our body’s cells.
      PubDate: 2015-07-24T15:09:53Z
      DOI: 10.12688/f1000research.6835.1
      Issue No: Vol. 4 (2015)
       
  • Case Report: Perioperative management of a pregnant poly trauma patient
           for spine fixation surgery [v2; indexed, http://f1000r.es/5oo]

    • Authors: Rashmi Vandse, Meghan Cook, Sergio Bergese
      Abstract: Trauma is estimated to complicate approximately one in twelve pregnancies, and is currently a leading non-obstetric cause of maternal death. Pregnant trauma patients requiring non-obstetric surgery pose a number of challenges for anesthesiologists. Here we present the successful perioperative management of a pregnant trauma patient with multiple injuries including occult pneumothorax who underwent T9 to L1 fusion in prone position, and address the pertinent perioperative anesthetic considerations and management.
      PubDate: 2015-07-24T09:21:12Z
      DOI: 10.12688/f1000research.6659.2
      Issue No: Vol. 4 (2015)
       
  • Cerebrospinal Fluid Biomarkers of Japanese Encephalitis [v1; indexed,
           http://f1000r.es/5n3]

    • Authors: Nabonita Sengupta, Sriparna Mukherjee, Piyush Tripathi, Rashmi Kumar, Amol Suryavanshi, Anirban Basu
      Abstract: Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia. Acute encephalitis syndrome (AES) is a group of central nervous system (CNS) disorders caused by a wide range of viruses, bacteria, fungi, chemicals and toxins. It is important to distinguish between various forms of infectious encephalitis with similar clinical manifestations in order to ensure specific and accurate diagnosis and development of subsequent therapeutic strategies. Cerebrospinal fluid (CSF) is in direct contact with the CNS and hence it is considered to be an excellent source for identifying biomarkers for various neurological disorders. With the recent advancement in proteomic methodologies, the field of biomarker research has received a remarkable boost.  The present study identifies potential biomarkers for JE using a proteomics based approach. The CSF proteomes from ten patients each with JE and Non-JE acute encephalitis were analyzed by 2D gel electrophoresis followed by mass spectrometry. Vitamin D-binding protein (DBP), fibrinogen gamma chain, fibrinogen beta chain, complement C4-B, complement C3 and cytoplasmic actin were found to be significantly elevated in case of JE indicating severe disruption of the blood brain barrier and DBP can be suggested to be an important diagnostic marker.
      PubDate: 2015-07-23T13:20:31Z
      DOI: 10.12688/f1000research.6801.1
      Issue No: Vol. 4 (2015)
       
  • Examining Factors Influencing Colorectal Cancer Screening of Rural
           Nebraskans Using Data from Clinics Participating in an Accountable Care
           Organization: A Study Protocol [v1; indexed, http://f1000r.es/5me]

    • Authors: Lufei Young, Jungyoon Kim, Hongmei Wang, Li-Wu Chen
      Abstract: Background: Although mortality rates of colorectal cancer (CRC) can be significantly reduced through increased screening, rural communities are still experiencing lower rates of screening compared to urban counterparts. Understanding and eliminating barriers to cancer screening will decrease cancer burden and lead to substantial gains in quality and quantity of life for rural populations. However, existing studies have shown inconsistent findings and fail to address how contextual and provider-level factors impact CRC screening in addition to individual-level factors.  Purpose: The purpose of the study is to examine multi-level factors related to CRC screening, and providers’ perception of barriers and facilitators of CRC screening in rural patients cared for by accountable care organization (ACO) clinics. Methods/Design: This is a convergent mixed method design. For the quantitative component, multiple data sources, such as electronic health records (EHRs), Area Resource File (ARF), and provider survey data, will be used to examine patient-, provider-, clinic-, and county-level factors. About 21,729 rural patients aged between 50 and 75 years who visited the participating ACO clinics in the past 12 months are included in the quantitative analysis. The qualitative methods include semi-structured in-depth interviews with healthcare professionals in selected rural clinics. Both quantitative and qualitative data will be merged for result interpretation. Quantitative data identifies “what” factors influence CRC screening, while qualitative data explores “how” these factors interact with CRC screening. The study setting is 10 ACO clinics located in nine rural Nebraska counties. Discussion: This will be the first study examining multi-level factors related to CRC screening in the new healthcare delivery system (i.e., ACO clinics) in rural communities. The study findings will enhance our understanding of how the ACO model, particularly in rural areas, interacts with provider- and patient-level factors influencing the CRC screening rate of rural patients.
      PubDate: 2015-07-22T13:19:41Z
      DOI: 10.12688/f1000research.6782.1
      Issue No: Vol. 4 (2015)
       
  • SwissPalm: Protein Palmitoylation database [v1; indexed,
           http://f1000r.es/5co]

    • Abstract: Protein S-palmitoylation is a reversible post-translational modification that regulates many key biological processes, although the full extent and functions of protein S-palmitoylation remain largely unexplored. Recent developments of new chemical methods have allowed the establishment of palmitoyl-proteomes of a variety of cell lines and tissues from different species.  As the amount of information generated by these high-throughput studies is increasing, the field requires centralization and comparison of this information. Here we present SwissPalm (http://swisspalm.epfl.ch), our open, comprehensive, manually curated resource to study protein S-palmitoylation. It currently encompasses more than 5000 S-palmitoylated protein hits from seven species, and contains more than 500 specific sites of S-palmitoylation. SwissPalm also provides curated information and filters that increase the confidence in true positive hits, and integrates predictions of S-palmitoylated cysteine scores, orthologs and isoform multiple alignments. Systems analysis of the palmitoyl-proteome screens indicate that 10% or more of the human proteome is susceptible to S-palmitoylation. Moreover, ontology and pathway analyses of the human palmitoyl-proteome reveal that key biological functions involve this reversible lipid modification. Comparative analysis finally shows a strong crosstalk between S-palmitoylation and other post-translational modifications. Through the compilation of data and continuous updates, SwissPalm will provide a powerful tool to unravel the global importance of protein S-palmitoylation.
      PubDate: 2015-07-16T14:25:46Z
      DOI: 10.12688/f1000research.6464.1
      Issue No: Vol. 4 (2015)
       
  • PHENOstruct: Prediction of human phenotype ontology terms using
           heterogeneous data sources [v1; indexed, http://f1000r.es/5j2]

    • Authors: Indika Kahanda, Christopher Funk, Karin Verspoor, Asa Ben-Hur
      Abstract: The human phenotype ontology (HPO) was recently developed as a standardized vocabulary for describing the phenotype abnormalities associated with human diseases. At present, only a small fraction of human protein coding genes have HPO annotations. But, researchers believe that a large portion of currently unannotated genes are related to disease phenotypes. Therefore, it is important to predict gene-HPO term associations using accurate computational methods. In this work we demonstrate the performance advantage of the structured SVM approach which was shown to be highly effective for Gene Ontology term prediction in comparison to several baseline methods. Furthermore, we highlight a collection of informative data sources suitable for the problem of predicting gene-HPO associations, including large scale literature mining data.
      PubDate: 2015-07-16T11:35:23Z
      DOI: 10.12688/f1000research.6670.1
      Issue No: Vol. 4 (2015)
       
  • Re-analysis of metagenomic sequences from acute flaccid myelitis patients
           reveals alternatives to enterovirus D68 infection [v2; indexed,
           http://f1000r.es/5mz]

    • Authors: Florian P. Breitwieser, Carlos A. Pardo, Steven L. Salzberg
      Abstract: Metagenomic sequence data can be used to detect the presence of infectious viruses and bacteria, but normal microbial flora make this process challenging. We re-analyzed metagenomic RNA sequence data collected during a recent outbreak of acute flaccid myelitis (AFM), caused in some cases by infection with enterovirus D68. We found that among the patients whose symptoms were previously attributed to enterovirus D68, one patient had clear evidence of infection with Haemophilus influenzae, and a second patient had a severe Staphylococcus aureus infection caused by a methicillin-resistant strain. Neither of these bacteria were identified in the original study. These observations may have relevance in cases that present with flaccid paralysis because bacterial infections, co-infections or post-infection immune responses may trigger pathogenic processes that may present as poliomyelitis-like syndromes and may mimic AFM.  A separate finding was that large numbers of human sequences were present in each of the publicly released samples, although the original study reported that human sequences had been removed before deposition.
      PubDate: 2015-07-13T10:50:00Z
      DOI: 10.12688/f1000research.6743.2
      Issue No: Vol. 4 (2015)
       
  • An unexpected effect of TNF-α on F508del-CFTR maturation and function
           [v1; indexed, http://f1000r.es/5jf]

    • Abstract: Cystic fibrosis (CF) is a multifactorial disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR), which encodes a cAMP-dependent Cl- channel. The most frequent mutation, F508del, leads to the synthesis of a prematurely degraded, otherwise partially functional protein. CFTR is expressed in many epithelia, with major consequences in the airways of patients with CF, characterized by both fluid transport abnormalities and persistent inflammatory responses. The relationship between the acute phase of inflammation and the expression of wild type (WT) CFTR or F508del-CFTR is poorly understood. The aim of the present study was to investigate this effect. The results show that 10 min exposure to TNF-alpha (0.5-50ng/ml) of F508del-CFTR-transfected HeLa cells and human bronchial cells expressing F508del-CFTR in primary culture (HBE) leads to the maturation of F508del-CFTR and induces CFTR chloride currents. The enhanced CFTR expression and function upon TNFα is sustained, in HBE cells, for at least 24 h. The underlying mechanism of action involves a protein kinase C (PKC) signaling pathway, and occurs through insertion of vesicles containing F508del-CFTR to the plasma membrane, with TNFα behaving as a corrector molecule. In conclusion, a novel and unexpected action of TNFα has been discovered and points to the importance of systematic studies on the roles of inflammatory mediators in the maturation of abnormally folded proteins in general and in the context of CF in particular.
      PubDate: 2015-07-10T16:23:01Z
      DOI: 10.12688/f1000research.6683.1
      Issue No: Vol. 4 (2015)
       
  • Journal ratings as predictors of articles quality in Arts, Humanities and
           Social Sciences: an analysis based on the Italian Research Evaluation
           Exercise [v1; indexed, http://f1000r.es/5d3]

    • Authors: Andrea Bonaccorsi, Tindaro Cicero, Antonio Ferrara, Marco Malgarini
      Abstract: The aim of this paper is to understand whether the probability of receiving positive peer reviews is influenced by having published in an independently assessed, high-ranking journal: we eventually interpret a positive relationship among peer evaluation and journal ranking as evidence that journal ratings are good predictors of article quality. The analysis is based on a large dataset of over 11,500 research articles published in Italy in the period 2004-2010 in the areas of architecture, arts and humanities, history and philosophy, law, sociology and political sciences. These articles received a score by a large number of externally appointed referees in the context of the Italian research assessment exercise (VQR); similarly, journal scores were assigned in a panel-based independent assessment, which involved all academic journals in which Italian scholars have published, carried out under a different procedure. The score of an article is compared with that of the journal it is published in: more specifically, we first estimate an ordered probit model, assessing the probability for a paper of receiving a higher score, the higher the score of the journal; in a second step, we concentrate on the top papers, evaluating the probability of a paper receiving an excellent score having been published in a top-rated journal. In doing so, we control for a number of characteristics of the paper and its author, including the language of publication, the scientific field and its size, the age of the author and the academic status. We add to the literature on journal classification by providing for the first time a large scale test of the robustness of expert-based classification.
      PubDate: 2015-07-07T15:45:06Z
      DOI: 10.12688/f1000research.6478.1
      Issue No: Vol. 4 (2015)
       
  • An ORCID based synchronization framework for a national CRIS ecosystem
           [v1; indexed, http://f1000r.es/5dr]

    • Abstract: PTCRIS (Portuguese Current Research Information System) is a program aiming at the creation and sustained development of a national integrated information ecosystem, to support research management according to the best international standards and practices. This paper reports on the experience of designing and prototyping a synchronization framework for PTCRIS based on ORCID (Open Researcher and Contributor ID). This framework embraces the "input once, re-use often" principle, and will enable a substantial reduction of the research output management burden by allowing automatic information exchange between the various national systems. The design of the framework followed best practices in rigorous software engineering, namely well-established principles in the research field of consistency management, and relied on formal analysis techniques and tools for its validation and verification. The notion of consistency between the services was formally specified and discussed with the stakeholders before the technical aspects on how to preserve said consistency were explored. Formal specification languages and automated verification tools were used to analyze the specifications and generate usage scenarios, useful for validation with the stakeholder and essential to certificate compliant services.
      PubDate: 2015-07-06T14:54:37Z
      DOI: 10.12688/f1000research.6499.1
      Issue No: Vol. 4 (2015)
       
  • Kvik: three-tier data exploration tools for flexible analysis of genomic
           data in epidemiological studies [v2; indexed, http://f1000r.es/5hl]

    • Abstract: Kvik is an open-source framework that we developed for explorative analysis of functional genomics data from large epidemiological studies. Creating such studies requires a significant amount of time and resources. It is therefore usual to reuse the data from one study for several research projects. Often each project requires implementing new analysis code, integration with specific knowledge bases, and specific visualizations. Although existing data exploration tools are available for single study data exploration, no tool provides all the required functionality for multistudy data exploration. We have therefore used the Kvik framework to develop Kvik Pathways, an application for exploring gene expression data in the context of biological pathways. We have used Kvik Pathways to explore data from both a cross-sectional study design and a case-control study within the Norwegian Women and Cancer (NOWAC) cohort. Kvik Pathways follows the three-tier architecture in web applications using a powerful back-end for statistical analyses and retrieval of metadata.In this note, we describe how we used the Kvik framework to develop the Kvik Pathways application. Kvik Pathways was used by our team of epidemiologists toexplore gene expression data from healthy women with high and low plasma ratios of essential fatty acids.
      PubDate: 2015-06-16T16:15:39Z
      DOI: 10.12688/f1000research.6238.2
      Issue No: Vol. 4 (2015)
       
  • Non-invasive imaging to monitor lupus nephritis and neuropsychiatric
           systemic lupus erythematosus [v1; indexed, http://f1000r.es/5gh]

    • Authors: Joshua Thurman, Natalie Serkova
      Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect multiple different organs, including the kidneys and central nervous system (CNS). Conventional radiological examinations in SLE patients include volumetric/ anatomical computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound (US). The utility of these modalities is limited, however, due to the complexity of the disease. Furthermore, CT and MRI contrast agents are contraindicated in patients with renal impairment. Various radiologic methods are currently being developed to improve disease characterization in patients with SLE beyond simple anatomical endpoints. Physiological non-contrast MRI protocols have been developed to assess tissue oxygenation, glomerular filtration, renal perfusion, interstitial diffusion, and inflammation-driven fibrosis in lupus nephritis (LN) patients. For neurological symptoms, vessel size imaging (VSI, an MRI approach utilizing T2-relaxing iron oxide nanoparticles) has shown promise as a diagnostic tool. Molecular imaging probes (mostly for MRI and nuclear medicine imaging) have also been developed for diagnosing SLE with high sensitivity, and for monitoring disease activity. This paper reviews the challenges in evaluating disease activity in patients with LN and neuropsychiatric systemic lupus erythematosus (NPSLE). We describe novel MRI and positron-emission tomography (PET) molecular imaging protocols using targeted iron oxide nanoparticles and radioactive ligands, respectively, for detection of SLE-associated inflammation.
      PubDate: 2015-06-16T09:34:20Z
      DOI: 10.12688/f1000research.6587.1
      Issue No: Vol. 4 (2015)
       
  • agINFRA: a research data hub for agriculture, food and the environment
           [v2; indexed, http://f1000r.es/5hk]

    • Authors: Andreas Drakos, Vassilis Protonotarios, Nikos Manouselis
      Abstract: The agINFRA project (www.aginfra.eu) was a European Commission funded project under the 7th Framework Programme that aimed to introduce agricultural scientific communities to the vision of open and participatory data-intensive science. agINFRA has now evolved into the European hub for data-powered research on agriculture, food and the environment, serving the research community through multiple roles. Working on enhancing the interoperability between heterogeneous data sources, the agINFRA project has left a set of grid- and cloud- based services that can be reused by future initiatives and adopted by existing ones, in order to facilitate the dissemination of agricultural research, educational and other types of data. On top of that, agINFRA provided a set of domain-specific recommendations for the publication of agri-food research outcomes. This paper discusses the concept of the agINFRA project and presents its major outcomes, as adopted by existing initiatives activated in the context of agricultural research and education.
      PubDate: 2015-06-15T14:15:19Z
      DOI: 10.12688/f1000research.6349.2
      Issue No: Vol. 4 (2015)
       
  • Absence of kdr resistance alleles in the Union of the Comoros, East Africa
           [v1; indexed, http://f1000r.es/5fw]

    • Authors: Yoosook Lee, Natalie Olson, Youki Yamasaki, Allison Chang, Clare Marsden, Ahmed Ouledi, Gregory Lanzaro, Anthony Cornel
      Abstract: Knockdown resistance (kdr) and CYP9K1 genotypes were detected by a MOLDI-TOF based SNP genotyping assay (Sequenom iPLEX) in samples of Anopheles gambiae collected at 13 sites throughout the Union of the Comoros and Dar es Salaam, Tanzania during February and March 2011. All A. gambiae specimens collected in the Comoros were homozygous for the susceptible kdr alleles (+/+) while 96% of A. gambiae from Dar es Salaam were homozygous for the East African kdr resistant genotype (E/E). In contrast, all specimens from Dar es Salaam and the Comoros were homozygous for the cyp3 allele (c3/c3) at the CYP9K1 locus; the locus has been implicated in metabolic resistance against pyrethroid insecticides in West Africa. All specimens had typical A. gambiae genotypes for SNPs within the divergence Islands on all three chromosomes. Although further spatial and temporal studies are needed, the distribution of kdr genotypes between the Comoros and Tanzania further supports isolation of the Comoros populations from A. gambiae populations on mainland Africa.
      PubDate: 2015-06-09T15:08:57Z
      DOI: 10.12688/f1000research.6567.1
      Issue No: Vol. 4 (2015)
       
  • A resistant-starch enriched yogurt: fermentability, sensory
           characteristics, and a pilot study in children [v1; indexed,
           http://f1000r.es/5cb]

    • Authors: Kayanush Aryana, Frank Greenway, Nikhil Dhurandhar, Richard Tulley, John Finley, Michael Keenan, Roy Martin, Christine Pelkman, Douglas Olson, Jolene Zheng
      Abstract: The rising prevalence of obesity and the vulnerability of the pediatric age group have highlighted the critical need for a careful consideration of effective, safe, remedial and preventive dietary interventions.  Amylose starch (RS2) from high-amylose maize (HAM) ferments in the gut and affects body weight.   One hundred and ten children, of 7-8 (n=91) or 13-14 (n=19) years of age scored the sensory qualities of a yogurt supplemented with either HAM-RS2 or an amylopectin starch.  The amylopectin starch yogurt was preferred to the HAM-RS2-enriched yogurt by 7-8 year old panelists (P
      PubDate: 2015-06-01T16:04:05Z
      DOI: 10.12688/f1000research.6451.1
      Issue No: Vol. 4 (2015)
       
  • AGRIS: providing access to agricultural research data exploiting open data
           on the web [v1; indexed, http://f1000r.es/599]

    • Authors: Fabrizio Celli, Thembani Malapela, Karna Wegner, Imma Subirats, Elena Kokoliou, Johannes Keizer
      Abstract: AGRIS is the International System for Agricultural Science and Technology. It is supported by a large community of data providers, partners and users. AGRIS is a database that aggregates bibliographic data, and through this core data, related content across online information systems is retrieved by taking advantage of Semantic Web capabilities. AGRIS is a global public good and its vision is to be a responsive service to its user needs by facilitating contributions and feedback regarding the AGRIS core knowledgebase, AGRIS’s future and its continuous development. Periodic AGRIS e-consultations, partner meetings and user feedback are assimilated to the development of the AGRIS application and content coverage. This paper outlines the current AGRIS technical set-up, its network of partners, data providers and users as well as how AGRIS’s responsiveness to clients’ needs inspires the continuous technical development of the application. The paper concludes by providing a use case of how the AGRIS stakeholder input and the subsequent AGRIS e-consultation results influence the development of the AGRIS application, knowledgebase and service delivery.
      PubDate: 2015-05-08T16:00:41Z
      DOI: 10.12688/f1000research.6354.1
      Issue No: Vol. 4 (2015)
       
  • The unfolded protein response and its potential role in Huntington ́s
           disease elucidated by a systems biology approach [v1; indexed,
           http://f1000r.es/59e]

    • Authors: Ravi Kiran Reddy Kalathur, Joaquin Giner-Lamia, Susana Machado, Kameshwar R S Ayasolla, Matthias E. Futschik
      Abstract: Huntington ́s disease (HD) is a progressive, neurodegenerative disease with a fatal outcome. Although the disease-causing gene (huntingtin) has been known for over 20 years, the exact mechanisms leading to neuronal cell death are still controversial. One potential mechanism contributing to the massive loss of neurons observed in the brain of HD patients could be the unfolded protein response (UPR) activated by accumulation of misfolded proteins in the endoplasmic reticulum (ER). As an adaptive response to counter-balance accumulation of un- or misfolded proteins, the UPR upregulates transcription of chaperones, temporarily attenuates new translation, and activates protein degradation via the proteasome. However, persistent ER stress and an activated UPR can also cause apoptotic cell death. Although different studies have indicated a role for the UPR in HD, the evidence remains inconclusive. Here, we present extensive bioinformatic analyses that revealed UPR activation in different experimental HD models based on transcriptomic data. Accordingly, we have identified 58 genes, including RAB5A, HMGB1, CTNNB1, DNM1, TUBB, TSG101, EEF2, DYNC1H1 and SLC12A5 that provide a potential link between UPR and HD. To further elucidate the potential role of UPR as a disease-relevant process, we examined its connection to apoptosis based on molecular interaction data, and identified a set of 40 genes including ADD1, HSP90B1, IKBKB, IKBKG, RPS3A and LMNB1, which seem to be at the crossroads between these two important cellular processes.
      PubDate: 2015-05-01T10:58:01Z
      DOI: 10.12688/f1000research.6358.1
      Issue No: Vol. 4 (2015)
       
  • A new hypothesis on HIV cure [v1; indexed, http://f1000r.es/3qj]

    • Authors: Florian Hladik
      Abstract: In this opinion article, I provide the rationale for my hypothesis that nucleoside reverse transcriptase inhibitors (NRTIs) may prevent human immunodeficiency virus (HIV) cure by promoting the survival of cells with integrated provirus. If correct, we may be closer to a cure than we realize.
      PubDate: 2015-03-24T16:04:40Z
      DOI: 10.12688/f1000research.4529.1
      Issue No: Vol. 4 (2015)
       
  • Countries’ Biomedical Publications and Attraction Scores. A
           PubMed-based assessment [v2; indexed, http://f1000r.es/5q4]

    • Authors: Qinyi Xu, Andrea Boggio, Andrea Ballabeni
      Abstract: Studying publication volumes at the country level is key to understanding and improving a country’s research system. PubMed is a public search engine of publications in all life sciences areas. Here, we show how this search engine can be used to assess the outputs of life science-related research by country. We have measured the numbers of publications during different time periods based on the country of affiliation of the first authors. Moreover, we have designed scores, which we have named Attraction Scores, to appraise the relative focus either toward particular types of studies, such as clinical trials or reviews, or toward specific research areas, such as public health and pharmacogenomics, or toward specific topics, for instance embryonic stem cells; we have also investigated a possible use of these Attraction Scores in connection with regulatory policies. We have weighed the statistics against general indicators such as country populations and gross domestic products (GDP). During the 5-year period 2008-2012, the United States was the country with the highest number of publications and Denmark the one with the highest number of publications per capita. Among the 40 countries with the highest GDPs, Israel had the highest publications-to-GDP ratio. Among the 20 countries with the most publications, Japan had the highest Attraction Score for induced pluripotent stem (iPS) cells and Italy the highest proportion of review publications. More than 50% of publications in English were from countries in which English is not the primary language. We show an assorted and extensive collection of rankings and charts that will inform scholars and policymakers in studying and improving the research systems both at the national and international level.
      PubDate: 2015-08-11T10:57:39Z
      DOI: 10.12688/f1000research.5775.2
      Issue No: Vol. 3 (2015)
       
  • Case Report: Neuropathic pain in a patient with congenital insensitivity
           to pain [v2; indexed, http://f1000r.es/5iu]

    • Authors: Daniel W. Wheeler, Michael C.H. Lee, E. Katherine Harrison, David K. Menon, C. Geoffrey Woods
      Abstract: We report a unique case of a woman with Channelopathy-associated Insensitivity to Pain (CIP) Syndrome, who developed features of neuropathic pain after sustaining pelvic fractures and an epidural hematoma that impinged on the right fifth lumbar (L5) nerve root. Her pelvic injuries were sustained during painless labor, which culminated in a Cesarean section. She had been diagnosed with CIP as child, which was later confirmed when she was found to have null mutations of the SCN9A gene that encodes the voltage-gated sodium channel Nav1.7. She now complains of troubling continuous buzzing in both legs and a vice-like squeezing in the pelvis on walking. Quantitative sensory testing showed that sensory thresholds to mechanical stimulation of the dorsum of both feet had increased more than 10-fold on both sides compared with tests performed before her pregnancy. These findings fulfill the diagnostic criteria for neuropathic pain. Notably, she mostly only experiences the negative symptoms (such as numbness and tingling, but also electric shocks), and she has not reported sharp or burning sensations, although the value of verbal descriptors is somewhat limited in a person who has never felt pain before. However, her case strongly suggests that at least some of the symptoms of neuropathic pain can persist despite the absence of the Nav1.7 channel. Pain is a subjective experience and this case sheds light on the transmission of neuropathic pain in humans that cannot be learned from knockout mice.
      PubDate: 2015-06-19T14:19:29Z
      DOI: 10.12688/f1000research.2642.2
      Issue No: Vol. 3 (2015)
       
  • Audit of antenatal screening for syphilis and HIV in migrant and refugee
           women on the Thai-Myanmar border: a descriptive study [v2; indexed,
           http://f1000r.es/5dn]

    • Abstract: Objective: The antenatal prevalence of syphilis and HIV/AIDS in migrants and refugees is poorly documented. The aim of this study was to audit the first year of routine syphilis screening in the same population and reassess the trends in HIV rates. Methods: From August 2012 to July 2013, 3600 pregnant women were screened for HIV (ELISA) and syphilis (VDRL with TPHA confirmation) at clinics along the Thai-Myanmar border. Results: Seroprevalence for HIV 0.47% (95% CI 0.30-0.76) (17/3,599), and syphilis 0.39% (95% CI 0.23-0.65) (14/3,592), were low. Syphilis was significantly lower in refugees (0.07% 95% CI 0.01-0.38) (1/1,469), than in migrants (0.61% 95% CI 0.36-1.04) (13/2,123). The three active (VDRL≥1:8 and TPHA reactive) syphilis cases with VDRL titres of 1:32 were easy to counsel and treat. Women with low VDRL titres (>75% were < 1:8) and TPHA reactive results, in the absence of symptoms and both the woman and her husband having only one sexual partner in their lifetime, and the inability to determine the true cause of the positive results presented ethical difficulties for counsellors. Conclusion: As HIV and syphilis testing becomes available in more and more settings, the potential impact of false positive results should be considered, especially in populations with low prevalence for these diseases. This uncertainty must be considered in order to counsel patients and partners accurately and safely about the results of these tests, without exposing women to increased risk for abuse or abandonment. Our findings highlight the complexities of counselling patients about these tests and the global need for more conclusive syphilis testing strategies.
      PubDate: 2015-05-15T16:05:04Z
      DOI: 10.12688/f1000research.4190.2
      Issue No: Vol. 3 (2015)
       
 
 
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