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Journal Cover F1000Research
  [SJR: 0.56]   [H-I: 9]   [4 followers]  Follow
    
  This is an Open Access Journal Open Access journal
   ISSN (Online) 2046-1402
   Published by Faculty of 1000 Homepage  [1 journal]
  • How to decrease bronchopulmonary dysplasia in your neonatal intensive care
           unit today and “tomorrow” [version 1; referees: 2 approved]

    • Authors: Leif D. Nelin, Vineet Bhandari
      Abstract: Bronchopulmonary dysplasia, or BPD, is the most common chronic lung disease in infants. Genetic predisposition and developmental vulnerability secondary to antenatal and postnatal infections, compounded with exposure to hyperoxia and invasive mechanical ventilation to an immature lung, result in persistent inflammation, culminating in the characteristic pulmonary phenotype of BPD of impaired alveolarization and dysregulated vascularization. In this article, we highlight specific areas in current management, and speculate on therapeutic strategies that are on the horizon, that we believe will make an impact in decreasing the incidence of BPD in your neonatal intensive care units.
      PubDate: 2017-04-21T09:39:53Z
      DOI: 10.12688/f1000research.10832.1
      Issue No: Vol. 6 (2017)
       
  • What’s new in the management of adult bronchiectasis' [version
           1; referees: 2 approved]

    • Authors: Usma Koser, Adam Hill
      Abstract: Bronchiectasis is a heterogeneous, chronic condition with many aetiologies. It poses a significant burden on patients and healthcare practitioners and services. Clinical exacerbations often result in reduced quality of life, increased rate of lung function decline, increased hospitalisation, and mortality. Recent focus in respiratory research, guidelines, and future management options has improved this clinical field in evidence-based practice, but further work and phase III clinical trials are required. This article aims to summarise and explore advances in management strategies in recent years and highlight areas of research and future focus.
      PubDate: 2017-04-20T14:53:05Z
      DOI: 10.12688/f1000research.10613.1
      Issue No: Vol. 6 (2017)
       
  • Looking at the recent advances in understanding α-synuclein and its
           aggregation through the proteoform prism [version 1; referees: 2 approved]
           

    • Authors: Vladimir N. Uversky
      Abstract: Despite attracting the close attention of multiple researchers for the past 25 years, α-synuclein continues to be an enigma, hiding sacred truth related to its structure, function, and dysfunction, concealing mechanisms of its pathological spread within the affected brain during disease progression, and, above all, covering up the molecular mechanisms of its multipathogenicity, i.e. the ability to be associated with the pathogenesis of various diseases. The goal of this article is to present the most recent advances in understanding of this protein and its aggregation and to show that the remarkable structural, functional, and dysfunctional multifaceted nature of α-synuclein can be understood using the proteoform concept.
      PubDate: 2017-04-20T13:35:36Z
      DOI: 10.12688/f1000research.10536.1
      Issue No: Vol. 6 (2017)
       
  • “Mesenchymal stem cells”: fact or fiction, and implications in their
           therapeutic use [version 1; referees: 2 approved]

    • Authors: Pamela G. Robey
      Abstract: The concept of a post-natal “mesenchymal stem cell” (“MSC”) originated from studies focused on bone marrow stromal cells (BMSCs), which are non-hematopoietic adherent cells, a subset of which are skeletal stem cells (SSCs), able to form cartilage, bone, hematopoiesis-supportive stroma, and marrow adipocytes based on rigorous clonal and differentiation assays. Subsequently, it was speculated that BMSCs could form other mesodermal derivatives and even cell types from other germ layers. Based on BMSC surface markers, representative of fibroblastic cells, and imprecise differentiation assays, it was further imagined that “MSCs” are ubiquitous and equipotent. However, “MSCs” do not have a common embryonic origin and are not a lineage, but recent studies indicate that they are tissue-specific stem/progenitor cells. These cells share cell surface features owing to their fibroblastic nature, but they are not identical. They display different differentiation capacities based on their tissue origin but do not “trans-differentiate” outside of their lineage, based on rigorous assays. For these reasons, the “MSC” term should be abandoned. Tissue-specific stem/progenitor cells provide the opportunity to devise methods for tissue regeneration by the cells themselves (tissue engineering). Their use in other forms of regenerative medicine based on paracrine, immunosuppressive, and immunomodulatory effects is far less clear.
      PubDate: 2017-04-20T12:30:53Z
      DOI: 10.12688/f1000research.10955.1
      Issue No: Vol. 6 (2017)
       
  • Recent advances in the management and understanding of macular
           degeneration [version 1; referees: 2 approved]

    • Authors: Sepehr Bahadorani, Michael Singer
      Abstract: Current management of age-related macular degeneration (AMD) is directed at intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors for the treatment of wet AMD and supplementation with oral antioxidants for the treatment of dry AMD. In this article, we will review recent clinical trials for the treatment of dry and wet AMD.
      PubDate: 2017-04-20T09:54:34Z
      DOI: 10.12688/f1000research.10998.1
      Issue No: Vol. 6 (2017)
       
  • DNA nanochannels [version 1; referees: 2 approved]

    • Authors: Dianming Wang, Yiyang Zhang, Dongsheng Liu
      Abstract: Transmembrane proteins are mostly nanochannels playing a highly important role in metabolism. Understanding their structures and functions is vital for revealing life processes. It is of fundamental interest to develop chemical devices to mimic biological channels. Structural DNA nanotechnology has been proven to be a promising method for the preparation of fine DNA nanochannels as a result of the excellent properties of DNA molecules. This review presents the development history and current situation of three different types of DNA nanochannel: tile-based nanotube, DNA origami nanochannel, and DNA bundle nanochannel.
      PubDate: 2017-04-18T11:13:37Z
      DOI: 10.12688/f1000research.10464.1
      Issue No: Vol. 6 (2017)
       
  • Recent advances in preoperative management of esophageal adenocarcinoma
           [version 1; referees: 2 approved]

    • Authors: Kazuto Harada, Dilsa Mizrak Kaya, Hideo Baba, Jaffer A. Ajani
      Abstract: Esophageal cancer is an aggressive malignancy with increasing incidence, and the prognosis of patients treated by surgery alone remains dismal. Preoperative treatment can modestly prolong overall survival. Preoperative chemotherapy or chemoradiation is the standard of care for resectable esophageal cancer (greater than clinical stage I and less than clinical stage IV). One of the challenges is to predict complete response in the surgical specimen from preoperative therapy and to avoid surgery in some patients but also predict ineffectiveness of preoperative therapy if the tumor is resistant and avoid such therapies altogether. In-depth understanding of the molecular biology could lead to personalized therapy, and in the future, clinical trials designed according to molecular features are expected. Here, we summarize preoperative treatment for esophageal adenocarcinoma and their potential.
      PubDate: 2017-04-18T09:43:42Z
      DOI: 10.12688/f1000research.10794.1
      Issue No: Vol. 6 (2017)
       
  • Selective vulnerabilities and biomarkers in neurocognitive aging [version
           1; referees: 4 approved]

    • Authors: Zachariah Reagh, Michael Yassa
      Abstract: As the world’s population continues to age, an understanding of the aging brain becomes increasingly crucial. This review focuses on several recent ideas and findings in the study of neurocognitive aging, specifically focusing on episodic memory, and discusses how they can be considered and used to guide us moving forward. Topics include dysfunction in neural circuits, the roles of neurogenesis and inhibitory signaling, vulnerability in the entorhinal cortex, individual differences, and comorbidities. These avenues of study provide a brief overview of promising themes in the field and together provide a snapshot of what we believe will be important emerging topics in selective vulnerabilities in the aging brain.
      PubDate: 2017-04-13T15:12:14Z
      DOI: 10.12688/f1000research.10652.1
      Issue No: Vol. 6 (2017)
       
  • The evolution of medulloblastoma therapy to personalized medicine [version
           1; referees: 3 approved]

    • Authors: Soma Sengupta, Daniel Pomeranz Krummel, Scott Pomeroy
      Abstract: Recent advances in cancer genomics have revolutionized the characterization and classification of medulloblastomas. According to the current WHO guidelines, medulloblastomas are now classified into the following molecularly defined groups: Wnt signaling pathway (WNT)-activated, sonic hedgehog signaling pathway (SHH)-activated and tumor suppressor protein p53 (TP53)-mutant, SHH-activated and TP53-wildtype, and non-WNT/non-SHH (i.e. group 3 and group 4). Importantly, genomic, epigenomic, and proteomic advances have created a potential paradigm shift in therapeutic options. The challenge now is to (i) translate these observations into new therapeutic approaches and (ii) employ these observations in clinical practice, utilizing the classification following a molecular analysis for diagnosis and application of new subgroup-specific targeted therapeutics.
      PubDate: 2017-04-13T12:53:58Z
      DOI: 10.12688/f1000research.10859.1
      Issue No: Vol. 6 (2017)
       
  • Recent advances in the management of acute ischemic stroke [version 1;
           referees: 2 approved]

    • Authors: Philip Chang, Shyam Prabhakaran
      Abstract: In recent years, several landmark trials have transformed acute ischemic stroke care. The most dramatic results from the field of acute endovascular intervention demonstrate unequivocal benefit for a select group of patients with moderate to severe deficits presenting within 7 hours from onset and with occlusions of proximal arteries in the anterior circulation. In addition, technological advances and workflow efficiencies have facilitated more rapid delivery of acute stroke interventions. This review provides an overview of recent advances in the management of acute ischemic stroke.
      PubDate: 2017-04-13T08:38:59Z
      DOI: 10.12688/f1000research.9191.1
      Issue No: Vol. 6 (2017)
       
  • Linking cortical microtubule attachment and exocytosis [version 1;
           referees: 2 approved]

    • Authors: Ivar Noordstra, Anna Akhmanova
      Abstract: Exocytosis is a fundamental cellular process whereby secreted molecules are packaged into vesicles that move along cytoskeletal filaments and fuse with the plasma membrane. To function optimally, cells are strongly dependent on precisely controlled delivery of exocytotic cargo. In mammalian cells, microtubules serve as major tracks for vesicle transport by motor proteins, and thus microtubule organization is important for targeted delivery of secretory carriers. Over the years, multiple microtubule-associated and cortical proteins have been discovered that facilitate the interaction between the microtubule plus ends and the cell cortex. In this review, we focus on mammalian protein complexes that have been shown to participate in both cortical microtubule capture and exocytosis, thereby regulating the spatial organization of secretion. These complexes include microtubule plus-end tracking proteins, scaffolding factors, actin-binding proteins, and components of vesicle docking machinery, which together allow efficient coordination of cargo transport and release.
      PubDate: 2017-04-12T14:21:00Z
      DOI: 10.12688/f1000research.10729.1
      Issue No: Vol. 6 (2017)
       
  • Unwinding focal segmental glomerulosclerosis [version 1; referees: 3
           approved]

    • Authors: Vasil Peev, Eunsil Hahm, Jochen Reiser
      Abstract: Focal segmental glomerulosclerosis (FSGS) represents the most common primary glomerular disease responsible for the development of end-stage renal disease (ESRD) in the United States (US). The disease progresses from podocyte injury to chronic kidney disease (CKD), ultimately leading to total nephron degeneration. Extensive basic science research has been conducted to unwind the mechanisms of FSGS and, with those insights, understand major contributors of CKD in general. As a result, several putative molecules and pathways have been studied, all implicated in the disease; some serve, in addition, as early biomarkers. The ongoing research is currently focusing on understanding how these molecules and pathways can interplay and be utilized as potential diagnostic and therapeutic targets. Among these molecules, the soluble urokinase plasminogen activating receptor (suPAR) has been studied in detail, both clinically and from a basic science perspective. By now, it has emerged as the earliest and most robust marker of future CKD. Other circulating factors harming podocytes include anti-CD40 auto-antibody and possibly cardiotrophin-like cytokine factor-1. Understanding these factors will aid our efforts to ultimately cure FSGS and possibly treat a larger portion of CKD patients much more effectively.
      PubDate: 2017-04-12T09:38:04Z
      Issue No: Vol. 6 (2017)
       
  • Advancing psychological therapies for chronic pain [version 1; referees: 2
           approved]

    • Authors: Christopher Eccleston, Geert Crombez
      Abstract: There is a strong tradition of therapy development and evaluation in the field of psychological interventions for chronic pain. However, despite this research production, the effects of treatments remain uncertain, and treatment development has stalled. This review summarises the current evidence but focusses on promising areas for improvement. Advancing psychological therapies for chronic pain will come from a radical re-imagining of the content, delivery, place, and control of therapy. The next generation of therapeutic interventions will also need alternative methods of measurement and evaluation, and options are discussed.
      PubDate: 2017-04-11T11:04:47Z
      DOI: 10.12688/f1000research.10612.1
      Issue No: Vol. 6 (2017)
       
  • The rise of photoresponsive protein technologies applications in vivo: a
           spotlight on zebrafish developmental and cell biology [version 1;
           referees: 2 approved]

    • Authors: Renee Wei-Yan Chow, Julien Vermot
      Abstract: The zebrafish (Danio rerio) is a powerful vertebrate model to study cellular and developmental processes in vivo. The optical clarity and their amenability to genetic manipulation make zebrafish a model of choice when it comes to applying optical techniques involving genetically encoded photoresponsive protein technologies. In recent years, a number of fluorescent protein and optogenetic technologies have emerged that allow new ways to visualize, quantify, and perturb developmental dynamics. Here, we explain the principles of these new tools and describe some of their representative applications in zebrafish.
      PubDate: 2017-04-11T10:35:19Z
      DOI: 10.12688/f1000research.10617.1
      Issue No: Vol. 6 (2017)
       
  • hackseq: Catalyzing collaboration between biological and computational
           scientists via hackathon [version 2; referees: 2 approved]

    • Authors: hackseq Organizing Committee 2016
      Abstract: hackseq (http://www.hackseq.com) was a genomics hackathon with the aim of bringing together a diverse set of biological and computational scientists to work on collaborative bioinformatics projects. In October 2016, 66 participants from nine nations came together for three days for hackseq and collaborated on nine projects ranging from data visualization to algorithm development. The response from participants was overwhelmingly positive with 100% (n = 54) of survey respondents saying they would like to participate in future hackathons. We detail key steps for others interested in organizing a successful hackathon and report excerpts from each project.
      PubDate: 2017-04-10T08:43:31Z
      DOI: 10.12688/f1000research.10964.2
      Issue No: Vol. 6 (2017)
       
  • Non-infectious chemotherapy-associated acute toxicities during childhood
           acute lymphoblastic leukemia therapy [version 1; referees: 3 approved]

    • Authors: Kjeld Schmiegelow, Klaus Müller, Signe Sloth Mogensen, Pernille Rudebeck Mogensen, Benjamin Ole Wolthers, Ulrik Kristoffer Stoltze, Ruta Tuckuviene, Thomas Frandsen
      Abstract: During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs.
      PubDate: 2017-04-07T08:21:48Z
      DOI: 10.12688/f1000research.10768.1
      Issue No: Vol. 6 (2017)
       
  • AR2, a novel automatic muscle artifact reduction software method for ictal
           EEG interpretation: Validation and comparison of performance with
           commercially available software [version 2; referees: 2 approved]

    • Authors: Shennan Aibel Weiss, Ali A Asadi-Pooya, Sitaram Vangala, Stephanie Moy, Dale H Wyeth, Iren Orosz, Michael Gibbs, Lara Schrader, Jason Lerner, Christopher K Cheng, Edward Chang, Rajsekar Rajaraman, Inna Keselman, Perdro Churchman, Christine Bower-Baca, Adam L Numis, Michael G Ho, Lekha Rao, Annapoorna Bhat, Joanna Suski, Marjan Asadollahi, Timothy Ambrose, Andres Fernandez, Maromi Nei, Christopher Skidmore, Scott Mintzer, Dawn S Eliashiv, Gary W Mathern, Marc R Nuwer, Michael Sperling, Jerome Engel Jr, John M Stern
      Abstract: Objective: To develop a novel software method (AR2) for reducing muscle contamination of ictal scalp electroencephalogram (EEG), and validate this method on the basis of its performance in comparison to a commercially available software method (AR1) to accurately depict seizure-onset location. Methods: A blinded investigation used 23 EEG recordings of seizures from 8 patients. Each recording was uninterpretable with digital filtering because of muscle artifact and processed using AR1 and AR2 and reviewed by 26 EEG specialists. EEG readers assessed seizure-onset time, lateralization, and region, and specified confidence for each determination. The two methods were validated on the basis of the number of readers able to render assignments, confidence, the intra-class correlation (ICC), and agreement with other clinical findings. Results: Among the 23 seizures, two-thirds of the readers were able to delineate seizure-onset time in 10 of 23 using AR1, and 15 of 23 using AR2 (p
      PubDate: 2017-04-04T14:58:07Z
      DOI: 10.12688/f1000research.10569.2
      Issue No: Vol. 6 (2017)
       
  • Type-1 metabotropic glutamate receptor signaling in cerebellar Purkinje
           cells in health and disease [version 1; referees: 3 approved]

    • Authors: Masanobu Kano, Takaki Watanabe
      Abstract: The cerebellum is a brain structure involved in coordination, control, and learning of movements, as well as certain aspects of cognitive function. Purkinje cells are the sole output neurons from the cerebellar cortex and therefore play crucial roles in the overall function of the cerebellum. The type-1 metabotropic glutamate receptor (mGluR1) is a key “hub” molecule that is critically involved in the regulation of synaptic wiring, excitability, synaptic response, and synaptic plasticity of Purkinje cells. In this review, we aim to highlight how mGluR1 controls these events in Purkinje cells. We also describe emerging evidence that altered mGluR1 signaling in Purkinje cells underlies cerebellar dysfunctions in several clinically relevant mouse models of human ataxias.
      PubDate: 2017-04-04T08:55:37Z
      DOI: 10.12688/f1000research.10485.1
      Issue No: Vol. 6 (2017)
       
  • Midlife interventions are critical in prevention, delay, or improvement of
           Alzheimer’s disease and vascular cognitive impairment and dementia
           [version 1; referees: 2 approved]

    • Authors: Sam Gandy, Tamas Bartfai, Graham V. Lees, Mary Sano
      Abstract: The basic strategy for focusing exclusively on genetically identified targets for intervening in late life dementias was formulated 30 years ago.  Three decades and billions of dollars later, all efforts at disease-modifying interventions have failed.  Over that same period, evidence has accrued pointing to dementias as late-life clinical phenotypes that begin as midlife pathologies.  Effective prevention therefore may need to begin in midlife, in order to succeed. No current interventions are sufficiently safe to justify their use in midlife dementia prevention trials.  Observational studies could be informative in testing the proposal that amyloid imaging and APOEε4 genotype can predict those who are highly likely to develop Alzheimer’s disease and in whom higher risk interventions might be justifiable. A naturally occurring, diet-responsive cognitive decline syndrome occurs in canines that closely resembles human Alzheimer’s.  Canine cognitive dysfunction could be useful in estimating how early intervention must begin in order to succeed.  This model may also help identify and assess novel targets and strategies.  New approaches to dementia prevention are urgently required, since none of the world’s economies can sustain the costs of caring for this epidemic of brain failure that is devastating half of the over 85-year-olds globally.
      PubDate: 2017-04-03T14:32:30Z
      DOI: 10.12688/f1000research.11140.1
      Issue No: Vol. 6 (2017)
       
  • Patterns of ocular inflammation in patients with miliary tuberculosis
           [version 1; referees: 2 approved]

    • Authors: Salil Mehta
      Abstract: Background: Ocular morbidity associated with systemic tuberculosis is common. The clinical picture varies from anterior uveitis, intermediate uveitis and posterior uveitis to even panuveitis. There is little data on the correlation between specific systemic presentations and the ocular inflammation. We conducted a retrospective review of the ocular findings in the case records of patients admitted with a diagnosis of miliary tuberculosis. These patients were then referred for a more detailed ophthalmic evaluation. Methods: We analysed the case records of patients with a clinical diagnosis of miliary tuberculosis over a 10-year period at Lilavati Hospital  and Research Center, Mumbai. Results: In total, 11 immunocompetent patients were identified. All 22 eyes showed normal findings on slit lamp examination. Dilated fundus examination showed single or multiple tubercles. In our cohort, the ocular findings were exclusively in the form of choroidal tuberculosis, either unilaterally or bilaterally. Slit lamp examination revealed no anterior segment inflammation Conclusions: We suggest that this pattern of choroidal/retinal tuberculosis in the absence of anterior and intermediate segment inflammation is specific for miliary tuberculosis and may be related to a specific immune response.
      PubDate: 2017-04-03T13:57:39Z
      DOI: 10.12688/f1000research.11035.1
      Issue No: Vol. 6 (2017)
       
  • Treatment with penicillin G and hydrocortisone reduces ALS-associated
           symptoms: a case series of three patients [version 1; referees: 2
           approved]

    • Authors: Bert Tuk, Harmen Jousma, Pieter J. Gaillard
      Abstract: Three male Caucasian patients with ALS were admitted to the hospital due to progressive dysphagia and dysarthria. During two 21-day courses of penicillin G and hydrocortisone, these patients’ dysphagia and dysarthria resolved. The patient’s other ALS-associated symptoms also improved, including respiratory function, coordination, walking, and muscle strength. This is the first report of a treatment with a protocol for treating dysphagia, dysarthria, respiratory depression and other ALS-related symptoms. Furthermore, the observations are consistent with the recent hypothesis that the successful treatment of ALS symptoms with this treatment course in six patients with syphilitic ALS was not directly due to the treatment of syphilis; but that the administered penicillin G and/or hydrocortisone treated these patients’ ALS symptoms due the off-target pharmacological activity of penicillin G and/or hydrocortisone. This report therefore underscores the need to evaluate the efficacy of this treatment course in a clinical trial.
      PubDate: 2017-04-03T13:11:16Z
      DOI: 10.12688/f1000research.10534.1
      Issue No: Vol. 6 (2017)
       
  • Associative memory cells: Formation, function and perspective [version 2;
           referees: 3 approved]

    • Authors: Jin-Hui Wang, Shan Cui
      Abstract: Associative learning and memory are common activities in life, and their cellular infrastructures constitute the basis of cognitive processes. Although neuronal plasticity emerges after memory formation, basic units and their working principles for the storage and retrieval of associated signals remain to be revealed. Current reports indicate that associative memory cells, through their mutual synapse innervations among the co-activated sensory cortices, are recruited to fulfill the integration, storage and retrieval of multiple associated signals, and serve associative thinking and logical reasoning. In this review, we aim to summarize associative memory cells in their formation, features and functional impacts.
      PubDate: 2017-03-30T08:42:52Z
      DOI: 10.12688/f1000research.11096.2
      Issue No: Vol. 6 (2017)
       
  • New drugs in psychiatry: focus on new pharmacological targets [version 1;
           referees: 3 approved]

    • Authors: Filippo Caraci, Gian Marco Leggio, Salvatore Salomone, Filippo Drago
      Abstract: The approval of psychotropic drugs with novel mechanisms of action has been rare in recent years. To address this issue, further analysis of the pathophysiology of neuropsychiatric disorders is essential for identifying new pharmacological targets for psychotropic medications. In this report, we detail drug candidates being examined as treatments for psychiatric disorders. Particular emphasis is placed on agents with novel mechanisms of action that are being tested as therapies for depression, schizophrenia, or Alzheimer’s disease. All of the compounds considered were recently approved for human use or are in advanced clinical trials. Drugs included here are new antipsychotic medications endowed with a preferential affinity at dopamine D3 receptor (cariprazine) or at glutamatergic or cannabinoid receptors, as well as vortioxetine, a drug approved for managing the cognitive deficits associated with major depression. New mechanistic approaches for the treatment of depression include intravenous ketamine or esketamine or intranasal esketamine. As for Alzheimer’s disease, the possible value of passive immunotherapy with agents such as aducanumab is considered to be a potential disease-modifying approach that could slow or halt the progressive decline associated with this devastating disorder.
      PubDate: 2017-03-30T08:37:51Z
      DOI: 10.12688/f1000research.10233.1
      Issue No: Vol. 6 (2017)
       
  • B-cell tolerance and autoimmunity [version 1; referees: 2 approved]

    • Authors: Takeshi Tsubata
      Abstract: Self-reactive B cells are tolerized at various stages of B-cell development and differentiation, including the immature B-cell stage (central tolerance) and the germinal center (GC) B-cell stage, and B-cell tolerance involves various mechanisms such as deletion, anergy, and receptor editing. Self-reactive B cells generated by random immunoglobulin variable gene rearrangements are tolerized by central tolerance and anergy in the periphery, and these processes involve apoptosis regulated by Bim, a pro-apoptotic member of the Bcl-2 family, and regulation of B-cell signaling by various phosphatases, including SHIP-1 and SHP-1. Self-reactive B cells generated by somatic mutations during GC reaction are also eliminated. Fas is not directly involved in this process but prevents persistence of GC reaction that allows generation of less stringently regulated B cells, including self-reactive B cells. Defects in self-tolerance preferentially cause lupus-like disease with production of anti-nuclear antibodies, probably due to the presence of a large potential B-cell repertoire reactive to nucleic acids and the presence of nucleic acid-induced activation mechanisms in various immune cells, including B cells and dendritic cells. A feed-forward loop composed of anti-nuclear antibodies produced by B cells and type 1 interferons secreted from nucleic acid-activated dendritic cells plays a crucial role in the development of systemic lupus erythematosus.
      PubDate: 2017-03-29T15:13:44Z
      DOI: 10.12688/f1000research.10583.1
      Issue No: Vol. 6 (2017)
       
  • Recent advances in understanding Epstein-Barr virus [version 1; referees:
           4 approved]

    • Authors: Brent A. Stanfield, Micah A. Luftig
      Abstract: Epstein-Barr virus (EBV) is a common human herpes virus known to infect the majority of the world population. Infection with EBV is often asymptomatic but can manifest in a range of pathologies from infectious mononucleosis to severe cancers of epithelial and lymphocytic origin. Indeed, in the past decade, EBV has been linked to nearly 10% of all gastric cancers. Furthermore, recent advances in high-throughput next-generation sequencing and the development of humanized mice, which effectively model EBV pathogenesis, have led to a wealth of knowledge pertaining to strain variation and host-pathogen interaction. This review highlights some recent advances in our understanding of EBV biology, focusing on new findings on the early events of infection, the role EBV plays in gastric cancer, new strain variation, and humanized mouse models of EBV infection.
      PubDate: 2017-03-29T10:34:32Z
      DOI: 10.12688/f1000research.10591.1
      Issue No: Vol. 6 (2017)
       
  • Bringing a genomic perspective to the safety of drug treatment in oncology
           [version 1; referees: 3 approved]

    • Authors: Federico Innocenti
      Abstract: This article describes the clinical relevance of toxicity of therapies administered to patients with cancer, putting the patient, rather than disease, at the center of the evaluation of safety of anti-cancer therapy. Hence, the implications of adverse events are described from the patient perspective, focusing on the impact of patient safety on quality of life and efficacy of treatment. Issues revolving around other types of safety, such as financial toxicity, are also discussed. The role played by genetics in the assessment of a patient’s risk of adverse events is also discussed, both in relation to the potential of genomic research and in the context of current tools of fruition in clinical care.
      PubDate: 2017-03-29T08:18:47Z
      DOI: 10.12688/f1000research.10475.1
      Issue No: Vol. 6 (2017)
       
  • What causes amyotrophic lateral sclerosis' [version 1; referees: 3
           approved]

    • Authors: Sarah Martin, Ahmad Al Khleifat, Ammar Al-Chalabi
      Abstract: Amyotrophic lateral sclerosis is a neurodegenerative disease predominantly affecting upper and lower motor neurons, resulting in progressive paralysis and death from respiratory failure within 2 to 3 years. The peak age of onset is 55 to 70 years, with a male predominance. The causes of amyotrophic lateral sclerosis are only partly known, but they include some environmental risk factors as well as several genes that have been identified as harbouring disease-associated variation. Here we review the nature, epidemiology, genetic associations, and environmental exposures associated with amyotrophic lateral sclerosis.
      PubDate: 2017-03-28T14:41:21Z
      DOI: 10.12688/f1000research.10476.1
      Issue No: Vol. 6 (2017)
       
  • Neuraxial opioids as analgesia in labour, caesarean section and
           hysterectomy: A questionnaire survey in Sweden [version 2; referees: 2
           approved]

    • Authors: Anette Hein, Caroline Gillis-Haegerstrand, Jan G. Jakobsson
      Abstract: Background: Neuraxial opioids improve labour analgesia and analgesia after caesarean section (CS) and hysterectomy. Undesirable side effects and difficulties in arranging postoperative monitoring might influence the use of these opioids. The aim of the present survey was to assess the use of intrathecal and epidural morphine in gynaecology and obstetrics in Sweden. Methods: A questionnaire was sent to all anaesthetic obstetric units in Sweden concerning the use and postoperative monitoring of morphine, sufentanil and fentanyl in spinal/epidural anaesthesia. Results: A total of 32 of 47 (68%) units responded representing 83% of annual CS in Sweden. In CS spinal anaesthesia, 20/32 units use intrathecal morphine, the most common dose of which was 100 μg (17/21). Intrathecal fentanyl (10-20 μg) was used by 21 units and sufentanil (2.5 -10 μg) by 9/32 of the responding units. In CS epidural anaesthesia, epidural fentanyl (50-100 μg) or sufentanil (5-25 μg) were commonly used (25/32), and 12/32 clinics used epidural morphine, the majority of units used a 2 mg dose. Intrathecal morphine for hysterectomy was used by 20/30 units, with 200 μg as the most common dose (9/32). Postoperative monitoring was organized in adherence to the National Guidelines; the patient is monitored postoperative care or an obstetrical ward over 2-6 hours and up-to 12 hours in an ordinary surgical ward. Risk of respiratory depression/difficult to monitor was a reason for not using intrathecal opioids. Conclusions: Neuraxial morphine is used widely in Sweden in CS and hysterectomy, but is still restricted in some units because of the concern for respiratory depression and difficulties in monitoring.
      PubDate: 2017-03-28T09:01:54Z
      DOI: 10.12688/f1000research.10705.2
      Issue No: Vol. 6 (2017)
       
  • RNA and Proteins: Mutual Respect [version 1; referees: 3 approved]

    • Authors: Kathleen B. Hall
      Abstract: Proteins and RNA are often found in ribonucleoprotein particles (RNPs), where they function in cellular processes to synthesize proteins (the ribosome), chemically modify RNAs (small nucleolar RNPs), splice pre-mRNAs (the spliceosome), and, on a larger scale, sequester RNAs, degrade them, or process them (P bodies, Cajal bodies, and nucleoli). Each RNA–protein interaction is a story in itself, as both molecules can change conformation, compete for binding sites, and regulate cellular functions. Recent studies of Xist long non-coding RNP, the U4/5/6 tri-small nuclear RNP complex, and an activated state of a spliceosome reveal new features of RNA interactions with proteins, and, although their stories are incomplete, they are already fascinating.
      PubDate: 2017-03-27T14:24:22Z
      DOI: 10.12688/f1000research.10572.1
      Issue No: Vol. 6 (2017)
       
  • X chromosome inactivation: new players in the initiation of gene silencing
           [version 1; referees: 2 approved]

    • Authors: Ines Pinheiro, Edith Heard
      Abstract: X chromosome inactivation (XCI) is a dosage compensation process that was adopted by female mammals to balance gene dosage between XX females and XY males. XCI starts with the upregulation of the non-coding RNA Xist, after which most X-linked genes are silenced and acquire a repressive chromatin state. Even though the chromatin marks of the inactive X have been fairly well described, the mechanisms responsible for the initiation of XCI remain largely unknown. In this review, we discuss recent developments that revealed unexpected factors playing a role in XCI and that might be of crucial importance to understand the mechanisms responsible for the very first steps of this chromosome-wide gene-silencing event.
      PubDate: 2017-03-27T13:49:47Z
      DOI: 10.12688/f1000research.10707.1
      Issue No: Vol. 6 (2017)
       
  • Wars between microbes on roots and fruits [version 1; referees: 3
           approved]

    • Authors: Ben Lugtenberg, Daniel E. Rozen, Faina Kamilova
      Abstract: Microbes in nature often live in unfavorable conditions. To survive, they have to occupy niches close to food sources and efficiently utilize nutrients that are often present in very low concentrations. Moreover, they have to possess an arsenal of attack and defense mechanisms against competing bacteria. In this review, we will discuss strategies used by microbes to compete with each other in the rhizosphere and on fruits, with a focus on mechanisms of inter- and intra-species antagonism. Special attention will be paid to the recently discovered roles of volatile organic compounds. Several microbes with proven capabilities in the art of warfare are being applied in products used for the biological control of plant diseases, including post-harvest control of fruits and vegetables.
      PubDate: 2017-03-27T09:37:31Z
      DOI: 10.12688/f1000research.10696.1
      Issue No: Vol. 6 (2017)
       
  • Hermaphroditism in the white spot grouper Epinephelus coeruleopunctatus
           (Pisces: Serranidae) harvested from Padang City waters, Indonesia [version
           1; referees: 2 approved, 1 approved with reservations]

    • Authors: Usman Bulanin, Masrizal Masrizal, Zainal A. Muchlisin
      Abstract: The objective of the present study was to determine the length (mm) for sex transformation of hermaphroditism in white spot grouper Epinephelus coeruleopunctatus as a basis for developing breeding technology. Fish sampling was carried out between April and October 2013 in Padang City waters, Indonesia. A total of 56 white spot groupers were recorded during the study; of these 22 were male, 28 female and 6 samples were not recognized regarding sex preference. Sex differentiation was detected at a length of 183 mm, and at this size the fish are female. Sex transformation to male begun to occur at 302 mm total length.
      PubDate: 2017-03-24T16:01:05Z
      DOI: 10.12688/f1000research.11090.1
      Issue No: Vol. 6 (2017)
       
  • Studying human immunodeficiencies in humans: advances in fundamental
           concepts and therapeutic interventions [version 1; referees: 3 approved]

    • Authors: Helen Su
      Abstract: Immunodeficiencies reveal the crucial role of the immune system in defending the body against microbial pathogens. Given advances in genomics and other technologies, this is currently best studied in humans who have inherited monogenic diseases. Such investigations have provided insights into how gene products normally function in the natural environment and have opened the door to new, exciting treatments for these diseases.
      PubDate: 2017-03-24T14:03:41Z
      DOI: 10.12688/f1000research.10594.1
      Issue No: Vol. 6 (2017)
       
  • When TADs go bad: chromatin structure and nuclear organisation in human
           disease [version 1; referees: 2 approved]

    • Authors: Vera B Kaiser, Colin A Semple
      Abstract: Chromatin in the interphase nucleus is organised as a hierarchical series of structural domains, including self-interacting domains called topologically associating domains (TADs). This arrangement is thought to bring enhancers into closer physical proximity with their target genes, which often are located hundreds of kilobases away in linear genomic distance. TADs are demarcated by boundary regions bound by architectural proteins, such as CTCF and cohesin, although much remains to be discovered about the structure and function of these domains. Recent studies of TAD boundaries disrupted in engineered mouse models show that boundary mutations can recapitulate human developmental disorders as a result of aberrant promoter-enhancer interactions in the affected TADs. Similar boundary disruptions in certain cancers can result in oncogene overexpression, and CTCF binding sites at boundaries appear to be hyper-mutated across cancers. Further insights into chromatin organisation, in parallel with accumulating whole genome sequence data for disease cohorts, are likely to yield additional valuable insights into the roles of noncoding sequence variation in human disease.
      PubDate: 2017-03-24T09:46:27Z
      DOI: 10.12688/f1000research.10792.1
      Issue No: Vol. 6 (2017)
       
  • HIV-associated neurocognitive disorders: recent advances in pathogenesis,
           biomarkers, and treatment [version 1; referees: 4 approved]

    • Authors: Antonia Carroll, Bruce Brew
      Abstract: HIV-associated neurocognitive disorders (HAND) remain prevalent despite plasma viral suppression by antiretroviral agents. In fact, the prevalence of milder subtypes of cognitive impairment is increasing. Neuropsychologic testing remains the “gold standard” of diagnosis; however, this is time consuming and costly in a resource-poor environment. Recently developed screening tools, such as CogState and the revised HIV dementia scale, have very good sensitivity and specificity in the more severe stages of HAND. However, questions remain regarding the utility of, optimal population for, and insensitivity of tests in mild HAND. Recognition of ongoing viral persistence and the inflammatory milieu in the central nervous system (CNS) has advanced our understanding of the pathogenesis of HAND and facilitated the development of biomarkers of CNS disease. The importance of the monocyte-macrophage lineage cell and the astrocyte as viral reservoirs, HIV viral proteins, self-perpetuating CNS inflammation, and CCR5 chemokine receptor neurotropism has been identified. Whilst biomarkers demonstrate monocyte activation, inflammation, and neuronal injury, they remain limited in their clinical utility. The improved understanding of pathogenic mechanisms has led to novel approaches to the treatment of HAND; however, despite these advances, the optimal management is still undefined.
      PubDate: 2017-03-23T15:55:50Z
      DOI: 10.12688/f1000research.10651.1
      Issue No: Vol. 6 (2017)
       
  • Reframing the science and policy of nicotine, illegal drugs and alcohol
           – conclusions of the ALICE RAP Project [version 1; referees: 2 approved]
           

    • Authors: Peter Anderson, Virginia Berridge, Patricia Conrod, Robert Dudley, Matilda Hellman, Dirk Lachenmeier, Anne Lingford-Hughes, David Miller, Jürgen Rehm, Robin Room, Laura Schmidt, Roger Sullivan, Tamyko Ysa, Antoni Gual
      Abstract: In 2013, illegal drug use was responsible for 1.8% of years of life lost in the European Union, alcohol was responsible for 8.2% and tobacco for 18.2%, imposing economic burdens in excess of 2.5% of GDP. No single European country has optimal governance structures for reducing the harm done by nicotine, illegal drugs and alcohol, and existing ones are poorly designed, fragmented, and sometimes cause harm. Reporting the main science and policy conclusions of a transdisciplinary five-year analysis of the place of addictions in Europe, researchers from 67 scientific institutions addressed these problems by reframing an understanding of addictions.  A new paradigm needs to account for evolutionary evidence which suggests that humans are biologically predisposed to seek out drugs, and that, today, individuals face availability of high drug doses, consequently increasing the risk of harm.  New definitions need to acknowledge that the defining element of addictive drugs is ‘heavy use over time’, a concept that could replace the diagnostic artefact captured by the clinical term ‘substance use disorder’, thus opening the door for new substances to be considered such as sugar. Tools of quantitative risk assessment that recognize drugs as toxins could be further deployed to assess regulatory approaches to reducing harm. Re-designed governance of drugs requires embedding policy within a comprehensive societal well-being frame that encompasses a range of domains of well-being, including quality of life, material living conditions and sustainability over time; such a frame adds arguments to the inappropriateness of policies that criminalize individuals for using drugs and that continue to categorize certain drugs as illegal. A health footprint, modelled on the carbon footprint, and using quantitative measures such as years of life lost due to death or disability, could serve as the accountability tool that apportions responsibility for who and what causes drug-related harm.
      PubDate: 2017-03-17T15:28:28Z
      DOI: 10.12688/f1000research.10860.1
      Issue No: Vol. 6 (2017)
       
  • General guidelines for biomedical software development [version 1;
           referees: 2 approved]

    • Authors: Luis Bastiao Silva, Rafael C. Jimenez, Niklas Blomberg, José Luis Oliveira
      Abstract: Most bioinformatics tools available today were not written by professional software developers, but by people that wanted to solve their own problems, using computational solutions and spending the minimum time and effort possible, since these were just the means to an end. Consequently, a vast number of software applications are currently available, hindering the task of identifying the utility and quality of each. At the same time, this situation has hindered regular adoption of these tools in clinical practice. Typically, they are not sufficiently developed to be used by most clinical researchers and practitioners. To address these issues, it is necessary to re-think how biomedical applications are built and adopt new strategies that ensure quality, efficiency, robustness, correctness and reusability of software components. We also need to engage end-users during the development process to ensure that applications fit their needs. In this review, we present a set of guidelines to support biomedical software development, with an explanation of how they can be implemented and what kind of open-source tools can be used for each specific topic.
      PubDate: 2017-03-15T10:35:32Z
      DOI: 10.12688/f1000research.10750.1
      Issue No: Vol. 6 (2017)
       
  • Mitogenomes of Giant-Skipper Butterflies reveal an ancient split between
           deep and shallow root feeders [version 1; referees: 2 approved]

    • Authors: Jing Zhang, Qian Cong, Xiao-Ling Fan, Rongjiang Wang, Min Wang, Nick V. Grishin
      Abstract: Background: Giant-Skipper butterflies from the genus Megathymus are North American endemics. These large and thick-bodied Skippers resemble moths and are unique in their life cycles. Grub-like at the later stages of development, caterpillars of these species feed and live inside yucca roots. Adults do not feed and are mostly local, not straying far from the patches of yucca plants. Methods: Pieces of muscle were dissected from the thorax of specimens and genomic DNA was extracted (also from the abdomen of a specimen collected nearly 60 years ago). Paired-end libraries were prepared and sequenced for 150bp from both ends. The mitogenomes were assembled from the reads followed by a manual gap-closing procedure and a phylogenetic tree was constructed using a maximum likelihood method from an alignment of the mitogenomes. Results: We determined mitogenome sequences of nominal subspecies of all five known species of Megathymus and Agathymus mariae to confidently root the phylogenetic tree. Pairwise sequence identity indicates the high similarity, ranging from 88-96% among coding regions for 13 proteins, 22 tRNAs and 2 rRNA, with a gene order typical for mitogenomes of Lepidoptera. Phylogenetic analysis confirms that Giant-Skippers (Megathymini) originate within the subfamily Hesperiinae and do not warrant a subfamily rank. Genus Megathymus is monophyletic and splits into two species groups. M. streckeri and M. cofaqui caterpillars feed deep in the main root system of yucca plants and deposit frass underground. M. ursus, M. beulahae and M. yuccae feed in the yucca caudex and roots near the ground, and deposit frass outside through a "tent" (a silk tube projecting from the center of yucca plant). M. yuccae and M. beulahae are sister species consistently with morphological similarities between them. Conclusions: We constructed the first DNA-based phylogeny of the genus Megathymus from their mitogenomes. The phylogeny agrees with morphological considerations.
      PubDate: 2017-03-06T11:48:37Z
      DOI: 10.12688/f1000research.10970.1
      Issue No: Vol. 6 (2017)
       
  • Age-specific acceleration in malignant melanoma [version 2; referees: 2
           approved]

    • Authors: Brian L Diffey, Steven A Frank
      Abstract: Background: The overall incidence of melanoma has increased steadily for several years. The relative change in incidence at different ages has not been fully described. Objective: To describe how incidence at different ages has changed over time and to consider what aspects of tumour biology may explain the observed pattern of change in incidence. Methods: The slope of incidence vs age measures the acceleration of cancer incidence with age. We described the pattern of change over time in the overall incidence of melanoma, as well as in acceleration. We used data for males and females from 3 different countries in the 17 sequential 5-year birth-cohort categories from 1895-99 to 1975-79, from which we derived the incidence patterns. Results: Over time, there has been a tendency for the overall incidence of melanoma to increase and for the acceleration (slope) of the age-incidence curves to decline. The changing patterns of melanoma incidence and acceleration differ between males and females and between the countries analysed. Conclusions: The observed pattern in melanoma of rising incidence and declining acceleration occurs in other cancers in response to genetic knockouts of mechanisms that protect against cancer. Perhaps some protective mechanism with respect to melanoma may be less effective now than in the past, possibly because of more intense environmental challenges.
      PubDate: 2017-02-24T09:47:04Z
      DOI: 10.12688/f1000research.10491.2
      Issue No: Vol. 6 (2017)
       
  • Open Online Courses in Public Health: experience from Peoples-uni [version
           1; referees: 1 approved, 2 approved with reservations]

    • Authors: Richard F. Heller, Robert Zurynski, Alan Barrett, Omo Oaiya, Rajan Madhok
      Abstract: Open Online Courses (OOCs) are offered by Peoples-uni at http://ooc.peoples-uni.org to complement the courses run on a separate site for academic credit at http://courses.peoples-uni.org. They provide a wide range of online learning resources beyond those usually found in credit bearing Public Health courses. They are self-paced, and students can enrol themselves at any time and utilise Open Educational Resources free of copyright restrictions.  In the two years that courses have been running, 1174 students from 100 countries have registered and among the 1597 enrollments in 15 courses, 15% gained a certificate of completion. Easily accessible and appealing to a wide geographical and professional audience, OOCs have the potential to play a part in establishing global Public Health capacity building programmes.
      PubDate: 2017-02-21T10:37:22Z
      DOI: 10.12688/f1000research.10728.1
      Issue No: Vol. 6 (2017)
       
  • Cell growth inhibition and apoptotic effects of a specific anti-RTFscFv
           antibody on prostate cancer, but not glioblastoma, cells [version 1;
           referees: 2 approved, 1 approved with reservations]

    • Authors: Foroogh Nejatollahi, Payam Bayat, Bahareh Moazen
      Abstract: Background: Single chain antibody (scFv) has shown interesting results in cancer immunotargeting approaches, due to its advantages over monoclonal antibodies. Regeneration and tolerance factor (RTF) is one of the most important regulators of extracellular and intracellular pH in eukaryotic cells. In this study, the inhibitory effects of a specific anti-RTF scFv were investigated and compared between three types of prostate cancer and two types of glioblastoma cells. Methods: A phage antibody display library of scFv was used to select specific scFvs against RTF using panning process. The reactivity of a selected scFv was assessed by phage ELISA. The anti-proliferative and apoptotic effects of the antibody on prostate cancer (PC-3, Du-145 and LNCaP) and glioblastoma (U-87 MG and A-172) cell lines were investigated by MTT and Annexin V/PI assays. Results: A specific scFv with frequency 35% was selected against RTF epitope. This significantly inhibited the proliferation of the prostate cells after 24 h. The percentages of cell viability (using 1000 scFv/cell) were 52, 61 and 73% for PC-3, Du-145 and LNCaP cells, respectively, compared to untreated cells. The antibody (1000 scFv/cell) induced apoptosis at 50, 40 and 25% in PC-3, Du-145 and LNCaP cells, respectively. No growth inhibition and apoptotic induction was detected for U-87 and A172 glioblastoma cells. Conclusions: Anti-RTFscFv significantly reduced the proliferation of the prostate cancer cells. The inhibition of cell growth and apoptotic induction effects in PC-3 cells were greater than Du-145 and LNCaP cells. This might be due to higher expression of RTF antigen in PC-3 cells and/or better accessibility of RTF to scFv antibody. The resistance of glioblastoma cells to anti-RTF scFv offers the existence of mechanism(s) that abrogate the inhibitory effect(s) of the antibody to RTF. The results suggest that the selected anti-RTF scFv antibody could be an effective new alternative for prostate cancer immunotherapy.
      PubDate: 2017-02-17T11:12:41Z
      DOI: 10.12688/f1000research.10803.1
      Issue No: Vol. 6 (2017)
       
  • Health care and social media: What patients really understand [version 1;
           referees: 2 approved]

    • Authors: Kyle Hoedebecke, Lindsey Beaman, Joy Mugambi, Sanam Shah, Marwa Mohasseb, Cheyanne Vetter, Kim Yu, Irini Gergianaki, Emily Couvillon
      Abstract: Background: Low health literacy is associated with decreased patient compliance and worse outcomes - with clinicians increasingly relying on printed materials to lower such risks. Yet, many of these documents exceed recommended comprehension levels. Furthermore, patients look increasingly to social media (SoMe) to answer healthcare questions. The character limits built into Twitter encourage users to publish small quantities of text, which are more accessible to patients with low health literacy. The present authors hypothesize that SoMe posts are written at lower grade levels than traditional medical sources, improving patient health literacy. Methods: The data sample consisted of the first 100 original tweets from three trending medical hashtags, leading to a total of 300 tweets. The Flesch-Kincaid Readability Formula (FKRF) was used to derive grade level of the tweets. Data was analyzed via descriptive and inferential statistics. Results: The readability scores for the data sample had a mean grade level of 9.45. A notable 47.6% of tweets were above ninth grade reading level. An independent-sample t-test comparing FKRF mean scores of different hashtags found differences between the means of the following: #hearthealth versus #diabetes (t = 3.15, p = 0.002); #hearthealth versus #migraine (t = 0.09, p = 0.9); and #diabetes versus #migraine (t = 3.4, p = 0.001). Conclusions: Tweets from this data sample were written at a mean grade level of 9.45, signifying a level between the ninth and tenth grades. This is higher than desired, yet still better than traditional sources, which have been previously analyzed. Ultimately, those responsible for health care SoMe posts must continue to improve efforts to reach the recommended reading level (between the sixth and eighth grade), so as to ensure optimal comprehension of patients.
      PubDate: 2017-02-08T14:46:44Z
      DOI: 10.12688/f1000research.10637.1
      Issue No: Vol. 6 (2017)
       
  • Annotated mitochondrial genome with Nanopore R9 signal for Nippostrongylus
           brasiliensis [version 1; referees: 1 approved, 2 approved with
           reservations]

    • Authors: Jodie Chandler, Mali Camberis, Tiffany Bouchery, Mark Blaxter, Graham Le Gros, David A Eccles
      Abstract: Nippostrongylus brasiliensis, a nematode parasite of rodents, has a parasitic life cycle that is an extremely useful model for the study of human hookworm infection, particularly in regards to the induced immune response. The current reference genome for this parasite is highly fragmented with minimal annotation, but new advances in long-read sequencing suggest that a more complete and annotated assembly should be an achievable goal. We de-novo assembled a single contig mitochondrial genome from N. brasiliensis using MinION R9 nanopore data. The assembly was error-corrected using existing Illumina HiSeq reads, and annotated in full (i.e. gene boundary definitions without substantial gaps) by comparing with annotated genomes from similar parasite relatives. The mitochondrial genome has also been annotated with a preliminary electrical consensus sequence, using raw signal data generated from a Nanopore R9 flow cell.
      PubDate: 2017-01-19T12:50:10Z
      DOI: 10.12688/f1000research.10545.1
      Issue No: Vol. 6 (2017)
       
  • A voltage-dependent fluorescent indicator for optogenetic applications,
           archaerhodopsin-3: Structure and optical properties from in silico
           modeling [version 2; referees: 1 approved, 2 approved with reservations]

    • Authors: Dmitrii M. Nikolaev, Anton Emelyanov, Vitaly M. Boitsov, Maxim S Panov, Mikhail N. Ryazantsev
      Abstract: It was demonstrated in recent studies that some rhodopsins can be used in optogenetics as fluorescent indicators of membrane voltage. One of the promising candidates for these applications is archaerhodopsin-3. However, the fluorescent signal for wild-type achaerhodopsin-3 is not strong enough for real applications. Rational design of mutants with an improved signal is an important task, which requires both experimental and theoretical studies. Herein, we used a homology-based computational approach to predict the three-dimensional structure of archaerhodopsin-3, and a Quantum Mechanics/Molecular Mechanics (QM/MM) hybrid approach with high-level multireference ab initio methodology (SORCI+Q/AMBER) to model optical properties of this protein. We demonstrated that this methodology allows for reliable prediction of structure and spectral properties of archaerhodopsin-3. The results of this study can be utilized for computational molecular design of efficient fluorescent indicators of membrane voltage for modern optogenetics on the basis of archaerhodopsin-3.
      PubDate: 2017-01-17T15:55:07Z
      DOI: 10.12688/f1000research.10541.2
      Issue No: Vol. 6 (2017)
       
  • Animating and exploring phylogenies with fibre plots [version 3; referees:
           1 approved, 2 approved with reservations]

    • Authors: William D. Pearse
      Abstract: Despite the progress that has been made in many other aspects of data visualisation, phylogenies are still represented in much the same way as they first were by Darwin. In this brief essay, I give a short review of what I consider to be some recent major advances, and outline a new kind of phylogenetic visualisation. This new graphic, the fibre plot, uses the metaphor of sections through a tree to describe change in a phylogeny. I suggest it is a useful tool in gaining an rapid overview of the timing and scale of diversification in large phylogenies.
      PubDate: 2017-04-05T15:13:54Z
      DOI: 10.12688/f1000research.10274.3
      Issue No: Vol. 5 (2017)
       
  • A multi-scale computational model of the effects of TMS on motor cortex
           [version 2; referees: 2 approved]

    • Authors: Hyeon Seo, Natalie Schaworonkow, Sung Chan Jun, Jochen Triesch
      Abstract: The detailed biophysical mechanisms through which transcranial magnetic stimulation (TMS) activates cortical circuits are still not fully understood. Here we present a multi-scale computational model to describe and explain the activation of different pyramidal cell types in motor cortex due to TMS. Our model determines precise electric fields based on an individual head model derived from magnetic resonance imaging and calculates how these electric fields activate morphologically detailed models of different neuron types. We predict neural activation patterns for different coil orientations consistent with experimental findings. Beyond this, our model allows us to calculate activation thresholds for individual neurons and precise initiation sites of individual action potentials on the neurons’ complex morphologies. Specifically, our model predicts that cortical layer 3 pyramidal neurons are generally easier to stimulate than layer 5 pyramidal neurons, thereby explaining the lower stimulation thresholds observed for I-waves compared to D-waves. It also shows differences in the regions of activated cortical layer 5 and layer 3 pyramidal cells depending on coil orientation. Finally, it predicts that under standard stimulation conditions, action potentials are mostly generated at the axon initial segment of cortical pyramidal cells, with a much less important activation site being the part of a layer 5 pyramidal cell axon where it crosses the boundary between grey matter and white matter. In conclusion, our computational model offers a detailed account of the mechanisms through which TMS activates different cortical pyramidal cell types, paving the way for more targeted application of TMS based on individual brain morphology in clinical and basic research settings.
      PubDate: 2017-02-17T13:57:00Z
      DOI: 10.12688/f1000research.9277.2
      Issue No: Vol. 5 (2017)
       
  • Crafting minds and communities with Minecraft [version 2; referees: 2
           approved]

    • Authors: Benjamin C. Riordan, Damian Scarf
      Abstract: Minecraft is a first-person perspective video game in which players roam freely in a large three-dimensional environment. Players mine the landscape for minerals and use these minerals to create structures (e.g., houses) and mould the landscape. But can Minecraft be used to craft communities and minds' In this opinion piece, we highlight the enormous potential of Minecraft for fostering social connectedness, collaboration, and its potential as an educational tool. We highlight the recent use of Minecraft to aid socialization in individuals with Autistic Spectrum Disorder (ASD) and promote civic engagement via the United Nations Human Settlement Program. We further provide novel links between Minecraft and recent on work on the role of social cures and community empowerment in enhancing mental health, wellbeing, and resilience.
      PubDate: 2017-01-09T10:17:48Z
      DOI: 10.12688/f1000research.9625.2
      Issue No: Vol. 5 (2017)
       
  • Meta-analysis of crowdsourced data compendia suggests pan-disease
           transcriptional signatures of autoimmunity [version 1; referees: 2
           approved]

    • Authors: William W. Lau, Rachel Sparks, OMiCC Jamboree Working Group, John S. Tsang
      Abstract: Background: The proliferation of publicly accessible large-scale biological data together with increasing availability of bioinformatics tools have the potential to transform biomedical research. Here we report a crowdsourcing Jamboree that explored whether a team of volunteer biologists without formal bioinformatics training could use OMiCC, a crowdsourcing web platform that facilitates the reuse and (meta-) analysis of public gene expression data, to compile and annotate gene expression data, and design comparisons between disease and control sample groups. Methods: The Jamboree focused on several common human autoimmune diseases, including systemic lupus erythematosus (SLE), multiple sclerosis (MS), type I diabetes (DM1), and rheumatoid arthritis (RA), and the corresponding mouse models. Meta-analyses were performed in OMiCC using comparisons constructed by the participants to identify 1) gene expression signatures for each disease (disease versus healthy controls at the gene expression and biological pathway levels), 2) conserved signatures across all diseases within each species (pan-disease signatures), and 3) conserved signatures between species for each disease and across all diseases (cross-species signatures). Results: A large number of differentially expressed genes were identified for each disease based on meta-analysis, with observed overlap among diseases both within and across species. Gene set/pathway enrichment of upregulated genes suggested conserved signatures (e.g., interferon) across all human and mouse conditions. Conclusions: Our Jamboree exercise provides evidence that when enabled by appropriate tools, a "crowd" of biologists can work together to accelerate the pace by which the increasingly large amounts of public data can be reused and meta-analyzed for generating and testing hypotheses. Our encouraging experience suggests that a similar crowdsourcing approach can be used to explore other biological questions.
      PubDate: 2016-12-20T14:28:09Z
      DOI: 10.12688/f1000research.10465.1
      Issue No: Vol. 5 (2016)
       
  • A data-driven approach to estimating the number of clusters in
           hierarchical clustering [version 1; referees: 2 approved, 1 approved with
           reservations]

    • Authors: Antoine E. Zambelli
      Abstract: DNA microarray and gene expression problems often require a researcher to perform clustering on their data in a bid to better understand its structure. In cases where the number of clusters is not known, one can resort to hierarchical clustering methods. However, there currently exist very few automated algorithms for determining the true number of clusters in the data. We propose two new methods (mode and maximum difference) for estimating the number of clusters in a hierarchical clustering framework to create a fully automated process with no human intervention. These methods are compared to the established elbow and gap statistic algorithms using simulated datasets and the Biobase Gene ExpressionSet. We also explore a data mixing procedure inspired by cross validation techniques. We find that the overall performance of the maximum difference method is comparable or greater to that of the gap statistic in multi-cluster scenarios, and achieves that performance at a fraction of the computational cost. This method also responds well to our mixing procedure, which opens the door to future research. We conclude that both the mode and maximum difference methods warrant further study related to their mixing and cross-validation potential. We particularly recommend the use of the maximum difference method in multi-cluster scenarios given its accuracy and execution times, and present it as an alternative to existing algorithms.
      PubDate: 2016-12-01T14:23:37Z
      DOI: 10.12688/f1000research.10103.1
      Issue No: Vol. 5 (2016)
       
 
 
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