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Journal Cover F1000Research
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  This is an Open Access Journal Open Access journal
   ISSN (Online) 2046-1402
   Published by Faculty of 1000 Homepage  [1 journal]
  • Respiratory rhythm generation: triple oscillator hypothesis [version 1;
           referees: 3 approved]

    • Authors: Tatiana M. Anderson, Jan-Marino Ramirez
      Abstract: Breathing is vital for survival but also interesting from the perspective of rhythm generation. This rhythmic behavior is generated within the brainstem and is thought to emerge through the interaction between independent oscillatory neuronal networks. In mammals, breathing is composed of three phases – inspiration, post-inspiration, and active expiration – and this article discusses the concept that each phase is generated by anatomically distinct rhythm-generating networks: the preBötzinger complex (preBötC), the post-inspiratory complex (PiCo), and the lateral parafacial nucleus (pFL), respectively. The preBötC was first discovered 25 years ago and was shown to be both necessary and sufficient for the generation of inspiration. More recently, networks have been described that are responsible for post-inspiration and active expiration. Here, we attempt to collate the current knowledge and hypotheses regarding how respiratory rhythms are generated, the role that inhibition plays, and the interactions between the medullary networks. Our considerations may have implications for rhythm generation in general.
      PubDate: 2017-02-14T10:56:47Z
      DOI: 10.12688/f1000research.10193.1
      Issue No: Vol. 6 (2017)
  • Cytomegalovirus in pregnancy and the neonate [version 1; referees: 2

    • Authors: Vincent C. Emery, Tiziana Lazzarotto
      Abstract: Congenital cytomegalovirus (CMV) remains a leading cause of disability in children. Understanding the pathogenesis of infection from the mother via the placenta to the neonate is crucial if we are to produce new interventions and provide supportive mechanisms to improve the outcome of congenitally infected children. In recent years, some major goals have been achieved, including the diagnosis of primary maternal CMV infection in pregnant women by using the anti-CMV IgG avidity test and the diagnosis and prognosis of foetal CMV infection by using polymerase chain reaction real-time tests to detect and quantify the virus in amniotic fluid. This review summarises recent advances in our understanding and highlights where challenges remain, especially in vaccine development and anti-viral therapy of the pregnant woman and the neonate. Currently, no therapeutic options during pregnancy are available except those undergoing clinical trials, whereas valganciclovir treatment is recommended for congenitally infected neonates with moderately to severely symptomatic disease.
      PubDate: 2017-02-14T10:55:33Z
      DOI: 10.12688/f1000research.10276.1
      Issue No: Vol. 6 (2017)
  • Apolipoprotein B-containing lipoproteins and atherosclerotic
           cardiovascular disease [version 1; referees: 2 approved]

    • Authors: Michael D. Shapiro, Sergio Fazio
      Abstract: Cholesterol-rich, apolipoprotein B (apoB)-containing lipoproteins are now widely accepted as the most important causal agents of atherosclerotic cardiovascular disease. Multiple unequivocal and orthogonal lines of evidence all converge on low-density lipoprotein and related particles as being the principal actors in the genesis of atherosclerosis. Here, we review the fundamental role of atherogenic apoB-containing lipoproteins in cardiovascular disease and several other humoral and parietal factors that are required to initiate and maintain arterial degeneration. The biology of foam cells and their interactions with high-density lipoproteins, including cholesterol efflux, are also briefly reviewed.
      PubDate: 2017-02-13T15:28:10Z
      DOI: 10.12688/f1000research.9845.1
      Issue No: Vol. 6 (2017)
  • Serotonin receptors in depression: from A to B [version 1; referees: 3

    • Authors: Katherine M. Nautiyal, René Hen
      Abstract: The role of serotonin in major depressive disorder (MDD) is the focus of accumulating clinical and preclinical research. The results of these studies reflect the complexity of serotonin signaling through many receptors, in a large number of brain regions, and throughout the lifespan. The role of the serotonin transporter in MDD has been highlighted in gene by environment association studies as well as its role as a critical player in the mechanism of the most effective antidepressant treatments – selective serotonin reuptake inhibitors. While the majority of the 15 known receptors for serotonin have been implicated in depression or depressive-like behavior, the serotonin 1A (5-HT1A) and 1B (5-HT1B) receptors are among the most studied. Human brain imaging and genetic studies point to the involvement of 5-HT1A and 5-HT1B receptors in MDD and the response to antidepressant treatment. In rodents, the availability of tissue-specific and inducible knockout mouse lines has made possible the identification of the involvement of 5-HT1A and 5-HT1B receptors throughout development and in a cell-type specific manner. This, and other preclinical pharmacology work, shows that autoreceptor and heteroreceptor populations of these receptors have divergent roles in modulating depression-related behavior as well as responses to antidepressants and also have different functions during early postnatal development compared to during adulthood.
      PubDate: 2017-02-09T16:50:08Z
      DOI: 10.12688/f1000research.9736.1
      Issue No: Vol. 6 (2017)
  • Molecular signature of anastasis for reversal of apoptosis [version 2;
           referees: 2 approved]

    • Authors: Ho Man Tang, C. Conover Talbot Jr, Ming Chiu Fung, Ho Lam Tang
      Abstract: Anastasis (Greek for "rising to life") is a cell recovery phenomenon that rescues dying cells from the brink of cell death. We recently discovered anastasis to occur after the execution-stage of apoptosis in vitro and in vivo. Promoting anastasis could in principle preserve injured cells that are difficult to replace, such as cardiomyocytes and neurons. Conversely, arresting anastasis in dying cancer cells after cancer therapies could improve treatment efficacy. To develop new therapies that promote or inhibit anastasis, it is essential to identify the key regulators and mediators of anastasis – the therapeutic targets. Therefore, we performed time-course microarray analysis to explore the molecular mechanisms of anastasis during reversal of ethanol-induced apoptosis in mouse primary liver cells. We found striking changes in transcription of genes involved in multiple pathways, including early activation of pro-cell survival, anti-oxidation, cell cycle arrest, histone modification, DNA-damage and stress-inducible responses, and at delayed times, angiogenesis and cell migration. Validation with RT-PCR confirmed similar changes in the human liver cancer cell line, HepG2, during anastasis. Here, we present the time-course whole-genome gene expression dataset revealing gene expression profiles during the reversal of apoptosis. This dataset provides important insights into the physiological, pathological, and therapeutic implications of anastasis.
      PubDate: 2017-02-09T16:47:27Z
      DOI: 10.12688/f1000research.10568.2
      Issue No: Vol. 6 (2017)
  • Recent advances in understanding and treating nephrotic syndrome [version
           1; referees: 2 approved]

    • Authors: Agnieszka Bierzynska, Moin Saleem
      Abstract: Idiopathic nephrotic syndrome (INS) is one of the most common glomerular diseases in children and adults, and the central event is podocyte injury. INS is a heterogeneous disease, and treatment is largely empirical and in many cases unsuccessful, and steroids are the initial mainstay of therapy. Close to 70% of children with INS have some response to steroids and are labelled as steroid-‘sensitive’, and the rest as steroid-‘resistant’ (also termed focal segmental glomerulosclerosis), and single-gene mutations underlie a large proportion of the latter group. The burden of morbidity is enormous, both to patients with lifelong chronic disease and to health services, particularly in managing dialysis and transplantation. The target cell of nephrotic syndrome is the glomerular podocyte, and podocyte biology research has exploded over the last 15 years. Major advances in genetic and biological understanding now put clinicians and researchers at the threshold of a major reclassification of the disease and testing of targeted therapies both identified and novel. That potential is based on complete genetic analysis, deep clinical phenotyping, and the introduction of mechanism-derived biomarkers into clinical practice. INS can now be split off into those with a single-gene defect, of which currently at least 53 genes are known to be causative, and the others. Of the others, the majority are likely to be immune-mediated and caused by the presence of a still-unknown circulating factor or factors, and whether there is a third (or more) mechanistic group or groups remains to be discovered. Treatment is therefore now being refined towards separating out the monogenic cases to minimise immunosuppression and further understanding how best to stratify and appropriately direct immunosuppressive treatments within the immune group. Therapies directed specifically towards the target cell, the podocyte, are in their infancy but hold considerable promise for the near future.
      PubDate: 2017-02-09T15:32:56Z
      DOI: 10.12688/f1000research.10165.1
      Issue No: Vol. 6 (2017)
  • A review of perioperative anesthesia and analgesia for infants: updates
           and trends to watch [version 1; referees: 2 approved]

    • Authors: Lizabeth D Martin, Nathalia Jimenez, Anne M Lynn
      Abstract: This review focuses on pharmacokinetics and pharmacodynamics of opioid and non-opioid analgesics in neonates and infants. The unique physiology of this population differs from that of adults and impacts drug handling. Morphine and remifentanil are described as examples of older versus recently developed opiates to compare and contrast pharmacokinetics and pharmacodynamics in infants. Exploration of genetics affecting both pharmacokinetics and pharmacodynamics of opiates is an area of active research, as is the investigation of a new class of mu-opiate-binding agents which seem selective for analgesic pathways while having less activity in pathways linked to side effects. The kinetics of acetaminophen and of ketorolac as examples of parenteral non-steroidal analgesics in infants are also discussed. The growth in regional anesthesia for peri-operative analgesia in infants can fill an important role minimizing intra-operative anesthetic exposure to opioids and transitioning to post-operative care. Use of multi-modal techniques is recommended to decrease undesirable opiate-related side effects in this vulnerable population.
      PubDate: 2017-02-08T15:09:24Z
      DOI: 10.12688/f1000research.10272.1
      Issue No: Vol. 6 (2017)
  • Recent advances in plant-herbivore interactions [version 1; referees: 2

    • Authors: Deron E. Burkepile, John D. Parker
      Abstract: Plant-herbivore interactions shape community dynamics across marine, freshwater, and terrestrial habitats. From amphipods to elephants and from algae to trees, plant-herbivore relationships are the crucial link generating animal biomass (and human societies) from mere sunlight. These interactions are, thus, pivotal to understanding the ecology and evolution of virtually any ecosystem. Here, we briefly highlight recent advances in four areas of plant-herbivore interactions: (1) plant defense theory, (2) herbivore diversity and ecosystem function, (3) predation risk aversion and herbivory, and (4) how a changing climate impacts plant-herbivore interactions. Recent advances in plant defense theory, for example, highlight how plant life history and defense traits affect and are affected by multiple drivers, including enemy pressure, resource availability, and the local plant neighborhood, resulting in trait-mediated feedback loops linking trophic interactions with ecosystem nutrient dynamics. Similarly, although the positive effect of consumer diversity on ecosystem function has long been recognized, recent advances using DNA barcoding to elucidate diet, and Global Positioning System/remote sensing to determine habitat selection and impact, have shown that herbivore communities are probably even more functionally diverse than currently realized. Moreover, although most diversity-function studies continue to emphasize plant diversity, herbivore diversity may have even stronger impacts on ecosystem multifunctionality. Recent studies also highlight the role of risk in plant-herbivore interactions, and risk-driven trophic cascades have emerged as landscape-scale patterns in a variety of ecosystems. Perhaps not surprisingly, many plant-herbivore interactions are currently being altered by climate change, which affects plant growth rates and resource allocation, expression of chemical defenses, plant phenology, and herbivore metabolism and behavior. Finally, we conclude by noting that although the field is advancing rapidly, the world is changing even more rapidly, challenging our ability to manage these pivotal links in the food chain.
      PubDate: 2017-02-08T14:57:25Z
      DOI: 10.12688/f1000research.10313.1
      Issue No: Vol. 6 (2017)
  • Recent advances in (therapeutic protein) drug development [version 1;
           referees: 2 approved]

    • Authors: H.A. Daniel Lagassé, Aikaterini Alexaki, Vijaya L. Simhadri, Nobuko H. Katagiri, Wojciech Jankowski, Zuben E. Sauna, Chava Kimchi-Sarfaty
      Abstract: Therapeutic protein drugs are an important class of medicines serving patients most in need of novel therapies. Recently approved recombinant protein therapeutics have been developed to treat a wide variety of clinical indications, including cancers, autoimmunity/inflammation, exposure to infectious agents, and genetic disorders. The latest advances in protein-engineering technologies have allowed drug developers and manufacturers to fine-tune and exploit desirable functional characteristics of proteins of interest while maintaining (and in some cases enhancing) product safety or efficacy or both. In this review, we highlight the emerging trends and approaches in protein drug development by using examples of therapeutic proteins approved by the U.S. Food and Drug Administration over the previous five years (2011–2016, namely January 1, 2011, through August 31, 2016).
      PubDate: 2017-02-07T14:11:35Z
      DOI: 10.12688/f1000research.9970.1
      Issue No: Vol. 6 (2017)
  • Disinhibition, an emerging pharmacology of learning and memory [version 1;
           referees: 3 approved]

    • Authors: Hanns Möhler, Uwe Rudolph
      Abstract: Learning and memory are dependent on interactive excitatory and inhibitory mechanisms. In this review, we discuss a mechanism called disinhibition, which is the release of an inhibitory constraint that effectively results in an increased activity in the target neurons (for example, principal or projection neurons). We focus on discussing the role of disinhibition in learning and memory at a basic level and in disease models with cognitive deficits and highlight a strategy to reverse cognitive deficits caused by excess inhibition, through disinhibition of α5-containing GABAA receptors mediating tonic inhibition in the hippocampus, based on subtype-selective negative allosteric modulators as a novel class of drugs.
      PubDate: 2017-02-03T15:13:33Z
      DOI: 10.12688/f1000research.9947.1
      Issue No: Vol. 6 (2017)
  • The role of cDC1s in vivo: CD8 T cell priming through cross-presentation
           [version 1; referees: 3 approved]

    • Authors: Derek Theisen, Kenneth Murphy
      Abstract: The cDC1 subset of classical dendritic cells is specialized for priming CD8 T cell responses through the process of cross-presentation. The molecular mechanisms of cross-presentation remain incompletely understood because of limited biochemical analysis of rare cDC1 cells, difficulty in their genetic manipulation, and reliance on in vitro systems based on monocyte- and bone-marrow-derived dendritic cells. This review will discuss cross-presentation from the perspective of studies with monocyte- or bone-marrow-derived dendritic cells while highlighting the need for future work examining cDC1 cells. We then discuss the role of cDC1s as a cellular platform to combine antigen processing for class I and class II MHC presentation to allow the integration of “help” from CD4 T cells during priming of CD8 T cell responses.
      PubDate: 2017-02-01T14:39:14Z
      DOI: 10.12688/f1000research.9997.1
      Issue No: Vol. 6 (2017)
  • Recent advances in understanding/assessing toxicity to the epigenome
           [version 1; referees: 2 approved]

    • Authors: Kevin Sweder
      Abstract: The ability of non-genotoxic agents to induce cancer has been documented and clearly requires a reassessment of testing for environmental and human safety. Drug safety testing has historically relied on test batteries designed to detect DNA damage leading to mutation and cancer. The standard genetic toxicology testing battery has been a reliable tool set to identify small molecules/chemicals as hazards that could lead to genetic changes in organisms and induction of cancer. While pharmaceutical companies and regulatory agencies have extensively used the standard battery, it is not suitable for compounds that may induce epigenetic changes. Additionally, many pharmaceutical companies have changed their product portfolios to include peptides and/or other biological molecules, which are not expected to be genotoxic in their own right. If we are to best use our growing knowledge regarding chemicals and biomolecules that induce heritable changes via epigenetic mechanisms, then we must ask what changes may be needed in our testing paradigm to predict long-term downstream effects through epigenetic mechanisms.
      PubDate: 2017-02-01T09:49:06Z
      DOI: 10.12688/f1000research.9649.1
      Issue No: Vol. 6 (2017)
  • One size doesn’t fit all: Should we reconsider the introduction of
           cold-stored platelets in blood bank inventories' [version 1; referees:
           2 approved]

    • Authors: Alessandra Berzuini, Marta Spreafico, Daniele Prati
      Abstract: Platelet concentrates are universally prepared with a standard method and stored for 5 days at room temperature (20–24°C) in gentle agitation. Currently, there is a renewed interest in the possibility of storing platelet concentrates below the standard temperatures. In fact, cold platelets might be more effective in bleeding patients and have a lower risk of bacterial transmission. Inventories including platelets at different temperatures may favour patient-centred strategies for prophylactic or therapeutic transfusions.
      PubDate: 2017-02-01T09:47:58Z
      DOI: 10.12688/f1000research.10363.1
      Issue No: Vol. 6 (2017)
  • Mechanisms of pathogenesis of emerging adenoviruses [version 1; referees:
           2 approved]

    • Authors: James Cook, Jay Radke
      Abstract: Periodic outbreaks of human adenovirus infections can cause severe illness in people with no known predisposing conditions. The reasons for this increased viral pathogenicity are uncertain. Adenoviruses are constantly undergoing mutation during circulation in the human population, but related phenotypic changes of the viruses are rarely detected because of the infrequency of such outbreaks and the limited biological studies of the emergent strains. Mutations and genetic recombinations have been identified in these new strains. However, the linkage between these genetic changes and increased pathogenicity is poorly understood. It has been observed recently that differences in virus-induced immunopathogenesis can be associated with altered expression of non-mutant viral genes associated with changes in viral modulation of the host innate immune response. Initial small animal studies indicate that these changes in viral gene expression can be associated with enhanced immunopathogenesis in vivo. Available evidence suggests the hypothesis that there is a critical threshold of expression of certain viral genes that determines both the sustainability of viral transmission in the human population and the enhancement of immunopathogenesis. Studies of this possibility will require extension of the analysis of outbreak viral strains from a sequencing-based focus to biological studies of relationships between viral gene expression and pathogenic responses. Advances in this area will require increased coordination among public health organizations, diagnostic microbiology laboratories, and research laboratories to identify, catalog, and systematically study differences between prototype and emergent viral strains that explain the increased pathogenicity that can occur during clinical outbreaks.
      PubDate: 2017-01-30T15:49:06Z
      DOI: 10.12688/f1000research.10152.1
      Issue No: Vol. 6 (2017)
  • Recent advances in managing systemic sclerosis [version 1; referees: 2

    • Authors: Martin Aringer, Anne Erler
      Abstract: How the main components in systemic sclerosis—namely autoimmunity, vasculopathy, and fibrosis—fit together is still not sufficiently clear. However, vascular treatment options are well established, the body of evidence for the efficacy of immunomodulatory approaches is increasing, and now at least one hopeful substance that may directly interfere with fibrosis is being tested. Although we still wait for important breakthroughs, there is grounds for hope that better therapeutic options will be available in the near future.
      PubDate: 2017-01-30T09:51:13Z
      DOI: 10.12688/f1000research.10022.1
      Issue No: Vol. 6 (2017)
  • Advances in the treatment of opioid use disorders [version 1; referees: 3

    • Authors: George E. Woody
      Abstract: The development of medications for treating persons with opioid use disorders has expanded the number of evidence-based treatment options, particularly for persons with the most severe disorders. It has also improved outcomes compared to psychosocial treatment alone and expanded treatment availability by increasing the number of physicians involved in treatment and the settings where patients can be treated. The medications include methadone, buprenorphine, buprenorphine/naloxone, and extended-release injectable naltrexone. Studies have shown that they are most effective when used over an extended, but as-yet-unspecified, period of time and with counseling and other services, particularly for the many with psychosocial problems. Though controversial in some cultures, well-designed studies in Switzerland, the Netherlands, Germany, and Canada have demonstrated the efficacy of supervised heroin injecting for persons who responded poorly to other treatments, and this treatment option has been approved by Switzerland and a few other E.U. countries. The degree to which medication-assisted therapies are available is dependent on many variables, including national and local regulations, preferences of individual providers and their geographical location, treatment costs, and insurance policies. Greater availability of medication-assisted therapies has become a major focus in the U.S. and Canada, where there has been a marked increase in deaths associated with heroin and prescription opioid use. This paper provides a brief summary of these developments.
      PubDate: 2017-01-27T17:08:25Z
      DOI: 10.12688/f1000research.10184.1
      Issue No: Vol. 6 (2017)
  • Of the Phrensy: an update on the epidemiology and pathogenesis of
           bacterial meningitis in the pediatric population [version 1; referees: 3

    • Authors: Andrew Janowski, Jason Newland
      Abstract: In the past century, advances in antibiotics and vaccination have dramatically altered the incidence and clinical outcomes of bacterial meningitis. We review the shifting epidemiology of meningitis in children, including after the implementation of vaccines that target common meningitic pathogens and the introduction of intrapartum antibiotic prophylaxis offered to mothers colonized with Streptococcus agalactiae. We also discuss what is currently known about the pathogenesis of meningitis. Recent studies of the human microbiome have illustrated dynamic relationships of bacterial and viral populations with the host, which may potentiate the risk of bacterial meningitis.
      PubDate: 2017-01-27T16:36:30Z
      DOI: 10.12688/f1000research.8533.1
      Issue No: Vol. 6 (2017)
  • Recent Advances in Understanding, Diagnosing, and Treating Ovarian Cancer
           [version 1; referees: 3 approved]

    • Authors: Kathryn Mills, Katherine Fuh
      Abstract: Ovarian cancer, a term that encompasses ovarian, fallopian, and peritoneal cancers, is the leading cause of gynecologic cancer mortality. To improve patient outcomes, the field is currently focused on defining the mechanisms of cancer formation and spread, early diagnosis and prevention, and developing novel therapeutic options. This review summarizes recent advances in these areas.
      PubDate: 2017-01-27T16:30:28Z
      DOI: 10.12688/f1000research.9977.1
      Issue No: Vol. 6 (2017)
  • Rituximab therapy in pemphigus and other autoantibody-mediated diseases
           [version 1; referees: 3 approved]

    • Authors: Nina A. Ran, Aimee S. Payne
      Abstract: Rituximab, a monoclonal antibody targeting the B cell marker CD20, was initially approved in 1997 by the United States Food and Drug Administration (FDA) for the treatment of non-Hodgkin lymphoma. Since that time, rituximab has been FDA-approved for rheumatoid arthritis and vasculitides, such as granulomatosis with polyangiitis and microscopic polyangiitis. Additionally, rituximab has been used off-label in the treatment of numerous other autoimmune diseases, with notable success in pemphigus, an autoantibody-mediated skin blistering disease. The efficacy of rituximab therapy in pemphigus has spurred interest in its potential to treat other autoantibody-mediated diseases. This review summarizes the efficacy of rituximab in pemphigus and examines its off-label use in other select autoantibody-mediated diseases.
      PubDate: 2017-01-27T16:29:05Z
      DOI: 10.12688/f1000research.9476.1
      Issue No: Vol. 6 (2017)
  • Human parvovirus 4 ‘PARV4’ remains elusive despite a decade of study
           [version 1; referees: 3 approved]

    • Authors: Philippa C. Matthews, Colin Sharp, Peter Simmonds, Paul Klenerman
      Abstract: Human parvovirus 4 (‘PARV4’) is a small DNA tetraparvovirus, first reported in 2005. In some populations, PARV4 infection is uncommon, and evidence of exposure is found only in individuals with risk factors for parenteral infection who are infected with other blood-borne viruses. In other settings, seroprevalence studies suggest an endemic, age-associated transmission pattern, independent of any specific risk factors. The clinical impact of PARV4 infection remains uncertain, but reported disease associations include an influenza-like syndrome, encephalitis, acceleration of HIV disease, and foetal hydrops. In this review, we set out to report progress updates from the recent literature, focusing on the investigation of cohorts in different geographical settings, now including insights from Asia, the Middle East, and South America, and discussing whether attributes of viral or host populations underpin the striking differences in epidemiology. We review progress in understanding viral phylogeny and biology, approaches to diagnostics, and insights that might be gained from studies of closely related animal pathogens. Crucial questions about pathogenicity remain unanswered, but we highlight new evidence supporting a possible link between PARV4 and an encephalitis syndrome. The unequivocal evidence that PARV4 is endemic in certain populations should drive ongoing research efforts to understand risk factors and routes of transmission and to gain new insights into the impact of this virus on human health.
      PubDate: 2017-01-27T16:25:12Z
      DOI: 10.12688/f1000research.9828.1
      Issue No: Vol. 6 (2017)
  • Recent Advances in Endometrial Cancer [version 1; referees: 2 approved]

    • Authors: Arthur-Quan Tran, Paola Gehrig
      Abstract: Endometrial cancer is the most common gynecologic malignancy in the United States, with yearly rates continuing to increase. Most women present with early stage disease; however, advanced disease carries a grave prognosis. As a result, novel therapies are currently under investigation for the treatment of endometrial cancer. These advances include a better understanding of the genetic basis surrounding the development of endometrial cancer, novel surgical therapies, and new molecular targets for the treatment of this disease. This review explores the literature regarding these advancements in endometrial cancer.
      PubDate: 2017-01-27T16:24:30Z
      DOI: 10.12688/f1000research.10020.1
      Issue No: Vol. 6 (2017)
  • Novel approaches for treating hypertension [version 1; referees: 2

    • Authors: Andrew J. Freeman, Antony Vinh, Robert E. Widdop
      Abstract: Hypertension, or high blood pressure, is a prevalent yet modifiable risk factor for cardiovascular disease. While there are many effective treatments available to combat hypertension, patients often require at least two to three medications to control blood pressure, although there are patients who are resistant to such therapies. This short review will briefly update on recent clinical advances and potential emerging therapies and is intended for a cross-disciplinary readership.
      PubDate: 2017-01-27T10:03:35Z
      DOI: 10.12688/f1000research.10117.1
      Issue No: Vol. 6 (2017)
  • Recent advances in understanding noroviruses [version 1; referees: 2

    • Authors: Eric Bartnicki, Juliana Bragazzi Cunha, Abimbola O. Kolawole, Christiane E. Wobus
      Abstract: Noroviruses are the leading cause of acute gastroenteritis around the world. An individual living in the United States is estimated to develop norovirus infection five times in his or her lifetime. Despite this, there is currently no antiviral or vaccine to combat the infection, in large part because of the historical lack of cell culture and small animal models. However, the last few years of norovirus research were marked by a number of ground-breaking advances that have overcome technical barriers and uncovered novel aspects of norovirus biology. Foremost among them was the development of two different in vitro culture systems for human noroviruses. Underappreciated was the notion that noroviruses infect cells of the immune system as well as epithelial cells within the gastrointestinal tract and that human norovirus infection of enterocytes requires or is promoted by the presence of bile acids. Furthermore, two proteinaceous receptors are now recognized for murine norovirus, marking the first discovery of a functional receptor for any norovirus. Recent work further points to a role for certain bacteria, including those found in the gut microbiome, as potential modulators of norovirus infection in the host, emphasizing the importance of interactions with organisms from other kingdoms of life for viral pathogenesis. Lastly, we will highlight the adaptation of drop-based microfluidics to norovirus research, as this technology has the potential to reveal novel insights into virus evolution. This review aims to summarize these new findings while also including possible future directions.
      PubDate: 2017-01-26T16:29:17Z
      DOI: 10.12688/f1000research.10081.1
      Issue No: Vol. 6 (2017)
  • Where does axon guidance lead us' [version 1; referees: 2 approved]

    • Authors: Esther Stoeckli
      Abstract: During neural circuit formation, axons need to navigate to their target cells in a complex, constantly changing environment. Although we most likely have identified most axon guidance cues and their receptors, we still cannot explain the molecular background of pathfinding for any subpopulation of axons. We lack mechanistic insight into the regulation of interactions between guidance receptors and their ligands. Recent developments in the field of axon guidance suggest that the regulation of surface expression of guidance receptors comprises transcriptional, translational, and post-translational mechanisms, such as trafficking of vesicles with specific cargos, protein-protein interactions, and specific proteolysis of guidance receptors. Not only axon guidance molecules but also the regulatory mechanisms that control their spatial and temporal expression are involved in synaptogenesis and synaptic plasticity. Therefore, it is not surprising that genes associated with axon guidance are frequently found in genetic and genomic studies of neurodevelopmental disorders.
      PubDate: 2017-01-25T14:40:09Z
      DOI: 10.12688/f1000research.10126.1
      Issue No: Vol. 6 (2017)
  • The benefits of youth are lost on the young cardiac arrest patient
           [version 1; referees: 2 approved]

    • Authors: Brian Griffith, Patrick Kochanek, Cameron Dezfulian
      Abstract: Children and young adults tend to have reduced mortality and disability after acquired brain injuries such as trauma or stroke and across other disease processes seen in critical care medicine. However, after out-of-hospital cardiac arrest (OHCA), outcomes are remarkably similar across age groups. The consistent lack of witnessed arrests and a high incidence of asphyxial or respiratory etiology arrests among pediatric and young adult patients with OHCA account for a substantial portion of the difference in outcomes. Additionally, in younger children, differences in pre-hospital response and the activation of developmental apoptosis may explain more severe outcomes after OHCA. These require us to consider whether present practices are in line with the science. The present recommendations for compression-only cardiopulmonary resuscitation in young adults, normothermia as opposed to hypothermia (33°C) after asphyxial arrests, and paramedic training are considered within this review in light of existing evidence. Modifications in present standards of care may help restore the benefits of youth after brain injury to the young survivor of OHCA.
      PubDate: 2017-01-25T13:42:06Z
      DOI: 10.12688/f1000research.9316.1
      Issue No: Vol. 6 (2017)
  • Rejuvenating stem cells to restore muscle regeneration in aging [version
           1; referees: 3 approved]

    • Authors: Eyal Bengal, Eusebio Perdiguero, Antonio L. Serrano, Pura Muñoz-Cánoves
      Abstract: Adult muscle stem cells, originally called satellite cells, are essential for muscle repair and regeneration throughout life. Besides a gradual loss of mass and function, muscle aging is characterized by a decline in the repair capacity, which blunts muscle recovery after injury in elderly individuals. A major effort has been dedicated in recent years to deciphering the causes of satellite cell dysfunction in aging animals, with the ultimate goal of rejuvenating old satellite cells and improving muscle function in elderly people. This review focuses on the recently identified network of cell-intrinsic and -extrinsic factors and processes contributing to the decline of satellite cells in old animals. Some studies suggest that aging-related satellite-cell decay is mostly caused by age-associated extrinsic environmental changes that could be reversed by a “youthful environment”. Others propose a central role for cell-intrinsic mechanisms, some of which are not reversed by environmental changes. We believe that these proposals, far from being antagonistic, are complementary and that both extrinsic and intrinsic factors contribute to muscle stem cell dysfunction during aging-related regenerative decline. The low regenerative potential of old satellite cells may reflect the accumulation of deleterious changes during the life of the cell; some of these changes may be inherent (intrinsic) while others result from the systemic and local environment (extrinsic). The present challenge is to rejuvenate aged satellite cells that have undergone reversible changes to provide a possible approach to improving muscle repair in the elderly.
      PubDate: 2017-01-25T12:36:55Z
      DOI: 10.12688/f1000research.9846.1
      Issue No: Vol. 6 (2017)
  • Genetics of multiple endocrine neoplasia type 1 syndrome: what's new and
           what's old [version 1; referees: 3 approved]

    • Authors: Alberto Falchetti
      Abstract: Despite its identification in 1997, the functions of the MEN1 gene—the main gene underlying multiple endocrine neoplasia type 1 syndrome—are not yet fully understood. In addition, unlike the RET—MEN2 causative gene—no hot-spot mutational areas or genotype–phenotype correlations have been identified. More than 1,300 MEN1 gene mutations have been reported and are mostly "private” (family specific). Even when mutations are shared at an intra- or inter-familial level, the spectrum of clinical presentation is highly variable, even in identical twins. Despite these inherent limitations for genetic counseling, identifying MEN1 mutations in individual carriers offers them the opportunity to have lifelong clinical surveillance schemes aimed at revealing MEN1-associated tumors and lesions, dictates the timing and scope of surgical procedures, and facilitates specific mutation analysis of relatives to define presymptomatic carriers.
      PubDate: 2017-01-24T16:23:09Z
      DOI: 10.12688/f1000research.7230.1
      Issue No: Vol. 6 (2017)
  • Treatment of Hypogonadism: Current and Future Therapies [version 1;
           referees: 2 approved]

    • Authors: Arthi Thirumalai, Kathryn E. Berkseth, John K. Amory
      Abstract: The treatment of hypogonadism in men is of great interest to both patients and providers. There are a number of testosterone formulations currently available and several additional formulations under development. In addition, there are some lesser-used alternative therapies for the management of male hypogonadism, which may have advantages for certain patient groups. The future of hypogonadism therapy may lie in the development of selective androgen receptor modulators that allow the benefits of androgens whilst minimizing unwanted side effects.
      PubDate: 2017-01-23T14:54:41Z
      DOI: 10.12688/f1000research.10102.1
      Issue No: Vol. 6 (2017)
  • Fact or fiction: updates on how protein-coding genes might emerge de novo
           from previously non-coding DNA [version 1; referees: 3 approved]

    • Authors: Jonathan F Schmitz, Erich Bornberg-Bauer
      Abstract: Over the last few years, there has been an increasing amount of evidence for the de novo emergence of protein-coding genes, i.e. out of non-coding DNA. Here, we review the current literature and summarize the state of the field. We focus specifically on open questions and challenges in the study of de novo protein-coding genes such as the identification and verification of de novo-emerged genes. The greatest obstacle to date is the lack of high-quality genomic data with very short divergence times which could help precisely pin down the location of origin of a de novo gene. We conclude that, while there is plenty of evidence from a genetics perspective, there is a lack of functional studies of bona fide de novo genes and almost no knowledge about protein structures and how they come about during the emergence of de novo protein-coding genes. We suggest that future studies should concentrate on the functional and structural characterization of de novo protein-coding genes as well as the detailed study of the emergence of functional de novo protein-coding genes.
      PubDate: 2017-01-19T15:13:59Z
      DOI: 10.12688/f1000research.10079.1
      Issue No: Vol. 6 (2017)
  • Nephrotoxicities [version 1; referees: 2 approved]

    • Authors: Stuart L. Goldstein
      Abstract: Nephrotoxic medication exposure is nearly ubiquitous in hospitalized patients and represents one of the most common causes of acute kidney injury (AKI) in the hospitalized setting. Although provision of medications that are nephrotoxic has led to improved outcomes in terms of treatment of underlying illness, unnecessary nephrotoxic medication exposure can be viewed as a potentially modifiable adverse safety event if AKI can be prevented. The advancements in electronic health record development, standardization of AKI definitions, and the ability to identify AKI risk and development in near real time provide opportunities to reduce harm from nephrotoxicity.
      PubDate: 2017-01-19T09:59:28Z
      DOI: 10.12688/f1000research.10192.1
      Issue No: Vol. 6 (2017)
  • Effect of antibiotics on bacterial populations: a multi-hierachical
           selection process [version 1; referees: 2 approved]

    • Authors: José Luis Martínez
      Abstract: Antibiotics have been widely used for a number of decades for human therapy and farming production. Since a high percentage of antibiotics are discharged from the human or animal body without degradation, this means that different habitats, from the human body to river water or soils, are polluted with antibiotics. In this situation, it is expected that the variable concentration of this type of microbial inhibitor present in different ecosystems may affect the structure and the productivity of the microbiota colonizing such habitats. This effect can occur at different levels, including changes in the overall structure of the population, selection of resistant organisms, or alterations in bacterial physiology. In this review, I discuss the available information on how the presence of antibiotics may alter the microbiota and the consequences of such alterations for human health and for the activity of microbiota from different habitats.
      PubDate: 2017-01-17T11:16:35Z
      DOI: 10.12688/f1000research.9685.1
      Issue No: Vol. 6 (2017)
  • Alport syndrome: facts and opinions [version 1; referees: 2 approved]

    • Authors: Clifford Kashtan
      Abstract: In this commentary, I review recent advances in Alport syndrome genetics, diagnostics, and therapeutics. I also offer some opinions regarding strategies to optimize the early identification of affected individuals to promote early therapeutic intervention.
      PubDate: 2017-01-17T11:15:43Z
      DOI: 10.12688/f1000research.9636.1
      Issue No: Vol. 6 (2017)
  • An ELISA DYRK1A non-radioactive assay suitable for the characterization of
           inhibitors [version 1; referees: 2 approved]

    • Authors: Yong Liu, Tatyana Adayev, Yu-Wen Hwang
      Abstract: The DYRK1A (dual specificity tyrosine phosphorylation-regulated kinase 1A) gene encodes a proline-directed Ser/Thr kinase. Elevated expression and/or altered distribution of the kinase have been implicated in the neurological impairments associated with Down syndrome (DS) and Alzheimer’s disease (AD). Consequently, DYRK1A inhibition has been of significant interest as a potential strategy for therapeutic intervention of DS and AD. Many classes of novel inhibitors have been described in the past decade. Although non-radioactive methods for analyzing DYRK1A inhibition have been developed, methods employing radioactive tracers are still commonly used for quantitative characterization of DYRK1A inhibitors. Here, we present a non-radioactive ELISA assay based on the detection of DYRK1A-phosphorylated dynamin 1a fragment using a phosphorylation site-specific antibody. The assay was verified by the use of two well-characterized DYRK1A inhibitors, epigallocatechin gallate (EGCG) and harmine. The IC50s for EGCG and harmine determined by the ELISA method were found to be comparable to those previously measured by radioactive tracing methods.  Furthermore, we determined the mode of inhibition for EGCG and harmine by a modification of the ELISA assay. This assay confirms the mode of inhibition of EGCG (non-ATP-competitive) and harmine (ATP-competitive), as previously determined. We conclude that the ELISA platform demonstrated here is a viable alternative to the traditional radioactive tracer assays for analyzing DYRK1A inhibitors.
      PubDate: 2017-01-13T14:41:13Z
      DOI: 10.12688/f1000research.10582.1
      Issue No: Vol. 6 (2017)
  • Case Report: Severe hypernatremia from psychogenic adipsia [version 1;
           referees: 2 approved]

    • Authors: Sarah Manning, Rehan Shaffie, Shitij Arora
      Abstract: Hypernatremia is a common emergency room presentation and carries high mortality. We describe a case of a 56-year-old male patient with who presents with refusal to drink water for several weeks leading to the admission. He was diagnosed with psychogenic adipsia and was treated successfully with fluids, mirtazapine and clonazepam.
      PubDate: 2017-01-11T15:40:57Z
      DOI: 10.12688/f1000research.9181.1
      Issue No: Vol. 6 (2017)
  • STAT5 and CD4+ T Cell Immunity [version 1; referees: 4 approved]

    • Authors: David L. Owen, Michael A. Farrar
      Abstract: STAT5 plays a critical role in the development and function of many cell types. Here, we review the role of STAT5 in the development of T lymphocytes in the thymus and its subsequent role in the differentiation of distinct CD4+ helper and regulatory T-cell subsets.
      PubDate: 2017-01-11T14:02:11Z
      DOI: 10.12688/f1000research.9838.1
      Issue No: Vol. 6 (2017)
  • Healthcare benefits linked with Below Poverty Line registration in India:
           Observations from Maharashtra Anaemia Study (MAS) [version 1; referees: 2

    • Authors: Anand Ahankari, Andrew Fogarty, Laila Tata, Puja Myles
      Abstract: A 2015 Lancet paper by Patel et al. on healthcare access in India comprehensively discussed national health programmes where some benefits are linked with the country’s Below Poverty Line (BPL) registration scheme. BPL registration aims to support poor families by providing free/subsidised healthcare. Technical issues in obtaining BPL registration by poor families have been previously reported in the Indian literature; however there are no data on family assets of BPL registrants. Here, we provide evidence of family-level assets among BPL registration holders (and non-BPL households) using original research data from the Maharashtra Anaemia Study (MAS).   Social and health data from 287 pregnant women and 891 adolescent girls (representing 1178 family households) across 34 villages in Maharashtra state, India, were analysed. Several assets were shown to be similarly distributed between BPL and non-BPL households; a large proportion of families who would probably be eligible were not registered, whereas BPL-registered families often had significant assets that should not make them eligible. This is likely to be the first published evidence where asset distribution such as agricultural land, housing structures and livestock are compared between BPL and non-BPL households in a rural population. These findings may help planning BPL administration to allocate health benefits equitably, which is an integral part of national health programmes.
      PubDate: 2017-01-09T15:57:55Z
      DOI: 10.12688/f1000research.10556.1
      Issue No: Vol. 6 (2017)
  • Engaging high school students in systems biology through an e-internship
           program [version 1; referees: 2 approved]

    • Authors: Wim E Crusio, Cynthia Rubino, Anna Delprato
      Abstract: In this article, we describe the design and implementation of an e-internship program that BioScience Project offers high school students over the summer. Project topics are in the areas of behavioral neuroscience and brain disorders. All research, teaching, and communication is done online using open access databases and webtools, a learning management system, and Google apps. Students conduct all aspects of a research project from formulating a question to collecting and analyzing the data, to presenting their results in the form of a scientific poster. Results from a pilot study indicate that students are capable of comprehending and successfully completing such a project, and benefit both intellectually and professionally from participating in the e-internship program.
      PubDate: 2017-01-09T14:36:28Z
      DOI: 10.12688/f1000research.10570.1
      Issue No: Vol. 6 (2017)
  • Case Report: Use of reinforced buccal mucosa graft over gracilis muscle
           flap in management of post high intensity focused ultrasound (HIFU)
           rectourethral fistula [version 2; referees: 2 approved]

    • Authors: Shrikant Jai, Arvind Ganpule, Abhishek Singh, Mohankumar Vijaykumar, Vinod Bopaiah, Ravindra Sabnis, Mahesh Desai
      Abstract: High intensity focused ultrasound (HIFU) has come forward as alternative treatment for carcinoma of the prostate. Though minimally invasive,HIFUhas potential side effects. Urethrorectal fistula is one such rare side effect. Management of these fistulas has been described by Vanni et al. This case report describes points of technique that will help successful management of resilient rectourethral fistula. Urinary and faecal diversion in the form of suprapubic catheter and colostomy is vital. Adequate time between stoma formation, fistula closure and then finally stoma closure is needed. Lithotomy position and perineal approach gives best exposure to the fistula. The rectum should be dissected 2cm above the fistula; this aids in tension free closure of the rectal defect. Similarly buccal mucosal graft was used on the urethra to achieve tension free closure. A good vascular pedicle gracilis muscle flap is used to interpose between the two repairs. This not only provides a physical barrier but also provides a vascular bed for BMG uptake. Perfect haemostasis is essential, as any collection may become a site of infection thus compromising results.  We strongly recommend rectourethral fistula be directly repaired with gracilis muscle flap with reinforced buccal mucosa graft without attempting any less invasive repairs because the “first chance is the best chance”.
      PubDate: 2017-02-13T11:38:56Z
      DOI: 10.12688/f1000research.10245.2
      Issue No: Vol. 5 (2017)
  • Candida antifungal drug resistance in sub-Saharan African populations: A
           systematic review [version 2; referees: 2 approved]

    • Authors: Charlene Wilma Joyce Africa, Pedro Miguel dos Santos Abrantes
      Abstract: Background: Candida infections are responsible for increased morbidity and mortality rates in at-risk patients, especially in developing countries where there is limited access to antifungal drugs and a high burden of HIV co-infection. Objectives: This study aimed to identify antifungal drug resistance patterns within the subcontinent of Africa. Methods: A literature search was conducted on published studies that employed antifungal susceptibility testing on clinical Candida isolates from sub-Saharan African countries using Pubmed and Google Scholar. Results: A total of 21 studies from 8 countries constituted this review. Only studies conducted in sub-Saharan Africa and employing antifungal drug susceptibility testing were included. Regional differences in Candida species prevalence and resistance patterns were identified. Discussion: The outcomes of this review highlight the need for a revision of antifungal therapy guidelines in regions most affected by Candida drug resistance.  Better controls in antimicrobial drug distribution and the implementation of regional antimicrobial susceptibility surveillance programmes are required in order to reduce the high Candida drug resistance levels seen to be emerging in sub-Saharan Africa.
      PubDate: 2017-01-20T14:55:03Z
      DOI: 10.12688/f1000research.10327.2
      Issue No: Vol. 5 (2017)
  • Fairness in scientific publishing [version 2; referees: 3 approved]

    • Authors: Philippa C. Matthews
      Abstract: Major changes are afoot in the world of academic publishing, exemplified by innovations in publishing platforms, new approaches to metrics, improvements in our approach to peer review, and a focus on developing and encouraging open access to scientific literature and data. The FAIR acronym recommends that authors and publishers should aim to make their output Findable, Accessible, Interoperable and Reusable. In this opinion article, I explore the parallel view that we should take a collective stance on making the dissemination of scientific data fair in the conventional sense, by being mindful of equity and justice for patients, clinicians, academics, publishers, funders and academic institutions. The views I represent are founded on oral and written dialogue with clinicians, academics and the publishing industry. Further progress is needed to improve collaboration and dialogue between these groups, to reduce misinterpretation of metrics, to minimise inequity that arises as a consequence of geographic setting, to improve economic sustainability, and to broaden the spectrum, scope, and diversity of scientific publication.
      PubDate: 2017-01-17T11:22:03Z
      DOI: 10.12688/f1000research.10318.2
      Issue No: Vol. 5 (2017)
  • Human brain harbors single nucleotide somatic variations in functionally
           relevant genes possibly mediated by oxidative stress [version 3; referees:
           2 approved]

    • Authors: Anchal Sharma, Asgar Hussain Ansari, Renu Kumari, Rajesh Pandey, Rakhshinda Rehman, Bharati Mehani, Binuja Varma, Bapu K. Desiraju, Ulaganathan Mabalirajan, Anurag Agrawal, Arijit Mukhopadhyay
      Abstract: Somatic variation in DNA can cause cells to deviate from the preordained genomic path in both disease and healthy conditions. Here, using exome sequencing of paired tissue samples, we show that the normal human brain harbors somatic single base variations measuring up to 0.48% of the total variations. Interestingly, about 64% of these somatic variations in the brain are expected to lead to non-synonymous changes, and as much as 87% of these represent G:C>T:A transversion events. Further, the transversion events in the brain were mostly found in the frontal cortex, whereas the corpus callosum from the same individuals harbors the reference genotype. We found a significantly higher amount of 8-OHdG (oxidative stress marker) in the frontal cortex compared to the corpus callosum of the same subjects (pT:A transversions in the cortex. We found significant enrichment for axon guidance and related pathways for genes harbouring somatic variations. This could represent either a directed selection of genetic variations in these pathways or increased susceptibility of some loci towards oxidative stress. This study highlights that oxidative stress possibly influence single nucleotide somatic variations in normal human brain.
      PubDate: 2017-01-12T10:12:12Z
      DOI: 10.12688/f1000research.9495.3
      Issue No: Vol. 5 (2017)
  • Puzzles in modern biology. III.Two kinds of causality in age-related
           disease [version 2; referees: 2 approved]

    • Authors: Steven A. Frank
      Abstract: The two primary causal dimensions of age-related disease are rate and function. Change in rate of disease development shifts the age of onset. Change in physiological function provides necessary steps in disease progression. A causal factor may alter the rate of physiological change, but that causal factor itself may have no direct physiological role. Alternatively, a causal factor may provide a necessary physiological function, but that causal factor itself may not alter the rate of disease onset. The rate-function duality provides the basis for solving puzzles of age-related disease. Causal factors of cancer illustrate the duality between rate processes of discovery, such as somatic mutation, and necessary physiological functions, such as invasive penetration across tissue barriers. Examples from cancer suggest general principles of age-related disease.
      PubDate: 2017-01-10T11:52:04Z
      DOI: 10.12688/f1000research.9789.2
      Issue No: Vol. 5 (2017)
  • biojs-io-biom, a BioJS component for handling data in Biological
           Observation Matrix (BIOM) format [version 2; referees: 1 approved, 2
           approved with reservations]

    • Authors: Markus J. Ankenbrand, Niklas Terhoeven, Sonja Hohlfeld, Frank Förster, Alexander Keller
      Abstract: The Biological Observation Matrix (BIOM) format is widely used to store data from high-throughput studies. It aims at increasing interoperability of bioinformatic tools that process this data. However, due to multiple versions and implementation details, working with this format can be tricky. Currently, libraries in Python, R and Perl are available, whilst such for JavaScript are lacking. Here, we present a BioJS component for parsing BIOM data in all format versions. It supports import, modification, and export via a unified interface. This module aims to facilitate the development of web applications that use BIOM data. Finally, we demonstrate its usefulness by two applications that already use this component. Availability:,
      PubDate: 2017-01-09T14:33:01Z
      DOI: 10.12688/f1000research.9618.2
      Issue No: Vol. 5 (2017)
  • Health communication, information technology and the public’s attitude
           toward periodic general health examinations [version 1; referees: 2

    • Authors: Quan-Hoang Vuong
      Abstract: Background: Periodic general health examinations (GHEs) are gradually becoming more popular as they employ subclinical screenings, as a means of early detection. This study considers the effect of information technology (IT), health communications and the public’s attitude towards GHEs in Vietnam. Methods: A total of 2,068 valid observations were obtained from a survey in Hanoi and its surrounding areas. Results: In total, 42.12% of participants stated that they were willing to use IT applications to recognise illness symptoms, and nearly 2/3 of them rated the healthcare quality at average level or below. Discussion: The data, which was processed by the BCL model, showed that IT applications (apps) reduce hesitation toward GHEs; however, older people seem to have less confidence in using these apps. Health communications and government’s subsidy also increased the likelihood of people attending periodic GHEs. The probability of early check-ups where there is a cash subsidy could reach approximately 80%.
      PubDate: 2016-12-30T11:49:47Z
      DOI: 10.12688/f1000research.10508.1
      Issue No: Vol. 5 (2016)
  • Inducible targeting of CNS astrocytes in Aldh1l1-CreERT2 BAC transgenic
           mice [version 1; referees: 2 approved]

    • Authors: Jan Winchenbach, Tim Düking, Stefan A. Berghoff, Sina K. Stumpf, Swen Hülsmann, Klaus-Armin Nave, Gesine Saher
      Abstract: Background: Studying astrocytes in higher brain functions has been hampered by the lack of genetic tools for the efficient expression of inducible Cre recombinase throughout the CNS, including the neocortex. Methods: Therefore, we generated BAC transgenic mice, in which CreERT2 is expressed under control of the Aldh1l1 regulatory region. Results: When crossbred to Cre reporter mice, adult Aldh1l1-CreERT2 mice show efficient gene targeting in astrocytes. No such Cre-mediated recombination was detectable in CNS neurons, oligodendrocytes, and microglia. As expected, Aldh1l1-CreERT2 expression was evident in several peripheral organs, including liver and kidney. Conclusions: Taken together, Aldh1l1-CreERT2 mice are a useful tool for studying astrocytes in neurovascular coupling, brain metabolism, synaptic plasticity and other aspects of neuron-glia interactions.
      PubDate: 2016-12-30T11:40:17Z
      DOI: 10.12688/f1000research.10509.1
      Issue No: Vol. 5 (2016)
  • Lightning Injury is a disaster in Bangladesh' - Exploring its
           magnitude and public health needs [version 1; referees: 3 approved, 1
           approved with reservations]

    • Authors: Animesh Biswas, Koustuv Dalal, Jahangir Hossain, Kamran Ul Baset, Fazlur Rahman, Saidur Rahman Mashreky
      Abstract: Background: Lightning injury is a global public health issue. Low and middle-income countries in the tropical and subtropical regions of the world are most affected by lightning. Bangladesh is one of the countries at particular risk, with a high number of devastating lightning injuries in the past years, causing high mortality and morbidity. The exact magnitude of the problem is still unknown and therefore this study investigates the epidemiology of lightning injuries in Bangladesh, using a national representative sample. Methods: A mixed method was used. The study is based on results from a nationwide cross-sectional survey performed in 2003 in twelve randomly selected districts. In the survey, a total of 819,429 respondents from 171,336 households were interviewed using face-to-face interviews. In addition, qualitative information was obtained by reviewing national and international newspaper reports of lightning injuries sustained in Bangladesh between 13 and 15 May 2016. Results: The annual mortality rate was 3.661 (95% CI 0.9313–9.964) per 1,000,000 people. The overall incidence of lightning injury was 19.89/100,000 people. Among the victims, 60.12% (n=98) were males and 39.87% (n=65) were females. Males were particularly vulnerable, with a 1.46 times increased risk compared with females (RR 1.46, 95% CI 1.06–1.99). Rural populations were more vulnerable, with a 8.73 times higher risk, than urban populations (RR 8.73, 95% CI 5.13–14.86). About 43% of injuries occurred between 12 noon and 6 pm. The newspapers reported 81 deaths during 2 days of electric storms in 2016. Lightning has been declared a natural disaster in Bangladesh. Conclusions: The current study indicates that lightning injuries are a public health problem in Bangladesh. The study recommends further investigations to develop interventions to reduce lightning injuries, mortality and related burden in Bangladesh.
      PubDate: 2016-12-29T14:25:13Z
      DOI: 10.12688/f1000research.9537.1
      Issue No: Vol. 5 (2016)
  • Systematic assessment of multi-gene predictors of pan-cancer cell line
           sensitivity to drugs exploiting gene expression data [version 1; referees:
           2 approved]

    • Authors: Linh Nguyen, Cuong C Dang, Pedro Ballester
      Abstract: Background: Selected gene mutations are routinely used to guide the selection of cancer drugs for a given patient tumour. Large pharmacogenomic data sets were introduced to discover more of these single-gene markers of drug sensitivity. Very recently, machine learning regression has been used to investigate how well cancer cell line sensitivity to drugs is predicted depending on the type of molecular profile. The latter has revealed that gene expression data is the most predictive profile in the pan-cancer setting. However, no study to date has exploited GDSC data to systematically compare the performance of machine learning models based on multi-gene expression data against that of widely-used single-gene markers based on genomics data. Methods: Here we present this systematic comparison using Random Forest (RF) classifiers exploiting the expression levels of 13,321 genes and an average of 501 tested cell lines per drug. To account for time-dependent batch effects in IC50 measurements, we employ independent test sets generated with more recent GDSC data than that used to train the predictors and show that this is a more realistic validation than K-fold cross-validation. Results and Discussion: Across 127 GDSC drugs, our results show that the single-gene markers unveiled by the MANOVA analysis tend to achieve higher precision than these RF-based multi-gene models, at the cost of generally having a poor recall (i.e. correctly detecting only a small part of the cell lines sensitive to the drug). Regarding overall classification performance, about two thirds of the drugs are better predicted by multi-gene RF classifiers. Among the drugs with the most predictive of these models, we found pyrimethamine, sunitinib and 17-AAG. Conclusions: We now know that this type of models can predict in vitro tumour response to these drugs. These models can thus be further investigated on in vivo tumour models.
      PubDate: 2016-12-28T16:02:56Z
      DOI: 10.12688/f1000research.10529.1
      Issue No: Vol. 5 (2016)
  • TCGA Workflow: Analyze cancer genomics and epigenomics data using
           Bioconductor packages [version 2; referees: 1 approved, 2 approved with

    • Authors: Tiago C. Silva, Antonio Colaprico, Catharina Olsen, Fulvio D'Angelo, Gianluca Bontempi, Michele Ceccarelli, Houtan Noushmehr
      Abstract: Biotechnological advances in sequencing have led to an explosion of publicly available data via large international consortia such as The Cancer Genome Atlas (TCGA), The Encyclopedia of DNA Elements (ENCODE), and The NIH Roadmap Epigenomics Mapping Consortium (Roadmap). These projects have provided unprecedented opportunities to interrogate the epigenome of cultured cancer cell lines as well as normal and tumor tissues with high genomic resolution. The Bioconductor project offers more than 1,000 open-source software and statistical packages to analyze high-throughput genomic data. However, most packages are designed for specific data types (e.g. expression, epigenetics, genomics) and there is no one comprehensive tool that provides a complete integrative analysis of the resources and data provided by all three public projects. A need to create an integration of these different analyses was recently proposed. In this workflow, we provide a series of biologically focused integrative analyses of different molecular data. We describe how to download, process and prepare TCGA data and by harnessing several key Bioconductor packages, we describe how to extract biologically meaningful genomic and epigenomic data. Using Roadmap and ENCODE data, we provide a work plan to identify biologically relevant functional epigenomic elements associated with cancer. To illustrate our workflow, we analyzed two types of brain tumors: low-grade glioma (LGG) versus high-grade glioma (glioblastoma multiform or GBM). This workflow introduces the following Bioconductor packages: AnnotationHub, ChIPSeeker, ComplexHeatmap, pathview, ELMER, GAIA, MINET, RTCGAToolbox, TCGAbiolinks.
      PubDate: 2016-12-28T13:14:08Z
      DOI: 10.12688/f1000research.8923.2
      Issue No: Vol. 5 (2016)
  • Effects of sub-lethal teratogen exposure during larval development on egg
           laying and egg quality in adult Caenorhabditis elegans [version 1;
           referees: 2 approved]

    • Authors: Alexis Killeen, Caralina Marin de Evsikova
      Abstract: Background: Acute high dose exposure to teratogenic chemicals alters the proper development of an embryo leading to infertility, impaired fecundity, and few viable offspring. However, chronic exposure to sub-toxic doses of teratogens during early development may also have long-term impacts on egg quality and embryo viability. Methods: To test the hypothesis that low dose exposure during early development can impact long-term reproductive health, Caenorhabditis elegans larvae were exposed to 10 teratogens during larval development, and subsequently were examined for the pattern of egg-laying and egg quality (hatched larvae and embryo viability) as gravid adults. After the exposure, adult gravid worms were transferred to untreated plates and the numbers of eggs laid were recorded every 3 hours, and the day following exposure the numbers of hatched larvae were counted. Results: While fecundity and fertility were typically impaired by teratogens, unexpectedly, many teratogens initially increased egg-laying at the earliest interval compared to control but not at later intervals. However, egg quality, as assessed by embryo viability, remained the same because many of the eggs (
      PubDate: 2016-12-28T12:43:22Z
      DOI: 10.12688/f1000research.8934.1
      Issue No: Vol. 5 (2016)
  • The novel POSEIDON stratification of ‘Low prognosis patients in Assisted
           Reproductive Technology’ and its proposed marker of successful outcome
           [version 1; referees: 2 approved, 1 approved with reservations]

    • Authors: Peter Humaidan, Carlo Alviggi, Robert Fischer, Sandro C. Esteves
      Abstract: In reproductive medicine little progress has been achieved regarding the clinical management of patients with a reduced ovarian reserve or poor ovarian response (POR) to stimulation with exogenous gonadotropins -a frustrating experience for clinicians as well as patients. Despite the efforts to optimize the definition of this subgroup of patients, the existing POR criteria unfortunately comprise a heterogeneous population and, importantly, do not offer any recommendations for clinical handling. Recently, the POSEIDON group (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) proposed a new stratification of assisted reproductive technology (ART) in patients with a reduced ovarian reserve or unexpected inappropriate ovarian response to exogenous gonadotropins. In brief, four subgroups have been suggested based on quantitative and qualitative parameters, namely, i. Age and the expected aneuploidy rate; ii. Ovarian biomarkers (i.e. antral follicle count [AFC] and anti-Müllerian hormone [AMH]), and iii. Ovarian response - provided a previous stimulation cycle was performed. The new classification introduces a more nuanced picture of the “low prognosis patient” in ART, using clinically relevant criteria to guide the physician to most optimally manage this group of patients. The POSEIDON group also introduced a new measure for successful ART treatment, namely, the ability to retrieve the number of oocytes needed for the specific patient to obtain at least one euploid embryo for transfer. This feature represents a pragmatic endpoint to clinicians and enables the development of prediction models aiming to reduce the time-to-pregnancy (TTP). Consequently, the POSEIDON stratification should not be applied for retrospective analyses having live birth rate (LBR) as endpoint. Such an approach would fail as the attribution of patients to each Poseidon group is related to specific requirements and could only be made prospectively. On the other hand, any prospective approach (i.e. RCT) should be performed separately in each specific group.
      PubDate: 2016-12-23T14:26:48Z
      DOI: 10.12688/f1000research.10382.1
      Issue No: Vol. 5 (2016)
  • Case Report: A giant myopericytoma involving the occipital region of the
           scalp - a rare entity [version 1; referees: 3 approved]

    • Authors: Sunil Munakomi, Pramod Chaudhary
      Abstract: Herein we report a rare case of a giant myopericytoma presenting in a 16-year-old girl as a slowly progressive swelling involving the scalp in the occipital region. It was managed by complete excision. Histological examination of the lesion revealed  spindle-shaped cells forming characteristic rosettes around the blood vessels, and positive staining with smooth muscle actin.
      PubDate: 2016-12-22T15:19:25Z
      DOI: 10.12688/f1000research.10505.1
      Issue No: Vol. 5 (2016)
  • An open and transparent process to select ELIXIR Node Services as
           implemented by ELIXIR-UK [version 1; referees: 1 approved, 2 approved with

    • Authors: John M. Hancock, Alf Game, Chris P. Ponting, Carole A. Goble
      Abstract: ELIXIR is the European infrastructure established specifically for the sharing and sustainability of life science data. To provide up-to-date resources and services, ELIXIR needs to undergo a continuous process of refreshing the services provided by its national Nodes. Here we present the approach taken by ELIXIR-UK to address the advice by the ELIXIR Scientific Advisory Board that Nodes need to develop “mechanisms to ensure that each Node continues to be representative of the Bioinformatics efforts within the country”. ELIXIR-UK put in place an open and transparent process to identify potential ELIXIR resources within the UK during late 2015 and early to mid-2016. Areas of strategic strength were identified and Expressions of Interest in these priority areas were requested from the UK community. A set of criteria were established, in discussion with the ELIXIR Hub, and prospective ELIXIR-UK resources were assessed by an independent committee set up by the Node for this purpose. Of 19 resources considered, 14 were judged to be immediately ready to be included in the UK ELIXIR Node’s portfolio. A further five were placed on the Node’s roadmap for future consideration for inclusion. ELIXIR-UK expects to repeat this process regularly to ensure its portfolio continues to reflect its community’s strengths.
      PubDate: 2016-12-21T16:02:09Z
      DOI: 10.12688/f1000research.10473.1
      Issue No: Vol. 5 (2016)
  • Impact of antiretroviral therapy on clinical outcomes in HIV+ kidney
           transplant recipients: Review of 58 cases [version 1; referees: 2

    • Authors: Rossana Rosa, Jose F. Suarez, Marco A. Lorio, Michele I. Morris, Lilian M. Abbo, Jacques Simkins, Giselle Guerra, David Roth, Warren L. Kupin, Adela Mattiazzi, Gaetano Ciancio, Linda J. Chen, George W. Burke, Jose M. Figueiro, Phillip Ruiz, Jose F. Camargo
      Abstract: Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients.  We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV+ kidney transplant recipients. Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV- to HIV+ adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation.  The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant. Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% (p=0.06) and 82% vs. 100% (p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02).  Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01). Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV+ kidney transplant recipients.
      PubDate: 2016-12-21T15:35:25Z
      DOI: 10.12688/f1000research.10414.1
      Issue No: Vol. 5 (2016)
  • The ISMARA client [version 1; referees: 2 approved]

    • Authors: Panu Artimo, Séverine Duvaud, Mikhail Pachkov, Vassilios Ioannidis, Erik van Nimwegen, Heinz Stockinger
      Abstract: ISMARA ( automatically infers the key regulators and regulatory interactions from high-throughput gene expression or chromatin state data. However, given the large sizes of current next generation sequencing (NGS) datasets, data uploading times are a major bottleneck. Additionally, for proprietary data, users may be uncomfortable with uploading entire raw datasets to an external server. Both these problems could be alleviated by providing a means by which users could pre-process their raw data locally, transferring only a small summary file to the ISMARA server. We developed a stand-alone client application that pre-processes large input files (RNA-seq or ChIP-seq data) on the user's computer for performing ISMARA analysis in a completely automated manner, including uploading of small processed summary files to the ISMARA server. This reduces file sizes by up to a factor of 1000, and upload times from many hours to mere seconds. The client application is available from
      PubDate: 2016-12-15T11:45:43Z
      DOI: 10.12688/f1000research.9794.1
      Issue No: Vol. 5 (2016)
  • Integration of EGA secure data access into Galaxy [version 1; referees: 2

    • Authors: Youri Hoogstrate, Chao Zhang, Alexander Senf, Jochem Bijlard, Saskia Hiltemann, David van Enckevort, Susanna Repo, Jaap Heringa, Guido Jenster, Remond J.A. Fijneman, Jan-Willem Boiten, Gerrit A. Meijer, Andrew Stubbs, Jordi Rambla, Dylan Spalding, Sanne Abeln
      Abstract: High-throughput molecular profiling techniques are routinely generating vast amounts of data for translational medicine studies. Secure access controlled systems are needed to manage, store, transfer and distribute these data due to its personally identifiable nature. The European Genome-phenome Archive (EGA) was created to facilitate access and management to long-term archival of bio-molecular data. Each data provider is responsible for ensuring a Data Access Committee is in place to grant access to data stored in the EGA. Moreover, the transfer of data during upload and download is encrypted. ELIXIR, a European research infrastructure for life-science data, initiated a project (2016 Human Data Implementation Study) to understand and document the ELIXIR requirements for secure management of controlled-access data. As part of this project, a full ecosystem was designed to connect archived raw experimental molecular profiling data with interpreted data and the computational workflows, using the CTMM Translational Research IT (CTMM-TraIT) infrastructure as an example. Here we present the first outcomes of this project, a framework to enable the download of EGA data to a Galaxy server in a secure way. Galaxy provides an intuitive user interface for molecular biologists and bioinformaticians to run and design data analysis workflows. More specifically, we developed a tool -- ega_download_streamer - that can download data securely from EGA into a Galaxy server, which can subsequently be further processed. This tool will allow a user within the browser to run an entire analysis containing sensitive data from EGA, and to make this analysis available for other researchers in a reproducible manner, as shown with a proof of concept study.  The tool ega_download_streamer is available in the Galaxy tool shed:
      PubDate: 2016-12-12T16:24:58Z
      DOI: 10.12688/f1000research.10221.1
      Issue No: Vol. 5 (2016)
  • Aiming for long-term, objective-driven science communication in the UK
           [version 2; referees: 1 approved, 2 approved with reservations]

    • Authors: Andreas Prokop, Sam Illingworth
      Abstract: Communicating science to wider lay audiences is an increasingly important part of a scientist's remit, and is something that many scientists are keen to embrace. However, based on surveys carried out amongst the UK public, as well as our own experiences in developing and delivering such activities, we believe that they are not always as effective at engaging members of the general public as they could be. In this opinion article we argue that in order to achieve more effective science communication, we need more objective-driven and long-term initiatives. As well as being implemented by the scientists themselves, funding organisations can play an important role in helping to drive such initiatives, and we suggest a list of actionable items that might allow for some of these ideas to be implemented.
      PubDate: 2016-12-08T12:24:13Z
      DOI: 10.12688/f1000research.9079.2
      Issue No: Vol. 5 (2016)
  • Cluster Flow: A user-friendly bioinformatics workflow tool [version 1;
           referees: 2 approved]

    • Authors: Philip Ewels, Felix Krueger, Max Käller, Simon Andrews
      Abstract: Pipeline tools are becoming increasingly important within the field of bioinformatics. Using a pipeline manager to manage and run workflows comprised of multiple tools reduces workload and makes analysis results more reproducible. Existing tools require significant work to install and get running, typically needing pipeline scripts to be written from scratch before running any analysis. We present Cluster Flow, a simple and flexible bioinformatics pipeline tool designed to be quick and easy to install. Cluster Flow comes with 40 modules for common NGS processing steps, ready to work out of the box. Pipelines are assembled using these modules with a simple syntax that can be easily modified as required. Core helper functions automate many common NGS procedures, making running pipelines simple. Cluster Flow is available with an GNU GPLv3 license on GitHub. Documentation, examples and an online demo are available at
      PubDate: 2016-12-06T16:17:50Z
      DOI: 10.12688/f1000research.10335.1
      Issue No: Vol. 5 (2016)
  • Matching target dose to target organ [version 1; referees: 2 approved]

    • Authors: Desmond I. Bannon, Marc A. Williams
      Abstract: In vitro assays have become a mainstay of modern approaches to toxicology with the promise of replacing or reducing the number of in vivo tests required to establish benchmark doses, as well as increasing mechanistic understanding. However, matching target dose to target organ is an often overlooked aspect of in vitro assays, and the calibration of in vitro exposure against in vivo benchmark doses is often ignored, inadvertently or otherwise.  An example of this was recently published in Environmental Health Perspectives by Wagner et al., where neural stems cells were used to model the molecular toxicity of lead.  On closer examination of the in vitro work, the doses used in media reflected in vivo lead doses that would be at the highest end of lead toxicity, perhaps even lethal.  Here we discuss the doses used and suggest more realistic doses for future work with stem cells or other neuronal cell lines.
      PubDate: 2016-11-29T11:47:57Z
      DOI: 10.12688/f1000research.10055.1
      Issue No: Vol. 5 (2016)
  • Peripheral refraction with different designs of progressive soft contact
           lenses in myopes [version 1; referees: 2 approved]

    • Authors: Kareem Allinjawi, Sharanjeet-Kaur Sharanjeet-Kaur, Saadah Mohamed Akhir, Haliza Abdul Mutalib
      Abstract: Aim: The purpose of this study was to compare the changes in relative peripheral refractive error produced by two different designs of progressive soft contact lenses in myopic schoolchildren. Methods: Twenty-seven myopic schoolchildren age between 13 to 15 years were included in this study. The measurements of central and peripheral refraction were made using a Grand-Seiko WR-5100K open-field autorefractometer without correction (baseline), and two different designs of progressive contact lenses (PCLs) (Multistage from SEED & Proclear from Cooper Vision) with an addition power of +1.50 D. Refractive power was measured at center and at eccentricities between 35º temporal to 35º nasal visual field (in 5º steps). Results: Both PCLs showed a reduction in hyperopic defocus at periphery. However, this reduction was only significant for the Multistage PCL (p= 0.015), (Proclear PCL p= 0.830).  Conclusion: Multistage PCLs showed greater reduction in peripheral retinal hyperopic defocus among myopic schoolchildren in comparison to Proclear PCLs.
      PubDate: 2016-11-22T15:17:26Z
      DOI: 10.12688/f1000research.9971.1
      Issue No: Vol. 5 (2016)
  • Differentially correlated genes in co-expression networks control
           phenotype transitions [version 1; referees: 1 approved, 2 approved with

    • Authors: Lina D. Thomas, Dariia Vyshenska, Natalia Shulzhenko, Anatoly Yambartsev, Andrey Morgun
      Abstract: Background: Co-expression networks are a tool widely used for analysis of “Big Data” in biology that can range from transcriptomes to proteomes, metabolomes and more recently even microbiomes. Several methods were proposed to answer biological questions interrogating these networks. Differential co-expression analysis is a recent approach that measures how gene interactions change when a biological system transitions from one state to another. Although the importance of differentially co-expressed genes to identify dysregulated pathways has been noted, their role in gene regulation is not well studied. Herein we investigated differentially co-expressed genes in a relatively simple mono-causal process (B lymphocyte deficiency) and in a complex multi-causal system (cervical cancer). Methods: Co-expression networks of B cell deficiency (Control and BcKO) were reconstructed using Pearson correlation coefficient for two mus musculus datasets: B10.A strain (12 normal, 12 BcKO) and BALB/c strain (10 normal, 10 BcKO). Co-expression networks of cervical cancer (normal and cancer) were reconstructed using local partial correlation method for five datasets (total of 64 normal, 148 cancer). Differentially correlated pairs were identified along with the location of their genes in BcKO and in cancer networks. Minimum Shortest Path and Bi-partite Betweenness Centrality where statistically evaluated for differentially co-expressed genes in corresponding networks.    Results: We show that in B cell deficiency the differentially co-expressed genes are highly enriched with immunoglobulin genes (causal genes). In cancer we found that differentially co-expressed genes act as “bottlenecks” rather than causal drivers with most flows that come from the key driver genes to the peripheral genes passing through differentially co-expressed genes. Using in vitro knockdown experiments for two out of 14 differentially co-expressed genes found in cervical cancer (FGFR2 and CACYBP), we showed that they play regulatory roles in cancer cell growth. Conclusion: Identifying differentially co-expressed genes in co-expression networks is an important tool in detecting regulatory genes involved in alterations of phenotype.
      PubDate: 2016-11-22T10:54:15Z
      DOI: 10.12688/f1000research.9708.1
      Issue No: Vol. 5 (2016)
  • Electroantennogram response of the parasitoid, Microplitis croceipes to
           host-related odors: The discrepancy between relative abundance and level
           of antennal responses to volatile compound [version 1; referees: 2

    • Authors: Tolulope Morawo, Matthew Burrows, Henry Fadamiro
      Abstract: Herbivores emit volatile organic compounds (VOCs) after feeding on plants. Parasitoids exploit these VOCs as odor cues to locate their hosts. In nature, host-related odors are emitted as blends of various compounds occurring in different proportions, and minor blend components can sometimes have profound effects on parasitoid responses. In a previous related study, we identified and quantified VOCs emitted by cotton plant-fed Heliothis virescens (Lepidoptera: Noctuidae) larvae, an herbivore host of the parasitoid Microplitis croceipes (Hymenoptera: Braconidae). In the present study, the olfactory response of female M. croceipes to synthetic versions of 15 previously identified compounds was tested in electroantennogram (EAG) bioassays. Using M. croceipes as a model species, we further asked the question: does the relative abundance of a volatile compound match the level of antennal response in parasitoids? Female M. croceipes showed varying EAG responses to test compounds, indicating different levels of bioactivity in the insect antenna. Eight compounds, including decanal, 1-octen-3-ol, 3-octanone, 2-ethylhexanol, tridecane, tetradecane, α-farnesene and bisabolene, elicited EAG responses above or equal to the 50th percentile rank of all responses. Interestingly, decanal, which represented only 1% of the total amount of odors emitted by cotton-fed hosts, elicited the highest (0.82 mV) EAG response in parasitoids. On the other hand, (E)-β-caryophyllene, the most abundant (29%) blend component, elicited a relatively low (0.17 mV) EAG response. The results suggest that EAG response to host-related volatiles in parasitoids is probably more influenced by the ecological relevance or functional role of the compound in the blend, rather than its relative abundance.
      PubDate: 2016-11-21T16:29:16Z
      DOI: 10.12688/f1000research.10104.1
      Issue No: Vol. 5 (2016)
  • Environmental volunteer well-being: Managers’ perception and actual
           well-being of volunteers [version 1; referees: 2 approved]

    • Authors: Gitte Kragh, Rick Stafford, Susanna Curtin, Anita Diaz
      Abstract: Background: Environmental volunteering can increase well-being, but environmental volunteer well-being has rarely been compared to participant well-being associated with other types of volunteering or nature-based activities. This paper aims to use a multidimensional approach to well-being to explore the immediately experienced and later remembered well-being of environmental volunteers and to compare this to the increased well-being of participants in other types of nature-based activities and volunteering. Furthermore, it aims to compare volunteer managers’ perceptions of their volunteers’ well-being with the self-reported well-being of the volunteers. Methods: Onsite surveys were conducted of practical conservation and biodiversity monitoring volunteers, as well as their control groups (walkers and fieldwork students, respectively), to measure general well-being before their nature-based activity and activity-related well-being immediately after their activity. Online surveys of current, former and potential volunteers and volunteer managers measured remembered volunteering-related well-being and managers’ perceptions of their volunteers’ well-being. Data were analysed based on Seligman’s multidimensional PERMA (‘positive emotion’, ‘engagement’, ‘positive relationship’, ‘meaning’, ‘achievement’) model of well-being. Factor analysis recovered three of the five PERMA elements, ‘engagement’, ‘relationship’ and ‘meaning’, as well as ‘negative emotion’ and ‘health’ as factors. Results: Environmental volunteering significantly improved positive elements and significantly decreased negative elements of participants’ immediate well-being, and it did so more than walking or student fieldwork. Even remembering their volunteering up to six months later, volunteers rated their volunteering-related well-being higher than volunteers rated their well-being generally in life. However, volunteering was not found to have an effect on overall mean well-being generally in life. Volunteer managers did not perceive the significant increase in well-being that volunteers reported. Conclusions: This study showed how environmental volunteering immediately improved participants’ well-being, even more than other nature-based activities. It highlights the benefit of regarding well-being as a multidimensional construct to more systematically understand, support and enhance volunteer well-being.
      PubDate: 2016-11-16T11:13:16Z
      DOI: 10.12688/f1000research.10016.1
      Issue No: Vol. 5 (2016)
  • Complete genome of Pieris rapae, a resilient alien, a cabbage pest, and a
           source of anti-cancer proteins [version 1; referees: 2 approved]

    • Authors: Jinhui Shen, Qian Cong, Lisa N. Kinch, Dominika Borek, Zbyszek Otwinowski, Nick V. Grishin
      Abstract: The Small Cabbage White (Pieris rapae) is originally a Eurasian butterfly. Being accidentally introduced into North America, Australia, and New Zealand a century or more ago, it spread throughout the continents and rapidly established as one of the most abundant butterfly species. Although it is a serious pest of cabbage and other mustard family plants with its caterpillars reducing crops to stems, it is also a source of pierisin, a protein unique to the Whites that shows cytotoxicity to cancer cells. To better understand the unusual biology of this omnipresent agriculturally and medically important butterfly, we sequenced and annotated the complete genome from USA specimens. At 246 Mbp, it is among the smallest Lepidoptera genomes reported to date. While 1.5% positions in the genome are heterozygous, they are distributed highly non-randomly along the scaffolds, and nearly 20% of longer than 1000 base-pair segments are SNP-free (median length: 38000 bp). Computational simulations of population evolutionary history suggest that American populations started from a very small number of introduced individuals, possibly a single fertilized female, which is in agreement with historical literature. Comparison to other Lepidoptera genomes reveals several unique families of proteins that may contribute to the unusual resilience of Pieris. The nitrile-specifier proteins divert the plant defense chemicals to non-toxic products. The apoptosis-inducing pierisins could offer a defense mechanism against parasitic wasps. While only two pierisins from Pieris rapae were characterized before, the genome sequence revealed eight, offering additional candidates as anti-cancer drugs. The reference genome we obtained lays the foundation for future studies of the Cabbage White and other Pieridae species.
      PubDate: 2016-11-03T17:27:47Z
      DOI: 10.12688/f1000research.9765.1
      Issue No: Vol. 5 (2016)
  • Evaluation of the Postoperative Quality of Recovery Scale test and re-test
           in Swedish among healthy volunteers [version 1; referees: 2 approved]

    • Authors: Pether Jildenstål, Johan Eriksson, Margareta Warren Stomberg, Jan G. Jakobsson
      Abstract: Introduction Patient outcome measures are required to assess the quality of healthcare. Tools for a patients’ self-assessment of quality of recovery, during perioperative care, have been developed during the last decade. The Postoperative Quality of Recovery Scale (PostopQRS) questionnaire is one of the most well-accepted and validated tools available. Here we assess the PostopORS questionnaire in Swedish. Methods Sixty-one students from the Bachelor Program in Nursing, (50 female and 11 male; mean age, 25; range, 21-46) filled in the Swedish translation of the PostopQRS questionnaire twice. They also evaluated whether they found the queries easy to understand and respond to. Results The participants found the Swedish translation of the PostopQRS questionnaire easy to read and understand. There were minor differences in test responses between the initial test and the re-test 48 hours later. We found that the PostopQRS questionnaire has some background noise; 12 out of 61 participants (20%) reported mild pain, 25 (41%) scored some depression and 33 scored mild anxiety (54%). The cognitive domain showed a learning effect between tests in “word recall” and “word generation”, while “digit recall forward” and “digit recall backward” showed no change. We found a difference in cognitive test performance with age; younger participants had higher mean cognitive test scores compared to participants >30 years. Overall, nine participants showed a decrease in re-test scores; two experienced a mild increase in pain; one experienced a mild increase in anxiety; and six performed more poorly on cognitive tests. Conclusion The Swedish translation of the PostopQRS was found to be adequate for use in the assessment of quality of recovery, and the questions were well understood by participants. Our study shows the importance of baseline testing for assessment of recovery, since recovery is assessed as a return to or improvement in each individual’s baseline score.
      PubDate: 2016-10-21T13:32:13Z
      DOI: 10.12688/f1000research.9740.1
      Issue No: Vol. 5 (2016)
  • Kv4.2 knockout mice display learning and memory deficits in the Lashley
           maze [version 1; referees: 2 approved]

    • Authors: Gregory D. Smith, Nan Gao, Joaquin N. Lugo
      Abstract: Background: Potassium channels have been shown to be involved in neural plasticity and learning. Kv4.2 is a subunit of the A-type potassium channel. Kv4.2 channels modulate excitability in the dendrites of pyramidal neurons in the cortex and hippocampus. Deletion of Kv4.2 results in spatial learning and conditioned fear deficits; however, previous studies have only examined deletion of Kv4.2 in aversive learning tests. Methods: For the current study, we used the Lashley maze as an appetitive learning test. We examined Kv4.2 wildtype (WT) and knockout (KO) mice in the Lashley maze over 4 days during adulthood. The first day consisted of habituating the mice to the maze. The mice then received five trials per day for the next 3 days. The number of errors and the time to the goal box was recorded for each trial. The goal box contained a weigh boat with an appetitive reward (gelatin with sugar). There was an intertrial interval of 15 minutes. Results: We found that Kv4.2 KO mice committed more errors across the trials compared to the WT mice p
      PubDate: 2016-10-05T15:57:48Z
      DOI: 10.12688/f1000research.9664.1
      Issue No: Vol. 5 (2016)
  • Targeted pharmacotherapy after somatic cancer mutation screening [version
           2; referees: 2 approved]

    • Authors: Thomas M. Polasek, Karen Ambler, Hamish S. Scott, Michael J. Sorich, Peter A. Kaub, Andrew Rowland, Michael D. Wiese, Ganessan Kichenadasse
      Abstract: Many patients with solid tumours are treated with targeted pharmacotherapy based on the results of genetic testing (‘precision medicine’). This study investigated the use of targeted drugs after OncoFOCUS™+KIT screening in patients with malignant melanoma, non-small cell lung cancer and metastatic colorectal cancer, and then audited the results against the National Comprehensive Cancer Network (NCCN) guidelines. Patients who were not indicated for targeted pharmacotherapy did not receive such treatment (99%, 100/101). Of the patients indicated for targeted drugs, 79% (33/42) received treatment according to NCCN guidelines. In 48% (20/42) of these patients the results from OncoFOCUS™+KIT screening were required for targeted drug selection, with the remaining 52% (22/42) prescribed drugs independent of the screening results for various reasons. This study highlights the growing importance of precision medicine approaches in directing pharmacotherapy in medical oncology.
      PubDate: 2016-09-20T13:52:22Z
      DOI: 10.12688/f1000research.9040.2
      Issue No: Vol. 5 (2016)
  • The use of collagen matrix (Ologen) as a patch graft in glaucoma tube
           shunt surgery, a retrospective chart review [version 1; referees: 2
           approved, 1 approved with reservations]

    • Authors: John D. Stephens, Steven R. Sarkisian; Jr.
      Abstract: Purpose: To determine the safety and efficacy of collagen matrix as a patch graft in glaucoma drainage surgery. Collagen matrix grafts may be advantageous because they do not need to be harvested from human donors. Methods: An institutional, retrospective review of 43 patients with at least 12 months follow-up status post-glaucoma drainage implant surgery were evaluated for signs of tube erosion after initial placement of collagen matrix patch graft. Results: Forty-one of 43 eyes (95.3%) required no intervention for patch graft melting with tube erosion. Average time of follow-up was 32 months (range: 12-45). Two cases had tube erosion at 4 months and 26 months post-op requiring tube revision, which was successfully revised with conjunctiva (4 month erosion) and donor sclera (26 month erosion). Conclusion:  Our results suggest that collagen matrix patch grafts may be used successfully as a patch graft in glaucoma tube shunt surgery, and may be advantageous because they do not have to be harvested from human donors. It is possible that exposure rates may be higher after longer follow-up and with larger numbers of patients. Further research is needed to compare Ologen to traditional graft materials to conclusively determine the safety and efficacy of collagen matrix as a novel patch graft material.
      PubDate: 2016-08-01T14:54:50Z
      DOI: 10.12688/f1000research.9232.1
      Issue No: Vol. 5 (2016)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
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Fax: +00 44 (0)131 4513327
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