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Journal Cover F1000Research
  [SJR: 0.56]   [H-I: 9]   [4 followers]  Follow
  This is an Open Access Journal Open Access journal
   ISSN (Online) 2046-1402
   Published by Faculty of 1000 Homepage  [1 journal]
  • Plasticity of the Leishmania genome leading to gene copy number variations
           and drug resistance [version 1; referees: 5 approved]

    • Authors: Marie-Claude N. Laffitte, Philippe Leprohon, Barbara Papadopoulou, Marc Ouellette
      Abstract: Leishmania has a plastic genome, and drug pressure can select for gene copy number variation (CNV). CNVs can apply either to whole chromosomes, leading to aneuploidy, or to specific genomic regions. For the latter, the amplification of chromosomal regions occurs at the level of homologous direct or inverted repeated sequences leading to extrachromosomal circular or linear amplified DNAs. This ability of Leishmania to respond to drug pressure by CNVs has led to the development of genomic screens such as Cos-Seq, which has the potential of expediting the discovery of drug targets for novel promising drug candidates.
      PubDate: 2016-09-20T13:27:05Z
      DOI: 10.12688/f1000research.9218.1
      Issue No: Vol. 5 (2016)
  • Recent advances in T-cell engineering for use in immunotherapy [version 1;
           referees: 3 approved]

    • Authors: Preeti Sharma, David M. Kranz
      Abstract: Adoptive T-cell therapies have shown exceptional promise in the treatment of cancer, especially B-cell malignancies. Two distinct strategies have been used to redirect the activity of ex vivo engineered T cells. In one case, the well-known ability of the T-cell receptor (TCR) to recognize a specific peptide bound to a major histocompatibility complex molecule has been exploited by introducing a TCR against a cancer-associated peptide/human leukocyte antigen complex. In the other strategy, synthetic constructs called chimeric antigen receptors (CARs) that contain antibody variable domains (single-chain fragments variable) and signaling domains have been introduced into T cells. Whereas many reviews have described these two approaches, this review focuses on a few recent advances of significant interest. The early success of CARs has been followed by questions about optimal configurations of these synthetic constructs, especially for efficacy against solid tumors. Among the many features that are important, the dimensions and stoichiometries of CAR/antigen complexes at the synapse have recently begun to be appreciated. In TCR-mediated approaches, recent evidence that mutated peptides (neoantigens) serve as targets for endogenous T-cell responses suggests that these neoantigens may also provide new opportunities for adoptive T-cell therapies with TCRs.
      PubDate: 2016-09-19T12:58:26Z
      DOI: 10.12688/f1000research.9073.1
      Issue No: Vol. 5 (2016)
  • Multi-site tumor sampling (MSTS) improves the performance of histological
           detection of intratumor heterogeneity in clear cell renal cell carcinoma
           (CCRCC) [version 2; referees: 5 approved]

    • Abstract: Current standard-of-care tumor sampling protocols for CCRCC (and other cancers) are not efficient at detecting intratumoural heterogeneity (ITH). We have demonstrated in silico that an alternative protocol, multi-site tumor sampling (MSTS) based upon the divide and conquer (DAC) algorithm, can significantly increase the efficiency of ITH detection without extra costs. Now we test this protocol on routine hematoxylin-eosin (HE) sections in a series of 38 CCRCC cases. MSTS was found to outperform traditional sampling when detecting either high grade (p=0.0136) or granular/eosinophilic cells (p=0.0114). We therefore propose that MSTS should be used in routine clinical practice.
      PubDate: 2016-09-16T14:26:53Z
      DOI: 10.12688/f1000research.9419.2
      Issue No: Vol. 5 (2016)
  • Ending the HIV/AIDS epidemic in low- and middle-income countries by 2030:
           is it possible' [version 1; referees: 2 approved]

    • Authors: Anthony D. Harries, Amitabh B. Suthar, Kudakwashe C. Takarinda, Hannock Tweya, Nang Thu Thu Kyaw, Katie Tayler-Smith, Rony Zachariah
      Abstract: The international community has committed to ending the epidemics of HIV/AIDS, tuberculosis, malaria, and neglected tropical infections by 2030, and this bold stance deserves universal support. In this paper, we discuss whether this ambitious goal is achievable for HIV/AIDS and what is needed to further accelerate progress. The joint United Nations Program on HIV/AIDS (UNAIDS) 90-90-90 targets and the related strategy are built upon currently available health technologies that can diagnose HIV infection and suppress viral replication in all people with HIV. Nonetheless, there is much work to be done in ensuring equitable access to these HIV services for key populations and those who remain outside the rims of the traditional health services. Identifying a cure and a preventive vaccine would further help accelerate progress in ending the epidemic. Other disease control programmes could learn from the response to the HIV/AIDS epidemic.
      PubDate: 2016-09-15T14:49:38Z
      DOI: 10.12688/f1000research.9247.1
      Issue No: Vol. 5 (2016)
  • How leukocytes trigger opening and sealing of gaps in the endothelial
           barrier [version 1; referees: 3 approved]

    • Authors: Debashree Goswami, Dietmar Vestweber
      Abstract: The entry of leukocytes into tissues requires well-coordinated interactions between the immune cells and endothelial cells which form the inner lining of blood vessels. The molecular basis for recognition, capture, and adhesion of leukocytes to the endothelial apical surface is well studied. This review will focus on recent advances in our understanding of events following the firm interaction of leukocytes with the inner surface of the blood vessel wall. We will discuss how leukocytes initiate the transmigration (diapedesis) process, trigger the opening of gaps in the endothelial barrier, and eventually move through this boundary.
      PubDate: 2016-09-14T13:23:50Z
      DOI: 10.12688/f1000research.9185.1
      Issue No: Vol. 5 (2016)
  • Epidemiology, virulence factors and management of the pneumococcus
           [version 1; referees: 2 approved]

    • Authors: Charles Feldman, Ronald Anderson
      Abstract: Pneumococcal infections continue to cause significant morbidity and mortality in patients throughout the world. This microorganism remains the most common bacterial cause of community-acquired pneumonia and is associated with a considerable burden of disease and health-care costs in both developed and developing countries. Emerging antibiotic resistance has been a concern because of its potential negative impact on the outcome of patients who receive standard antibiotic therapy. However, there have been substantial changes in the epidemiology of this pathogen in recent years, not least of which has been due to the use of pneumococcal conjugate vaccines in children, with subsequent herd protection in unvaccinated adults and children. Furthermore, much recent research has led to a better understanding of the virulence factors of this pathogen and their role in the pathogenesis of severe pneumococcal disease, including the cardiac complications, as well as the potential role of adjunctive therapy in the management of severely ill cases. This review will describe recent advances in our understanding of the epidemiology, virulence factors, and management of pneumococcal community-acquired pneumonia.
      PubDate: 2016-09-14T13:20:39Z
      DOI: 10.12688/f1000research.9283.1
      Issue No: Vol. 5 (2016)
  • Recent advances in covalent, site-specific protein immobilization [version
           1; referees: 3 approved]

    • Authors: Morten Meldal, Sanne Schoffelen
      Abstract: The properties of biosensors, biomedical implants, and other materials based on immobilized proteins greatly depend on the method employed to couple the protein molecules to their solid support. Covalent, site-specific immobilization strategies are robust and can provide the level of control that is desired in this kind of application. Recent advances include the use of enzymes, such as sortase A, to couple proteins in a site-specific manner to materials such as microbeads, glass, and hydrogels. Also, self-labeling tags such as the SNAP-tag can be employed. Last but not least, chemical approaches based on bioorthogonal reactions, like the azide–alkyne cycloaddition, have proven to be powerful tools. The lack of comparative studies and quantitative analysis of these immobilization methods hampers the selection process of the optimal strategy for a given application. However, besides immobilization efficiency, the freedom in selecting the site of conjugation and the size of the conjugation tag and the researcher’s expertise regarding molecular biology and/or chemical techniques will be determining factors in this regard.
      PubDate: 2016-09-12T15:39:51Z
      DOI: 10.12688/f1000research.9002.1
      Issue No: Vol. 5 (2016)
  • The RhoA-ROCK pathway in the regulation of T and B cell responses [version
           1; referees: 3 approved]

    • Authors: Edd Ricker, Luvana Chowdhury, Woelsung Yi, Alessandra B. Pernis
      Abstract: Effective immune responses require the precise regulation of dynamic interactions between hematopoietic and non-hematopoietic cells. The Rho subfamily of GTPases, which includes RhoA, is rapidly activated downstream of a diverse array of biochemical and biomechanical signals, and is emerging as an important mediator of this cross-talk. Key downstream effectors of RhoA are the Rho kinases, or ROCKs. The ROCKs are two serine-threonine kinases that can act as global coordinators of a tissue’s response to stress and injury because of their ability to regulate a wide range of biological processes. Although the RhoA-ROCK pathway has been extensively investigated in the non-hematopoietic compartment, its role in the immune system is just now becoming appreciated. In this commentary, we provide a brief overview of recent findings that highlight the contribution of this pathway to lymphocyte development and activation, and the impact that dysregulation in the activation of RhoA and/or the ROCKs may exert on a growing list of autoimmune and lymphoproliferative disorders.
      PubDate: 2016-09-12T10:52:31Z
      DOI: 10.12688/f1000research.7522.1
      Issue No: Vol. 5 (2016)
  • Integrating succession and community assembly perspectives [version 1;
           referees: 2 approved]

    • Authors: Cynthia Chang, Janneke HilleRisLambers
      Abstract: Succession and community assembly research overlap in many respects, such as through their focus on how ecological processes like dispersal, environmental filters, and biotic interactions influence community structure. Indeed, many recent advances have been made by successional studies that draw on modern analytical techniques introduced by contemporary community assembly studies. However, community assembly studies generally lack a temporal perspective, both on how the forces structuring communities might change over time and on how historical contingency (e.g. priority effects and legacy effects) and complex transitions (e.g. threshold effects) might alter community trajectories. We believe a full understanding of the complex interacting processes that shape community dynamics across large temporal scales can best be achieved by combining concepts, tools, and study systems into an integrated conceptual framework that draws upon both succession and community assembly theory.
      PubDate: 2016-09-12T10:07:03Z
      DOI: 10.12688/f1000research.8973.1
      Issue No: Vol. 5 (2016)
  • An annotation of cuts, depicted locations, and temporal progression in the
           motion picture "Forrest Gump" [version 1; referees: 2 approved]

    • Abstract: Here we present an annotation of locations and temporal progression depicted in the movie “Forrest Gump”, as an addition to a large public functional brain imaging dataset ( The annotation provides information about the exact timing of each of the 870 shots, and the depicted location after every cut with a high, medium, and low level of abstraction. Additionally, four classes are used to distinguish the differences of the depicted time between shots. Each shot is also annotated regarding the type of location (interior/exterior) and time of day. This annotation enables further studies of visual perception, memory of locations, and the perception of time under conditions of real-life complexity using the studyforrest dataset.
      PubDate: 2016-09-08T13:57:34Z
      DOI: 10.12688/f1000research.9536.1
      Issue No: Vol. 5 (2016)
  • EGF receptor ligands: recent advances [version 1; referees: 3 approved]

    • Authors: Bhuminder Singh, Graham Carpenter, Robert J. Coffey
      Abstract: Seven ligands bind to and activate the mammalian epidermal growth factor (EGF) receptor (EGFR/ERBB1/HER1): EGF, transforming growth factor-alpha (TGFA), heparin-binding EGF-like growth factor (HBEGF), betacellulin (BTC), amphiregulin (AREG), epiregulin (EREG), and epigen (EPGN). Of these, EGF, TGFA, HBEGF, and BTC are thought to be high-affinity ligands, whereas AREG, EREG, and EPGN constitute low-affinity ligands. This focused review is meant to highlight recent studies related to actions of the individual EGFR ligands, the interesting biology that has been uncovered, and relevant advances related to ligand interactions with the EGFR.
      PubDate: 2016-09-08T10:02:54Z
      DOI: 10.12688/f1000research.9025.1
      Issue No: Vol. 5 (2016)
  • Actomyosin stress fiber mechanosensing in 2D and 3D [version 1; referees:
           3 approved]

    • Authors: Stacey Lee, Sanjay Kumar
      Abstract: Mechanotransduction is the process through which cells survey the mechanical properties of their environment, convert these mechanical inputs into biochemical signals, and modulate their phenotype in response. These mechanical inputs, which may be encoded in the form of extracellular matrix stiffness, dimensionality, and adhesion, all strongly influence cell morphology, migration, and fate decisions. One mechanism through which cells on planar or pseudo-planar matrices exert tensile forces and interrogate microenvironmental mechanics is through stress fibers, which are bundles composed of actin filaments and, in most cases, non-muscle myosin II filaments. Stress fibers form a continuous structural network that is mechanically coupled to the extracellular matrix through focal adhesions. Furthermore, myosin-driven contractility plays a central role in the ability of stress fibers to sense matrix mechanics and generate tension. Here, we review the distinct roles that non-muscle myosin II plays in driving mechanosensing and focus specifically on motility. In a closely related discussion, we also describe stress fiber classification schemes and the differing roles of various myosin isoforms in each category. Finally, we briefly highlight recent studies exploring mechanosensing in three-dimensional environments, in which matrix content, structure, and mechanics are often tightly interrelated. Stress fibers and the myosin motors therein represent an intriguing and functionally important biological system in which mechanics, biochemistry, and architecture all converge.
      PubDate: 2016-09-07T15:06:13Z
      DOI: 10.12688/f1000research.8800.1
      Issue No: Vol. 5 (2016)
  • Deep brain stimulation in Gilles de la Tourette syndrome: killing several
           birds with one stone' [version 1; referees: 2 approved]

    • Authors: Andreas Hartmann
      Abstract: In patients with severe, treatment-refractory Gilles de la Tourette syndrome (GTS), deep brain stimulation (DBS) of various targets has been increasingly explored over the past 15 years. The multiplicity of surgical targets is intriguing and may be partly due to the complexity of GTS, specifically the various and frequent associated psychiatric comorbidities in this disorder. Thus, the target choice may not only be aimed at reducing tics but also comorbidities. While this approach is laudable, it also carries the risk to increase confounding factors in DBS trials and patient evaluation. Moreover, I question whether DBS should really be expected to alleviate multiple symptoms at a time. Rather, I argue that tic reduction should remain our primary objective in severe GTS patients and that this intervention may subsequently allow an improved psychotherapeutic and/or pharmacological treatment of comorbidities. Thus, I consider DBS in GTS not as a single solution for all our patients’ ailments but as a stepping stone to improved holistic care made possible by tic reduction.
      PubDate: 2016-09-07T11:24:20Z
      DOI: 10.12688/f1000research.9521.1
      Issue No: Vol. 5 (2016)
  • Salutary effects of high-intensity interval training in persons with
           elevated cardiovascular risk [version 1; referees: 3 approved]

    • Authors: Jerome L. Fleg
      Abstract: Although moderate-intensity continuous training (MICT) has been the traditional model for aerobic exercise training for over four decades, a growing body of literature has demonstrated equal if not greater improvement in aerobic capacity and similar beneficial effects on body composition, glucose metabolism, blood pressure, and quality of life from high-intensity interval training (HIIT). An advantage of HIIT over MICT is the shorter time required to perform the same amount of energy expenditure. The current brief review summarizes the effects of HIIT on peak aerobic capacity and cardiovascular risk factors in healthy adults and those with various cardiovascular diseases, including coronary artery disease, chronic heart failure, and post heart transplantation.
      PubDate: 2016-09-07T11:16:42Z
      DOI: 10.12688/f1000research.8778.1
      Issue No: Vol. 5 (2016)
  • Recent advances in cardiac magnetic resonance [version 1; referees: 3

    • Authors: Simon Greulich, Andrew E. Arai, Udo Sechtem, Heiko Mahrholdt
      Abstract: Cardiac magnetic resonance (CMR) is a non-invasive imaging modality that has rapidly emerged during the last few years and has become a valuable, well-established clinical tool. Beside the evaluation of anatomy and function, CMR has its strengths in providing detailed non-invasive myocardial tissue characterization, for which it is considered the current diagnostic gold standard. Late gadolinium enhancement (LGE), with its capability to detect necrosis and to separate ischemic from non-ischemic cardiomyopathies by distinct LGE patterns, offers unique clinical possibilities. The presence of LGE has also proven to be a good predictor of an adverse outcome in various studies. T2-weighted (T2w) images, which are supposed to identify areas of edema and inflammation, are another CMR approach to tissue characterization. However, T2w images have not held their promise owing to several technical limitations and potential physiological concerns. Newer mapping techniques may overcome some of these limitations: they assess quantitatively myocardial tissue properties in absolute terms and show promising results in studies for characterization of diffuse fibrosis (T1 mapping) and/or inflammatory processes (T2 mapping). However, these techniques are still research tools and are not part of the clinical routine yet. T2* CMR has had significant impact in the management of thalassemia because it is possible to image the amount of iron in the heart and the liver, improving both diagnostic imaging and the management of patients with thalassemia. CMR findings frequently have clinical impact on further patient management, and CMR seems to be cost effective in the clinical routine.
      PubDate: 2016-09-07T11:13:06Z
      DOI: 10.12688/f1000research.8383.1
      Issue No: Vol. 5 (2016)
  • Recent advances in understanding and diagnosing hepatitis B virus
           infection [version 1; referees: 2 approved]

    • Authors: Slim Fourati, Jean-Michel Pawlotsky
      Abstract: Hepatitis B virus (HBV) infects approximately 240 million individuals worldwide. Recent advances in the virology, immunopathogenesis, and diagnosis of HBV infection are summarized in this review article. The identification of a hepatocyte-specific cellular receptor for HBV, the sodium taurocholate co-transporting polypeptide (NTCP), made it possible to develop reliable cell culture systems and better understand the early steps of the viral lifecycle. Viral and host factors involved in covalently closed circular DNA synthesis, stability, and transcriptional regulation have also been identified and provide potential targets for new drugs. Based on recent evidence showing trained immunity in immune-tolerant patients, the immune tolerance and immune clearance phases have been renamed the non-inflammatory and inflammatory phases, respectively. New diagnostic and monitoring tools are now available, including rapid diagnostic tests for hepatitis B surface antigen (HBsAg) detection, HBsAg quantification assays, anti-HBc antibody quantification assays, an HBV core-related antigen (HBcrAg) quantification test, new HBV DNA detection and quantification assays, and an HBV RNA quantification test. Their clinical utility is under study. Finally, new antiviral and immune modulation approaches are in the preclinical or early clinical developmental stages, with the goal to achieve functional cure or ideally (if possible) eradication of HBV infection.
      PubDate: 2016-09-06T16:06:51Z
      DOI: 10.12688/f1000research.8983.1
      Issue No: Vol. 5 (2016)
  • Evaluation of unique identifiers used as keys to match identical
           publications in Pure and SciVal – a case study from health science
           [version 2; referees: 1 approved, 2 approved with reservations]

    • Authors: Heidi Holst Madsen, Dicte Madsen, Marianne Gauffriau
      Abstract: Unique identifiers (UID) are seen as an effective key to match identical publications across databases or identify duplicates in a database. The objective of the present study is to investigate how well UIDs work as match keys in the integration between Pure and SciVal, based on a case with publications from the health sciences. We evaluate the matching process based on information about coverage, precision, and characteristics of publications matched versus not matched with UIDs as the match keys. We analyze this information to detect errors, if any, in the matching process. As an example we also briefly discuss how publication sets formed by using UIDs as the match keys may affect the bibliometric indicators number of publications, number of citations, and the average number of citations per publication.  The objective is addressed in a literature review and a case study. The literature review shows that only a few studies evaluate how well UIDs work as a match key. From the literature we identify four error types: Duplicate digital object identifiers (
      DOI ), incorrect
      DOI s in reference lists and databases,
      DOI s not registered by the database where a bibliometric analysis is performed, and erroneous optical or special character recognition. The case study explores the use of UIDs in the integration between the databases Pure and SciVal. Specifically journal publications in English are matched between the two databases. We find all error types except erroneous optical or special character recognition in our publication sets. In particular the duplicate
      DOI s constitute a problem for the calculation of bibliometric indicators as both keeping the duplicates to improve the reliability of citation counts and deleting them to improve the reliability of publication counts will distort the calculation of average number of citations per publication. The use of UIDs as a match key in citation linking is implemented in many settings, and the availability of UIDs may become critical for the inclusion of a publication or a database in a bibliometric analysis.
      PubDate: 2016-09-06T15:24:43Z
      Issue No: Vol. 5 (2016)
  • Recent advances in understanding vitiligo [version 1; referees: 3

    • Authors: Prashiela Manga, Nada Elbuluk, Seth J. Orlow
      Abstract: Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation. The most significant progress in our understanding of disease etiology has been made on three fronts: (1) identifying cellular responses to stress, including antioxidant pathways and the unfolded protein response (UPR), as key players in disease onset, (2) characterizing immune responses that target melanocytes and drive disease progression, and (3) identifying major susceptibility genes. The current model for vitiligo pathogenesis postulates that oxidative stress causes cellular disruptions, including interruption of protein maturation in the endoplasmic reticulum (ER), leading to the activation of the UPR and expression of UPR-regulated chemokines such as interleukin 6 (IL-6) and IL-8. These chemokines recruit immune components to the skin, causing melanocytes to be targeted for destruction. Oxidative stress can further increase melanocyte targeting by promoting antigen presentation. Two key components of the autoimmune response that promote disease progression are the interferon (IFN)-γ/CXCL10 axis and IL-17-mediated responses. Several genome-wide association studies support a role for these pathways, with the antioxidant gene NRF2, UPR gene XBP1, and numerous immune-related genes including class I and class II major histocompatibility genes associated with a risk for developing vitiligo. Novel approaches to promote repigmentation in vitiligo are being investigated and may yield effective, long-lasting therapies.
      PubDate: 2016-09-06T09:33:59Z
      DOI: 10.12688/f1000research.8976.1
      Issue No: Vol. 5 (2016)
  • Opportunities and considerations for visualising neuroimaging data on very
           large displays [version 1; referees: 2 approved]

    • Authors: Matthew B. Wall, David Birch, May Y. Yong
      Abstract: Neuroimaging experiments can generate impressive volumes of data and many images of the results. This is particularly true of multi-modal imaging studies that use more than one imaging technique, or when imaging is combined with other assessments. A challenge for these studies is appropriate visualisation of results in order to drive insights and guide accurate interpretations. Next-generation visualisation technology therefore has much to offer the neuroimaging community. One example is the Imperial College London Data Observatory; a high-resolution (132 megapixel) arrangement of 64 monitors, arranged in a 313 degree arc, with a 6 metre diameter, powered by 32 rendering nodes. This system has the potential for high-resolution, large-scale display of disparate data types in a space designed to promote collaborative discussion by multiple researchers and/or clinicians. Opportunities for the use of the Data Observatory are discussed, with particular reference to applications in Multiple Sclerosis (MS) research and clinical practice. Technical issues and current work designed to optimise the use of the Data Observatory for neuroimaging are also discussed, as well as possible future research that could be enabled by the use of the system in combination with eye-tracking technology.
      PubDate: 2016-09-02T14:04:54Z
      DOI: 10.12688/f1000research.9522.1
      Issue No: Vol. 5 (2016)
  • Cardio-renal syndrome [version 1; referees: 3 approved]

    • Authors: Joseph Gnanaraj, Jai Radhakrishnan
      Abstract: Cardio-renal syndrome is a commonly encountered problem in clinical practice. Its pathogenesis is not fully understood. The purpose of this article is to highlight the interaction between the cardiovascular system and the renal system and how their interaction results in the complex syndrome of cardio-renal dysfunction. Additionally, we outline the available therapeutic strategies to manage this complex syndrome.
      PubDate: 2016-08-31T15:36:48Z
      DOI: 10.12688/f1000research.8004.1
      Issue No: Vol. 5 (2016)
  • Animal social learning: associations and adaptations [version 1; referees:
           2 approved]

    • Authors: Simon M. Reader
      Abstract: Social learning, learning from others, is a powerful process known to impact the success and survival of humans and non-human animals alike. Yet we understand little about the neurocognitive and other processes that underpin social learning. Social learning has often been assumed to involve specialized, derived cognitive processes that evolve and develop independently from other processes. However, this assumption is increasingly questioned, and evidence from a variety of organisms demonstrates that current, recent, and early life experience all predict the reliance on social information and thus can potentially explain variation in social learning as a result of experiential effects rather than evolved differences. General associative learning processes, rather than adaptive specializations, may underpin much social learning, as well as social learning strategies. Uncovering these distinctions is important to a variety of fields, for example by widening current views of the possible breadth and adaptive flexibility of social learning. Nonetheless, just like adaptationist evolutionary explanations, associationist explanations for social learning cannot be assumed, and empirical work is required to uncover the mechanisms involved and their impact on the efficacy of social learning. This work is being done, but more is needed. Current evidence suggests that much social learning may be based on ‘ordinary’ processes but with extraordinary consequences.
      PubDate: 2016-08-31T13:55:13Z
      DOI: 10.12688/f1000research.7922.1
      Issue No: Vol. 5 (2016)
  • Recent advances in synthetic biosafety [version 1; referees: 2 approved]

    • Authors: Anna J. Simon, Andrew D. Ellington
      Abstract: Synthetically engineered organisms hold promise for a broad range of medical, environmental, and industrial applications. Organisms can potentially be designed, for example, for the inexpensive and environmentally benign synthesis of pharmaceuticals and industrial chemicals, for the cleanup of environmental pollutants, and potentially even for biomedical applications such as the targeting of specific diseases or tissues. However, the use of synthetically engineered organisms comes with several reasonable safety concerns, one of which is that the organisms or their genes could escape their intended habitats and cause environmental disruption. Here we review key recent developments in this emerging field of synthetic biocontainment and discuss further developments that might be necessary for the widespread use of synthetic organisms. Specifically, we discuss the history and modern development of three strategies for the containment of synthetic microbes: addiction to an exogenously supplied ligand; self-killing outside of a designated environment; and self-destroying encoded DNA circuitry outside of a designated environment.
      PubDate: 2016-08-31T13:35:13Z
      DOI: 10.12688/f1000research.8365.1
      Issue No: Vol. 5 (2016)
  • Pathophysiological links between traumatic brain injury and post-traumatic
           headaches [version 1; referees: 3 approved]

    • Authors: Robert L. Ruff, Kayla Blake
      Abstract: This article reviews possible ways that traumatic brain injury (TBI) can induce migraine-type post-traumatic headaches (PTHs) in children, adults, civilians, and military personnel. Several cerebral alterations resulting from TBI can foster the development of PTH, including neuroinflammation that can activate neural systems associated with migraine. TBI can also compromise the intrinsic pain modulation system and this would increase the level of perceived pain associated with PTH. Depression and anxiety disorders, especially post-traumatic stress disorder (PTSD), are associated with TBI and these psychological conditions can directly intensify PTH. Additionally, depression and PTSD alter sleep and this will increase headache severity and foster the genesis of PTH. This article also reviews the anatomic loci of injury associated with TBI and notes the overlap between areas of injury associated with TBI and PTSD.
      PubDate: 2016-08-31T10:05:26Z
      DOI: 10.12688/f1000research.9017.1
      Issue No: Vol. 5 (2016)
  • Factors affecting stone free rate of primary percutaneous nephrolithotomy
           on staghorn calculi: a single center experience of 15 years [version 1;
           referees: 2 approved]

    • Authors: Widi Atmoko, Ponco Birowo, Nur Rasyid
      Abstract: Objectives: Percutaneous nephrolithotomy on staghorn calculi is challenging for urologists because it is difficult to remove all of the stones. The purpose of this study was to evaluate the associated factors of stone-free rate after primary percutaneous nephrolithotomy on staghorn calculi in a large series of patients at a single, tertiary referral, endourologic stone center. Methods: We collected data from medical record between January 2000 and December 2015. A total of 345 primary percutaneous nephrolithotomy procedures were performed for patients with staghorn calculi. This study included both and made no distinction between partial and complete staghorn calculi. Stone-free is defined as the absence of residual stones after undergoing percutaneous nephrolithotomy for the first time. Significant factors from univariate analysis that correlated with stone-free rate after primary percutaneous nephrolithotomy of staghorn stone were further analyzed using multivariate regression analysis. Results: The mean patient age was 52.23±10.38 years. The stone-free rate of percutaneous nephrolithotomy monotherapy was 62.6%. The mean operating time was 79.55±34.46 minutes. The mean length of stay in hospital was 4.29±3.00 days. Using the chi-square test, history of ipsilateral open renal stone surgery (p = 0.01), stone burden (p = < 0.001), and type of anesthesia (p = 0.04) had a significant impact on the stone-free. From multivariate analysis, the history of ipsilateral open renal stone surgery [OR 0.48; 95% CI 0.28-0.81; p 0.01] and the stone burden [OR 0.28; 95% CI 0.18-0.45; p 0.00] were significant independent risk factors for stone-free.
      PubDate: 2016-08-30T15:14:10Z
      DOI: 10.12688/f1000research.9509.1
      Issue No: Vol. 5 (2016)
  • Virotherapy: cancer gene therapy at last' [version 1; referees: 2

    • Authors: Alan E. Bilsland, Pavlina Spiliopoulou, T. R. Jeffry Evans
      Abstract: For decades, effective cancer gene therapy has been a tantalising prospect; for a therapeutic modality potentially able to elicit highly effective and selective responses, definitive efficacy outcomes have often seemed out of reach. However, steady progress in vector development and accumulated experience from previous clinical studies has finally led the field to its first licensed therapy. Following a pivotal phase III trial, Imlygic (talimogene laherparepvec/T-Vec) received US approval as a treatment for cutaneous and subcutaneous melanoma in October 2015, followed several weeks later by its European authorisation. These represent the first approvals for an oncolytic virotherapy. Imlygic is an advanced-generation herpesvirus-based vector optimised for oncolytic and immunomodulatory activities. Many other oncolytic agents currently remain in development, providing hope that current success will be followed by other diverse vectors that may ultimately come to constitute a new class of clinical anti-cancer agents. In this review, we discuss some of the key oncolytic viral agents developed in the adenovirus and herpesvirus classes, and the prospects for further enhancing their efficacy by combining them with novel immunotherapeutic approaches.
      PubDate: 2016-08-30T15:13:31Z
      DOI: 10.12688/f1000research.8211.1
      Issue No: Vol. 5 (2016)
  • Whose sample is it anyway' Widespread misannotation of samples in
           transcriptomics studies [version 1; referees: 2 approved]

    • Authors: Lilah Toker, Min Feng, Paul Pavlidis
      Abstract: Concern about the reproducibility and reliability of biomedical research has been rising. An understudied issue is the prevalence of sample mislabeling, one impact of which would be invalid comparisons. We studied this issue in a corpus of human transcriptomics studies by comparing the provided annotations of sex to the expression levels of sex-specific genes. We identified apparent mislabeled samples in 46% of the datasets studied, yielding a 99% confidence lower-bound estimate for all studies of 33%. In a separate analysis of a set of datasets concerning a single cohort of subjects, 2/4 had mislabeled samples, indicating laboratory mix-ups rather than data recording errors. While the number of mixed-up samples per study was generally small, because our method can only identify a subset of potential mix-ups, our estimate is conservative for the breadth of the problem. Our findings emphasize the need for more stringent sample tracking, and that re-users of published data must be alert to the possibility of annotation and labelling errors.
      PubDate: 2016-08-30T13:27:32Z
      DOI: 10.12688/f1000research.9471.1
      Issue No: Vol. 5 (2016)
  • New insights into cochlear sound encoding [version 1; referees: 2

    • Authors: Tobias Moser, Christian Vogl
      Abstract: The inner ear uses specialized synapses to indefatigably transmit sound information from hair cells to spiral ganglion neurons at high rates with submillisecond precision. The emerging view is that hair cell synapses achieve their demanding function by employing an unconventional presynaptic molecular composition. Hair cell active zones hold the synaptic ribbon, an electron-dense projection made primarily of RIBEYE, which tethers a halo of synaptic vesicles and is thought to enable a large readily releasable pool of vesicles and to contribute to its rapid replenishment. Another important presynaptic player is otoferlin, coded by a deafness gene, which assumes a multi-faceted role in vesicular exocytosis and, when disrupted, causes auditory synaptopathy. A functional peculiarity of hair cell synapses is the massive heterogeneity in the sizes and shapes of excitatory postsynaptic currents. Currently, there is controversy as to whether this reflects multiquantal release with a variable extent of synchronization or uniquantal release through a dynamic fusion pore. Another important question in the field has been the precise mechanisms of coupling presynaptic Ca2+ channels and vesicular Ca2+ sensors. This commentary provides an update on the current understanding of sound encoding in the cochlea with a focus on presynaptic mechanisms.
      PubDate: 2016-08-26T15:10:47Z
      DOI: 10.12688/f1000research.8924.1
      Issue No: Vol. 5 (2016)
  • Respondent driven sampling of wheelchair users: A lack of traction'
           [version 2; referees: 1 approved, 2 approved with reservations]

    • Authors: John A. Bourke, Philip J. Schluter, E. Jean C. Hay-Smith, Deborah L. Snell
      Abstract: Background: Internationally, wheelchair users are an emerging demographic phenomenon, due to their increased prevalence and rapidly increasing life-span. While having significant healthcare implications, basic robust epidemiological information about wheelchair users is often lacking due, in part, to this population’s ‘hidden’ nature. Increasingly popular in epidemiological research, Respondent Driven Sampling (RDS) provides a mechanism for generating unbiased population-based estimates for hard-to-reach populations, overcoming biases inherent within other sampling methods. This paper reports the first published study to employ RDS amongst wheelchair users. Methods: Between October 2015 and January 2016, a short, successfully piloted, internet-based national survey was initiated. Twenty seeds from diverse organisations were invited to complete the survey then circulate it to peers within their networks following a well-defined protocol. A predetermined reminder protocol was triggered when seeds or their peers failed to respond. All participants were entered into a draw for an iPad. Results: Overall, 19 people participated (nine women); 12 initial seeds, followed by seven second-wave participants arising from four seeds. Completion time for the survey ranged between 7 and 36 minutes. Despite repeated reminders, no further people were recruited. Discussion: While New Zealand wheelchair user numbers are unknown, an estimated 14% of people have physical impairments that limited mobility. The 19 respondents generated from adopting the RDS methodology here thus represents a negligible fraction of wheelchair users in New Zealand, and an insufficient number to ensure equilibrium required for unbiased analyses. While successful in other hard-to-reach populations, applying RDS methodology to wheelchair users requires further consideration. Formative research exploring areas of network characteristics, acceptability of RDS, appropriate incentive options, and seed selection amongst wheelchair users is needed.
      PubDate: 2016-08-26T09:58:04Z
      DOI: 10.12688/f1000research.8605.2
      Issue No: Vol. 5 (2016)
  • mTOR inhibitors in cancer therapy [version 1; referees: 3 approved]

    • Authors: Jianling Xie, Xuemin Wang, Christopher G. Proud
      Abstract: The mammalian target of rapamycin, mTOR, plays key roles in cell growth and proliferation, acting at the catalytic subunit of two protein kinase complexes: mTOR complexes 1 and 2 (mTORC1/2). mTORC1 signaling is switched on by several oncogenic signaling pathways and is accordingly hyperactive in the majority of cancers. Inhibiting mTORC1 signaling has therefore attracted great attention as an anti-cancer therapy. However, progress in using inhibitors of mTOR signaling as therapeutic agents in oncology has been limited by a number of factors, including the fact that the classic mTOR inhibitor, rapamycin, inhibits only some of the effects of mTOR; the existence of several feedback loops; and the crucial importance of mTOR in normal physiology.
      PubDate: 2016-08-25T14:29:54Z
      DOI: 10.12688/f1000research.9207.1
      Issue No: Vol. 5 (2016)
  • Recent advances in targeted therapy for Ewing sarcoma [version 1;
           referees: 2 approved]

    • Authors: Kathleen I. Pishas, Stephen L. Lessnick
      Abstract: Ewing sarcoma is an aggressive, poorly differentiated neoplasm of solid bone that disproportionally afflicts the young. Despite intensive multi-modal therapy and valiant efforts, 70% of patients with relapsed and metastatic Ewing sarcoma will succumb to their disease. The persistent failure to improve overall survival for this subset of patients highlights the urgent need for rapid translation of novel therapeutic strategies. As Ewing sarcoma is associated with a paucity of mutations in readily targetable signal transduction pathways, targeting the key genetic aberration and master regulator of Ewing sarcoma, the EWS/ETS fusion, remains an important goal.
      PubDate: 2016-08-25T14:26:18Z
      DOI: 10.12688/f1000research.8631.1
      Issue No: Vol. 5 (2016)
  • A real-world intention-to-treat analysis of a decade’s experience of
           treatment of hepatitis C with interferon-based therapies [version 1;
           referees: 2 approved]

    • Authors: Nowlan Selvapatt, Ashley Brown
      Abstract: Objectives: To assess the uptake of pegylated interferon (PegIFN) plus ribavirin (RBV)-based regimens in patients with hepatitis C virus (HCV) in a large, single-centre, real-world setting over 10 years. Methods: This was a single centre, retrospective analysis of data from patients who attended their first appointment for treatment of HCV genotype 1–3 between 2003 and 2013. Patients were stratified by HCV genotype. The total number of patients who attended their first appointment, incidence of patients who did not proceed to treatment and associated reasons, and incidence of patients treated were analysed. Sustained virological response (SVR) rates were also reported for all patient populations. Results: Overall, 1,132 patients attended their first appointment; 47.8% were included in the genotype 1 group (genotype 1a: 22.2%, genotype 1b: 13.3%, genotype 1 other: 12.3%), 7.7% in the genotype 2 group and 44.5% in the genotype 3 group. A greater proportion of patients received treatment versus those who did not receive treatment (84.4% vs 15.6%, respectively). Reasons for declining treatment included: patient declined treatment with PegIFN plus RBV: 35.0%, medical contraindications: 20.3% and mental health-related contraindications: 13.6%. An SVR was achieved in 52.6% of patients who attended their first appointment and 62.3% of patients who received treatment. Conclusions: Approximately half of the patients included in this study achieved an SVR. A noteworthy proportion of patients did not receive treatment due to a reluctance to receive PegIFN plus RBV or contraindications to therapy. Results suggest an ongoing need for improvement in the treatment uptake and overall outcomes – particularly for genotype 2 and 3 patients for whom availability of interferon-free regimens is limited. The introduction of more tolerable direct-acting antiviral regimes may help overcome barriers to uptake demonstrated within this cohort.
      PubDate: 2016-08-24T12:51:04Z
      DOI: 10.12688/f1000research.9114.1
      Issue No: Vol. 5 (2016)
  • Collecting clinical data in primary ciliary dyskinesia- challenges and
           opportunities [version 1; referees: 2 approved]

    • Authors: Israel Amirav, Mary Roduta Roberts, Huda Mussaffi, Avigdor Mandelberg, Yehudah Roth, Revital Abitbul, Anthony Luder, Hannah Blau, Soliman Alkrinawi, Micha Aviram, Marta Ben-Ami, Moshe Rotschild, Lea Bentur, David Shoseyov, Malena Cohen-Cymberknoh, Eitan Kerem, Avraham Avital, Chaim Springer, Avigdor Hevroni, Husein Dabbah, Arnon Elizur, Elie Picard, Shmuel Goldberg, Joseph Rivlin, Galit Livnat, Moran Lavie, Nael Alias, Ruth Soferman, Heike Olbrich, Johanna Raidt, Julia Wallmeier, Claudius Werner, Niki T. Loges, Heymut Omran
      Abstract: Rationale: Primary ciliary dyskinesia (PCD) is under diagnosed and underestimated. Most clinical research has used some form of questionnaires to capture data but none has been critically evaluated particularly with respect to its end-user feasibility and utility. Objective: To critically appraise a clinical data collection questionnaire for PCD used in a large national PCD consortium in order to apply conclusions in future PCD research. Methods: We describe the development, validation and revision process of a clinical questionnaire for PCD and its evaluation during a national clinical PCD study with respect to data collection and analysis, initial completion rates and user feedback. Results: 14 centers participating in the consortium successfully completed the revised version of the questionnaire for 173 patients with various completion rates for various items. While content and internal consistency analysis demonstrated validity, there were methodological deficiencies impacting completion rates and end-user utility. These deficiencies were addressed resulting in a more valid questionnaire. Conclusions: Our experience may be useful for future clinical research in PCD. Based on the feedback collected on the questionnaire through analysis of completion rates, judgmental analysis of the content, and feedback from experts and end users, we suggest a practicable framework for development of similar tools for various future PCD research.
      PubDate: 2016-08-18T10:08:32Z
      DOI: 10.12688/f1000research.9323.1
      Issue No: Vol. 5 (2016)
  • Using diverse U.S. beef cattle genomes to identify missense mutations in
           EPAS1, a gene associated with high-altitude pulmonary hypertension
           [version 1; referees: 2 approved]

    • Authors: Michael P. Heaton, Timothy P.L. Smith, Jacky K. Carnahan, Veronica Basnayake, Jiansheng Qiu, Barry Simpson, Theodore S. Kalbfleisch
      Abstract: The availability of whole genome sequence (WGS) data has made it possible to discover protein variants in silico. However, existing bovine WGS databases do not show data in a form conducive to protein variant analysis, and tend to under represent the breadth of genetic diversity in U.S. beef cattle. Thus, our first aim was to use 96 beef sires, sharing minimal pedigree relationships, to create a searchable and publicly viewable set of mapped genomes relevant for 19 popular breeds of U.S. cattle. Our second aim was to identify protein variants encoded by the bovine endothelial PAS domain-containing protein 1 gene (EPAS1), a gene associated with high-altitude pulmonary hypertension in Angus cattle. The identity and quality of genomic sequences were verified by comparing WGS genotypes to those derived from other methods. The average read depth, genotype scoring rate, and genotype accuracy exceeded 14, 99%, and 99%, respectively. The 96 genomes were used to discover four amino acid variants encoded by EPAS1 (E270Q, P362L, A671G, and L701F) and confirm two variants previously associated with disease (A606T and G610S). The six EPAS1 missense mutations were verified with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assays, and their frequencies were estimated in a separate collection of 1154 U.S. cattle representing 46 breeds. A rooted phylogenetic tree of eight polypeptide sequences provided a framework for evaluating the likely order of mutations and potential impact of EPAS1 alleles on the adaptive response to chronic hypoxia in U.S. cattle. This public, whole genome resource facilitates in silico identification of protein variants in diverse types of U.S. beef cattle, and provides a means of translating WGS data into a practical biological and evolutionary context for generating and testing hypotheses.
      PubDate: 2016-08-16T13:48:42Z
      DOI: 10.12688/f1000research.9254.1
      Issue No: Vol. 5 (2016)
  • Top 10 metrics for life science software good practices [version 1;
           referees: 2 approved]

    • Abstract: Metrics for assessing adoption of good development practices are a useful way to ensure that software is sustainable, reusable and functional. Sustainability means that the software used today will be available - and continue to be improved and supported - in the future. We report here an initial set of metrics that measure good practices in software development. This initiative differs from previously developed efforts in being a community-driven grassroots approach where experts from different organisations propose good software practices that have reasonable potential to be adopted by the communities they represent. We not only focus our efforts on understanding and prioritising good practices, we assess their feasibility for implementation and publish them here.
      PubDate: 2016-08-16T09:46:44Z
      DOI: 10.12688/f1000research.9206.1
      Issue No: Vol. 5 (2016)
  • Protein domain architectures provide a fast, efficient and scalable
           alternative to sequence-based methods for comparative functional genomics
           [version 1; referees: 1 approved, 2 approved with reservations]

    • Authors: Jasper J. Koehorst, Edoardo Saccenti, Peter J. Schaap, Vitor A. P. Martins dos Santos, Maria Suarez-Diez
      Abstract: A functional comparative genome analysis is essential to understand the mechanisms underlying bacterial evolution and adaptation. Detection of functional orthologs using standard global sequence similarity methods faces several problems; the need for defining arbitrary acceptance thresholds for similarity and alignment length, lateral gene acquisition and the high computational cost for finding bi-directional best matches at a large scale. We investigated the use of protein domain architectures for large scale functional comparative analysis as an alternative method. The performance of both approaches was assessed through functional comparison of 446 bacterial genomes sampled at different taxonomic levels. We show that protein domain architectures provide a fast and efficient alternative to methods based on sequence similarity to identify groups of functionally equivalent proteins within and across taxonomic bounderies. As the computational cost scales linearly, and not quadratically with the number of genomes, it is suitable for large scale comparative analysis. Running both methods in parallel pinpoints potential functional adaptations that may add to bacterial fitness.
      PubDate: 2016-08-15T10:12:31Z
      DOI: 10.12688/f1000research.9416.1
      Issue No: Vol. 5 (2016)
  • Rapid and high throughput molecular identification of diverse mosquito
           species by high resolution melting analysis [version 1; referees: 2

    • Authors: Yvonne Ukamaka Ajamma, Enock Mararo, David Omondi, Thomas Onchuru, Anne W. T. Muigai, Daniel Masiga, Jandouwe Villinger
      Abstract: Mosquitoes are a diverse group of invertebrates, with members that are among the most important vectors of diseases. The correct identification of mosquitoes is paramount to the control of the diseases that they transmit. However, morphological techniques depend on the quality of the specimen and often unavailable taxonomic expertise, which may still not be able to distinguish mosquitoes among species complexes (sibling and cryptic species). High resolution melting (HRM) analyses, a closed-tube, post-polymerase chain reaction (PCR) method used to identify variations in nucleic acid sequences, has been used to differentiate species within the Anopheles gambiae and Culex pipiens complexes. We validated the use of PCR-HRM analyses to differentiate species within Anopheles and within each of six genera of culicine mosquitoes, comparing primers targeting cytochrome b (cyt b), NADH dehydrogenase subunit 1 (ND1), intergenic spacer region (IGS) and cytochrome c oxidase subunit 1 (COI) gene regions. HRM analyses of amplicons from all the six primer pairs successfully differentiated two or more mosquito species within one or more genera (Aedes (Ae. vittatus from Ae. metallicus), Culex (Cx. tenagius from Cx. antennatus, Cx. neavei from Cx. duttoni, cryptic Cx. pipiens species), Anopheles (An. gambiae s.s. from An. arabiensis) and Mansonia (Ma. africana from Ma. uniformis)) based on their HRM profiles. However, PCR-HRM could not distinguish between species within Aedeomyia (Ad. africana and Ad. furfurea), Mimomyia (Mi. hispida and Mi. splendens) and Coquillettidia (Cq. aurites, Cq. chrysosoma, Cq. fuscopennata, Cq. metallica, Cq. microannulatus, Cq. pseudoconopas and Cq. versicolor) genera using any of the primers. The IGS and COI barcode region primers gave the best and most definitive separation of mosquito species among anopheline and culicine mosquito genera, respectively, while the other markers may serve to confirm identifications of closely related sub-species. This approach can be employed for rapid identification of mosquitoes.
      PubDate: 2016-08-11T10:10:08Z
      DOI: 10.12688/f1000research.9224.1
      Issue No: Vol. 5 (2016)
  • Unit testing, model validation, and biological simulation [version 1;
           referees: 2 approved, 1 approved with reservations]

    • Authors: Gopal P. Sarma, Travis W. Jacobs, Mark D. Watts, S. Vahid Ghayoomie, Stephen D. Larson, Richard C. Gerkin
      Abstract: The growth of the software industry has gone hand in hand with the development of tools and cultural practices for ensuring the reliability of complex pieces of software. These tools and practices are now acknowledged to be essential to the management of modern software. As computational models and methods have become increasingly common in the biological sciences, it is important to examine how these practices can accelerate biological software development and improve research quality. In this article, we give a focused case study of our experience with the practices of unit testing and test-driven development in OpenWorm, an open-science project aimed at modeling Caenorhabditis elegans. We identify and discuss the challenges of incorporating test-driven development into a heterogeneous, data-driven project, as well as the role of model validation tests, a category of tests unique to software which expresses scientific models.
      PubDate: 2016-08-10T14:02:52Z
      DOI: 10.12688/f1000research.9315.1
      Issue No: Vol. 5 (2016)
  • Case Report: Frontalis sign for early bedside consideration of impending
           uncal herniation [version 2; referees: 2 approved]

    • Authors: Sunil Munakomi, Bijoy Mohan Kumar
      Abstract: It is prudent to have early diagnosis and timely management of uncal herniation for better management of neurosurgical patients. There are several clinical and radiological armamentariums that aid in early recognition of the condition. Through this case report, we try to highlight a simple bedside clinical sign that can be a valuable adjunct in early recognition of the impending uncal herniation especially in scenarios wherein it is difficult to assess the pupillary size and reactivity correctly. The improvement in the sign also confirms the resolution of the mass effect in the postoperative period. This is especially helpful for doctors working in the periphery or in resource restrained areas, for a timely referral of the patient to tertiary centre.
      PubDate: 2016-08-04T10:59:14Z
      DOI: 10.12688/f1000research.7871.2
      Issue No: Vol. 5 (2016)
  • Navigating the Zika panic [version 1; referees: 2 approved]

    • Authors: Nathan D. Grubaugh, Kristian G. Andersen
      Abstract: The epidemics of Ebola virus in West Africa and Zika virus in America highlight how viruses can explosively emerge into new territories. These epidemics also exposed how unprepared we are to handle infectious disease emergencies. This is also true when we consider hypothesized new clinical features of infection, such as the associations between Zika virus infection and severe neurological disease, including microcephaly and Guillain-Barré syndrome. On the surface, these pathologies appear to be new features of Zika virus infection, however, causal relationships have not yet been established. Decades of limited Zika virus research are making us scramble to determine the true drivers behind the epidemic, often at the expense of over-speculation without credible evidence. Here we review the literature and find no conclusive evidence at this time for significant biological differences between the American Zika virus strains and those circulating elsewhere. Rather, the epidemic scale in the Americas may be facilitated by an abnormally warm climate, dense human and mosquito populations, and previous exposure to other viruses. Severe disease associated with Zika virus may therefore not be a new trait for the virus, rather it may have been overlooked due to previously small outbreaks. Much of the recent panic regarding Zika virus has been about the Olympics in Brazil. We do not find any substantial evidence that the Olympics will result in a significant number of new Zika virus infections (~10 predicted) or that the Olympics will promote further epidemic spread over what is already expected. The Zika virus epidemic in the Americas is a serious situation and decisions based on solid scientific evidence - not hyped media speculations - are required for effective outbreak response.
      PubDate: 2016-08-04T09:54:54Z
      DOI: 10.12688/f1000research.9370.1
      Issue No: Vol. 5 (2016)
  • The frequency distribution of vitamin D Receptor fok I gene polymorphism
           among Ugandan pulmonary TB patients [version 1; referees: 1 approved, 2
           approved with reservations]

    • Authors: Ester L. Acen, William Worodria, Peter Mulamba, Andrew Kambugu, Joseph Erume
      Abstract: Background: Mycobacterium tuberculosis (TB) is still a major problem globally and especially in Africa. Vitamin D deficiency has been linked to TB in the past and studies have found vitamin D deficiency to be common among Ugandan TB patients. The functional activity of vitamin D is dependent on the genotype of the vitamin D receptor (VDR) polymorphic genes. Recent findings have indicated that VDR polymorphisms may cause increased resistance or susceptibility to TB. The vitamin D ligand and its receptor play a pivotal role in innate immunity by eliciting antimicrobial activity, which is important in prevention of TB. The fok I vitamin D receptor gene has extensively been examined in TB patients but findings so far have been inconclusive. Objectives: This study sought to investigate the frequency distribution of the VDR fok I gene polymorphisms in pulmonary TB patients and controls. Methods: A pilot case control study of 41 newly diagnosed TB patients and 41 healthy workers was set up. Vitamin D receptor fok I gene was genotyped. Results: The frequency distribution of fok I genotype in Ugandan TB patients was 87.8% homozygous-dominant (FF), 7.3% (Ff) heterozygous and 4.8% (ff) homozygous recessive. For normal healthy subjects the frequencies were (FF) 92.6%, (Ff) 2.4% and (ff) 4.8%. No significant difference was observed in the FF and ff genotypes among TB patients and controls. The Ff heterozygous genotype distribution appeared more in TB patients than in controls. A significant difference was observed in the fok I genotype among gender p value 0.02. No significant difference was observed in ethnicity, p value 0.30. Conclusions: The heterozygous Ff fok I genotype may be associated with TB in the Ugandan population.
      PubDate: 2016-07-29T15:25:05Z
      DOI: 10.12688/f1000research.9109.1
      Issue No: Vol. 5 (2016)
  • Automated quality control for genome wide association studies [version 1;
           referees: 1 approved, 2 approved with reservations]

    • Authors: Sally R. Ellingson, David W. Fardo
      Abstract: This paper provides details on the necessary steps to assess and control data in genome wide association studies (GWAS) using genotype information on a large number of genetic markers for large number of individuals. Due to varied study designs and genotyping platforms between multiple sites/projects as well as potential genotyping errors, it is important to ensure high quality data. Scripts and directions are provided to facilitate others in this process.
      PubDate: 2016-07-29T14:13:04Z
      DOI: 10.12688/f1000research.9271.1
      Issue No: Vol. 5 (2016)
  • ddpcr: an R package and web application for analysis of droplet digital
           PCR data [version 1; referees: 2 approved]

    • Authors: Dean Attali, Roza Bidshahri, Charles Haynes, Jennifer Bryan
      Abstract: Droplet digital polymerase chain reaction (ddPCR) is a novel platform for exact quantification of DNA which holds great promise in clinical diagnostics. It is increasingly popular due to its digital nature, which provides more accurate quantification and higher sensitivity than traditional real-time PCR. However, clinical adoption has been slowed in part by the lack of software tools available for analyzing ddPCR data. Here, we present ddpcr – a new R package for ddPCR visualization and analysis. In addition, ddpcr includes a web application (powered by the Shiny R package) that allows users to analyze ddPCR data using an interactive graphical interface.
      PubDate: 2016-06-17T15:35:03Z
      DOI: 10.12688/f1000research.9022.1
      Issue No: Vol. 5 (2016)
  • Assessing change in patient-reported quality of life after elective
           surgery: protocol for an observational comparison study [version 1;
           referees: 2 approved]

    • Authors: Vanessa L. Kronzer, Michelle R. Jerry, Michael S. Avidan
      Abstract: Despite their widespread use, the two main methods of assessing quality of life after surgery have never been directly compared. To support patient decision-making and study design, we aim to compare these two methods. The first of these methods is to assess quality of life before surgery and again after surgery using the same validated scale. The second is simply to ask patients whether or not they think their post-operative quality of life is better, worse, or the same. Our primary objective is to assess agreement between the two measures. Secondary objectives are to calculate the minimum clinically important difference (MCID) and to describe the variation across surgical specialties. To accomplish these aims, we will administer surveys to patients undergoing elective surgery, both before surgery and again 30 days after surgery. This protocol follows detailed guidelines for observational study protocols.
      PubDate: 2016-05-24T10:16:54Z
      DOI: 10.12688/f1000research.8758.1
      Issue No: Vol. 5 (2016)
  • IncucyteDRC: An R package for the dose response analysis of live cell
           imaging data [version 1; referees: 2 approved]

    • Authors: Philip J. Chapman, Dominic I. James, Amanda J. Watson, Gemma V. Hopkins, Ian D. Waddell, Donald J. Ogilvie
      Abstract: We present IncucyteDRC, an R package for the analysis of data from live cell imaging cell proliferation experiments carried out on the Essen Biosciences IncuCyte ZOOM instrument. The package provides a simple workflow for summarising data into a form that can be used to calculate dose response curves and EC50 values for small molecule inhibitors. Data from different cell lines, or cell lines grown under different conditions, can be normalised as to their doubling time. A simple graphical web interface, implemented using shiny, is provided for the benefit of non-R users. The software is potentially useful to any research group studying the impact of small molecule inhibitors on cell proliferation using the IncuCyte ZOOM.
      PubDate: 2016-05-23T13:59:01Z
      DOI: 10.12688/f1000research.8694.1
      Issue No: Vol. 5 (2016)
  • pyGeno: A Python package for precision medicine and proteogenomics
           [version 2; referees: 1 approved, 2 approved with reservations]

    • Abstract: pyGeno is a Python package mainly intended for precision medicine applications that revolve around genomics and proteomics. It integrates reference sequences and annotations from Ensembl, genomic polymorphisms from the dbSNP database and data from next-gen sequencing into an easy to use, memory-efficient and fast framework, therefore allowing the user to easily explore subject-specific genomes and proteomes. Compared to a standalone program, pyGeno gives the user access to the complete expressivity of Python, a general programming language. Its range of application therefore encompasses both short scripts and large scale genome-wide studies.
      PubDate: 2016-05-10T13:20:32Z
      DOI: 10.12688/f1000research.8251.2
      Issue No: Vol. 5 (2016)
  • Case Report: A giant but silent adrenal pheochromocytoma – a rare entity
           [version 1; referees: 2 approved]

    • Authors: Sunil Munakomi, Saroj Rajbanshi, Prof Shailesh Adhikary
      Abstract: Herein we report a rare entity of a giant adrenal pheochromocytoma in a fifty-year-old male presenting with a vague abdominal pain. A computerised tomogram of the abdomen revealed a well-defined  left supraadrenal giant lesion with no evidence of invasion to surrounding structures.The patient underwent surgical excision without any untoward postoperative events. Histopathological study revealed a benign pheochromocytoma. This report highlights the importance of acknowledging the fact that sometimes a giant adrenal pheochromocytoma can present with paucity of clinical  signs and symptoms.Thorough investigations and a multidisciplinary team approach may lead  to a better outcome in these patients.
      PubDate: 2016-03-07T11:06:18Z
      DOI: 10.12688/f1000research.8168.1
      Issue No: Vol. 5 (2016)
  • EvolQG - An R package for evolutionary quantitative genetics [version 2;
           referees: 1 approved, 2 approved with reservations]

    • Authors: Diogo Melo, Guilherme Garcia, Alex Hubbe, Ana Paula Assis, Gabriel Marroig
      Abstract: We present an open source package for performing evolutionary quantitative genetics analyses in the R environment for statistical computing. Evolutionary theory shows that evolution depends critically on the available variation in a given population. When dealing with many quantitative traits this variation is expressed in the form of a covariance matrix, particularly the additive genetic covariance matrix or sometimes the phenotypic matrix, when the genetic matrix is unavailable and there is evidence the phenotypic matrix is sufficiently similar to the genetic matrix. Given this mathematical representation of available variation, the EvolQG package provides functions for calculation of relevant evolutionary statistics; estimation of sampling error; corrections for this error; matrix comparison via correlations, distances and matrix decomposition; analysis of modularity patterns; and functions for testing evolutionary hypotheses on taxa diversification.
      PubDate: 2016-06-27T10:53:51Z
      DOI: 10.12688/f1000research.7082.2
      Issue No: Vol. 4 (2016)
  • The developmental transcriptome of contrasting Arctic charr (Salvelinus
           alpinus) morphs [version 2; referees: 1 approved, 2 approved with

    • Authors: Johannes Gudbrandsson, Ehsan P. Ahi, Sigridur R. Franzdottir, Kalina H. Kapralova, Bjarni K. Kristjansson, S. Sophie Steinhaeuser, Valerie H. Maier, Isak M. Johannesson, Sigurdur S. Snorrason, Zophonias O. Jonsson, Arnar Palsson
      Abstract: Species and populations with parallel evolution of specific traits can help illuminate how predictable adaptations and divergence are at the molecular and developmental level. Following the last glacial period, dwarfism and specialized bottom feeding morphology evolved rapidly in several landlocked Arctic charr Salvelinus alpinus populations in Iceland.   To study the genetic divergence between small benthic morphs and limnetic morphs, we conducted RNA-sequencing charr embryos at four stages in early development. We studied two stocks with contrasting morphologies: the small benthic (SB) charr from Lake Thingvallavatn and Holar aquaculture (AC) charr. The data reveal significant differences in expression of several biological pathways during charr development. There was also an expression difference between SB- and AC-charr in genes involved in energy metabolism and blood coagulation genes. We confirmed differing expression of five genes in whole embryos with qPCR, including lysozyme and natterin-like which was previously identified as a fish-toxin of a lectin family that may be a putative immunopeptide. We also verified differential expression of 7 genes in the developing head that associated consistently with benthic v.s.limnetic morphology (studied in 4 morphs). Comparison of single nucleotide polymorphism (SNP) frequencies reveals extensive genetic differentiation between the SB and AC-charr (~1300 with more than 50% frequency difference). Curiously, three derived alleles in the otherwise conserved 12s and 16s mitochondrial ribosomal RNA genes are found in benthic charr. The data implicate multiple genes and molecular pathways in divergence of small benthic charr and/or the response of aquaculture charr to domestication. Functional, genetic and population genetic studies on more freshwater and anadromous populations are needed to confirm the specific loci and mutations relating to specific ecological traits in Arctic charr.
      PubDate: 2016-04-25T13:25:46Z
      DOI: 10.12688/f1000research.6402.2
      Issue No: Vol. 4 (2016)
  • Shark fisheries in the Southeast Pacific: A 61-year analysis from Peru
           [version 2; referees: 1 approved, 2 approved with reservations]

    • Authors: Adriana Gonzalez-Pestana, Carlos Kouri J., Ximena Velez-Zuazo
      Abstract: Peruvian waters exhibit high conservation value for sharks. This contrasts with a lag in initiatives for their management and a lack of studies about their biology, ecology and fishery. We investigated the dynamics of Peruvian shark fishery and its legal framework identifying information gaps for recommending actions to improve management. Further, we investigated the importance of the Peruvian shark fishery from a regional perspective. From 1950 to 2010, 372,015 tons of sharks were landed in Peru. From 1950 to 1969, we detected a significant increase in landings; but from 2000 to 2011 there was a significant decrease in landings, estimated at 3.5% per year. Six species represented 94% of landings: blue shark (Prionace glauca), shortfin mako (Isurus oxyrinchus), smooth hammerhead (Sphyrna zygaena), common thresher (Alopias vulpinus), smooth-hound (Mustelus whitneyi) and angel shark (Squatina californica). Of these, the angel shark exhibits a strong and significant decrease in landings: 18.9% per year from 2000 to 2010. Peru reports the highest accumulated historical landings in the Pacific Ocean; but its contribution to annual landings has decreased since 1968. Still, Peru is among the top 12 countries exporting shark fins to the Hong Kong market. Although the government collects total weight by species, the number of specimens landed as well as population parameters (e.g. sex, size and weight) are not reported. Further, for some genera, species-level identification is deficient and so overestimates the biomass landed by species and underestimates the species diversity. Recently, regional efforts to regulate shark fishery have been implemented to support the conservation of sharks but in Peru work remains to be done.
      PubDate: 2016-04-12T10:03:11Z
      DOI: 10.12688/f1000research.4412.2
      Issue No: Vol. 3 (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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