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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]
  • Mitochondrial apoptosis and BH3 mimetics [version 1; referees: 3 approved]

    • Authors: Haiming Dai, X. Wei Meng, Scott H. Kaufmann
      Abstract: The BCL2-selective BH3 mimetic venetoclax was recently approved for the treatment of relapsed, chromosome 17p-deleted chronic lymphocytic leukemia (CLL) and is undergoing extensive testing, alone and in combination, in lymphomas, acute leukemias, and solid tumors. Here we summarize recent advances in understanding of the biology of BCL2 family members that shed light on the action of BH3 mimetics, review preclinical and clinical studies leading to the regulatory approval of venetoclax, and discuss future investigation of this new class of antineoplastic agent.
      PubDate: 2016-12-01T10:12:50Z
      DOI: 10.12688/f1000research.9629.1
      Issue No: Vol. 5 (2016)
  • Hyphal ontogeny in Neurospora crassa: a model organism for all seasons
           [version 1; referees: 3 approved]

    • Authors: Meritxell Riquelme, Leonora Martínez-Núñez
      Abstract: Filamentous fungi have proven to be a better-suited model system than unicellular yeasts in analyses of cellular processes such as polarized growth, exocytosis, endocytosis, and cytoskeleton-based organelle traffic. For example, the filamentous fungus Neurospora crassa develops a variety of cellular forms. Studying the molecular basis of these forms has led to a better, yet incipient, understanding of polarized growth. Polarity factors as well as Rho GTPases, septins, and a localized delivery of vesicles are the central elements described so far that participate in the shift from isotropic to polarized growth. The growth of the cell wall by apical biosynthesis and remodeling of polysaccharide components is a key process in hyphal morphogenesis. The coordinated action of motor proteins and Rab GTPases mediates the vesicular journey along the hyphae toward the apex, where the exocyst mediates vesicle fusion with the plasma membrane. Cytoplasmic microtubules and actin microfilaments serve as tracks for the transport of vesicular carriers as well as organelles in the tubular cell, contributing to polarization. In addition to exocytosis, endocytosis is required to set and maintain the apical polarity of the cell. Here, we summarize some of the most recent breakthroughs in hyphal morphogenesis and apical growth in N. crassa and the emerging questions that we believe should be addressed.
      PubDate: 2016-11-30T15:39:39Z
      DOI: 10.12688/f1000research.9679.1
      Issue No: Vol. 5 (2016)
  • Genetic factors influencing risk to orofacial clefts: today’s challenges
           and tomorrow’s opportunities [version 1; referees: 2 approved]

    • Authors: Terri H. Beaty, Mary L. Marazita, Elizabeth J. Leslie
      Abstract: Orofacial clefts include cleft lip (CL), cleft palate (CP), and cleft lip and palate (CLP), which combined represent the largest group of craniofacial malformations in humans with an overall prevalence of one per 1,000 live births. Each of these birth defects shows strong familial aggregation, suggesting a major genetic component to their etiology. Genetic studies of orofacial clefts extend back centuries, but it has proven difficult to define any single etiologic mechanism because many genes appear to influence risk. Both linkage and association studies have identified several genes influencing risk, but these differ across families and across populations. Genome-wide association studies have identified almost two dozen different genes achieving genome-wide significance, and there are broad classes of ‘causal genes’ for orofacial clefts: a few genes strongly associated with risk and possibly directly responsible for Mendelian syndromes which include orofacial clefts as a key phenotypic feature of the syndrome, and multiple genes with modest individual effects on risk but capable of disrupting normal craniofacial development under the right circumstances (which may include exposure to environmental risk factors). Genomic sequencing studies are now underway which will no doubt reveal additional genes/regions where variants (sequence and structural) can play a role in controlling risk to orofacial clefts. The real challenge to medicine and public health is twofold: to identify specific genes and other etiologic factors in families with affected members and then to devise effective interventions for these different biological mechanisms controlling risk to complex and heterogeneous birth defects such as orofacial clefts.
      PubDate: 2016-11-30T15:26:28Z
      DOI: 10.12688/f1000research.9503.1
      Issue No: Vol. 5 (2016)
  • Understanding nontuberculous mycobacterial lung disease: it’s been a
           long time coming [version 1; referees: 4 approved]

    • Authors: David E. Griffith, Timothy R. Aksamit
      Abstract: With a surprising predictability, most studies and reviews addressing therapy for nontuberculous mycobacterial (NTM) lung disease either start or end by mentioning the paucity of data from randomized and controlled trials. That is a legitimate criticism for NTM lung disease therapy, but it also somehow seems to influence attitudes toward all aspects of NTM investigation. Certainly the study of NTM diseases in general and NTM lung disease in particular is a recent development. Previously, NTM were viewed as minor, if inconvenient, pathogens similar to Mycobacterium tuberculosis. However, over the last three decades, NTM have emerged as increasingly important pathogens that are clearly different compared with tuberculosis. Although there has been frustratingly slow progress in the treatment of NTM diseases, in contrast there has unquestionably been impressive progress in almost every other realm of investigation into NTM disease. Our understanding of NTM lung disease a) pathophysiology, including mechanisms of organism acquisition, b) epidemiology, including estimates of disease prevalence, c) mycobacteriology, including application of molecular laboratory techniques and matrix-assisted laser desorption ionization–time of flight (MALDI–TOF) mass spectrometry, and d) even treatment strategies, including the recognition of innate drug resistance mechanisms, has immeasurably and permanently changed and advanced the landscape for NTM lung disease. It is no longer necessary to apologize for the state of NTM lung disease knowledge and understanding, but rather it is time to recognize the great distance we have travelled over the last 30 years.
      PubDate: 2016-11-30T12:21:49Z
      DOI: 10.12688/f1000research.9272.1
      Issue No: Vol. 5 (2016)
  • Biting the hand that feeds: current opinion on the interpersonal causes,
           correlates, and consequences of borderline personality disorder [version
           1; referees: 2 approved]

    • Authors: Sheila E. Crowell
      Abstract: Borderline personality disorder (BPD) is a complex psychiatric diagnosis characterized by dysregulated behaviors, emotions, cognitions, and interpersonal relationships. In recent years, developmental psychopathologists have sought to identify early origins of BPD, with the ultimate goal of developing and providing effective preventative interventions for those at highest risk. In addition to heritable biological sensitivities, many scholars assert that environmental and interpersonal risk factors contribute to the emergence and maintenance of key borderline traits. Nonetheless, many BPD researchers examine only affected individuals, neglecting the family, peer, couple, and other dynamic contextual forces that impinge upon individual-level behavior. In the past decade, however, theoretical and empirical research has increasingly explored the interpersonal causes, correlates, and consequences of BPD. Such work has resulted in novel research and clinical theories intended to better understand and improve interpersonal dynamics among those with borderline traits. A major objective for the field is to better characterize how interpersonal dynamics affect (and are affected by) the behaviors, emotions, and thoughts of vulnerable individuals to either reduce or heighten risk for BPD.
      PubDate: 2016-11-30T11:47:49Z
      DOI: 10.12688/f1000research.9392.1
      Issue No: Vol. 5 (2016)
  • Recent advances in understanding Streptomyces [version 1; referees: 4

    • Authors: Keith F. Chater
      Abstract: About 2,500 papers dated 2014–2016 were recovered by searching the PubMed database for Streptomyces, which are the richest known source of antibiotics. This review integrates around 100 of these papers in sections dealing with evolution, ecology, pathogenicity, growth and development, stress responses and secondary metabolism, gene expression, and technical advances. Genomic approaches have greatly accelerated progress. For example, it has been definitively shown that interspecies recombination of conserved genes has occurred during evolution, in addition to exchanges of some of the tens of thousands of non-conserved accessory genes. The closeness of the association of Streptomyces with plants, fungi, and insects has become clear and is reflected in the importance of regulators of cellulose and chitin utilisation in overall Streptomyces biology. Interestingly, endogenous cellulose-like glycans are also proving important in hyphal growth and in the clumping that affects industrial fermentations. Nucleotide secondary messengers, including cyclic di-GMP, have been shown to provide key input into developmental processes such as germination and reproductive growth, while late morphological changes during sporulation involve control by phosphorylation. The discovery that nitric oxide is produced endogenously puts a new face on speculative models in which regulatory Wbl proteins (peculiar to actinobacteria) respond to nitric oxide produced in stressful physiological transitions. Some dramatic insights have come from a new model system for Streptomyces developmental biology, Streptomyces venezuelae, including molecular evidence of very close interplay in each of two pairs of regulatory proteins. An extra dimension has been added to the many complexities of the regulation of secondary metabolism by findings of regulatory crosstalk within and between pathways, and even between species, mediated by end products. Among many outcomes from the application of chromosome immunoprecipitation sequencing (ChIP-seq) analysis and other methods based on “next-generation sequencing” has been the finding that 21% of Streptomyces mRNA species lack leader sequences and conventional ribosome binding sites. Further technical advances now emerging should lead to continued acceleration of knowledge, and more effective exploitation, of these astonishing and critically important organisms.
      PubDate: 2016-11-30T11:22:37Z
      DOI: 10.12688/f1000research.9534.1
      Issue No: Vol. 5 (2016)
  • Design of chemical space networks incorporating compound distance
           relationships [version 2; referees: 2 approved]

    • Authors: Antonio de la Vega de León, Jürgen Bajorath
      Abstract: Networks, in which nodes represent compounds and edges pairwise similarity relationships, are used as coordinate-free representations of chemical space. So-called chemical space networks (CSNs) provide intuitive access to structural relationships within compound data sets and can be annotated with activity information. However, in such similarity-based networks, distances between compounds are typically determined for layout purposes and clarity and have no chemical meaning. By contrast, inter-compound distances as a measure of dissimilarity can be directly obtained from coordinate-based representations of chemical space. Herein, we introduce a CSN variant that incorporates compound distance relationships and thus further increases the information content of compound networks. The design was facilitated by adapting the Kamada-Kawai algorithm. Kamada-Kawai networks are the first CSNs that are based on numerical similarity measures, but do not depend on chosen similarity threshold values.
      PubDate: 2016-11-30T11:17:42Z
      DOI: 10.12688/f1000research.10021.2
      Issue No: Vol. 5 (2016)
  • Recent advances in the medical treatment of breast cancer [version 1;
           referees: 2 approved]

    • Authors: Daniel A. Vorobiof
      Abstract: Over the past few decades, the systemic therapy of breast cancer (early and advanced) has changed considerably. For the past 40–50 years, and since the discovery and further therapeutic use of tamoxifen, a selective estrogen receptor modulator, breast cancer treatment has become the model for the development and success of tailored medical treatment. Much still needs to be done in improving outcomes for all patients with breast cancer, and especially for those who have advanced breast cancer, a challenging area for medical oncologists. Ongoing international clinical trials are currently evaluating new therapeutic approaches and identifying specific biological subsets that could determine a patient’s ability to respond to particular chemotherapeutic drugs.
      PubDate: 2016-11-29T11:52:55Z
      DOI: 10.12688/f1000research.9619.1
      Issue No: Vol. 5 (2016)
  • Bacteriophage-based tools: recent advances and novel applications [version
           1; referees: 3 approved]

    • Authors: Lisa O'Sullivan, Colin Buttimer, Olivia McAuliffe, Declan Bolton, Aidan Coffey
      Abstract: Bacteriophages (phages) are viruses that infect bacterial hosts, and since their discovery over a century ago they have been primarily exploited to control bacterial populations and to serve as tools in molecular biology. In this commentary, we highlight recent diverse advances in the field of phage research, going beyond bacterial control using whole phage, to areas including biocontrol using phage-derived enzybiotics, diagnostics, drug discovery, novel drug delivery systems and bionanotechnology.
      PubDate: 2016-11-29T11:11:25Z
      DOI: 10.12688/f1000research.9705.1
      Issue No: Vol. 5 (2016)
  • The invariances of power law size distributions [version 3; referees: 2

    • Authors: Steven A. Frank
      Abstract: Size varies. Small things are typically more frequent than large things. The logarithm of frequency often declines linearly with the logarithm of size. That power law relation forms one of the common patterns of nature. Why does the complexity of nature reduce to such a simple pattern' Why do things as different as tree size and enzyme rate follow similarly simple patterns' Here I analyze such patterns by their invariant properties. For example, a common pattern should not change when adding a constant value to all observations. That shift is essentially the renumbering of the points on a ruler without changing the metric information provided by the ruler. A ruler is shift invariant only when its scale is properly calibrated to the pattern being measured. Stretch invariance corresponds to the conservation of the total amount of something, such as the total biomass and consequently the average size. Rotational invariance corresponds to pattern that does not depend on the order in which underlying processes occur, for example, a scale that additively combines the component processes leading to observed values. I use tree size as an example to illustrate how the key invariances shape pattern. A simple interpretation of common pattern follows. That simple interpretation connects the normal distribution to a wide variety of other common patterns through the transformations of scale set by the fundamental invariances.
      PubDate: 2016-11-28T11:58:05Z
      DOI: 10.12688/f1000research.9452.3
      Issue No: Vol. 5 (2016)
  • Plant adaptation to cold climates [version 1; referees: 2 approved]

    • Authors: Christian Körner
      Abstract: In this short review, I will first summarize criteria by which environments can be considered “cold”, with plant stature (size, height above ground) playing a central role for the climate actually experienced. Plants adapted to such environments have to cope with both extremes and with gradual influences of low temperature. The first requires freezing resistance, which is tightly coupled to developmental state (phenology) and prehistory (acclimation). Gradual low temperature constraints affect the growth process (meristems) long before they affect photosynthetic carbon gain. Hence, plants growing in cold climates are commonly not carbon limited.
      PubDate: 2016-11-25T16:39:47Z
      DOI: 10.12688/f1000research.9107.1
      Issue No: Vol. 5 (2016)
  • Advances in the management of osteosarcoma [version 1; referees: 2

    • Authors: Stefan S. Bielack, Stefanie Hecker-Nolting, Claudia Blattmann, Leo Kager
      Abstract: Osteosarcoma, a bone cancer most commonly seen in adolescents and young adults, is usually a high-grade malignancy characterized by a very high risk for the development of pulmonary metastases. High-grade osteosarcomas are usually treated by preoperative and postoperative chemotherapy and surgery, with a very limited number of active agents available. Rarer lower-grade variants such as parosteal and periosteal osteosarcoma or low-grade central osteosarcoma are treated by surgery only. Imaging to search for possible metastases focuses on the lung. Computed tomography is the most sensitive method but cannot reliably distinguish small metastases from benign lesions. Advances of local imaging and surgical reconstruction now allow the use of limb-salvage in an ever-increasing proportion of patients. While still troubled by complications, non-invasive endoprosthesis-lengthening mechanisms have led to an increased uptake of limb-salvage, even for young, skeletally immature patients. Radiotherapy is employed when osteosarcomas cannot be removed with clear margins, but very high doses are required, and both proton and carbon-ion radiotherapy are under investigation. Unfortunately, the past 30 years have witnessed few, if any, survival improvements. Novel agents have not led to universally accepted changes of treatment standards. In patients with operable high-grade osteosarcomas, the extent of histological response to preoperative chemotherapy is a significant predictive factor for both local and systemic control. Attempts to improve prognosis by adapting postoperative treatment to response, recently tested in a randomized, prospective setting by the European and American Osteosarcoma Study Group, have not been proven to be beneficial. Many agree that only increased knowledge about osteosarcoma biology will lead to novel, effective treatment approaches and will be able to move the field forward.
      PubDate: 2016-11-25T15:48:56Z
      DOI: 10.12688/f1000research.9465.1
      Issue No: Vol. 5 (2016)
  • Recent advances in understanding & managing male infertility [version
           1; referees: 5 approved]

    • Authors: Jared M. Bieniek, Kirk C. Lo
      Abstract: Male infertility remains a struggle to definitively diagnose and treat with many men labelled as “idiopathic infertility” and eventually requiring assisted reproductive techniques.  Along those lines, research groups are continuing to explore current social and environmental factors, including the obesity epidemic, and their effects on male fertility potential.  Novel biomarkers of natural fertility status and azoospermia etiology have additionally seen recent attention with ACRV1 and TEX101/ECM1 assays either currently or soon to be commercially available.  Despite these advancements, however, medical treatment options have seen little progress.  Though surgical therapies have similarly seen little transformation, groups are exploring the use of testicular sperm for couples with elevated sperm DNA fragmentation and either planned or previously failed IVF/ICSI.  Concerted collaborative efforts will be needed as we move forward to better understand the challenges men face when struggling to conceive.
      PubDate: 2016-11-24T10:40:14Z
      DOI: 10.12688/f1000research.9375.1
      Issue No: Vol. 5 (2016)
  • Recent advances in the management of pulmonary arterial hypertension
           [version 1; referees: 2 approved]

    • Authors: Halley Tsai, Yon K. Sung, Vinicio de Jesus Perez
      Abstract: Over the past 20 years, there has been an explosion in the development of therapeutics to treat pulmonary arterial hypertension (PAH), a rare but life-threatening disorder associated with progressive elevation of pulmonary pressures and severe right heart failure. Recently, the field has seen the introduction of riociguat, a soluble guanylate cyclase stimulator, a new endothelin receptor antagonist (macitentan), and oral prostanoids (treprostinil and selexipag). Besides new drugs, there have been significant advances in defining the role of upfront combination therapy in treatment-naïve patients as well as proposed methods to deliver systemic prostanoids by use of implantable pumps. In this review, we will touch upon the most important developments in PAH therapeutics over the last three years and how these have changed the guidelines for the treatment of PAH. These exciting developments herald a new era in the treatment of PAH which will be punctuated by the use of more clinically relevant endpoints in clinical research trials and a novel treatment paradigm that may involve upfront double- or triple-combination therapy. We anticipate that the future will make use of these strategies to test the efficacy of upcoming new drugs that aspire to reduce disease progression and improve survival in patients afflicted with this devastating disease.
      PubDate: 2016-11-24T10:36:08Z
      DOI: 10.12688/f1000research.9739.1
      Issue No: Vol. 5 (2016)
  • Recent advances in understanding neuropathic pain: glia, sex differences,
           and epigenetics [version 1; referees: 2 approved]

    • Authors: Halina Machelska, Melih Ö. Celik
      Abstract: Neuropathic pain results from diseases or trauma affecting the nervous system. This pain can be devastating and is poorly controlled. The pathophysiology is complex, and it is essential to understand the underlying mechanisms in order to identify the relevant targets for therapeutic intervention. In this article, we focus on the recent research investigating neuro-immune communication and epigenetic processes, which gain particular attention in the context of neuropathic pain. Specifically, we analyze the role of glial cells, including microglia, astrocytes, and oligodendrocytes, in the modulation of the central nervous system inflammation triggered by neuropathy. Considering epigenetics, we address DNA methylation, histone modifications, and the non-coding RNAs in the regulation of ion channels, G-protein-coupled receptors, and transmitters following neuronal damage. The goal was not only to highlight the emerging concepts but also to discuss controversies, methodological complications, and intriguing opinions.
      PubDate: 2016-11-22T15:32:22Z
      DOI: 10.12688/f1000research.9621.1
      Issue No: Vol. 5 (2016)
  • Disambiguate: An open-source application for disambiguating two species in
           next generation sequencing data from grafted samples [version 1; referees:
           2 approved]

    • Authors: Miika J. Ahdesmäki, Simon R. Gray, Justin H. Johnson, Zhongwu Lai
      Abstract: Grafting of cell lines and primary tumours is a crucial step in the drug development process between cell line studies and clinical trials. Disambiguate is a program for computationally separating the sequencing reads of two species derived from grafted samples. Disambiguate operates on alignments to the two species and separates the components at very high sensitivity and specificity as illustrated in artificially mixed human-mouse samples. This allows for maximum recovery of data from target tumours for more accurate variant calling and gene expression quantification. Given that no general use open source algorithm accessible to the bioinformatics community exists for the purposes of separating the two species data, the proposed Disambiguate tool presents a novel approach and improvement to performing sequence analysis of grafted samples. Both Python and C++ implementations are available and they are integrated into several open and closed source pipelines. Disambiguate is open source and is freely available at
      PubDate: 2016-11-22T11:51:10Z
      DOI: 10.12688/f1000research.10082.1
      Issue No: Vol. 5 (2016)
  • Recent advances in the management of migraine [version 1; referees: 3

    • Authors: Mark Obermann, Dagny Holle
      Abstract: Migraine remains one of the most disabling disorders worldwide. The high prevalence in the general population and the often-delicate treatment of patients account for that. Therapeutic management of migraine relies mainly on non-specific medical treatment and is affected by low patient adherence to the treatment regimens applied. The introduction of specific anti-migraine treatment occurred over 20 years ago when the first triptan was approved by regulatory authorities (sumatriptan, 28 December 1992). Triptan use is limited by side effects, time- and frequency-restricted application, and the risk of developing medication overuse headache. Within the past few years, new and promising drugs such as more specific 5-HT 1F receptor agonists (that is, lasmiditan) and monoclonal calcitonin gene-related peptide (CGRP) receptor antibodies entered advanced development phases while non-invasive neuromodulatory approaches were suggested to be potentially effective as non-pharmaceutical interventions for migraine.
      PubDate: 2016-11-21T16:46:44Z
      DOI: 10.12688/f1000research.9764.1
      Issue No: Vol. 5 (2016)
  • Anterior single odontoid screw placement for type II odontoid fractures:
           our modified surgical technique and initial results in a cohort study of
           15 patients [version 2; referees: 2 approved]

    • Authors: Sunil Munakomi, Karuna Tamrakar, Pramod Kumar Chaudhary, Binod Bhattarai
      Abstract: Objective: Anterior odontoid screw fixation for type II odontoid fracture is the ideal management option. However in the context of unavailability of an O-arm or neuro-navigation and poor images from the available C-arm may be an obstacle to ideal trajectory and placement of the odontoid screw. We herein detail  our surgical technique so as to ensure a correct trajectory and subsequent good fusion in Type II odontoid fractures. This may be advantageous  in clinical set ups lacking state of the art facilities.  Methods and Results: In this cohort study we included 15 consecutive patients who underwent anterior odontoid screw placement. We routinely dissect the longus colli to completely visualize the entire width of C3 body. We then perform a median C2-C3 disectomy followed by creating a gutter in the superior end of C3 body. We then guide the Kirchsner (K) wire purchasing adequate anterior cortex of C2. Rest of the procedure follows the similar steps as described for odontoid screw placement. We achieved 100% correct trajectory and screw placement in our study. There were no instances of screw break out, pull out or nonunion. There was one patient mortality following myocardial infarction in our study. Conclusion: Preoperative imaging details, proper patient positioning, meticulous dissection, thorough anatomical knowledge and few added surgical nuances are the cornerstones in ideal odontoid screw placement. This may be pivotal in managing  patients in developing nations having rudimentary neurosurgical set up.
      PubDate: 2016-11-21T16:30:35Z
      DOI: 10.12688/f1000research.9131.2
      Issue No: Vol. 5 (2016)
  • Monitoring the compliance of the academic enterprise with the Fair Labor
           Standards Act [version 1; referees: 2 approved, 1 approved with

    • Authors: Adriana Bankston, Gary S. McDowell
      Abstract: Background: On December 1 2016, the Fair Labor Standards Act (FLSA) will be updated by the U.S. Department of Labor. The key changes are an increase in the salary threshold for exemption from overtime for working more than 40 hours per week, and indexing the salary level so that it is updated automatically every 3 years. This update is predicted to have a profound effect on the academic enterprise as a large proportion of the postdoctoral researcher population is currently paid at a salary below the new threshold for exemption. Here we review the key changes to the FLSA, how they came about, and how the postdoctoral population is affected by the ruling. Methods: We describe recent data collection efforts (checking university websites and contacting HR departments) to uncover what institutions in the 2014 NSF Survey of Graduate Students and Postdoctorates in Science and Engineering are doing to comply with the FLSA ruling for postdocs. Results: Our data show that 41% of the estimated postdoctoral workforce in STEM and 57% of institutions checked have not decided or have no public decision yet available one month prior to implementation, and only 35.5% of institutions are planning to raise salaries to the new minimum. Conclusions: Our data show the uncertainty of postdoc salaries in the U.S. one month prior to implementation of the FLSA ruling. This implementation also gives rise to various issues that have arisen in an already strained research enterprise, including short-, medium- and long-term effects on academe.
      PubDate: 2016-11-17T16:54:04Z
      DOI: 10.12688/f1000research.10086.1
      Issue No: Vol. 5 (2016)
  • Making sense of the cause of Crohn’s – a new look at an old disease
           [version 2; referees: 2 approved]

    • Authors: Anthony W. Segal
      Abstract: The cause of Crohn’s disease (CD) has posed a conundrum for at least a century. A large body of work coupled with recent technological advances in genome research have at last started to provide some of the answers. Initially this review seeks to explain and to differentiate between bowel inflammation in the primary immunodeficiencies that generally lead to very early onset diffuse bowel inflammation in humans and in animal models, and the real syndrome of CD. In the latter, a trigger, almost certainly enteric infection by one of a multitude of organisms, allows the faeces access to the tissues, at which stage the response of individuals predisposed to CD is abnormal. Direct investigation of patients’ inflammatory response together with genome-wide association studies (GWAS) and DNA sequencing indicate that in CD the failure of acute inflammation and the clearance of bacteria from the tissues, and from within cells, is defective. The retained faecal products result in the characteristic chronic granulomatous inflammation and adaptive immune response. In this review I will examine the contemporary evidence that has led to this understanding, and look for explanations for the recent dramatic increase in the incidence of this disease.
      PubDate: 2016-11-16T15:48:59Z
      DOI: 10.12688/f1000research.9699.2
      Issue No: Vol. 5 (2016)
  • Two-step feature selection for predicting survival time of patients with
           metastatic castrate resistant prostate cancer [version 1; referees: 2

    • Authors: Motoki Shiga
      Abstract: Metastatic castrate resistant prostate cancer (mCRPC) is the major cause of death in prostate cancer patients. Even though some options for treatment of mCRPC have been developed, the most effective therapies remain unclear. Thus finding key patient clinical variables related with mCRPC is an important issue for understanding the disease progression mechanism of mCRPC and clinical decision making for these patients. The Prostate Cancer DREAM Challenge is a crowd-based competition to tackle this essential challenge using new large clinical datasets. This paper proposes an effective procedure for predicting global risks and survival times of these patients, aimed at sub-challenge 1a and 1b of the Prostate Cancer DREAM challenge. The procedure implements a two-step feature selection procedure, which first implements sparse feature selection for numerical clinical variables and statistical hypothesis testing of differences between survival curves caused by categorical clinical variables, and then implements a forward feature selection to narrow the list of informative features. Using Cox’s proportional hazards model with these selected features, this method predicted global risk and survival time of patients using a linear model whose input is a median time computed from the hazard model. The challenge results demonstrated that the proposed procedure outperforms the state of the art model by correctly selecting more informative features on both the global risk prediction and the survival time prediction.
      PubDate: 2016-11-16T11:08:49Z
      DOI: 10.12688/f1000research.8201.1
      Issue No: Vol. 5 (2016)
  • Recent advances in understanding and managing psoriatic arthritis [version
           1; referees: 2 approved]

    • Authors: Dafna D. Gladman
      Abstract: This article reviews recent advances in psoriatic arthritis (PsA) over the past several years with emphasis on early diagnosis, better understanding of pathogenesis, and new therapeutic approaches. Early diagnosis is important, since people who present late do not fare as well. There are a number of clinical, laboratory, and ultrasound features that can help identify patients destined to develop PsA, and several screening tools have been developed. It is recognized that genetic and epigenetic factors, as well as T cells and cytokines, play a role in the pathogenesis of PsA, and several targets have been identified for therapeutic interventions. New therapies have been developed and tested in PsA and have been found to be highly effective for both skin and joint manifestations of the disease. The expectation is that, in the future, PsA patients will be treated early and more aggressively and that there will not be significant progression of joint damage. Moreover, with effective treatment of the skin and joint disease and management of risk factors for the comorbidities, we can expect to reduce their occurrence and further reduce the excess mortality and reduced quality of life and function in these patients.
      PubDate: 2016-11-16T10:35:13Z
      DOI: 10.12688/f1000research.9592.1
      Issue No: Vol. 5 (2016)
  • Advances in analyzing RNA diversity in eukaryotic transcriptomes: peering
           through the Omics lens [version 1; referees: 3 approved]

    • Authors: Sushant Bangru, Auinash Kalsotra
      Abstract: Alternative splicing, polyadenylation, and chemical modifications of RNA generate astonishing complexity within eukaryotic transcriptomes. The last decade has brought numerous advances in sequencing technologies that allow biologists to investigate these phenomena with greater depth and accuracy while reducing time and cost. A commensurate development in biochemical techniques for the enrichment and analysis of different RNA variants has accompanied the advancement of global sequencing analysis platforms. Here, we present a detailed overview of the latest biochemical methods, along with bioinformatics pipelines that have aided in identifying different RNA variants. We also highlight the ongoing developments and challenges associated with RNA variant detection and quantification, including sample heterogeneity and isolation, as well as ‘Omics’ big data handling.
      PubDate: 2016-11-14T16:06:30Z
      DOI: 10.12688/f1000research.9511.1
      Issue No: Vol. 5 (2016)
  • Characterization of 5-(2-18F-fluoroethoxy)-L-tryptophan for PET imaging of
           the pancreas [version 2; referees: 2 approved]

    • Authors: Ahmed Abbas, Christine Beamish, Rebecca McGirr, John Demarco, Neil Cockburn, Dawid Krokowski, Ting-Yim Lee, Michael Kovacs, Maria Hatzoglou, Savita Dhanvantari
      Abstract: Purpose: In diabetes, pancreatic beta cell mass declines significantly prior to onset of fasting hyperglycemia. This decline may be due to endoplasmic reticulum (ER) stress, and the system L amino acid transporter LAT1 may be a biomarker of this process. In this study, we used 5-(2-18F-fluoroethoxy)-L-tryptophan (18F-L-FEHTP) to target LAT1 as a potential biomarker of beta cell function in diabetes. Procedures: Uptake of 18F-L-FEHTP was determined in wild-type C57BL/6 mice by ex vivo biodistribution. Both dynamic and static positron emission tomography (PET) images were acquired in wild-type and Akita mice, a model of ER stress-induced diabetes, as well as in mice treated with streptozotocin (STZ). LAT1 expression in both groups of mice was evaluated by immunofluorescence microscopy. Results: Uptake of 18F-L-FEHTP was highest in the pancreas, and static PET images showed highly specific pancreatic signal. Time-activity curves showed significantly reduced 18F-L-FEHTP uptake in Akita mice, and LAT1 expression was also reduced. However, mice treated with STZ, in which beta cell mass was reduced by 62%, showed no differences in 18F-L-FEHTP uptake in the pancreas, and there was no significant correlation of 18F-L-FEHTP uptake with beta cell mass. Conclusions: 18F-L-FEHTP is highly specific for the pancreas with little background uptake in kidney or liver. We were able to detect changes in LAT1 in a mouse model of diabetes, but these changes did not correlate with beta cell function or mass. Therefore, 18F-L-FEHTP PET is not a suitable method for the noninvasive imaging of changes in beta cell function during the progression of diabetes.
      PubDate: 2016-11-14T15:51:43Z
      DOI: 10.12688/f1000research.9129.2
      Issue No: Vol. 5 (2016)
  • Advances in the understanding and clinical management of mastocytosis and
           clonal mast cell activation syndromes [version 1; referees: 2 approved]

    • Authors: David González-de-Olano, Almudena Matito, Alberto Orfao, Luis Escribano
      Abstract: Clonal mast cell activation syndromes and indolent systemic mastocytosis without skin involvement are two emerging entities that sometimes might be clinically difficult to distinguish, and they involve a great challenge for the physician from both a diagnostic and a therapeutic point of view. Furthermore, final diagnosis of both entities requires a bone marrow study; it is recommended that this be done in reference centers. In this article, we address the current consensus and guidelines for the suspicion, diagnosis, classification, treatment, and management of these two entities.
      PubDate: 2016-11-14T14:03:26Z
      DOI: 10.12688/f1000research.9565.1
      Issue No: Vol. 5 (2016)
  • Zika mosquito vectors: the jury is still out [version 2; referees: 5

    • Authors: Walter S. Leal
      Abstract: After a 40-year hiatus, the International Congress of Entomology (ICE 2016) convened in Orlando, Florida (September 25-30, 2016). One of the symposia at ICE 2016, the Zika Symposium, covered multiple aspects of the Zika epidemic, including epidemiology, sexual transmission, genetic tools for reducing transmission, and particularly vector competence. While there was a consensus among participants that the yellow fever mosquito, Aedes aegypti, is a vector of the Zika virus, there is growing evidence indicating that the range of mosquito vectors might be wider than anticipated. In particular, three independent groups from Canada, China, and Brazil presented and discussed laboratory and field data strongly suggesting that the southern house mosquito, Culex quinquefasciatus, also known as the common mosquito, is highly likely to be a vector in certain environments.
      PubDate: 2016-11-14T10:52:32Z
      DOI: 10.12688/f1000research.9839.2
      Issue No: Vol. 5 (2016)
  • Current concepts and dilemmas in idiopathic interstitial pneumonias
           [version 1; referees: 4 approved]

    • Authors: Jay H. Ryu, Teng Moua, Natalya Azadeh, Misbah Baqir, Eunhee S. Yi
      Abstract: Idiopathic interstitial pneumonias comprise approximately one-third of interstitial lung diseases (also called diffuse parenchymal infiltrative lung diseases). The classification of idiopathic interstitial pneumonias has undergone several revisions since the initial description of 40 years ago, and the most recent version was published in 2013. Although some aspects have been clarified, this group of heterogeneous disorders continues to be a source of confusion and misunderstanding in clinical applications. In this article, we explore several topical themes in the evaluation and management of patients with idiopathic interstitial pneumonias.
      PubDate: 2016-11-10T15:39:06Z
      DOI: 10.12688/f1000research.9601.1
      Issue No: Vol. 5 (2016)
  • Developing food allergy: a potential immunologic pathway linking skin
           barrier to gut [version 1; referees: 2 approved]

    • Authors: Yui-Hsi Wang
      Abstract: Immunoglobulin E (IgE)-mediated food allergy is an adverse reaction to foods and is driven by uncontrolled type-2 immune responses. Current knowledge cannot explain why only some individuals among those with food allergy are prone to develop life-threatening anaphylaxis. It is increasingly evident that the immunologic mechanisms involved in developing IgE-mediated food allergy are far more complex than allergic sensitization. Clinical observations suggest that patients who develop severe allergic reactions to food are often sensitized through the skin in early infancy. Environmental insults trigger epidermal thymic stromal lymphopoietin and interleukin-33 (IL-33) production, which endows dendritic cells with the ability to induce CD4+TH2 cell-mediated allergic inflammation. Intestinal IL-25 propagates the allergic immune response by enhancing collaborative interactions between resident type-2 innate lymphoid cells and CD4+TH2 cells expanded by ingested antigens in the gastrointestinal tract. IL-4 signaling provided by CD4+TH2 cells induces emigrated mast cell progenitors to become multi-functional IL-9-producing mucosal mast cells, which then expand greatly after repeated food ingestions. Inflammatory cytokine IL-33 promotes the function and maturation of IL-9-producing mucosal mast cells, which amplify intestinal mastocytosis, resulting in increased clinical reactivity to ingested food allergens. These findings provide the plausible view that the combinatorial signals from atopic status, dietary allergen ingestions, and inflammatory cues may govern the perpetuation of allergic reactions from the skin to the gut and promote susceptibility to life-threatening anaphylaxis. Future in-depth studies of the molecular and cellular factors composing these stepwise pathways may facilitate the discovery of biomarkers and therapeutic targets for diagnosing, preventing, and treating food allergy.
      PubDate: 2016-11-10T14:52:35Z
      DOI: 10.12688/f1000research.9497.1
      Issue No: Vol. 5 (2016)
  • Recent advances in understanding and managing urolithiasis [version 1;
           referees: 3 approved]

    • Authors: Walter L. Strohmaier
      Abstract: During the last few years, there has been relevant progress in both understanding and managing urolithiasis. Our knowledge of stone formation has changed; although the importance of urine biochemistry was questioned by several investigators years ago, the decisive role of cellular processes (induced by oxidative stress) and the renal papilla has only recently been generally accepted as the most important step in stone formation. For calcium oxalate urolithiasis, the formation of papillary calcifications plays a key role and is of prognostic relevance. Further research has to concentrate on these aspects of preventing urolithiasis. Stone prevention (metaphylaxis) is a major issue when considering the burden it places on healthcare systems. An effective metaphylaxis could lower the cost of stone therapy significantly. For uric acid urolithiasis, so far there is only preliminary information available showing that papillary plaques are not as important as they are in calcium oxalate urolithiasis. Concerning stone management, endourology has improved stone therapy significantly during the last few years. Morbidity decreased and success (stone-free) rates increased. Therefore, the indications for extracorporeal shockwave lithotripsy (ESWL) narrowed. ESWL, however, still has its place in stone therapy. There is not one single treatment modality that is equally effective for all situations. It is important to observe the differential indications for different stones depending on size, localization, and composition.
      PubDate: 2016-11-08T15:49:04Z
      DOI: 10.12688/f1000research.9570.1
      Issue No: Vol. 5 (2016)
  • Whole genome resequencing of a laboratory-adapted Drosophila melanogaster
           population sample [version 1; referees: 2 approved]

    • Authors: William P. Gilks, Tanya M. Pennell, Ilona Flis, Matthew T. Webster, Edward H. Morrow
      Abstract: As part of a study into the molecular genetics of sexually dimorphic complex traits, we used next-generation sequencing to obtain data on genomic variation in an outbred laboratory-adapted fruit fly (Drosophila melanogaster) population. We successfully resequenced the whole genome of 220 hemiclonal females that were heterozygous for the same Berkeley reference line genome (BDGP6/dm6), and a unique haplotype from the outbred base population (LHM). The use of a static and known genetic background enabled us to obtain sequences from whole genome phased haplotypes. We used a BWA-Picard-GATK pipeline for mapping sequence reads to the dm6 reference genome assembly, at a median depth of coverage of 31X, and have made the resulting data publicly-available in the NCBI Short Read Archive (Accession number SRP058502). We used Haplotype Caller to discover and genotype 1,726,931 small genomic variants (SNPs and indels,
      PubDate: 2016-11-07T15:53:03Z
      DOI: 10.12688/f1000research.9912.1
      Issue No: Vol. 5 (2016)
  • A step-by-step workflow for low-level analysis of single-cell RNA-seq data
           with Bioconductor [version 2; referees: 1 approved, 4 approved with

    • Authors: Aaron T.L. Lun, Davis J. McCarthy, John C. Marioni
      Abstract: Single-cell RNA sequencing (scRNA-seq) is widely used to profile the transcriptome of individual cells. This provides biological resolution that cannot be matched by bulk RNA sequencing, at the cost of increased technical noise and data complexity. The differences between scRNA-seq and bulk RNA-seq data mean that the analysis of the former cannot be performed by recycling bioinformatics pipelines for the latter. Rather, dedicated single-cell methods are required at various steps to exploit the cellular resolution while accounting for technical noise. This article describes a computational workflow for low-level analyses of scRNA-seq data, based primarily on software packages from the open-source Bioconductor project. It covers basic steps including quality control, data exploration and normalization, as well as more complex procedures such as cell cycle phase assignment, identification of highly variable and correlated genes, clustering into subpopulations and marker gene detection. Analyses were demonstrated on gene-level count data from several publicly available datasets involving haematopoietic stem cells, brain-derived cells, T-helper cells and mouse embryonic stem cells. This will provide a range of usage scenarios from which readers can construct their own analysis pipelines.
      PubDate: 2016-10-31T15:52:03Z
      DOI: 10.12688/f1000research.9501.2
      Issue No: Vol. 5 (2016)
  • Genomic variant annotation workflow for clinical applications [version 2;
           referees: 2 approved]

    • Authors: Thomas Thurnherr, Franziska Singer, Daniel J. Stekhoven, Niko Beerenwinkel
      Abstract: Annotation and interpretation of DNA aberrations identified through next-generation sequencing is becoming an increasingly important task. Even more so in the context of data analysis pipelines for medical applications, where genomic aberrations are associated with phenotypic and clinical features. Here we describe a workflow to identify potential gene targets in aberrated genes or pathways and their corresponding drugs. To this end, we provide the R/Bioconductor package rDGIdb, an R wrapper to query the drug-gene interaction database (DGIdb). DGIdb accumulates drug-gene interaction data from 15 different resources and allows filtering on different levels. The rDGIdb package makes these resources and tools available to R users. Moreover, rDGIdb queries can be automated through incorporation of the rDGIdb package into NGS sequencing pipelines.
      PubDate: 2016-10-24T14:50:55Z
      DOI: 10.12688/f1000research.9357.2
      Issue No: Vol. 5 (2016)
  • dot-app: a Graphviz-Cytoscape conversion plug-in [version 1; referees: 1
           approved, 2 approved with reservations]

    • Authors: Braxton Fitts, Ziran Zhang, Massoud Maher, Barry Demchak
      Abstract: dot-app is a Cytoscape 3 app that allows Cytoscape to import and export Graphviz (*.dot, *.gv) files, also known as DOT files due to the *.dot extension and their conformance to the DOT language syntax. The DOT format was originally created in the early 2000s to represent graph topologies, layouts and formatting. DOT-encoded files are produced and consumed by a number of open-source graph applications, including GraphViz, Gephi, neato, smyrna, and others. While DOT-based graph applications are popular, they emphasize general graph layout and styling over the topological and semantic analysis functions available in domain-focused applications such as Cytoscape. While domain-focused applications have easy access to large networks (10,000 to 100,000 nodes) and advanced analysis and formatting, they do not offer all of the styling options that DOT-based applications (particularly GraphViz) do. dot-app enables the interchange of networks between Cytoscape and DOT-based applications so that users can benefit from the features of both. dot-app was first deployed to the Cytoscape App Store in August 2015, has since registered more than 1,200 downloads, and has been highly rated by more than 20 users.
      PubDate: 2016-10-20T15:26:36Z
      DOI: 10.12688/f1000research.9751.1
      Issue No: Vol. 5 (2016)
  • Puzzles in modern biology. IV. Neurodegeneration, localized origin and
           widespread decay [version 1; referees: 2 approved]

    • Authors: Steven A. Frank
      Abstract: The motor neuron disease amyotrophic lateral sclerosis (ALS) typically begins with localized muscle weakness. Progressive, widespread paralysis often follows over a few years. Does the disease begin with local changes in a small piece of neural tissue and then spread' Or does neural decay happen independently across diverse spatial locations' The distinction matters, because local initiation may arise by local changes in a tissue microenvironment, by somatic mutation, or by various epigenetic or regulatory fluctuations in a few cells. A local trigger must be coupled with a mechanism for spread. By contrast, independent decay across spatial locations cannot begin by a local change, but must depend on some global predisposition or spatially distributed change that leads to approximately synchronous decay. This article outlines the conceptual frame by which one contrasts local triggers and spread versus parallel spatially distributed decay. Various neurodegenerative diseases differ in their mechanistic details, but all can usefully be understood as falling along a continuum of interacting local and global processes. Cancer provides an example of disease progression by local triggers and spatial spread, setting a conceptual basis for clarifying puzzles in neurodegeneration. Heart disease also has crucial interactions between global processes, such as circulating lipid levels, and local processes in the development of atherosclerotic plaques. The distinction between local and global processes helps to understand these various age-related diseases.
      PubDate: 2016-10-19T16:03:14Z
      DOI: 10.12688/f1000research.9790.1
      Issue No: Vol. 5 (2016)
  • Zika antiviral chemotherapy: identification of drugs and promising
           starting points for drug discovery from an FDA-approved library [version
           1; referees: 2 approved]

    • Authors: Bruno S. Pascoalino, Gilles Courtemanche, Marli T. Cordeiro, Laura H. V. G. Gil, Lucio Freitas-Junior
      Abstract: Background The recent epidemics of Zika virus (ZIKV) implicated it as the cause of serious and potentially lethal congenital conditions such microcephaly and other central nervous system defects, as well as the development of the Guillain-Barré syndrome in otherwise healthy patients. Recent findings showed that anti-Dengue antibodies are capable of amplifying ZIKV infection by a mechanism similar to antibody-dependent enhancement, increasing the severity of the disease. This scenario becomes potentially catastrophic when the global burden of Dengue and the advent of the newly approved anti-Dengue vaccines in the near future are taken into account. Thus, antiviral chemotherapy should be pursued as a priority strategy to control the spread of the virus and prevent the complications associated with Zika. Methods Here we describe a fast and reliable cell-based, high-content screening assay for discovery of anti-ZIKV compounds. This methodology has been used to screen the National Institute of Health Clinical Collection compound library, a small collection of FDA-approved drugs. Results and conclusion From 725 FDA-approved compounds triaged, 29 (4%) were found to have anti-Zika virus activity, of which 22 had confirmed (76% of confirmation) by dose-response curves. Five candidates presented selective activity against ZIKV infection and replication in a human cell line. These hits have abroad spectrum of chemotypes and therapeutic uses, offering valuable opportunities for selection of leads for antiviral drug discovery.
      PubDate: 2016-10-14T15:29:25Z
      DOI: 10.12688/f1000research.9648.1
      Issue No: Vol. 5 (2016)
  • Case Report: Emergency awake craniotomy for cerebral abscess in a patient
           with unrepaired cyanotic congenital heart disease [version 1; referees: 2

    • Authors: Corinne D’Antico, André Hofer, Jens Fassl, Daniel Tobler, Daniel Zumofen, Nicolai Goettel
      Abstract: We report the case of a 39-year-old male with complex cyanotic congenital heart disease undergoing emergency craniotomy for a cerebral abscess. Maintenance of intraoperative hemodynamic stability and adequate tissue oxygenation during anesthesia may be challenging in patients with cyanotic congenital heart disease. In this case, we decided to perform the surgery as an awake craniotomy after interdisciplinary consensus. We discuss general aspects of anesthetic management during awake craniotomy and specific concerns in the perioperative care of patients with congenital heart disease.
      PubDate: 2016-10-14T14:44:02Z
      DOI: 10.12688/f1000research.9722.1
      Issue No: Vol. 5 (2016)
  • CELL5M: A geospatial database of agricultural indicators for Africa South
           of the Sahara [version 1; referees: 2 approved]

    • Authors: Jawoo Koo, Cindy M. Cox, Melanie Bacou, Carlo Azzarri, Zhe Guo, Ulrike Wood-Sichra, Queenie Gong, Liangzhi You
      Abstract: Recent progress in large-scale georeferenced data collection is widening opportunities for combining multi-disciplinary datasets from biophysical to socioeconomic domains, advancing our analytical and modeling capacity. Granular spatial datasets provide critical information necessary for decision makers to identify target areas, assess baseline conditions, prioritize investment options, set goals and targets and monitor impacts. However, key challenges in reconciling data across themes, scales and borders restrict our capacity to produce global and regional maps and time series. This paper provides overview, structure and coverage of CELL5M—an open-access database of geospatial indicators at 5 arc-minute grid resolution—and introduces a range of analytical applications and case-uses. CELL5M covers a wide set of agriculture-relevant domains for all countries in Africa South of the Sahara and supports our understanding of multi-dimensional spatial variability inherent in farming landscapes throughout the region.
      PubDate: 2016-10-10T14:58:27Z
      DOI: 10.12688/f1000research.9682.1
      Issue No: Vol. 5 (2016)
  • Breeding novel solutions in the brain: a model of Darwinian neurodynamics
           [version 1; referees: 1 approved, 2 approved with reservations]

    • Authors: András Szilágyi, István Zachar, Anna Fedor, Harold P. de Vladar, Eörs Szathmáry
      Abstract: Background: The fact that surplus connections and neurons are pruned during development is well established. We complement this selectionist picture by a proof-of-principle model of evolutionary search in the brain, that accounts for new variations in theory space. We present a model for Darwinian evolutionary search for candidate solutions in the brain. Methods: We combine known components of the brain – recurrent neural networks (acting as attractors), the action selection loop and implicit working memory – to provide the appropriate Darwinian architecture. We employ a population of attractor networks with palimpsest memory. The action selection loop is employed with winners-share-all dynamics to select for candidate solutions that are transiently stored in implicit working memory. Results: We document two processes: selection of stored solutions and evolutionary search for novel solutions. During the replication of candidate solutions attractor networks occasionally produce recombinant patterns, increasing variation on which selection can act. Combinatorial search acts on multiplying units (activity patterns) with hereditary variation and novel variants appear due to (i) noisy recall of patterns from the attractor networks, (ii) noise during transmission of candidate solutions as messages between networks, and, (iii) spontaneously generated, untrained patterns in spurious attractors. Conclusions: Attractor dynamics of recurrent neural networks can be used to model Darwinian search. The proposed architecture can be used for fast search among stored solutions (by selection) and for evolutionary search when novel candidate solutions are generated in successive iterations. Since all the suggested components are present in advanced nervous systems, we hypothesize that the brain could implement a truly evolutionary combinatorial search system, capable of generating novel variants.
      PubDate: 2016-09-28T11:30:43Z
      DOI: 10.12688/f1000research.9630.1
      Issue No: Vol. 5 (2016)
  • Building pathway graphs from BioPAX data in R [version 1; referees: 1
           approved, 2 approved with reservations]

    • Authors: Nirupama Benis, Dirkjan Schokker, Frank Kramer, Mari A. Smits, Maria Suarez-Diez
      Abstract: Biological pathways are increasingly available in the BioPAX format which uses an RDF model for data storage. We can retrieve the information in this data model in the scripting language R using the package rBiopaxParser, which converts the BioPAX format to one readable in R. It also has a function to build a regulatory network from the pathway information, here we describe an extension of this function. The new function will also include non-regulatory interactions in the pathway and thus allow extraction of maximum information. This function will be available as part of the rBiopaxParser distribution from Bioconductor.
      PubDate: 2016-09-28T09:45:57Z
      DOI: 10.12688/f1000research.9582.1
      Issue No: Vol. 5 (2016)
  • Creating a driving profile for older adults using GPS devices and
           naturalistic driving methodology [version 1; referees: 2 approved, 1
           approved with reservations]

    • Authors: Ganesh M. Babulal, Cindy M. Traub, Mollie Webb, Sarah H. Stout, Aaron Addison, David B. Carr, Brian R. Ott, John C. Morris, Catherine M. Roe
      Abstract: Background/Objectives: Road tests and driving simulators are most commonly used in research studies and clinical evaluations of older drivers. We adapted an existing, commercial, off-the-shelf, in-vehicle device for naturalistic, longitudinal research to better understand daily driving behavior in older drivers. Design: The Azuga G2 Tracking DeviceTM was installed in each participant’s vehicle, and we collected data over 5 months (speed, latitude/longitude) every 30-seconds when the vehicle was driven.  Setting: The Knight Alzheimer’s Disease Research Center at Washington University School of Medicine. Participants: Five individuals enrolled in a larger, longitudinal study assessing preclinical Alzheimer disease and driving performance.  Participants were aged 65+ years and had normal cognition. Measurements:  Spatial components included Primary Location(s), Driving Areas, Mean Centers and Unique Destinations.  Temporal components included number of trips taken during different times of the day.  Behavioral components included number of hard braking, speeding and sudden acceleration events. Methods:  Individual 30-second observations, each comprising one breadcrumb, and trip-level data were collected and analyzed in R and ArcGIS.  Results: Primary locations were confirmed to be 100% accurate when compared to known addresses.  Based on the locations of the breadcrumbs, we were able to successfully identify frequently visited locations and general travel patterns.  Based on the reported time from the breadcrumbs, we could assess number of trips driven in daylight vs. night.  Data on additional events while driving allowed us to compute the number of adverse driving alerts over the course of the 5-month period. Conclusions: This pilot study indicated that Driving Profiles for older adults can be created and compared month-to-month or year-to-year, allowing researchers to identify changes in driving patterns that are unavailable in controlled conditions.
      PubDate: 2016-09-26T14:39:10Z
      DOI: 10.12688/f1000research.9608.1
      Issue No: Vol. 5 (2016)
  • Lies, irony, and contradiction — an annotation of semantic conflict in
           the movie "Forrest Gump" [version 1; referees: 2 approved]

    • Authors: Michael Hanke, Pierre Ibe
      Abstract: Here we extend the information on the structure of the core stimulus of the studyforrest project ( with a description of semantic conflict in the “Forrest Gump” movie. Three observers annotated the movie independently regarding episodes with portrayal of lies, irony or sarcasm. We present frequency statistics, and inter-observer reliability measures that qualify and quantify semantic conflict in the stimulus. While the number of identified events is limited, this annotation nevertheless enriches the knowledge about the complex high-level structure of this stimulus, and can help to evaluate its utility for future studies, and the usability of the existing brain imaging data regarding this aspect of cognition.
      PubDate: 2016-09-26T14:36:26Z
      DOI: 10.12688/f1000research.9635.1
      Issue No: Vol. 5 (2016)
  • Visual acuity measured with luminance-modulated and contrast-modulated
           noise letter stimuli in young adults and adults above 50 years old
           [version 1; referees: 2 approved, 1 approved with reservations]

    • Authors: Pui Juan Woi, Sharanjeet-Kaur, Sarah J. Waugh, Mohd Izzuddin Hairol
      Abstract: The human visual system is sensitive in detecting objects that have different luminance level from their background, known as first-order or luminance-modulated (LM) stimuli. We are also able to detect objects that have the same mean luminance as their background, only differing in contrast (or other attributes). Such objects are known as second-order or contrast-modulated (CM), stimuli. CM stimuli are thought to be processed in higher visual areas compared to LM stimuli, and may be more susceptible to ageing. We compared visual acuities (VA) of five healthy older adults (54.0±1.83 years old) and five healthy younger adults (25.4±1.29 years old) with LM and CM letters under monocular and binocular viewing. For monocular viewing, age had no effect on VA [F(1, 8)= 2.50, p> 0.05]. However, there was a significant main effect of age on VA under binocular viewing [F(1, 8)= 5.67, p< 0.05].  Binocular VA with CM letters in younger adults was approximately two lines better than that in older adults. For LM, binocular summation ratios were similar for older (1.16±0.21) and younger (1.15±0.06) adults. For CM, younger adults had higher binocular summation ratio (1.39±0.08) compared to older adults (1.12±0.09). Binocular viewing improved VA with LM letters for both groups similarly. However, in older adults, binocular viewing did not improve VA with CM letters as much as in younger adults. This could reflect a decline of higher visual areas due to ageing process, most likely higher than V1, which may be missed if measured with luminance-based stimuli alone.
      PubDate: 2016-08-12T11:15:02Z
      Issue No: Vol. 5 (2016)
  • DNA barcoding of Clarias gariepinus, Coptodon zillii and Sarotherodon
           melanotheron from Southwestern Nigeria [version 1; referees: 2 approved]

    • Authors: Mofolusho O. Falade, Anthony J. Opene, Otarigho Benson
      Abstract: DNA barcoding has been adopted as a gold standard rapid, precise and unifying identification system for animal species and provides a database of genetic sequences that can be used as a tool for universal species identification. In this study, we employed mitochondrial genes 16S rRNA (16S) and cytochrome oxidase subunit I (COI) for the identification of some Nigerian freshwater catfish and Tilapia species. Approximately 655 bp were amplified from the 5′ region of the mitochondrial cytochrome C oxidase subunit I (COI) gene whereas 570 bp were amplified for the 16S rRNA gene. Nucleotide divergences among sequences were estimated based on Kimura 2-parameter distances and the genetic relationships were assessed by constructing phylogenetic trees using the neighbour-joining (NJ) and maximum likelihood (ML) methods. Analyses of consensus barcode sequences for each species, and alignment of individual sequences from within a given species revealed highly consistent barcodes (99% similarity on average), which could be compared with deposited sequences in public databases. The nucleotide distance between species belonging to different genera based on COI ranged from 0.17% between Sarotherodon melanotheron and Coptodon zillii to 0.49% between Clarias gariepinus and C. zillii, indicating that S. melanotheron and C. zillii are closely related. Based on the data obtained, the utility of COI gene was confirmed in accurate identification of three fish species from Southwest Nigeria.
      PubDate: 2016-06-08T09:27:35Z
      DOI: 10.12688/f1000research.7895.1
      Issue No: Vol. 5 (2016)
  • Analysis of red autofluorescence (650-670nm) in epidermal cell populations
           and its potential for distinguishing contributors to 'touch' biological
           samples [version 1; referees: 2 approved]

    • Authors: Cristina E. Stanciu, M. Katherine Philpott, Eduardo E. Bustamante, Ye Jin Kwon, Christopher J. Ehrhardt
      Abstract: Interpretation of touch DNA mixtures poses a significant challenge for forensic caseworking laboratories.  Front end techniques that facilitate separation of contributor cell populations before DNA extraction are a way to circumvent this problem. The goal of this study was to survey intrinsic fluorescence of epidermal cells collected from touch surfaces and investigate whether this property could potentially be used to discriminate between contributor cell populations in a biological mixture.  Analysis of red autofluorescence (650-670nm) showed that some contributors could be distinguished on this basis. Variation was also observed between autofluorescence profiles of epidermal cell populations from a single contributor sampled on different days. This dataset suggests that red autofluorescence may be a useful marker for identifying distinct cell populations in some mixtures. Future efforts should continue to investigate the extrinsic or intrinsic factors contributing to this signature, and to identify additional biomarkers that could complement this system.
      PubDate: 2016-02-16T16:10:34Z
      DOI: 10.12688/f1000research.8036.1
      Issue No: Vol. 5 (2016)
  • How to put plant root uptake into a soil water flow model [version 1;
           referees: 2 approved, 1 approved with reservations]

    • Authors: Xuejun Dong
      Abstract: The need for improved crop water use efficiency calls for flexible modeling platforms to implement new ideas in plant root uptake and its regulation mechanisms. This paper documents the details of modifying a soil infiltration and redistribution model to include (a) dynamic root growth, (b) non-uniform root distribution and water uptake, (c) the effect of water stress on plant water uptake, and (d) soil evaporation. The paper also demonstrates strategies of using the modified model to simulate soil water dynamics and plant transpiration considering different sensitivity of plants to soil dryness and different mechanisms of root water uptake. In particular, the flexibility of simulating various degrees of compensated uptake (whereby plants tend to maintain potential transpiration under mild water stress) is emphasized. The paper also describes how to estimate unknown root distribution and rooting depth parameters by the use of a simulation-based searching method. The full documentation of the computer code will allow further applications and new development.
      PubDate: 2016-01-08T16:56:15Z
      DOI: 10.12688/f1000research.7686.1
      Issue No: Vol. 5 (2016)
  • MetaGenSense: A web-application for analysis and exploration of high
           throughput sequencing metagenomic data [version 3; referees: 1 approved, 2
           approved with reservations]

    • Authors: Damien Correia, Olivia Doppelt-Azeroual, Jean-Baptiste Denis, Mathias Vandenbogaert, Valérie Caro
      Abstract: The detection and characterization of emerging infectious agents has been a continuing public health concern. High Throughput Sequencing (HTS) or Next-Generation Sequencing (NGS) technologies have proven to be promising approaches for efficient and unbiased detection of pathogens in complex biological samples, providing access to comprehensive analyses. As NGS approaches typically yield millions of putatively representative reads per sample, efficient data management and visualization resources have become mandatory. Most usually, those resources are implemented through a dedicated Laboratory Information Management System (LIMS), solely to provide perspective regarding the available information. We developed an easily deployable web-interface, facilitating management and bioinformatics analysis of metagenomics data-samples. It was engineered to run associated and dedicated Galaxy workflows for the detection and eventually classification of pathogens. The web application allows easy interaction with existing Galaxy metagenomic workflows, facilitates the organization, exploration and aggregation of the most relevant sample-specific sequences among millions of genomic sequences, allowing them to determine their relative abundance, and associate them to the most closely related organism or pathogen. The user-friendly Django-Based interface, associates the users’ input data and its metadata through a bio-IT provided set of resources (a Galaxy instance, and both sufficient storage and grid computing power). Galaxy is used to handle and analyze the user’s input data from loading, indexing, mapping, assembly and DB-searches. Interaction between our application and Galaxy is ensured by the BioBlend library, which gives API-based access to Galaxy’s main features. Metadata about samples, runs, as well as the workflow results are stored in the LIMS. For metagenomic classification and exploration purposes, we show, as a proof of concept, that integration of intuitive exploratory tools, like Krona for representation of taxonomic classification, can be achieved very easily. In the trend of Galaxy, the interface enables the sharing of scientific results to fellow team members.
      PubDate: 2016-12-01T10:26:14Z
      DOI: 10.12688/f1000research.6139.3
      Issue No: Vol. 4 (2016)
  • Increased abundance of ADAM9 transcripts in the blood is associated with
           tissue damage [version 2; referees: 2 approved, 1 approved with

    • Authors: Darawan Rinchai, Chidchamai Kewcharoenwong, Bianca Kessler, Ganjana Lertmemongkolchai, Damien Chaussabel
      Abstract: Background: Members of the ADAM (a disintegrin and metalloprotease domain) family have emerged as critical regulators of cell-cell signaling during development and homeostasis. ADAM9 is consistently overexpressed in various human cancers, and has been shown to play an important role in tumorigenesis. However, little is known about the involvement of ADAM9 during immune-mediated processes. Results: Mining of an extensive compendium of transcriptomic datasets identified important gaps in knowledge regarding the possible role of ADAM9 in immunological homeostasis and inflammation: 1) The abundance of ADAM9 transcripts in the blood was increased in patients with acute infection but, 2) changed very little after in vitro exposure to a wide range of pathogen-associated molecular patterns (PAMPs). 3) Furthermore it was found to increase significantly in subjects as a result of tissue injury or tissue remodeling, in absence of infectious processes. Conclusions: Our findings indicate that ADAM9 may constitute a valuable biomarker for the assessment of tissue damage, especially in clinical situations where other inflammatory markers are confounded by infectious processes.
      PubDate: 2016-10-24T14:24:50Z
      DOI: 10.12688/f1000research.6241.2
      Issue No: Vol. 4 (2016)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Tel: +00 44 (0)131 4513762
Fax: +00 44 (0)131 4513327
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