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Journal Cover   F1000Research
  [SJR: 0.219]   [H-I: 3]   [4 followers]  Follow
  This is an Open Access Journal Open Access journal
   ISSN (Online) 2046-1402
   Published by Faculty of 1000 Homepage  [1 journal]
  • Transversus abdominal plane (TAP) block for postoperative pain management:
           a review [version 1; referees: 2 approved]

    • Authors: Jan Jakobsson, Liselott Wickerts, Sune Forsberg, Gustaf Ledin
      Abstract: Transversus abdominal plane (TAP) block has a long history and there is currently extensive clinical experience around TAP blocks. The aim of this review is to provide a summary of the present evidence on the effects of TAP block and to provide suggestions for further studies. There are several approaches to performing abdominal wall blocks, with the rapid implementation of ultrasound-guided technique facilitating a major difference in TAP block performance. During surgery, an abdominal wall block may also be applied by the surgeon from inside the abdominal cavity. Today, there are more than 11 meta-analyses providing a compiled evidence base around the effects of TAP block. These analyses include different procedures, different techniques of TAP block administration and, importantly, they compare the TAP block with a variety of alternative analgesic regimes. The effects of TAP block during laparoscopic cholecystectomy seem to be equivalent to local infiltration analgesia and also seem to be beneficial during laparoscopic colon resection. The effects of TAP are more pronounced when it is provided prior to surgery and these effects are local anaesthesia dose-dependent. TAP block seems an interesting alternative in patients with, for example, severe obesity where epidural or spinal anaesthesia/analgesia is technically difficult and/or poses a risk. There is an obvious need for further high-quality studies comparing TAP block prior to surgery with local infiltration analgesia, single-shot spinal analgesia, and epidural analgesia. These studies should be procedure-specific and the effects should be evaluated, both regarding short-term pain and analgesic requirement and also including the effects on postoperative nausea and vomiting, recovery of bowel function, ambulation, discharge, and protracted recovery outcomes (assessed by e.g., postoperative quality of recovery scale).
      PubDate: 2015-11-26T15:24:11Z
      DOI: 10.12688/f1000research.7015.1
      Issue No: Vol. 4 (2015)
  • Varicella Zoster Virus in the Nervous System [version 1; referees: 3

    • Authors: Don Gilden, Maria Nagel, Randall Cohrs, Ravi Mahalingam, Nicholas Baird
      Abstract: Varicella zoster virus (VZV) is a ubiquitous, exclusively human alphaherpesvirus. Primary infection usually results in varicella (chickenpox), after which VZV becomes latent in ganglionic neurons along the entire neuraxis. As VZV-specific cell-mediated immunity declines in elderly and immunocompromised individuals, VZV reactivates and causes herpes zoster (shingles), frequently complicated by postherpetic neuralgia. VZV reactivation also produces multiple serious neurological and ocular diseases, such as cranial nerve palsies, meningoencephalitis, myelopathy, and VZV vasculopathy, including giant cell arteritis, with or without associated rash. Herein, we review the clinical, laboratory, imaging, and pathological features of neurological complications of VZV reactivation as well as diagnostic tests to verify VZV infection of the nervous system. Updates on the physical state of VZV DNA and viral gene expression in latently infected ganglia, neuronal, and primate models to study varicella pathogenesis and immunity are presented along with innovations in the immunization of elderly individuals to prevent VZV reactivation.
      PubDate: 2015-11-26T11:08:46Z
      DOI: 10.12688/f1000research.7153.1
      Issue No: Vol. 4 (2015)
  • Pathogenesis of Dengue: Dawn of a New Era [version 1; referees: 3

    • Authors: Scott B. Halstead
      Abstract: Dengue virus (DENV) infections of humans were long thought to be self-limited and of low mortality. Beginning in the 1950s, at the time when four different DENVs were discovered, a lethal variant of dengue emerged. Dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) initially observed in Southeast Asia now has spread throughout the world. Two risk factors for DHF/DSS are well-established: severe disease occurs during a second heterotypic DENV infection or during a first DENV infection in infants born to dengue-immune mothers. A large number of hypotheses have been proposed to explain severe dengue disease. As discussed, few of them attempt to explain why severe disease occurs under the two different immunological settings. New experimental evidence has demonstrated that DENV non-structural protein 1 (NS1) is toll-receptor 4 agonist that stimulates primary human myeloid cells to produce the same cytokines observed during the course of severe dengue disease. In addition, NS1 directly damages endothelial cells. These observations have been repeated and extended to an in vivo mouse model. The well-established phenomenon, antibody-dependent enhancement of DENV infection in Fc-receptor-bearing cells, should similarly enhance the production of DENV NS1 in humans, providing a unitary mechanism for severe disease in both immunological settings
      PubDate: 2015-11-25T15:25:03Z
      DOI: 10.12688/f1000research.7024.1
      Issue No: Vol. 4 (2015)
  • Quality of histone modification antibodies undermines chromatin biology
           research [version 2; referees: 1 approved, 2 approved with reservations]

    • Authors: Goran Kungulovski, Albert Jeltsch
      Abstract: Histone post-translational modification (PTM) antibodies are essential research reagents in chromatin biology. However, they suffer from variable properties and insufficient documentation of quality. Antibody manufacturers and vendors should provide detailed lot-specific documentation of quality, rendering further quality checks by end-customers unnecessary. A shift from polyclonal antibodies towards sustainable reagents like monoclonal or recombinant antibodies or histone binding domains would help to improve the reproducibility of experimental work in this field.
      PubDate: 2015-11-24T15:45:12Z
      DOI: 10.12688/f1000research.7265.2
      Issue No: Vol. 4 (2015)
  • Nocturnal Hypertension and Attenuated Nocturnal Blood Pressure Dipping is
           Common in Pediatric Lupus [version 2; referees: 2 approved, 1 approved
           with reservations]

    • Authors: J. Fallon Campbell, Sarah J. Swartz, Scott E. Wenderfer
      Abstract: Hypertension is an important manifestation of systemic lupus erythematosus (SLE) but reports of prevalence vary between 20-70% in published reports of adult and pediatric patients. For both children and adults with SLE, the clinical diagnosis and management of hypertension has traditionally been based on guidelines developed for the general population. In clinical trials, the criteria used for defining participants with hypertension are mostly undefined. As a first step towards formally assessing the blood pressure (BP) patterns of children diagnosed with SLE, 24-hr ambulatory BP monitoring data was analyzed on clinic patients who presented with prehypertension or stage I hypertension. In this pediatric SLE cohort (n=10), 20% met daytime criteria for a diagnosis of hypertension. Patterns of BP elevation varied widely with white coat, masked, isolated systolic, and diastolic nocturnal hypertension all identified. Nocturnal hypertension was detected in 60% and attenuated nocturnal BP dipping in 90% of both hypertensive and normotensive SLE patients. In SLE patients, the median nighttime systolic and diastolic loads were 25% and 15.5% compared with median daily loads of 12.5% and 11.5%. Daytime and nighttime systolic and diastolic BP load and nocturnal dipping was compared to a control population consisting of 85 non-SLE patients under 21 years old with prehypertension or stage 1 hypertension presenting to hypertension clinic. Median systolic BP dipped 5.3 mmHg in SLE patients compared to 11.9 mmHg in non-lupus (p-value = 0.001). Median diastolic BP dipped 12.9 mmHg versus 18.5 mmHg in non-lupus (p-value = 0.003). Patterns of BP dysregulation in pediatric SLE merit further exploration. Children with or without SLE displaying prehypertensive or stage 1 casual BP measurements had similar rates of hypertension by ambulatory BP monitoring. However, regardless of BP diagnosis, and independent of kidney involvement, there was an increased proportion with attenuated nocturnal dipping and nocturnal hypertension in SLE patients.
      PubDate: 2015-11-23T16:51:32Z
      DOI: 10.12688/f1000research.6532.2
      Issue No: Vol. 4 (2015)
  • Advances in understanding and managing bullous pemphigoid [version 1;
           referees: 2 approved]

    • Authors: Cathy Y. Zhao, Dedee F. Murrell
      Abstract: Bullous pemphigoid (BP) is the commonest subtype of autoimmune blistering disease in most countries of the world. It occurs most frequently in elderly patients and is characterised clinically by large, tense blisters in the skin preceded by urticarial plaques and pruritus. Immunopathologically, it is characterised by autoantibodies directed against the 180 kD antigen (BP180) and the 230 kD antigen (BP230). New knowledge regarding BP is being continually uncovered. This article reviews the recent advances in BP, including newer diagnostic tests, standardised outcome measures and emerging therapeutic options, as well as the evidence supporting their use.
      PubDate: 2015-11-20T15:40:31Z
      DOI: 10.12688/f1000research.6896.1
      Issue No: Vol. 4 (2015)
  • Post-translational control of RIPK3 and MLKL mediated necroptotic cell
           death [version 1; referees: 4 approved]

    • Authors: James M. Murphy, James E. Vince
      Abstract: Several programmed lytic and necrotic-like cell death mechanisms have now been uncovered, including the recently described receptor interacting protein kinase-3 (RIPK3)-mixed lineage kinase domain-like (MLKL)-dependent necroptosis pathway. Genetic experiments have shown that programmed necrosis, including necroptosis, can play a pivotal role in regulating host-resistance against microbial infections. Alternatively, excess or unwarranted necroptosis may be pathological in autoimmune and autoinflammatory diseases. This review highlights the recent advances in our understanding of the post-translational control of RIPK3-MLKL necroptotic signaling. We discuss the critical function of phosphorylation in the execution of necroptosis, and highlight the emerging regulatory roles for several ubiquitin ligases and deubiquitinating enzymes. Finally, based on current evidence, we discuss the potential mechanisms by which the essential, and possibly terminal, necroptotic effector, MLKL, triggers the disruption of cellular membranes to cause cell lysis.
      PubDate: 2015-11-19T16:02:20Z
      DOI: 10.12688/f1000research.7046.1
      Issue No: Vol. 4 (2015)
  • Advances in understanding and managing atopic dermatitis [version 1;
           referees: 2 approved]

    • Authors: Michael Barton, Robert Sidbury
      Abstract: Atopic dermatitis is a chronic, pruritic skin disease characterized by an improperly functioning skin barrier and immune dysregulation. We review proposed atopic dermatitis pathomechanisms, emphasizing how these impact current perspectives on natural history, role of allergic sensitization, and future therapeutic targets.
      PubDate: 2015-11-19T15:59:27Z
      DOI: 10.12688/f1000research.6972.1
      Issue No: Vol. 4 (2015)
  • Pharmacokinetic-pharmacodynamic relationship of anesthetic drugs: from
           modeling to clinical use [version 1; referees: 4 approved]

    • Authors: Valerie Billard
      Abstract: Anesthesia is a combination of unconsciousness, amnesia, and analgesia, expressed in sleeping patients by limited reaction to noxious stimulations. It is achieved by several classes of drugs, acting mainly on central nervous system. Compared to other therapeutic families, the anesthetic drugs, administered by intravenous or pulmonary route, are quickly distributed in the blood and induce in a few minutes effects that are fully reversible within minutes or hours. These effects change in parallel with the concentration of the drug, and the concentration time course of the drug follows with a reasonable precision mathematical models based on the Fick principle. Therefore, understanding concentration time course allows adjusting the dosing delivery scheme in order to control the effects.   The purpose of this short review is to describe the basis of pharmacokinetics and modeling, the concentration-effects relationship, and drug interactions modeling to offer to anesthesiologists and non-anesthesiologists an overview of the rules to follow to optimize anesthetic drug delivery.
      PubDate: 2015-11-18T16:39:29Z
      DOI: 10.12688/f1000research.6601.1
      Issue No: Vol. 4 (2015)
  • Current controversies in infective endocarditis [version 1; referees: 3

    • Authors: Thomas J. Cahill, Bernard D. Prendergast
      Abstract: Infective endocarditis is a life-threatening disease caused by a focus of infection within the heart. For clinicians and scientists, it has been a moving target that has an evolving microbiology and a changing patient demographic. In the absence of an extensive evidence base to guide clinical practice, controversies abound. Here, we review three main areas of uncertainty: first, in prevention of infective endocarditis, including the role of antibiotic prophylaxis and strategies to reduce health care-associated bacteraemia; second, in diagnosis, specifically the use of multimodality imaging; third, we discuss the optimal timing of surgical intervention and the challenges posed by increasing rates of cardiac device infection.
      PubDate: 2015-11-18T15:51:40Z
      DOI: 10.12688/f1000research.6949.1
      Issue No: Vol. 4 (2015)
  • Discovering, Indexing and Interlinking Information Resources [version 2;
           referees: 1 approved, 2 approved with reservations]

    • Abstract: The social media revolution is having a dramatic effect on the world of scientific publication. Scientists now publish their research interests, theories and outcomes across numerous channels, including personal blogs and other thematic web spaces where ideas, activities and partial results are discussed. Accordingly, information systems that facilitate access to scientific literature must learn to cope with this valuable and varied data, evolving to make this research easily discoverable and available to end users. In this paper we describe the incremental process of discovering web resources in the domain of agricultural science and technology. Making use of Linked Open Data methodologies, we interlink a wide array of custom-crawled resources with the AGRIS bibliographic database in order to enrich the user experience of the AGRIS website. We also discuss the SemaGrow Stack, a query federation and data integration infrastructure used to estimate the semantic distance between crawled web resources and AGRIS.
      PubDate: 2015-11-17T16:23:15Z
      DOI: 10.12688/f1000research.6848.2
      Issue No: Vol. 4 (2015)
  • Protein disorder reduced in Saccharomyces cerevisiae to survive heat shock
           [version 1; referees: 2 approved, 1 approved with reservations]

    • Authors: Esmeralda Vicedo, Zofia Gasik, Yu-An Dong, Tatyana Goldberg, Burkhard Rost
      Abstract: Recent experiments established that a culture of Saccharomyces cerevisiae (baker’s yeast) survives sudden high temperatures by specifically duplicating the entire chromosome III and two chromosomal fragments (from IV and XII). Heat shock proteins (HSPs) are not significantly over-abundant in the duplication. In contrast, we suggest a simple algorithm to “postdict” the experimental results: Find a small enough chromosome with minimal protein disorder and duplicate this region. This algorithm largely explains all observed duplications. In particular, all regions duplicated in the experiment reduced the overall content of protein disorder. The differential analysis of the functional makeup of the duplication remained inconclusive. Gene Ontology (GO) enrichment suggested over-representation in processes related to reproduction and nutrient uptake. Analyzing the protein-protein interaction network (PPI) revealed that few network-central proteins were duplicated. The predictive hypothesis hinges upon the concept of reducing proteins with long regions of disorder in order to become less sensitive to heat shock attack.
      PubDate: 2015-11-06T16:24:18Z
      DOI: 10.12688/f1000research.7178.1
      Issue No: Vol. 4 (2015)
  • Recent advances in understanding of chronic kidney disease [version 1;
           referees: 3 approved]

    • Authors: Junna Yamaguchi, Tetsuhiro Tanaka, Masaomi Nangaku
      Abstract: Chronic kidney disease (CKD) is defined as any condition that causes reduced kidney function over a period of time. Fibrosis, tubular atrophy and interstitial inflammation are the hallmark of pathological features in CKD. Regardless of initial insult, CKD has some common pathways leading CKD to end-stage kidney disease, including hypoxia in the tubulointerstitium and proteinuria. Recent advances in genome editing technologies and stem cell research give great insights to understand the pathogenesis of CKD, including identifications of the origins of renal myofibroblasts and tubular epithelial cells upon injury. Environmental factors such as hypoxia, oxidative stress, and epigenetic factors in relation to CKD are also discussed.
      PubDate: 2015-11-04T15:28:16Z
      DOI: 10.12688/f1000research.6970.1
      Issue No: Vol. 4 (2015)
  • Advances in the understanding of delayed cerebral ischaemia after
           aneurysmal subarachnoid haemorrhage [version 1; referees: 4 approved]

    • Authors: Liam Flynn, Peter Andrews
      Abstract: Delayed cerebral ischaemia has been described as the single most important cause of morbidity and mortality in patients who survive the initial aneurysmal subarachnoid haemorrhage. Our understanding of the pathophysiology of delayed cerebral ischaemia is meagre at best and the calcium channel blocker nimodipine remains the only intervention to consistently improve functional outcome after aneurysmal subarachnoid haemorrhage. There is substantial evidence to support cerebral vessel narrowing as a causative factor in delayed cerebral ischaemia, but contemporary research demonstrating improvements in vessel narrowing has failed to show improved functional outcomes. This has encouraged researchers to investigate other potential causes of delayed cerebral ischaemia, such as early brain injury, microthrombosis, and cortical spreading depolarisation. Adherence to a common definition of delayed cerebral ischaemia is needed in order to allow easier assessment of studies using multiple different terms. Furthermore, improved recognition of delayed cerebral ischaemia would not only allow for faster treatment but also better assessment of interventions. Finally, understanding nimodipine’s mechanism of action may allow us to develop similar agents with improved efficacy.
      PubDate: 2015-11-02T16:00:13Z
      DOI: 10.12688/f1000research.6635.1
      Issue No: Vol. 4 (2015)
  • What do we know about the participation of hematopoietic stem cells in
           hematopoiesis' [version 1; referees: 2 approved, 1 approved with

    • Authors: Nina Drize, Nataliya Petinati
      Abstract: The demonstrated presence in adult tissues of cells with sustained tissue regenerative potential has given rise to the concept of tissue stem cells. Assays to detect and measure such cells indicate that they have enormous proliferative potential and usually an ability to produce all or many of the mature cell types that define the specialized functionality of the tissue. In the hematopoietic system, one or only a few cells can restore lifelong hematopoiesis of the whole organism. To what extent is the maintenance of hematopoietic stem cells required during normal hematopoiesis' How does the constant maintenance of hematopoiesis occur and what is the behavior of the hematopoietic stem cells in the normal organism' How many of the hematopoietic stem cells are created during the development of the organism' How many hematopoietic stem cells are generating more mature progeny at any given moment' What happens to the population of hematopoietic stem cells in aging' This review will attempt to describe the results of recent research which contradict some of the ideas established over the past 30 years about how hematopoiesis is regulated.
      PubDate: 2015-10-29T10:51:46Z
      DOI: 10.12688/f1000research.6459.1
      Issue No: Vol. 4 (2015)
  • Should adults with type 2 diabetes be screened for atherosclerotic
           cardiovascular disease' [version 1; referees: 2 approved]

    • Authors: Yanglu Zhao, Nathan Wong
      Abstract: Diabetes mellitus is associated with greater risks for cardiovascular diseases (CVD). Multiple noninvasive screening tools for CVD including cardiac CT, carotid intima-media thickness test, myocardial perfusion imaging have been examined in those with diabetes, but the prognostic value of these tests vary and issues remain regarding their cost-benefit ratios, potential harms of radiation, and how they fit into screening algorithms for CVD. We discuss in this report the needs and criteria for screening tests and summarize the evidence from observational studies and clinical trials. We also explore whether there should be more sensitive screening modalities to better detect both short and long-term cardiovascular risk among asymptomatic patients with diabetes.
      PubDate: 2015-10-28T17:16:12Z
      DOI: 10.12688/f1000research.6625.1
      Issue No: Vol. 4 (2015)
  • Cancer Genomics [version 1; referees: 2 approved]

    • Authors: Elaine Mardis
      Abstract: Modern cancer genomics has emerged from the combination of the Human Genome Reference, massively parallel sequencing, and the comparison of tumor to normal DNA sequences, revealing novel insights into the cancer genome and its amazing diversity. Recent developments in applying our knowledge of cancer genomics have focused on the utility of these data for clinical applications. The emergent results of this translation into the clinical setting already are changing the clinical care and monitoring of cancer patients.
      PubDate: 2015-10-28T14:54:57Z
      DOI: 10.12688/f1000research.6645.1
      Issue No: Vol. 4 (2015)
  • Conservation in the face of climate change: recent developments [version
           1; referees: 3 approved]

    • Authors: Joshua Lawler, James Watson, Edward Game
      Abstract: An increased understanding of the current and potential future impacts of climate change has significantly influenced conservation in practice in recent years. Climate change has necessitated a shift toward longer planning time horizons, moving baselines, and evolving conservation goals and targets. This shift has resulted in new perspectives on, and changes in, the basic approaches practitioners use to conserve biodiversity. Restoration, spatial planning and reserve selection, connectivity modelling, extinction risk assessment, and species translocations have all been reimagined in the face of climate change. Restoration is being conducted with a new acceptance of uncertainty and an understanding that goals will need to shift through time. New conservation targets, such as geophysical settings and climatic refugia, are being incorporated into conservation plans. Risk assessments have begun to consider the potentially synergistic impacts of climate change and other threats. Assisted colonization has gained acceptance in recent years as a viable and necessary conservation tool. This evolution has paralleled a larger trend in conservation—a shift toward conservation actions that benefit both people and nature. As we look forward, it is clear that more change is on the horizon. To protect biodiversity and essential ecosystem services, conservation will need to anticipate the human response to climate change and to focus not only on resistance and resilience but on transitions to new states and new ecosystems.
      PubDate: 2015-10-28T09:52:06Z
      DOI: 10.12688/f1000research.6490.1
      Issue No: Vol. 4 (2015)
  • Early lessons from schistosomiasis mass drug administration programs
           [version 1; referees: 3 approved]

    • Authors: W. Evan Secor
      Abstract: Mass drug administration using praziquantel is the backbone of the current strategy for the control of schistosomiasis. As the theoretical plans have moved into practical application, certain challenges with this approach have surfaced, and it is likely that annual mass drug administration alone may not be sufficient to achieve program goals. However, mass drug administration is still the only available intervention that can be readily used in the wide variety of settings where schistosomiasis is endemic. The task then becomes how to improve this approach and identify what adjuncts to mass drug administration are effective, as programs move from morbidity control to elimination goals. Other aspects worthy of consideration include how best to employ new diagnostic tools to more easily identify where treatment is needed, and new formulations of praziquantel to extend the availability of treatment to all age groups. The aim of this review is to highlight both areas of challenge and of opportunity to improve the public health impact of schistosomiasis control programs.
      PubDate: 2015-10-28T09:46:13Z
      DOI: 10.12688/f1000research.6826.1
      Issue No: Vol. 4 (2015)
  • Bugs, genes, fatty acids, and serotonin: Unraveling inflammatory bowel
           disease' [version 1; referees: 3 approved]

    • Authors: Jonathan Kaunitz, Piyush Nayyar
      Abstract: The annual incidence of the inflammatory bowel diseases (IBDs) ulcerative colitis and Crohn’s disease has increased at an alarming rate. Although the specific pathophysiology underlying IBD continues to be elusive, it is hypothesized that IBD results from an aberrant and persistent immune response directed against microbes or their products in the gut, facilitated by the genetic susceptibility of the host and intrinsic alterations in mucosal barrier function. In this review, we will describe advances in the understanding of how the interaction of host genetics and the intestinal microbiome contribute to the pathogenesis of IBD, with a focus on bacterial metabolites such as short chain fatty acids (SCFAs) as possible key signaling molecules.  In particular, we will describe alterations of the intestinal microbiota in IBD, focusing on how genetic loci affect the gut microbial phylogenetic distribution and the production of their major microbial metabolic product, SCFAs. We then describe how enteroendocrine cells and myenteric nerves express SCFA receptors that integrate networks such as the cholinergic and serotonergic neural systems and the glucagon-like peptide hormonal pathway, to modulate gut inflammation, permeability, and growth as part of an integrated model of IBD pathogenesis.  Through this integrative approach, we hope that novel hypotheses will emerge that will be tested in reductionist, hypothesis-driven studies in order to examine the interrelationship of these systems in the hope of better understanding IBD pathogenesis and to inform novel therapies.
      PubDate: 2015-10-27T16:05:39Z
      DOI: 10.12688/f1000research.6456.1
      Issue No: Vol. 4 (2015)
  • Embryo-lethal phenotypes in early abp1 mutants are due to disruption of
           the neighboring BSM gene [version 1; referees: 3 approved]

    • Abstract: The Auxin Binding Protein1 (ABP1) has been identified based on its ability to bind auxin with high affinity and studied for a long time as a prime candidate for the extracellular auxin receptor responsible for mediating in particular the fast non-transcriptional auxin responses. However, the contradiction between the embryo-lethal phenotypes of the originally described Arabidopsis T-DNA insertional knock-out alleles (abp1-1 and abp1-1s) and the wild type-like phenotypes of other recently described loss-of-function alleles (abp1-c1 and abp1-TD1) questions the biological importance of ABP1 and relevance of the previous genetic studies. Here we show that there is no hidden copy of the ABP1 gene in the Arabidopsis genome but the embryo-lethal phenotypes of abp1-1 and abp1-1s alleles are very similar to the knock-out phenotypes of the neighboring gene, BELAYA SMERT (BSM). Furthermore, the allelic complementation test between bsm and abp1 alleles shows that the embryo-lethality in the abp1-1 and abp1-1s alleles is caused by the off-target disruption of the BSM locus by the T-DNA insertions. This clarifies the controversy of different phenotypes among published abp1 knock-out alleles and asks for reflections on the developmental role of ABP1.
      PubDate: 2015-10-23T15:16:37Z
      DOI: 10.12688/f1000research.7143.1
      Issue No: Vol. 4 (2015)
  • Oxygen changes drive non-uniform scaling in Drosophila melanogaster
           embryogenesis [version 1; referees: 2 approved, 1 approved with

    • Authors: Steven G. Kuntz, Michael B. Eisen
      Abstract: We previously demonstrated that, while changes in temperature produce dramatic shifts in the time elapsed during Drosophila melanogaster embryogenesis, the relative timing of events within embryogenesis does not change. However, it was unclear if this uniform scaling is an intrinsic property of developing embryos, or if it is specific to thermal fluctuations. To investigate this, here we characterize the embryonic response to changes in oxygen concentration, which also impact developmental rate, using time-lapse imaging, and find it fundamentally different from the temperature response. Most notably, changes in oxygen levels drive developmental heterochrony, with the timing of several morphological processes showing distinct scaling behaviors. Gut formation is severely slowed by decreases in oxygen, while head involution and syncytial development are less impacted than the rest of development, and the order of several developmental landmarks is inverted at different oxygen levels. These data reveal that the uniform scaling seen with changes in temperature is not a trivial consequence of adjusting developmental rate. The developmental rate changes produced by changing oxygen concentrations dwarf those induced by temperature, and greatly impact survival. While extreme temperatures increase early embryo mortality, mild hypoxia increases arrest and death during mid-embryogenesis and mild hyperoxia increases survival over normoxia.
      PubDate: 2015-10-23T11:06:17Z
      DOI: 10.12688/f1000research.7221.1
      Issue No: Vol. 4 (2015)
  • Case Report: Severe acute respiratory distress by tracheal obstruction due
           to a congenital thyroid teratoma. [version 3; referees: 2 approved]

    • Authors: Jose Colleti Junior, Uenis Tannuri, Felipe Monti Lora, Eliana Carla Armelin Benites, Walter Koga, Janete Honda Imamura, Patricia Rute Moutinho, Werther Brunow de Carvalho
      Abstract: Congenital teratoma is a rare condition and is a germ cell tumor composed of elements from one or more of the embryonic germ layers and contain tissues usually foreign to the anatomic site of origin. We report a case of a neck tumor diagnosed during pregnancy, initially thought to be a goiter. After birth the neck mass kept growing until it compressed the trachea and produced respiratory failure. The infant had a difficult tracheal intubation because of the compressing mass. The staff decided to surgically remove the neck mass. After that, the infant became eupneic. The histological analysis showed a mature teratoma with no atypias.
      PubDate: 2015-10-22T10:57:57Z
      DOI: 10.12688/f1000research.6589.3
      Issue No: Vol. 4 (2015)
  • MinION Analysis and Reference Consortium: Phase 1 data release and
           analysis [version 1; referees: 2 approved]

    • Authors: Camilla L.C. Ip, Matthew Loose, John R. Tyson, Mariateresa de Cesare, Bonnie L. Brown, Miten Jain, Richard M. Leggett, David A. Eccles, Vadim Zalunin, John M. Urban, Paolo Piazza, Rory J. Bowden, Benedict Paten, Solomon Mwaigwisya, Elizabeth M. Batty, Jared T. Simpson, Terrance P. Snutch, Ewan Birney, David Buck, Sara Goodwin, Hans J. Jansen, Justin O'Grady, Hugh E. Olsen, MinION Analysis; Reference Consortium
      Abstract: The advent of a miniaturized DNA sequencing device with a high-throughput contextual sequencing capability embodies the next generation of large scale sequencing tools. The MinION™ Access Programme (MAP) was initiated by Oxford Nanopore Technologies™ in April 2014, giving public access to their USB-attached miniature sequencing device. The MinION Analysis and Reference Consortium (MARC) was formed by a subset of MAP participants, with the aim of evaluating and providing standard protocols and reference data to the community. Envisaged as a multi-phased project, this study provides the global community with the Phase 1 data from MARC, where the reproducibility of the performance of the MinION was evaluated at multiple sites. Five laboratories on two continents generated data using a control strain of Escherichia coli K-12, preparing and sequencing samples according to a revised ONT protocol. Here, we provide the details of the protocol used, along with a preliminary analysis of the characteristics of typical runs including the consistency, rate, volume and quality of data produced. Further analysis of the Phase 1 data presented here, and additional experiments in Phase 2 of E. coli from MARC are already underway to identify ways to improve and enhance MinION performance.
      PubDate: 2015-10-15T12:37:48Z
      DOI: 10.12688/f1000research.7201.1
      Issue No: Vol. 4 (2015)
  • Leukocyte telomere length and hippocampus volume: a meta-analysis [version
           1; referees: 2 approved]

    • Abstract: Leukocyte telomere length has been shown to correlate to hippocampus volume, but effect estimates differ in magnitude and are not uniformly positive. This study aimed primarily to investigate the relationship between leukocyte telomere length and hippocampus gray matter volume by meta-analysis and secondarily to investigate possible effect moderators. Five studies were included with a total of 2107 participants, of which 1960 were contributed by one single influential study. A random-effects meta-analysis estimated the effect to r = 0.12 [95% CI -0.13, 0.37] in the presence of heterogeneity and a subjectively estimated moderate to high risk of bias. There was no evidence that apolipoprotein E (APOE) genotype was an effect moderator, nor that the ratio of leukocyte telomerase activity to telomere length was a better predictor than leukocyte telomere length for hippocampus volume. This meta-analysis, while not proving a positive relationship, also is not able to disprove the earlier finding of a positive correlation in the one large study included in analyses. We propose that a relationship between leukocyte telomere length and hippocamus volume may be mediated by transmigrating monocytes which differentiate into microglia in the brain parenchyma.
      PubDate: 2015-10-15T09:45:04Z
      DOI: 10.12688/f1000research.7198.1
      Issue No: Vol. 4 (2015)
  • AnalogExplorer2 – Stereochemistry sensitive graphical analysis of
           large analog series [version 1; referees: 2 approved]

    • Abstract: AnalogExplorer is a computational methodology for the extraction and organization of series of structural analogs from compound data sets and their graphical analysis. The method is suitable for the analysis of large analog series originating from lead optimization programs. Herein we report AnalogExplorer2 designed to explicitly take stereochemical information during graphical analysis into account and describe a freely available deposition of the original AnalogExplorer program, AnalogExplorer2, and exemplary compound sets to illustrate their use.
      PubDate: 2015-10-09T09:38:03Z
      DOI: 10.12688/f1000research.7146.1
      Issue No: Vol. 4 (2015)
  • Case Report: Pulmonary Kaposi Sarcoma in a non-HIV patient [version 1;
           referees: 2 approved]

    • Authors: Arber Kodra, Maciej Walczyszyn, Craig Grossman, Daniel Zapata, Tarak Rambhatla, Bushra Mina
      Abstract: Kaposi Sarcoma (KS) is an angioproliferative tumor associated with human herpes virus 8 (HHV-8).  Often known as one of the acquired immunodeficiency syndrome (AIDS)-defining skin diseases, pulmonary involvement in KS has only been discussed in a handful of case reports, rarely in a non-HIV patient. Herein we report the case of a 77 year-old- male who presented with a 6-week history of progressive dyspnea on exertion accompanied by productive cough of yellow sputum and intermittent hemoptysis. His past medical history was significant for Non-Hodgkin’s Follicular B-Cell Lymphoma (NHL). Patient also had biopsy-confirmed cutaneous KS. His physical exam was notable for a 2cm firm, non-tender, mobile right submandibular lymph node.  Lungs were clear to auscultation. He had multiple violet non-tender skin lesions localized to the lower extremities. CT scan of the chest showed numerous nodular opacities and small pleural effusions in both lungs. A thoracenthesis was performed, showing sero-sanguineous exudative effusions. Histopathology failed to demonstrate malignant cells or lymphoma. A subsequent bronchoscopy revealed diffusely hyperemic, swollen mucosa of the lower airways with mucopurulent secretions. Bronchoalveolar lavage PCR for HHV-8 showed 5800 DNA copies/mL.  It was believed that his pulmonary symptoms were likely due to disseminated KS.  This case illustrates the potential for significant lung injury from KS. It also demonstrates the use of PCR for HHV-8 to diagnose KS in a bronchoalveolar lavage sample in a case when bronchoscopic biopsy was not safe. Furthermore, this case is unique in that the patient did not match the typical KS subgroups as HIV infection and other immune disorders were ruled out. Recognition of this syndrome is critical to the institution of appropriate therapy. As such, this case should be of interest to a broad readership across internal medicine including the specialties of Pulmonology and Critical Care.
      PubDate: 2015-10-07T15:33:17Z
      DOI: 10.12688/f1000research.7137.1
      Issue No: Vol. 4 (2015)
  • Matching Behavior as a Tradeoff Between Reward Maximization and Demands on
           Neural Computation [version 2; referees: 2 approved]

    • Authors: Jan Kubanek, Lawrence H. Snyder
      Abstract: When faced with a choice, humans and animals commonly distribute their behavior in proportion to the frequency of payoff of each option. Such behavior is referred to as matching and has been captured by the matching law. However, matching is not a general law of economic choice. Matching in its strict sense seems to be specifically observed in tasks whose properties make matching an optimal or a near-optimal strategy. We engaged monkeys in a foraging task in which matching was not the optimal strategy. Over-matching the proportions of the mean offered reward magnitudes would yield more reward than matching, yet, surprisingly, the animals almost exactly matched them. To gain insight into this phenomenon, we modeled the animals' decision-making using a mechanistic model. The model accounted for the animals' macroscopic and microscopic choice behavior. When the models' three parameters were not constrained to mimic the monkeys' behavior, the model over-matched the reward proportions and in doing so, harvested substantially more reward than the monkeys. This optimized model revealed a marked bottleneck in the monkeys' choice function that compares the value of the two options. The model featured a very steep value comparison function relative to that of the monkeys. The steepness of the value comparison function had a profound effect on the earned reward and on the level of matching. We implemented this value comparison function through responses of simulated biological neurons. We found that due to the presence of neural noise, steepening the value comparison requires an exponential increase in the number of value-coding neurons. Matching may be a compromise between harvesting satisfactory reward and the high demands placed by neural noise on optimal neural computation.
      PubDate: 2015-10-02T16:06:54Z
      DOI: 10.12688/f1000research.6574.2
      Issue No: Vol. 4 (2015)
  • Circulating nucleic acids: a new class of physiological mobile genetic
           elements [version 1; referees: 2 approved]

    • Authors: Indraneel Mittra
      Abstract: Mobile genetic elements play a major role in shaping biotic genomes and bringing about evolutionary transformations. Herein, a new class of mobile genetic elements is proposed in the form of circulating nucleic acids (CNAs) derived from the billions of cells that die in the body every day due to normal physiology and that act intra-corporeally. A recent study shows that CNAs can freely enter into healthy cells, integrate into their genomes by a unique mechanism and cause damage to their DNA. Being ubiquitous and continuously arising, CNA-induced DNA damage may be the underlying cause of ageing, ageing-related disabilities and the ultimate demise of the organism. Thus, DNA seems to act in the paradoxical roles of both preserver and destroyer of life. This new class of mobile genetic element may be relevant not only to multi-cellular organisms with established circulatory systems, but also to other multi-cellular organisms in which intra-corporeal mobility of nucleic acids may be mediated via the medium of extra-cellular fluid.
      PubDate: 2015-09-30T09:28:12Z
      DOI: 10.12688/f1000research.7095.1
      Issue No: Vol. 4 (2015)
  • A citation-based, author- and age-normalized, logarithmic index for
           evaluation of individual researchers independently of publication counts
           [version 1; referees: 2 approved]

    • Authors: Aleksey V. Belikov, Vitaly V. Belikov
      Abstract: The use of citation metrics for evaluation of individual researchers has dramatically increased over the last decade. However, currently existing indices either are based on misleading premises or are cumbersome to implement. This leads to poor assessment of researchers and creates dangerous trends in science, such as overproduction of low quality articles. Here we propose an index (namely, the L-index) that does not depend on the number of publications, accounts for different co-author contributions and age of publications, and scales from 0.0 to 9.9. Moreover, it can be calculated with the help of freely available software.
      PubDate: 2015-09-22T11:05:24Z
      DOI: 10.12688/f1000research.7070.1
      Issue No: Vol. 4 (2015)
  • The ICR1000 UK exome series: a resource of gene variation in an outbred
           population [version 1; referees: 2 approved]

    • Abstract: To enhance knowledge of gene variation in outbred populations, and to provide a dataset with utility in research and clinical genomics, we performed exome sequencing of 1,000 UK individuals from the general population and applied a high-quality analysis pipeline that includes high sensitivity and specificity for indel detection. Each UK individual has, on average, 21,978 gene variants including 160 rare (0.1%) variants not present in any other individual in the series. These data provide a baseline expectation for gene variation in an outbred population. Summary data of all 295,391 variants we detected are included here and the individual exome sequences are available from the European Genome-phenome Archive as the ICR1000 UK exome series. Furthermore, samples and other phenotype and experimental data for these individuals are obtainable through application to the 1958 Birth Cohort committee.
      PubDate: 2015-09-22T09:38:52Z
      DOI: 10.12688/f1000research.7049.1
      Issue No: Vol. 4 (2015)
  • Individuality, phenotypic differentiation, dormancy and
           ‘persistence’ in culturable bacterial systems: commonalities
           shared by environmental, laboratory, and clinical microbiology [version 2;
           referees: 2 approved, 1 approved with reservations]

    • Authors: Douglas Kell, Marnie Potgieter, Etheresia Pretorius
      Abstract: For bacteria, replication mainly involves growth by binary fission. However, in a very great many natural environments there are examples of phenotypically dormant, non-growing cells that do not replicate immediately and that are phenotypically ‘nonculturable’ on media that normally admit their growth. They thereby evade detection by conventional culture-based methods. Such dormant cells may also be observed in laboratory cultures and in clinical microbiology. They are usually more tolerant to stresses such as antibiotics, and in clinical microbiology they are typically referred to as ‘persisters’. Bacterial cultures necessarily share a great deal of relatedness, and inclusive fitness theory implies that there are conceptual evolutionary advantages in trading a variation in growth rate against its mean, equivalent to hedging one’s bets. There is much evidence that bacteria exploit this strategy widely. We here bring together data that show the commonality of these phenomena across environmental, laboratory and clinical microbiology. Considerable evidence, using methods similar to those common in environmental microbiology, now suggests that many supposedly non-communicable, chronic and inflammatory diseases are exacerbated (if not indeed largely caused) by the presence of dormant or persistent bacteria (the ability of whose components to cause inflammation is well known). This dormancy (and resuscitation therefrom) often reflects the extent of the availability of free iron. Together, these phenomena can provide a ready explanation for the continuing inflammation common to such chronic diseases and its correlation with iron dysregulation. This implies that measures designed to assess and to inhibit or remove such organisms (or their access to iron) might be of much therapeutic benefit.
      PubDate: 2015-09-07T13:57:54Z
      DOI: 10.12688/f1000research.6709.2
      Issue No: Vol. 4 (2015)
  • Molecular Dynamics Simulations of the Temperature Induced Unfolding of
           Crambin Follow the Arrhenius Equation. [version 1; referees: 1 approved, 2
           approved with reservations]

    • Authors: Andrew Dalby, Mohd Shahir Shamsir
      Abstract: Molecular dynamics simulations have been used extensively to model the folding and unfolding of proteins. The rates of folding and unfolding should follow the Arrhenius equation over a limited range of temperatures. This study shows that molecular dynamic simulations of the unfolding of crambin between 500K and 560K do follow the Arrhenius equation. They also show that while there is a large amount of variation between the simulations the average values for the rate show a very high degree of correlation.
      PubDate: 2015-08-20T13:25:47Z
      DOI: 10.12688/f1000research.6831.1
      Issue No: Vol. 4 (2015)
  • SLiMScape 3.x: a Cytoscape 3 app for discovery of Short Linear Motifs in
           protein interaction networks [version 1; referees: 2 approved]

    • Abstract: Short linear motifs (SLiMs) are small protein sequence patterns that mediate a large number of critical protein-protein interactions, involved in processes such as complex formation, signal transduction, localisation and stabilisation. SLiMs show rapid evolutionary dynamics and are frequently the targets of molecular mimicry by pathogens. Identifying enriched sequence patterns due to convergent evolution in non-homologous proteins has proven to be a successful strategy for computational SLiM prediction. Tools of the SLiMSuite package use this strategy, using a statistical model to identify SLiM enrichment based on the evolutionary relationships, amino acid composition and predicted disorder of the input proteins. The quality of input data is critical for successful SLiM prediction. Cytoscape provides a user-friendly, interactive environment to explore interaction networks and select proteins based on common features, such as shared interaction partners. SLiMScape embeds tools of the SLiMSuite package for de novo SLiM discovery (SLiMFinder and QSLiMFinder) and identifying occurrences/enrichment of known SLiMs (SLiMProb) within this interactive framework. SLiMScape makes it easier to (1) generate high quality hypothesis-driven datasets for these tools, and (2) visualise predicted SLiM occurrences within the context of the network. To generate new predictions, users can select nodes from a protein network or provide a set of Uniprot identifiers. SLiMProb also requires additional query motif input. Jobs are then run remotely on the SLiMSuite server ( for subsequent retrieval and visualisation. SLiMScape can also be used to retrieve and visualise results from jobs run directly on the server. SLiMScape and SLiMSuite are open source and freely available via GitHub under GNU licenses.
      PubDate: 2015-08-05T14:17:57Z
      DOI: 10.12688/f1000research.6773.1
      Issue No: Vol. 4 (2015)
  • Chemotherapy for Late-Stage Cancer Patients: Meta-Analysis of Complete
           Response Rates [version 1; referees: 2 approved]

    • Authors: Martin L. Ashdown, Andrew P. Robinson, Steven L. Yatomi-Clarke, M. Luisa Ashdown, Andrew Allison, Derek Abbott, Svetomir N. Markovic, Brendon J. Coventry
      Abstract: Complete response (CR) rates reported for cytotoxic chemotherapy for late-stage cancer patients are generally low, with few exceptions, regardless of the solid cancer type or drug regimen. We investigated CR rates reported in the literature for clinical trials using chemotherapy alone, across a wide range of tumour types and chemotherapeutic regimens, to determine an overall CR rate for late-stage cancers. A total of 141 reports were located using the PubMed database. A meta-analysis was performed of reported CR from 68 chemotherapy trials (total 2732 patients) using standard agents across late-stage solid cancers—a binomial model with random effects was adopted. Mean CR rates were compared for different cancer types, and for chemotherapeutic agents with different mechanisms of action, using a logistic regression. Our results showed that the CR rates for chemotherapy treatment of late-stage cancer were generally low at 7.4%, regardless of the cancer type or drug regimen used. We found no evidence that CR rates differed between different chemotherapy drug types, but amongst different cancer types small CR differences were evident, although none exceeded a mean CR rate of 11%. This remarkable concordance of CR rates regardless of cancer or therapy type remains currently unexplained, and motivates further investigation.
      PubDate: 2015-07-13T10:02:57Z
      DOI: 10.12688/f1000research.6760.1
      Issue No: Vol. 4 (2015)
  • Case Report: Stevens-Johnson syndrome following a single double dosing of
           nevirapine-containing regimen once in an HIV-infected woman on long-term
           antiretroviral therapy. [version 1; referees: 1 approved, 2 approved with

    • Authors: Betty Kakande, Thuraya Isaacs, Rudzani Muloiwa, Sipho Dlamini, Rannakoe Lehloenya
      Abstract: A 31-year old HIV-infected African woman on nevirapine, tenofovir and lamivudine for more than 4 years presented with an 8-day history of symptoms and signs of Stevens-Johnson syndrome. She was on no other medication. Her viral load was undetectable and she had maintained a CD4 count of between 356 and 387cells/mm3 in the preceding 2½ years. She missed her antiretrovirals 10 days before the onset of her symptoms and subsequently doubled her daily dose the following day. She had been on no other medication in the preceding 8 weeks. Her ARVs were stopped and she fully re-epithelialized with the exception of the lips, over the following 10 days. She was started on a daily single tablet of Odimune® (a fixed drug combination antiretroviral containing tenofovir, emtricitabine and efavirenz).   Nevirapine is the most common offender in cases of antiretroviral-associated SJS in published literature. Lamivudine is very rarely implicated while there are no similar reports with tenofovir.  We concluded that nevirapine was by far the most likely offender in this case. Nevirapine toxicity is associated with high CD4 counts, undetectable viral load and high drug plasma level. We postulate that the sudden increase of the plasma levels of nevirapine in a patient with a high CD4 count and undetectable viral load created a perfect storm for the development of SJS in our patient, who had been on the NVP-containing regimen for many years. Clinicians should be aware that severe adverse drug reactions are dynamic and can occur even when the drug has been in use for a long time.
      PubDate: 2015-06-30T10:24:30Z
      DOI: 10.12688/f1000research.6715.1
      Issue No: Vol. 4 (2015)
  • Following specific podocyte injury captopril protects against progressive
           long term renal damage [version 1; referees: 1 approved, 2 approved with

    • Authors: Yu S Zhou, Ihmoda A Ihmoda, Richard G Phelps, Christopher OS Bellamy, A Neil Turner
      Abstract: Background: Angiotensin converting enzyme inhibitors (ACEi) reduce proteinuria and preserve kidney function in proteinuric renal diseases. Their nephroprotective effect exceeds that attributable to lowering of blood pressure alone. This study examines the potential of ACEi to protect from progression of injury after a highly specific injury to podocytes in a mouse model. Methods: We created transgenic (Podo-DTR) mice in which graded specific podocyte injury could be induced by a single injection of diphtheria toxin. Transgenic and wild-type mice were given the ACEi captopril in drinking water, or water alone, commencing 24h after toxin injection. Kidneys were examined histologically at 8 weeks and injury assessed by observers blinded to experimental group. Results: After toxin injection, Podo-DTR mice developed acute proteinuria, and at higher doses transient renal impairment, which subsided within 3 weeks to be followed by a slow glomerular scarring process. Captopril treatment in Podo-DTR line 57 after toxin injection at 5ng/g body weight reduced proteinuria and ameliorated glomerular scarring, matrix accumulation and glomerulosclerosis almost to baseline (toxin: 17%; toxin + ACEi 10%, p
      PubDate: 2015-06-29T10:38:29Z
      DOI: 10.12688/f1000research.4030.1
      Issue No: Vol. 4 (2015)
  • Study Protocol: The influence of Running Therapy on executive functions
           and sleep of prisoners [version 1; referees: 2 approved]

    • Authors: Jesse Meijers, Joke Harte, Gerben Meynen, Pim Cuijpers
      Abstract: Background: Executive dysfunction appears to be related to increased recidivism. Of note is that sleep disturbances, which are highly prevalent in prisons, may attenuate executive functions. Thus, improving executive functions, either directly or indirectly through the improvement of sleep, may reduce recidivism. It is hypothesised that physical exercise, in the form of Running Therapy, has a direct positive effect on executive functions as well as an indirect effect through the improvement of sleep. Methods/Design: Seventy two (N = 72) detainees in various penitentiary institutions in the Netherlands will be recruited in this study. A baseline measurement, including six neuropsychological tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB), an assessment of sleep quality and duration using the Actiwatch (Actiwatch 2, Philips Respironics, Murrysville, PA, USA) and various other measurements will be administered before the start of the treatment. After 3 months of Running Therapy, participants will be assessed again with the same tests for neuropsychological and physical functioning. Primary outcomes are executive functioning and various sleep variables. Discussion: This study will be the first to investigate the possible influence of Running Therapy on the cognitive functioning, sleep and aggression in prisoners.
      PubDate: 2015-06-15T13:40:00Z
      DOI: 10.12688/f1000research.6469.1
      Issue No: Vol. 4 (2015)
  • G-Links: a gene-centric link acquisition service [version 2; referees: 2

    • Authors: Kazuki Oshita, Masaru Tomita, Kazuharu Arakawa
      Abstract: With the availability of numerous curated databases, researchers are now able to efficiently use the multitude of biological data by integrating these resources via hyperlinks and cross-references. A large proportion of bioinformatics research tasks, however, may include labor-intensive tasks such as fetching, parsing, and merging datasets and functional annotations from distributed multi-domain databases. This data integration issue is one of the key challenges in bioinformatics. We aim to provide an identifier conversion and data aggregation system as a part of solution to solve this problem with a service named G-Links, 1) by gathering resource URI information from 130 databases and 30 web services in a gene-centric manner so that users can retrieve all available links about a given gene, 2) by providing RESTful API for easy retrieval of links including facet searching based on keywords and/or predicate types, and 3) by producing a variety of outputs as visual HTML page, tab-delimited text, and in Semantic Web formats such as Notation3 and RDF. G-Links as well as other relevant documentation are available at
      PubDate: 2015-11-18T15:01:17Z
      DOI: 10.12688/f1000research.5754.2
      Issue No: Vol. 3 (2015)
  • Rampant software errors may undermine scientific results [version 2;
           referees: 2 approved]

    • Authors: David A. W. Soergel
      Abstract: The opportunities for both subtle and profound errors in software and data management are boundless, yet they remain surprisingly underappreciated. Here I estimate that any reported scientific result could very well be wrong if data have passed through a computer, and that these errors may remain largely undetected.  It is therefore necessary to greatly expand our efforts to validate scientific software and computed results.
      PubDate: 2015-07-29T10:40:37Z
      DOI: 10.12688/f1000research.5930.2
      Issue No: Vol. 3 (2015)
  • The PDB database is a rich source of alpha-helical anti-microbial peptides
           to combat disease causing pathogens [version 2; referees: 2 approved, 1
           approved with reservations]

    • Abstract: The therapeutic potential of α-helical anti-microbial peptides (AH-AMP) to combat pathogens is fast gaining prominence. Based on recently published open access software for characterizing α-helical peptides (PAGAL), we elucidate a search methodology (SCALPEL) that leverages the massive structural data pre-existing in the PDB database to obtain AH-AMPs belonging to the host proteome. We provide in vitro validation of SCALPEL on plant pathogens (Xylella fastidiosa, Xanthomonas arboricola and Liberibacter crescens) by identifying AH-AMPs that mirror the function and properties of cecropin B, a well-studied AH-AMP. The identified peptides include a linear AH-AMP present within the existing structure of phosphoenolpyruvate carboxylase (PPC20), and an AH-AMP mimicing the properties of the two α-helices of cecropin B from chitinase (CHITI25). The minimum inhibitory concentration of these peptides are comparable to that of cecropin B, while anionic peptides used as control failed to show any inhibitory effect on these pathogens. Substitute therapies in place of conventional chemotherapies using membrane permeabilizing peptides like these might also prove effective to target cancer cells. The use of native structures from the same organism could possibly ensure that administration of such peptides will be better tolerated and not elicit an adverse immune response. We suggest a similar approach to target Ebola epitopes, enumerated using PAGAL recently, by selecting suitable peptides from the human proteome, especially in wake of recent reports of cationic amphiphiles inhibiting virus entry and infection.
      PubDate: 2015-06-16T15:13:58Z
      DOI: 10.12688/f1000research.5802.2
      Issue No: Vol. 3 (2015)
  • Using Akaike's information theoretic criterion in mixed-effects modeling
           of pharmacokinetic data: a simulation study [version 3; referees: 2
           approved, 1 approved with reservations]

    • Authors: Erik Olofsen, Albert Dahan
      Abstract: Akaike's information theoretic criterion for model discrimination (AIC) is often stated to "overfit", i.e., it selects models with a higher dimension than the dimension of the model that generated the data. However, with experimental pharmacokinetic data it may not be possible to identify the correct model, because of the complexity of the processes governing drug disposition. Instead of trying to find the correct model, a more useful objective might be to minimize the prediction error of drug concentrations in subjects with unknown disposition characteristics. In that case, the AIC might be the selection criterion of choice. We performed Monte Carlo simulations using a model of pharmacokinetic data (a power function of time) with the property that fits with common multi-exponential models can never be perfect - thus resembling the situation with real data. Prespecified models were fitted to simulated data sets, and AIC and AICc (the criterion with a correction for small sample sizes) values were calculated and averaged. The average predictive performances of the models, quantified using simulated validation sets, were compared to the means of the AICs. The data for fits and validation consisted of 11 concentration measurements each obtained in 5 individuals, with three degrees of interindividual variability in the pharmacokinetic volume of distribution. Mean AICc corresponded very well, and better than mean AIC, with mean predictive performance. With increasing interindividual variability, there was a trend towards larger optimal models, but with respect to both lowest AICc and best predictive performance. Furthermore, it was observed that the mean square prediction error itself became less suitable as a validation criterion, and that a predictive performance measure should incorporate interindividual variability. This simulation study showed that, at least in a relatively simple mixed-effects modelling context with a set of prespecified models, minimal mean AICc corresponded to best predictive performance even in the presence of relatively large interindividual variability.
      PubDate: 2015-07-27T16:24:39Z
      DOI: 10.12688/f1000research.2-71.v3
      Issue No: Vol. 2 (2015)
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