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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]
  • The ubiquitous and ancient ER membrane protein complex (EMC): tether or
           not' [version 2; referees: 2 approved]

    • Authors: Jeremy G. Wideman
      Abstract: The recently discovered endoplasmic reticulum (ER) membrane protein complex (EMC) has been implicated in ER-associated degradation (ERAD), lipid transport and tethering between the ER and mitochondrial outer membranes, and assembly of multipass ER-membrane proteins. The EMC has been studied in both animals and fungi but its presence outside the Opisthokont clade (animals + fungi + related protists) has not been demonstrated. Here, using homology-searching algorithms, I show that the EMC is truly an ancient and conserved protein complex, present in every major eukaryotic lineage. Very few organisms have completely lost the EMC, and most, even over 2 billion years of eukaryote evolution, have retained a majority of the complex members. I identify Sop4 and YDR056C in Saccharomyces cerevisiae as Emc7 and Emc10, respectively, subunits previously thought to be specific to animals. This study demonstrates that the EMC was present in the last eukaryote common ancestor (LECA) and is an extremely important component of eukaryotic cells even though its primary function remains elusive.
      PubDate: 2015-10-05T15:57:14Z
      DOI: 10.12688/f1000research.6944.2
      Issue No: Vol. 4 (2015)
  • Dynamic reorganization of the actin cytoskeleton [version 1; referees: 2

    • Abstract: Cellular processes, including morphogenesis, polarization, and motility, rely on a variety of actin-based structures. Although the biochemical composition and filament organization of these structures are different, they often emerge from a common origin. This is possible because the actin structures are highly dynamic. Indeed, they assemble, grow, and disassemble in a time scale of a second to a minute. Therefore, the reorganization of a given actin structure can promote the formation of another. Here, we discuss such transitions and illustrate them with computer simulations.
      PubDate: 2015-10-01T16:26:06Z
      DOI: 10.12688/f1000research.6374.1
      Issue No: Vol. 4 (2015)
  • Anti-dsDNA Antibodies are one of the many autoantibodies in systemic lupus
           erythematosus [version 1; referees: 2 approved]

    • Authors: Shu Man Fu, Chao Dai, Zhenhuan Zhao, Felicia Gaskin
      Abstract: Anti-dsDNA antibodies are the most studied antibodies of the lupus-related autoantibodies. The dogma is that these are the most important autoantibodies in systemic lupus erythematosus. In this review, evidence is presented to show that these antibodies (as measured by modern clinical laboratories) are not the most important autoantibodies in the diagnosis of systemic lupus erythematosus, and are of limited value in clinical correlation and in predicting disease flares. In addition, they are not likely to be the initiating autoantibodies in lupus nephritis. Thus, several pervasively held beliefs on anti-dsDNA antibodies are not valid. We suggest that anti-dsDNA antibodies should be considered as just one of the many autoantibodies associated with systemic lupus erythematosus.
      PubDate: 2015-10-01T15:37:44Z
      DOI: 10.12688/f1000research.6875.1
      Issue No: Vol. 4 (2015)
  • Leishmania carbon metabolism in the macrophage phagolysosome- feast or
           famine' [version 1; referees: 3 approved]

    • Authors: Malcolm J. McConville, Eleanor C. Saunders, Joachim Kloehn, Michael J. Dagley
      Abstract: A number of medically important microbial pathogens target and proliferate within macrophages and other phagocytic cells in their mammalian hosts. While the majority of these pathogens replicate within the host cell cytosol or non-hydrolytic vacuolar compartments, a few, including protists belonging to the genus Leishmania, proliferate long-term within mature lysosome compartments.  How these parasites achieve this feat remains poorly defined. In this review, we highlight recent studies that suggest that Leishmania virulence is intimately linked to programmed changes in the growth rate and carbon metabolism of the obligate intra-macrophage stages. We propose that activation of a slow growth and a stringent metabolic response confers resistance to multiple stresses (oxidative, temperature, pH), as well as both nutrient limitation and nutrient excess within this niche. These studies highlight the importance of metabolic processes as key virulence determinants in Leishmania.
      PubDate: 2015-10-01T15:11:56Z
      DOI: 10.12688/f1000research.6724.1
      Issue No: Vol. 4 (2015)
  • Cytotoxic granule secretion by lymphocytes and its link to immune
           homeostasis [version 1; referees: 2 approved]

    • Abstract: The granule-dependent cytotoxic activity of T and natural killer lymphocytes has progressively emerged as an important effector pathway not only for host defence but also for immune regulation. The analysis of an early-onset, severe, primary immune dysregulatory syndrome known as hemophagocytic lymphohistiocytosis (HLH) has been decisive in highlighting this latter role and identifying key effectors on the basis of gene mutation analyses and mediators in the maturation and secretion of cytotoxic granules. Studies of cytotoxicity-deficient murine counterparts have helped to define primary HLH as a syndrome in which uncontrolled T-cell activation in response to lymphocytic choriomeningitis virus infection results in excessive macrophage activation and inflammation-associated cytopenia. Recent recognition of late-onset HLH, which occurs in a variety of settings, in association with hypomorphic, monoallelic mutations in genes encoding components of the granule-dependent cytotoxic pathway or even in the absence of such mutations has broadened our view about the mechanisms that underlie the perturbation of immune homeostasis. These findings have led to the development of a model in which disease occurs when a threshold is reached through the accumulation of genetic and environmental risk factors. Nevertheless, validation of this model will require further investigations.
      PubDate: 2015-09-30T14:33:05Z
      DOI: 10.12688/f1000research.6754.1
      Issue No: Vol. 4 (2015)
  • Hot topics in biodiversity and climate change research [version 1;
           referees: 2 approved]

    • Authors: Barry W. Brook, Damien A. Fordham
      Abstract: With scientific and societal interest in biodiversity impacts of climate change growing enormously over the last decade, we analysed directions and biases in the recent most highly cited data papers in this field of research (from 2012 to 2014). The majority of this work relied on leveraging large databases of already collected historical information (but not paleo- or genetic data), and coupled these to new methodologies for making forward projections of shifts in species’ geographical ranges, with a focus on temperate and montane plants. A consistent finding was that the pace of climate-driven habitat change, along with increased frequency of extreme events, is outpacing the capacity of species or ecological communities to respond and adapt.
      PubDate: 2015-09-30T13:10:36Z
      DOI: 10.12688/f1000research.6508.1
      Issue No: Vol. 4 (2015)
  • Chemoprevention of cancer: current evidence and future prospects [version
           1; referees: 3 approved]

    • Authors: Vassiliki Benetou, Areti Lagiou, Pagona Lagiou
      Abstract: Cancer chemoprevention refers to the use of agents for the inhibition, delay, or reversal of carcinogenesis before invasion. In the present review, agents examined in the context of cancer chemoprevention are classified in four major categories—hormonal, medications, diet-related agents, and vaccines—and the main representatives of each category are presented. Although there are serious constraints in the documentation of effectiveness of chemopreventive agents, mainly stemming from the long latency of the condition they are addressing and the frequent lack of intermediate biomarkers, there is little disagreement about the role of aspirin, whereas a diet rich in vegetables and fruits appears to convey more protection than individual micronutrients. Among categories of cancer chemopreventive agents, hormonal ones and vaccines might hold more promise for the future. Also, the identification of individuals who would benefit most from chemopreventive interventions on the basis of their genetic profiles could open new prospects for cancer chemoprevention.
      PubDate: 2015-09-28T16:17:16Z
      DOI: 10.12688/f1000research.6684.1
      Issue No: Vol. 4 (2015)
  • Recent advances in echocardiography for valvular heart disease [version 1;
           referees: 3 approved]

    • Authors: Rebecca Hahn
      Abstract: Echocardiography is the imaging modality of choice for the assessment of patients with valvular heart disease. Echocardiographic advancements may have particular impact on the assessment and management of patients with valvular heart disease. This review will summarize the current literature on advancements, such as three-dimensional echocardiography, strain imaging, intracardiac echocardiography, and fusion imaging, in this patient population.
      PubDate: 2015-09-28T15:58:16Z
      DOI: 10.12688/f1000research.6446.1
      Issue No: Vol. 4 (2015)
  • Impact of a structured review session on medical student psychiatry
           subject examination performance [version 1; referees: 2 approved]

    • Authors: Shan H. Siddiqi, Kevin J. Black, Fay Y. Womer
      Abstract: Introduction: The National Board of Medical Examiners (NBME) subject examinations are used as a standardized metric for performance in required clerkships for third-year medical students. While several medical schools have implemented a review session to help consolidate knowledge acquired during the clerkship, the effects of such an intervention are not yet well-established. One prior study reported an improvement in NBME psychiatry examination scores with a 1.5-hour review session, but this study was limited by a small sample size and the fact that attendance at the review session was optional, leading to likely selection bias.   Methods: A 1.5-hour structured review session was conducted for medical students in the last week of each 4-week psychiatry clerkship between September 2014 and July 2015. Students were required to attend unless excused due to scheduling conflicts. Scores on the NBME psychiatry subject exam were compared with those of students taking the examination in the corresponding time period in each of the previous two academic years.   Results: 83 students took the exam during the experimental period, while 176 took the exam during the control period. Statistically significant improvements were found in mean score (p=0.03), mean for the two lowest scores in each group (p
      PubDate: 2015-09-24T09:25:31Z
      DOI: 10.12688/f1000research.7091.1
      Issue No: Vol. 4 (2015)
  • Hippocampal development and the dissociation of cognitive-spatial mapping
           from motor performance [version 2; referees: 2 approved]

    • Authors: Bryan D. Devan, Christopher Magalis, Robert J. McDonald
      Abstract: The publication of a recent article in F1000Research has led to discussion of, and correspondence on a broader issue that has a long history in the fields of neuroscience and psychology.  Namely, is it possible to separate the cognitive components of performance, in this case spatial behavior, from the motoric demands of a task'  Early psychological experiments attempted such a dissociation by studying a form of spatial maze learning where initially rats were allowed to explore a complex maze, termed “latent learning,” before reinforcement was introduced.  Those rats afforded the latent learning experience solved the task faster than those that were not, implying that cognitive map learning during exploration aided in the performance of the task once a motivational component was introduced.  This form of latent learning was interpreted as successfully demonstrating that an exploratory cognitive map component was acquired irrespective of performing a learned spatial response under deprivation/motivational conditions.  The neural substrate for cognitive learning was hypothesized to depend on place cells within the hippocampus.  Subsequent behavioral studies attempted to directly eliminate the motor component of spatial learning by allowing rats to passively view the distal environment before performing any motor response using a task that is widely considered to be hippocampal-dependent.  Latent learning in the water maze, using a passive placement procedure has met with mixed results.  One constraint on viewing cues before performing a learned swimming response to a hidden goal has been the act of dynamically viewing distal cues while moving through a part of the environment where an optimal learned spatial escape response would be observed.  We briefly review these past findings obtained with adult animals to the recent efforts of establishing a “behavioral topology” separating cognitive-spatial learning from tasks differing in motoric demands in an attempt to define when cognitive-spatial behavior emerges during development.
      PubDate: 2015-09-21T13:09:48Z
      DOI: 10.12688/f1000research.6966.2
      Issue No: Vol. 4 (2015)
  • The Antibody Two-Step Solution [version 1; referees: 2 approved]

    • Authors: Mike Browning
      Abstract: Problems with antibody quality have been described in numerous recent publications.  In the present commentary it is argued that these quality problems are due primarily to issues of antibody variability and antibody validation.  Further it is argued that the problem of antibody variability must be solved before validation can be useful.  A two-step solution to the antibody problem is thus proposed.
      PubDate: 2015-09-15T13:17:49Z
      DOI: 10.12688/f1000research.7055.1
      Issue No: Vol. 4 (2015)
  • Fatty acids from diet and microbiota regulate energy metabolism [version
           1; referees: 2 approved]

    • Authors: Joe Alcock, Henry C. Lin
      Abstract: A high-fat diet and elevated levels of free fatty acids are known risk factors for metabolic syndrome, insulin resistance, and visceral obesity. Although these disease associations are well established, it is unclear how different dietary fats change the risk of insulin resistance and metabolic syndrome. Here, we review emerging evidence that insulin resistance and fat storage are linked to changes in the gut microbiota. The gut microbiota and intestinal barrier function, in turn, are highly influenced by the composition of fat in the diet. We review findings that certain fats (for example, long-chain saturated fatty acids) are associated with dysbiosis, impairment of intestinal barrier function, and metabolic endotoxemia. In contrast, other fatty acids, including short-chain and certain unsaturated fatty acids, protect against dysbiosis and impairment of barrier function caused by other dietary fats. These fats may promote insulin sensitivity by inhibiting metabolic endotoxemia and dysbiosis-driven inflammation. During dysbiosis, the modulation of metabolism by diet and microbiota may represent an adaptive process that compensates for the increased fuel demands of an activated immune system.
      PubDate: 2015-09-09T10:30:12Z
      DOI: 10.12688/f1000research.6078.1
      Issue No: Vol. 4 (2015)
  • Viscoelastic Properties of Hyaluronan in Physiological Conditions [version
           1; referees: 2 approved]

    • Authors: Mary K. Cowman, Tannin A. Schmidt, Preeti Raghavan, Antonio Stecco
      Abstract: Hyaluronan (HA) is a high molecular weight glycosaminoglycan of the extracellular matrix (ECM), which is particularly abundant in soft connective tissues. Solutions of HA can be highly viscous with non-Newtonian flow properties. These properties affect the movement of HA-containing fluid layers within and underlying the deep fascia. Changes in the concentration, molecular weight, or even covalent modification of HA in inflammatory conditions, as well as changes in binding interactions with other macromolecules, can have dramatic effects on the sliding movement of fascia. The high molecular weight and the semi-flexible chain of HA are key factors leading to the high viscosity of dilute solutions, and real HA solutions show additional nonideality and greatly increased viscosity due to mutual macromolecular crowding. The shear rate dependence of the viscosity, and the viscoelasticity of HA solutions, depend on the relaxation time of the molecule, which in turn depends on the HA concentration and molecular weight. Temperature can also have an effect on these properties. High viscosity can additionally affect the lubricating function of HA solutions. Immobility can increase the concentration of HA, increase the viscosity, and reduce lubrication and gliding of the layers of connective tissue and muscle. Over time, these changes can alter both muscle structure and function. Inflammation can further increase the viscosity of HA-containing fluids if the HA is modified via covalent attachment of heavy chains derived from Inter-α-Inhibitor. Hyaluronidase hydrolyzes HA, thus reducing its molecular weight, lowering the viscosity of the extracellular matrix fluid and making outflow easier. It can also disrupt any aggregates or gel-like structures that result from HA being modified. Hyaluronidase is used medically primarily as a dispersion agent, but may also be useful in conditions where altered viscosity of the fascia is desired, such as in the treatment of muscle stiffness.
      PubDate: 2015-08-25T10:41:21Z
      DOI: 10.12688/f1000research.6885.1
      Issue No: Vol. 4 (2015)
  • Murine Cep290 phenotypes are modified by genetic backgrounds and provide
           an impetus for investigating disease modifier alleles [version 1;
           referees: 2 approved]

    • Authors: Simon Ramsbottom, Colin Miles, John Sayer
      Abstract: The study of primary cilia is of broad interest both in terms of disease pathogenesis and the fundamental biological role of these structures. Murine models of ciliopathies provide valuable tools for the study of these diseases. However, it is important to consider the precise phenotype of murine models and how dependant it is upon genetic background. Here we compare and contrast murine models of Cep290, a frequent genetic cause of Joubert syndrome in order to refine our concept of genotype-phenotype correlations.
      PubDate: 2015-08-20T14:05:54Z
      DOI: 10.12688/f1000research.6959.1
      Issue No: Vol. 4 (2015)
  • NetMatchStar: an enhanced Cytoscape network querying app [version 1;
           referees: 2 approved]

    • Authors: Fabio Rinnone, Giovanni Micale, Vincenzo Bonnici, Gary D. Bader, Dennis Shasha, Alfredo Ferro, Alfredo Pulvirenti, Rosalba Giugno
      Abstract: We present NetMatchStar, a Cytoscape app to find all the occurrences of a query graph in a network and check for its significance as a motif with respect to seven different random models. The query can be uploaded or built from scratch using Cytoscape facilities. The app significantly enhances the previous NetMatch in style, performance and functionality. Notably NetMatchStar allows queries with wildcards.
      PubDate: 2015-08-05T14:25:46Z
      DOI: 10.12688/f1000research.6656.1
      Issue No: Vol. 4 (2015)
  • Deep Sequencing of the T-cell Receptor Repertoire Demonstrates Polyclonal
           T-cell Infiltrates in Psoriasis [version 1; referees: 2 approved]

    • Authors: Jamie L. Harden, David Hamm, Nicholas Gulati, Michelle A. Lowes, James G. Krueger
      Abstract: It is well known that infiltration of pathogenic T-cells plays an important role in psoriasis pathogenesis. However, the antigen specificity of these activated T-cells is relatively unknown. Previous studies using T-cell receptor polymerase chain reaction technology (TCR-PCR) have suggested there are expanded T-cell receptor (TCR) clones in psoriatic skin, suggesting a response to an unknown psoriatic antigen. Here we describe the results of high-throughput deep sequencing of the entire αβ- and γδ- TCR repertoire in normal healthy skin and psoriatic lesional and non-lesional skin. From this study, we were able to determine that there is a significant increase in the abundance of unique β- and γ- TCR sequences in psoriatic lesional skin compared to non-lesional and normal skin, and that the entire T-cell repertoire in psoriasis is polyclonal, with similar diversity to normal and non-lesional skin. Comparison of the αβ- and γδ- TCR repertoire in paired non-lesional and lesional samples showed many common clones within a patient, and these close were often equally abundant in non-lesional and lesional skin, again suggesting a diverse T-cell repertoire. Although there were similar (and low) amounts of shared β-chain sequences between different patient samples, there was significantly increased sequence sharing of the γ-chain in psoriatic skin from different individuals compared to those without psoriasis. This suggests that although the T-cell response in psoriasis is highly polyclonal, particular γδ- T-cell subsets may be associated with this disease. Overall, our findings present the feasibility of this technology to determine the entire αβ- and γδ- T-cell repertoire in skin, and that psoriasis contains polyclonal and diverse αβ- and γδ- T-cell populations.
      PubDate: 2015-08-03T16:29:17Z
      DOI: 10.12688/f1000research.6756.1
      Issue No: Vol. 4 (2015)
  • Is suvorexant a better choice than alternative hypnotics? [version 1;
           referees: 2 approved]

    • Authors: Daniel F. Kripke
      Abstract: Suvorexant is a novel dual orexin receptor antagonist (DORA) newly introduced in the U.S. as a hypnotic, but no claim of superiority over other hypnotics has been offered.  The manufacturer argued that the 5 and 10 mg starting doses recommended by the FDA might be ineffective.  The manufacturer's main Phase III trials had not even included the 10 mg dosage, and the 5 mg dosage had not been tested at all in registered clinical trials at the time of approval.  Popular alternative hypnotics may be similarly ineffective, since the FDA has also reduced the recommended doses for zolpidem and eszopiclone.  The "not to exceed" suvorexant dosage of 20 mg does slightly increase sleep.  Because of slow absorption, suvorexant has little effect on latency to sleep onset but some small effect in suppressing wakening after sleep onset and in improving sleep efficiency. The FDA would not approve the manufacturer's preferred 40 mg suvorexant dosage, because of concern with daytime somnolence, driving impairment, and possible narcolepsy-like symptoms.  In its immediate benefits-to-risks ratio, suvorexant is unlikely to prove superior to currently available hypnotics—possibly worse—so there is little reason to prefer over the alternatives this likely more expensive hypnotic less-tested in practice.  Associations are being increasingly documented relating hypnotic usage with incident cancer, with dementia risks, and with premature death.  There is some basis to speculate that suvorexant might be safer than alternative hypnotics in terms of cancer, dementia, infections, and mortality.  These safety considerations will remain unproven speculations unless adequate long-term trials can be done that demonstrate suvorexant advantages.
      PubDate: 2015-08-03T11:05:12Z
      DOI: 10.12688/f1000research.6845.1
      Issue No: Vol. 4 (2015)
  • Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is
           controlled by both internal tunnels and active site water molecules
           [version 2; referees: 2 approved]

    • Abstract: Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb) family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O2 and •ŸNO to migrate easily from the solvent to the active site, whereas Mt-trHbO possesses tunnels interrupted by a few bulky residues, particularly a tryptophan at position G8. Differential ligand migration rates allow Mt-trHbN to detoxify Ÿ•NO, a crucial step for pathogen survival once under attack by the immune system, much more efficiently than Mt-trHbO. In order to investigate the differences between these proteins, we performed experimental kinetic measurements, Ÿ•NO decomposition, as well as molecular dynamics simulations of the wild type Mt-trHbN and two mutants, VG8F and VG8W. These mutations affect both the tunnels accessibility as well as the affinity of distal site water molecules, thus modifying the ligand access to the iron. We found that a single mutation allows Mt-trHbN to acquire ligand migration rates comparable to those observed for Mt-trHbO, confirming that ligand migration is regulated by the internal tunnel architecture as well as by water molecules stabilized in the active site.
      PubDate: 2015-07-22T13:41:23Z
      DOI: 10.12688/f1000research.5921.2
      Issue No: Vol. 4 (2015)
  • The role of new echocardiographic techniques in athlete’s heart
           [version 1; referees: 2 approved]

    • Abstract: ‘Athlete’s heart’ is a common term for the various adaptive changes induced by intensive exercise. Exercise causes alterations of the heart in hemodynamic response to the increased systemic and pulmonary demand during exercise. The understanding of these adaptations is of high importance, since they may overlap with those caused by pathological conditions. Cardiac imaging assessment of the athlete’s heart should begin with a complete echocardiographic examination. In recent years classical echocardiographic surveys have been joined by new developments: tissue Doppler imaging, strain rate echocardiography, and real-time 3-dimensional echocardiography. This review paper focuses on the importance of these new echocardiographic techniques in delineating the morphological characteristics and functional properties of the athlete’s heart.
      PubDate: 2015-07-20T14:02:36Z
      DOI: 10.12688/f1000research.6745.1
      Issue No: Vol. 4 (2015)
  • Tourette Syndrome research highlights 2014 [version 2; referees: 1
           approved, 2 approved with reservations]

    • Authors: Cheryl A Richards, Kevin J Black
      Abstract: About 200 journal articles reported research on Tourette syndrome and other tic disorders in 2014. Here we briefly summarize a few of the reports that seemed most important or interesting, ranging from animal models to human studies. Readers can comment on our choices or provide their own favorites using the tools on the online article.
      PubDate: 2015-07-14T13:56:23Z
      DOI: 10.12688/f1000research.6209.2
      Issue No: Vol. 4 (2015)
  • Constellation Map: Downstream visualization and interpretation of gene set
           enrichment results [version 1; referees: 2 approved]

    • Authors: Yan Tan, Felix Wu, Pablo Tamayo, W. Nicholas Haining, Jill P. Mesirov
      Abstract: Summary: Gene set enrichment analysis (GSEA) approaches are widely used to identify coordinately regulated genes associated with phenotypes of interest. Here, we present Constellation Map, a tool to visualize and interpret the results when enrichment analyses yield a long list of significantly enriched gene sets. Constellation Map identifies commonalities that explain the enrichment of multiple top-scoring gene sets and maps the relationships between them. Constellation Map can help investigators take full advantage of GSEA and facilitates the biological interpretation of enrichment results. Availability: Constellation Map is freely available as a GenePattern module at
      PubDate: 2015-06-24T15:38:08Z
      DOI: 10.12688/f1000research.6644.1
      Issue No: Vol. 4 (2015)
  • Combining complexity measures of EEG data: multiplying measures reveal
           previously hidden information [version 1; referees: 2 approved]

    • Authors: Thomas Burns, Ramesh Rajan
      Abstract: Many studies have noted significant differences among human electroencephalograph (EEG) results when participants or patients are exposed to different stimuli, undertaking different tasks, or being affected by conditions such as epilepsy or Alzheimer's disease. Such studies often use only one or two measures of complexity and do not regularly justify their choice of measure beyond the fact that it has been used in previous studies. If more measures were added to such studies, however, more complete information might be found about these reported differences. Such information might be useful in confirming the existence or extent of such differences, or in understanding their physiological bases. In this study we analysed publically-available EEG data using a range of complexity measures to determine how well the measures correlated with one another. The complexity measures did not all significantly correlate, suggesting that different measures were measuring unique features of the EEG signals and thus revealing information which other measures were unable to detect. Therefore, the results from this analysis suggests that combinations of complexity measures reveal unique information which is in addition to the information captured by other measures of complexity in EEG data. For this reason, researchers using individual complexity measures for EEG data should consider using combinations of measures to more completely account for any differences they observe and to ensure the robustness of any relationships identified.
      PubDate: 2015-06-01T15:27:20Z
      DOI: 10.12688/f1000research.6590.1
      Issue No: Vol. 4 (2015)
  • Theoretical modelling of epigenetically modified DNA sequences [version 2;
           referees: 2 approved]

    • Abstract: We report herein a set of calculations designed to examine the effects of epigenetic modifications on the structure of DNA. The incorporation of methyl, hydroxymethyl, formyl and carboxy substituents at the 5-position of cytosine is shown to hardly affect the geometry of CG base pairs, but to result in rather larger changes to hydrogen-bond and stacking binding energies, as predicted by dispersion-corrected density functional theory (DFT) methods. The same modifications within double-stranded GCG and ACA trimers exhibit rather larger structural effects, when including the sugar-phosphate backbone as well as sodium counterions and implicit aqueous solvation. In particular, changes are observed in the buckle and propeller angles within base pairs and the slide and roll values of base pair steps, but these leave the overall helical shape of DNA essentially intact. The structures so obtained are useful as a benchmark of faster methods, including molecular mechanics (MM) and hybrid quantum mechanics/molecular mechanics (QM/MM) methods. We show that previously developed MM parameters satisfactorily reproduce the trimer structures, as do QM/MM calculations which treat bases with dispersion-corrected DFT and the sugar-phosphate backbone with AMBER. The latter are improved by inclusion of all six bases in the QM region, since a truncated model including only the central CG base pair in the QM region is considerably further from the DFT structure. This QM/MM method is then applied to a set of double-stranded DNA heptamers derived from a recent X-ray crystallographic study, whose size puts a DFT study beyond our current computational resources. These data show that still larger structural changes are observed than in base pairs or trimers, leading us to conclude that it is important to model epigenetic modifications within realistic molecular contexts.
      PubDate: 2015-05-06T13:36:28Z
      DOI: 10.12688/f1000research.6148.2
      Issue No: Vol. 4 (2015)
  • Laryngeal mask placement in a teaching institution: analysis of difficult
           placements [v1; indexed,]

    • Authors: Anastasia D Katsiampoura, Peter V Killoran, Ruggero M Corso, Chunyan Cai, Carin A Hagberg, Davide Cattano
      Abstract: Background Laryngeal mask airway (LMA) placement is now considered a common airway management practice. Although there are many studies which focus on various airway techniques, research regarding difficult LMA placement is limited, particularly for anesthesiologist trainees. In our retrospective analysis we tried to identify predictive factors of difficult LMA placement in an academic training program. Methods This retrospective analysis was derived from a research airway database, where data were collected prospectively at the Memorial Hermann Hospital, Texas Medical Center, Houston, TX, USA, from 2008 to 2010. All non-obstetric adult patients presenting for elective surgery requiring general anesthesia, were enrolled in this study: anesthesiology residents primarily managed the airways. The level of difficulty, number of attempts, and type of the extraglottic device placement were retrieved. Results Sixty-nine unique Laryngeal Mask Airways (uLMAs) were utilized as a primary airway device. Two independent predictors for difficult LMA placement were identified: gender and neck circumference. The sensitivity for one factor is 87.5% with a specificity of 50%. However with two risk factors, the specificity increases to the level of 93% and the sensitivity is 63%. Conclusion In a large academic training program, besides uLMA not been used routinely, two risk factors for LMA difficulty were identified, female gender and large neck circumference. Neck circumference is increasingly being recognized as a significant predictor across the spectrum of airway management difficulties while female gender has not been previously reported as a risk factor for difficult LMA placement.
      PubDate: 2015-04-29T10:50:05Z
      DOI: 10.12688/f1000research.6415.1
      Issue No: Vol. 4 (2015)
  • MicroRNA levels quantified in whole blood varies from PBMCs [version 4;
           referees: 2 approved, 1 not approved]

    • Authors: Sadaf Atarod, Hannah Smith, Anne Dickinson, Xiao-Nong Wang
      Abstract: MicroRNAs are non-coding RNAs that negatively regulate mRNA expression and play significant roles in both health and disease. Differential microRNA expression has been used to aid diagnosis and discriminate disease stages. The accuracy and reliability of microRNA expression measurement is of utmost importance. Quantification of microRNA expression in human peripheral blood is commonly detected using total RNA extracted via different methods. To date, no convincing data are available showing whether microRNA quantification results can be influenced by the use of total RNA extracted from whole blood or peripheral blood mononuclear cells (PBMCs). This study examined miR-146a-5p and miR-155-5p expression using total RNA extracted in parallel from whole blood and PBMCs of 14 healthy volunteers. The data showed that the quantification of miRNA using total RNA extracted from whole blood varied from that of PBMCs, indicating that the miRNA expression was a result of all the different cell-types present in whole blood. Our results suggested that the source of total RNA and the statistical analyses performed are crucial considerations when designing miRNA research.
      PubDate: 2015-10-06T14:43:18Z
      DOI: 10.12688/f1000research.4884.4
      Issue No: Vol. 3 (2015)
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