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F1000Research
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  This is an Open Access Journal Open Access journal
     ISSN (Online) 2046-1402
     Published by Faculty of 1000 Homepage  [1 journal]
  • Late cardiac sodium current can be assessed using automated patch-clamp
           [v1; indexed, http://f1000r.es/4kj]

    • Authors: Morgan Chevalier, Bogdan Amuzescu, Vaibhavkumar Gawali, Hannes Todt, Thomas Knott, Olaf Scheel, Hugues Abriel
      Abstract: The cardiac late Na+ current is generated by a small fraction of voltage-dependent Na+ channels that undergo a conformational change to a burst-gating mode, with repeated openings and closures during the action potential (AP) plateau. Its magnitude can be augmented by inactivation-defective mutations, myocardial ischemia, or prolonged exposure to chemical compounds leading to drug-induced (di)-long QT syndrome, and results in an increased susceptibility to cardiac arrhythmias. Using CytoPatch™ 2 automated patch-clamp equipment, we performed whole-cell recordings in HEK293 cells stably expressing human Nav1.5, and measured the late Na+ component as average current over the last 100 ms of 300 ms depolarizing pulses to -10 mV from a holding potential of -100 mV, with a repetition frequency of 0.33 Hz. Averaged values in different steady-state experimental conditions were further corrected by the subtraction of current average during the application of tetrodotoxin (TTX) 30 μM. We show that ranolazine at 10 and 30 μM in 3 min applications reduced the late Na+ current to 75.0 ± 2.7% (mean ± SEM, n = 17) and 58.4 ± 3.5% (n = 18) of initial levels, respectively, while a 5 min application of veratridine 1 μM resulted in a reversible current increase to 269.1 ± 16.1% (n = 28) of initial values. Using fluctuation analysis, we observed that ranolazine 30 μM decreased mean open probability p from 0.6 to 0.38 without modifying the number of active channels n, while veratridine 1 μM increased n 2.5-fold without changing p. In human iPSC-derived cardiomyocytes, veratridine 1 μM reversibly increased APD90 2.12 ± 0.41-fold (mean ± SEM, n = 6). This effect is attributable to inactivation removal in Nav1.5 channels, since significant inhibitory effects on hERG current were detected at higher concentrations in hERG-expressing HEK293 cells, with a 28.9 ± 6.0% inhibition (mean ± SD, n = 10) with 50 μM veratridine.      
      PubDate: 2014-10-16
      DOI: 10.12688/f1000research.5544.1
      Issue No: Vol. 3 (2014)
       
  • Commercial antibodies and their validation [v2; indexed,
           http://f1000r.es/4jp]

    • Authors: JLA Voskuil
      Abstract: Despite an impressive growth in the business of research antibodies a general lack of trust in commercial antibodies remains in place. A variety of issues, each one potentially causing an antibody to fail, underpin the frustrations that scientists endure. Lots of money goes to waste in buying and trying one failing antibody after the other without realizing all the pitfalls that come with the product: Antibodies can get inactivated, both the biological material and the assay itself can potentially be flawed, a single antibody featuring in many different catalogues can be deemed as a set of different products, and a bad choice of antibody type, wrong dilutions, and lack of proper validation can all jeopardize the intended experiments. Antibodies endorsed by scientific research papers do not always meet the scientist’s requirements either due to flawed specifications, or due to batch-to-batch variations. Antibodies can be found with Quality Control data obtained from previous batches that no longer represent the batch on sale. In addition, one cannot assume that every antibody is fit for every application. The best chance of success is to try an antibody that already was confirmed to perform correctly in the required platform.
      PubDate: 2014-10-15
      DOI: 10.12688/f1000research.4966.2
      Issue No: Vol. 3 (2014)
       
  • Plasmodium falciparum infection rates for some Anopheles spp. from
           Guinea-Bissau, West Africa [v1; indexed, http://f1000r.es/4in]

    • Authors: Michelle R. Sanford, Anthony J. Cornel, Catelyn C. Nieman, Joao Dinis, Clare D. Marsden, Allison M. Weakley, Sarah Han, Amabelia Rodrigues, Gregory C. Lanzaro, Yoosook Lee
      Abstract: Presence of Plasmodium falciparum circumsporozoite protein (CSP) was detected by enzyme linked immunosorbent assay (ELISA) in a sample of Anopheles gambiae s.s., A. melas and A. pharoensis collected in Guinea-Bissau during October and November 2009. The percentage of P. falciparum infected samples (10.2% overall) was comparable to earlier studies from other sites in Guinea-Bissau (9.6-12.4%). The majority of the specimens collected were identified as A. gambiae which had an individual infection rate of 12.6 % across collection sites. A small number of specimens of A. coluzzii, A. coluzzii x A. gambiae hybrids, A. melas and A. pharoensis were collected and had infection rates of 4.3%, 4.1%, 11.1% and 33.3% respectively. Despite being present in low numbers in indoor collections, the exophilic feeding behaviors of A. melas (N=18) and A. pharoensis (N=6) and high infection rates observed in this survey suggest falciparum-malaria transmission potential outside of the protection of bed nets.
      PubDate: 2014-10-14
      DOI: 10.12688/f1000research.5485.1
      Issue No: Vol. 3 (2014)
       
  • Immunohistochemical visualization of mouse interneuron subtypes [v1;
           indexed, http://f1000r.es/4em]

    • Authors: Simon Molgaard, Maj Ulrichsen, Simon Boggild, Marie-Louise Holm, Christian Vaegter, Jens Nyengaard, Simon Glerup
      Abstract: The activity of excitatory neurons is controlled by a small, but highly diverse population of inhibitory interneurons. These cells show a high level of physiological, morphological and neurochemical heterogeneity, and play highly specific roles in neuronal circuits. In the mammalian hippocampus, these are divided into 21 different subtypes of GABAergic interneurons based on their expression of different markers, morphology and their electrophysiological properties. Ideally, all can be marked using an antibody directed against the inhibitory neurotransmitter GABA, but parvalbumin, calbindin, somatostatin, and calretinin are also commonly used as markers to narrow down the specific interneuron subtype. Here, we describe a journey to find the necessary immunological reagents for studying GABAergic interneurons of the mouse hippocampus. Based on web searches there are several hundreds of different antibodies on the market directed against these four markers. Searches in the literature databases allowed us to narrow it down to a subset of antibodies most commonly used in publications. However, in our hands the most cited ones did not work for immunofluorescence stainings of formaldehyde fixed tissue sections and cultured hippocampal neurons, and we had to immunostain our way through thirteen different commercial antibodies before finally finding a suitable antibody for each of the four markers. The antibodies were evaluated based on signal-to-noise ratios as well as if positive cells were found in layers of the hippocampus where they have previously been described. Additionally, the antibodies were also tested on sections from mouse spinal cord with similar criteria for specificity of the antibodies. Using the antibodies with a high rating on pAbmAbs, stainings with high signal-to-noise ratios and location of the immunostained cells in accordance with the literature could be obtained, making these antibodies suitable choices for studying the GABAergic system.
      PubDate: 2014-10-13
      DOI: 10.12688/f1000research.5349.1
      Issue No: Vol. 3 (2014)
       
  • Back to the drawing board: Re-thinking the role of GLI1 in pancreatic
           carcinogenesis [v1; indexed, http://f1000r.es/4du]

    • Authors: Tara Hogenson, Matthias Lauth, Marina Pasca diMagliano, Martin Fernandez-Zapico
      Abstract: Aberrant activation of the transcription factor GLI1, a central effector of the Hedgehog (HH) pathway, is associated with several malignancies, including pancreatic ductal adenocarcinoma (PDAC), one of most deadly human cancers. GLI1 has been described as an oncogene in PDAC, making it a promising target for drug therapy. Surprisingly, clinical trials targeting HH/GLI1 axis in advanced PDAC were unsuccessful, leaving investigators questioning the mechanism behind these failures. Recent evidence suggests the loss of GLI1 in the later stages of PDAC may actually accelerate disease. This indicates GLI1 may play a dual role in PDAC, acting as an oncogene in the early stages of disease and a tumor-suppressor in the late stages.
      PubDate: 2014-10-08
      DOI: 10.12688/f1000research.5324.1
      Issue No: Vol. 3 (2014)
       
  • Activity artifacts in drug discovery and different facets of compound
           promiscuity [v1; indexed, http://f1000r.es/4gz]

    • Authors: Jürgen Bajorath
      Abstract: Compounds with apparent activity in a variety of assays might disable target proteins or produce false assay signals in the absence of specific interactions. In some instances, such effects are easy to detect, in others they are not. Observed promiscuity of compounds might be due to such non-specific assay artifacts. By contrast, promiscuity might also result from specific interactions with multiple targets. In the latter case, promiscuous compounds can be attractive candidates for certain therapeutic applications. However, compounds with artificial activity readouts are often not recognized and are further progressed, which presents a substantial problem for drug discovery. In this context, the concept of PAINS (pan-assay interference compounds) should be seriously considered, which makes it possible to eliminate flawed compounds from the discovery pipeline, even if their activities appear to be sound at a first glance.
      PubDate: 2014-10-03
      DOI: 10.12688/f1000research.5426.1
      Issue No: Vol. 3 (2014)
       
  • Management of thrombocythemia [v1; indexed, http://f1000r.es/4ez]

    • Authors: Krisstina Gowin, Ruben Mesa
      Abstract: Essential thrombocythemia is a clonal myeloproliferative neoplasm characterized by an elevated platelet count, the potential for both microvascular and macrovascular sequelae, and a risk for transformation to myelofibrosis or acute myeloid leukemia. A systematic and detailed initial analysis is essential for accurate diagnosis of essential thrombocythemia, as many etiologies are reactive and benign. Once a diagnosis has been made, risk stratification and symptom assessment are vital to guide the subsequent therapy. Treatment may be required in high-risk disease, such as in cases of advanced age or prior thrombotic events. Systemic therapy is aimed at reducing the thrombotic risk and includes daily low dose aspirin and in some patients, cytoreductive therapy.  Currently, the first line cytoreductive therapy includes hydroxyurea or pegylated interferon, with a phase III clinical trial underway comparing these two important agents. Anagrelide and clinical trials are reserved for refractory or intolerant patients. Looking to the future, new therapies including Janus kinase 2 (JAK2) and telomerase inhibitors are promising and may become valuable to the treatment armamentarium for those afflicted with essential thrombocythemia.
      PubDate: 2014-09-29
      DOI: 10.12688/f1000research.5361.1
      Issue No: Vol. 3 (2014)
       
  • PAGAL - Properties and corresponding graphics of alpha helical structures
           in proteins [v2; indexed, http://f1000r.es/4e7]

    • Authors: Sandeep Chakraborty, Basuthkar Rao, Abhaya Dandekar
      Abstract: Alpha helices (AH) are peptide fragments characterized by regular patterns of hydrogen bonding between the carbonyl oxygen and amino nitrogen of residues regularly spaced in sequence, resulting in spiral conformations. Their preponderance in protein structures underlines their importance. Interestingly, AHs are present in most anti-microbial peptides, although they might remain in random-coil conformations depending on the solvent dielectric. For example, the cecropin component of the chimeric anti-microbial protein designed previously by our group comprises of two AHs linked by a short stretch of random coil. These anti-microbial peptides are often amphipathic (quantified by a hydrophobic moment), aligning hydrophobic residues on one surface and charged residues on the others. In the current work, we reproduce previously described computational methods to compute the hydrophobic moment of AHs - and provide open access to the source code (PAGAL). We simultaneously generated input files for TikZ (a package for creating high resolution graphics programmatically) to obtain the Edmundson wheel and showing the direction and magnitude of the hydrophobic moment, and Pymol scripts to generate color coded protein surfaces. Additionally, we have observed an empirical structural property of AHs: the distance between the Cα atoms of the ith and (i+4)th residue is equal to the distance between the carbonyl oxygens of the ith and (i+4)th residue. We validated this using 100 non-homologous high resolution structures from the PISCES database. The source code and manual is available at http://github.com/sanchak/pagal and on http://dx.doi.org/10.5281/zenodo.11136.
      PubDate: 2014-09-19
      DOI: 10.12688/f1000research.4952.2
      Issue No: Vol. 3 (2014)
       
  • Monitoring drug promiscuity over time [v1; indexed, http://f1000r.es/4bh]

    • Authors: Hu Ye, Jürgen Bajorath
      Abstract: Drug promiscuity and polypharmacology are much discussed topics in pharmaceutical research. Experimentally, promiscuity can be studied by profiling of compounds on arrays of targets. Computationally, promiscuity rates can be estimated by mining of compound activity data. In this study, we have assessed drug promiscuity over time by systematically collecting activity records for approved drugs. For 518 diverse drugs, promiscuity rates were determined over different time intervals. Significant differences between the number of reported drug targets and the promiscuity rates derived from activity records were frequently observed. On the basis of high-confidence activity data, an increase in average promiscuity rates from 1.5 to 3.2 targets per drug was detected between 2000 and 2014. These promiscuity rates are lower than often assumed. When the stringency of data selection criteria was reduced in subsequent steps, non-realistic increases in promiscuity rates from ~6 targets per drug in 2000 to more than 28 targets were obtained. Hence, estimates of drug promiscuity significantly differ depending on the stringency with which target annotations and activity data are considered.
      PubDate: 2014-09-11
      DOI: 10.12688/f1000research.5250.1
      Issue No: Vol. 3 (2014)
       
  • Chief’s seminar: turning interns into clinicians [v1; indexed,
           http://f1000r.es/4an]

    • Authors: Christopher Dittus, Vanya Grover, Georgia Panagopoulos, Kenar Jhaveri
      Abstract: Background: Recent changes in healthcare delivery have necessitated residency education reform. To adapt to these changes, graduate medical education can adopt a chief resident-led clinical curriculum. Chief residents are ideal clinical instructors, as they are recent graduates who have excelled in their residency programs. To effectively use the limited time available for education, chief residents can implement active learning techniques. We present a chief resident-led, small-group, problem-based curriculum for teaching first-year internal medicine residents, and provide preliminary data supporting the efficacy of this approach. Methods: The seminar consisted of 11 4-week modules. Week 1 was a team-based crossword competition. Weeks 2-4 were small-group, problem-based clinical reasoning sessions taught by chief residents. The program was evaluated via pre- and post-module multiple-choice tests. Resident satisfaction data were collected via self-reported, anonymous surveys. Results: Preliminary results revealed a statistically significant increase from pre-test to post-test score for 9 of the 11 modules. The chest pain, fever, abdominal pain, shock, syncope, jaundice, dizziness, anemia, and acute kidney injury modules achieved statistical significance. Additionally, resident satisfaction surveys show that this teaching approach was an enjoyable experience for our residents. Discussion: Our chief seminar is an evidence-based, clinical reasoning approach for graduate medical education that uses active learning techniques. This is an effective and enjoyable method for educating internal medicine residents. Because of its reproducibility, it can be applied throughout residency education.
      PubDate: 2014-09-08
      DOI: 10.12688/f1000research.5221.1
      Issue No: Vol. 3 (2014)
       
  • Difficult mask ventilation in general surgical population: observation of
           risk factors and predictors [v1; indexed, http://f1000r.es/47z]

    • Authors: Davide Cattano, Peter V. Killoran, Chunyan Cai, Anastasia D. Katsiampoura, Ruggero M. Corso, Carin A. Hagberg
      Abstract: Background: There are few predictors of difficult mask ventilation and a simple, objective, predictive system to identify patients at risk of difficult mask ventilation does not currently exist. We present a retrospective - subgroup analysis aimed at identifying predictive factors for difficult mask ventilation (DMV) in patients undergoing pre-operative airway assessment before elective surgery at a major teaching hospital. Methods: Data for this retrospective analysis were derived from a database of airway assessments, management plans, and outcomes that were collected prospectively from August 2008 to May 2010 at a Level 1 academic trauma center. Patients were stratified into two groups based on the difficulty of mask ventilation and the cohorts were analyzed using univariate analysis and stepwise selection method. Results: A total of 1399 pre-operative assessments were completed with documentation stating that mask ventilation was attempted. Of those 1399, 124 (8.9%) patients were found to be difficult to mask ventilate. A comparison of patients with and without difficult mask ventilation identified seven risk factors for DMV: age, body mass index (BMI), neck circumference, history of difficult intubation, presence of facial hair, perceived short neck and obstructive sleep apnea. Although seven risk factors were identified, no individual subject had more than four risk factors. Conclusion: The results of this study confirm that in a real world clinical setting, the incidence of DMV is not negligible and suggest the use of a simple bedside predictive score to improve the accuracy of DMV prediction, thereby improving patient safety. Further prospective studies to validate this score would be useful.
      PubDate: 2014-08-27
      DOI: 10.12688/f1000research.5131.1
      Issue No: Vol. 3 (2014)
       
  • CyKEGGParser: tailoring KEGG pathways to fit into systems biology analysis
           workflows [v2; indexed, http://f1000r.es/45p]

    • Authors: Lilit Nersisyan, Ruben Samsonyan, Arsen Arakelyan
      Abstract: The KEGG pathway database is a widely accepted source for biomolecular pathway maps. In this paper we present the CyKEGGParser app (http://apps.cytoscape.org/apps/cykeggparser) for Cytoscape 3 that allows manipulation with KEGG pathway maps. Along with basic functionalities for pathway retrieval, visualization and export in KGML and BioPAX formats, the app provides unique features for computer-assisted adjustment of inconsistencies in KEGG pathway KGML files and generation of tissue- and protein-protein interaction specific pathways. We demonstrate that using biological context-specific KEGG pathways created with CyKEGGParser makes systems biology analysis more sensitive and appropriate compared to original pathways.
      PubDate: 2014-08-14
      Issue No: Vol. 3 (2014)
       
  • Developing sustainable software solutions for bioinformatics by the
           “Butterfly” paradigm [v2; indexed, http://f1000r.es/40q]

    • Authors: Zeeshan Ahmed, Saman Zeeshan, Thomas Dandekar
      Abstract: Software design and sustainable software engineering are essential for the long-term development of bioinformatics software. Typical challenges in an academic environment are short-term contracts, island solutions, pragmatic approaches and loose documentation. Upcoming new challenges are big data, complex data sets, software compatibility and rapid changes in data representation. Our approach to cope with these challenges consists of iterative intertwined cycles of development (“Butterfly” paradigm) for key steps in scientific software engineering. User feedback is valued as well as software planning in a sustainable and interoperable way. Tool usage should be easy and intuitive. A middleware supports a user-friendly Graphical User Interface (GUI) as well as a database/tool development independently. We validated the approach of our own software development and compared the different design paradigms in various software solutions.
      PubDate: 2014-08-01
      DOI: 10.12688/f1000research.3681.2
      Issue No: Vol. 3 (2014)
       
  • Case Report: Group B Streptococcus meningitis in an adolescent  [v1;
           indexed, http://f1000r.es/3u4]

    • Authors: Roselle Vittorino, Joyce Hui-Yuen, Adam J. Ratner, Amy Starr, Teresa McCann
      Abstract: Streptococcus agalactiae (group B Streptococcus, GBS) usually colonizes the gastrointestinal and lower genital tracts of asymptomatic hosts, yet the incidence of invasive disease is on the rise. We describe a case of an 18 year old woman, recently diagnosed with lupus, who reported a spontaneous abortion six weeks prior to her hospitalization.  She presented with fever, altered mental status, and meningeal signs, paired with a positive blood culture for GBS. Magnetic resonance imaging of her brain demonstrated an extra-axial fluid collection, and she was diagnosed with meningitis.  She received prolonged intravenous antibiotic therapy and aggressive treatment for lupus, leading to clinical recovery. This case illustrates the importance of recognizing GBS as a potential pathogen in all patients presenting with CNS infection.  
      PubDate: 2014-07-22
      DOI: 10.12688/f1000research.4651.1
      Issue No: Vol. 3 (2014)
       
  • How do eubacterial organisms manage aggregation-prone proteome? [v1;
           indexed, http://f1000r.es/3k3]

    • Authors: Rishi Das Roy, Manju Bhardwaj, Vasudha Bhatnagar, Kausik Chakraborty, Debasis Dash
      Abstract: Eubacterial genomes vary considerably in their nucleotide composition. The percentage of genetic material constituted by guanosine and cytosine (GC) nucleotides ranges from 20% to 70%.  It has been posited that GC-poor organisms are more dependent on protein folding machinery. Previous studies have ascribed this to the accumulation of mildly deleterious mutations in these organisms due to population bottlenecks. This phenomenon has been supported by protein folding simulations, which showed that proteins encoded by GC-poor organisms are more prone to aggregation than proteins encoded by GC-rich organisms. To test this proposition using a genome-wide approach, we classified different eubacterial proteomes in terms of their aggregation propensity and chaperone-dependence using multiple machine learning models. In contrast to the expected decrease in protein aggregation with an increase in GC richness, we found that the aggregation propensity of proteomes increases with GC content. A similar and even more significant correlation was obtained with the GroEL-dependence of proteomes: GC-poor proteomes have evolved to be less dependent on GroEL than GC-rich proteomes. We thus propose that a decrease in eubacterial GC content may have been selected in organisms facing proteostasis problems.
      PubDate: 2014-06-27
      DOI: 10.12688/f1000research.4307.1
      Issue No: Vol. 3 (2014)
       
  • A case of severe psychosis induced by novel recreational drugs [v1;
           indexed, http://f1000r.es/2o2]

    • Authors: Filippo Dragogna, Lucio Oldani, Massimiliano Buoli, A. Carlo Altamura
      Abstract: Introduction:  The use of novel recreational drugs is becoming of public interest, especially after recent international alerts about their cardiovascular and neurological toxicity. Additionally, little is known about the psychiatric consequences of the long-term use of these compounds. Case presentation: We describe a case of severe psychotic episode likely induced by chronic use of a combination of new recreational drugs (methylenedioxypyrovalerone, mephedrone, butylone and alpha-pyrrolidinopentiophenone). The patient had no psychiatric history and showed poor response to conventional antipsychotic treatment (haloperidol). Conclusions: This case illustrates the potential negative effects of recreational drugs that cannot be limited to an acute psychotic episode but might determine a condition of prolonged paranoid psychosis. Although the use of these compounds is currently increasing, such molecules might often pass undetected in patients accessing the emergency room, leading to misdiagnosis (e.g. schizophrenic episode) and lack of appropriate treatment.
      PubDate: 2014-01-22
      DOI: 10.12688/f1000research.3-21.v1
      Issue No: Vol. 3 (2014)
       
  • Transitory expression of Dlx5 and Dlx6 in maxillary arch epithelial
           precursors is essential for upper jaw morphogenesis [v3; indexed,
           http://f1000r.es/4dd]

    • Authors: Yorick Gitton, Nicolas Narboux-Nême, Giovanni Levi
      Abstract: Asymmetric, articulated jaws are characteristic of most vertebrate species; they derive from the first pharyngeal arch (PA1) which generates both maxillary and mandibular components. PA1 is colonized by cranial neural crest cells (CNCCs) which give rise to most bones and tendons of the jaws. The elements formed by different CNCCs contingents are specified by the combinatorial expression of Dlx genes. Dlx5 and Dlx6 are predominantly expressed by mandibular CNCCs. Analysis of the phenotype of Dlx5 and Dlx6 double mutant mice has suggested that they are necessary and sufficient to specify mandibular identity. Here, using 3D reconstruction, we show that inactivation of Dlx5 and Dlx6 does not only affect the mandibular arch, but results in the simultaneous transformation of mandibular and maxillary skeletal elements which assume a similar morphology with gain of symmetry. As Dlx5- and Dlx6-expressing cells are not found in the maxillary bud, we have examined the lineage of Dlx5-expressing progenitors using an in vivo genetic approach. We find that a contingent of cells deriving from epithelial precursors transiently expressing Dlx5 participate in the formation of the maxillary arch. These cells are mostly located in the distal part of the maxillary arch and might derive from its lambdoidal junction with the olfactory pit. Our observations provide the first genetic demonstration of the ‘Hinge and Caps’ model[1]. We support the notion that ‘cap’ signals could originate from epithelial derivatives of Dlx5-expressing progenitors which migrate and colonize the maxillary arch epithelium. Our results imply that Dlx5 and Dlx6 control upper and lower jaw morphogenesis through different coordinated mechanisms to generate functional, articulated jaws.
      PubDate: 2014-09-16
      DOI: 10.12688/f1000research.2-261.v3
      Issue No: Vol. 2 (2014)
       
  • Ouabain inhibition of Na/K-ATPase across the retina prevents signed
           refractive compensation to lens-induced defocus, but not default ocular
           growth in young chicks [v1; indexed, http://f1000r.es/rt]

    • Authors: Melanie J Murphy, Sheila Gillard Crewther
      Abstract: Purpose: The relevance of retinal integrity and energy pathways to ocular growth and induction of refractive errors has seldom been investigated. Thus, we used ouabain to target the channels that are essential for the maintenance of membrane potentials in cells, sodium potassium ATPase (Na/K-ATPase), to examine refractive compensation and ocular growth in response to lens-induced defocus in the chick. Methods:  A single intravitreal injection of 1 mM ouabain in dimethyl sulfoxide (DMSO) carrier or DMSO alone was followed by monocular defocus with positive or negative 10 D lens (or no lens) from post-hatching days 5-9 under 12/12 hr light/dark conditions. Biometry and dark-adapted flash and electroretinography (ERG) were conducted on day 9, followed by immunohistological analyses. Results: Ouabain inhibited differential ocular growth and refractive compensation to signed defocus compared to DMSO. By 4-days post-ouabain injection all components of the typical ERG responses to light had been eliminated, and widespread histological damage was apparent, though some ‘default state’ ocular growth was measurable. Immunohistochemistry demonstrated reduction in the specialized water channel Aquaporin 4 (AQP4) expression and increased evidence of caspase 3 expression (a cell death associated protein) in ouabain-treated eyes compared with DMSO alone. Conclusion: The current study demonstrates that blockade of photoreceptor and inner retinal responses to light onset and offset by ouabain inhibits differential refractive compensation to optical blur, but does not prevent ocular growth.
      PubDate: 2013-03-28
      DOI: 10.12688/f1000research.2-97.v1
      Issue No: Vol. 2 (2013)
       
 
 
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