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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]
  • 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 Antibodies can be found with Quality Control data obtained from previous batches that no longer represent the batch on sale.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)
       
  • 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)
       
  • Electrical maturation of neurons derived from human embryonic stem cells
           [v2; indexed, http://f1000r.es/4gy]

    • Authors: Michael Telias, Menahem Segal, Dalit Ben-Yosef
      Abstract: In-vitro neuronal differentiation of human pluripotent stem cells has become a widely used tool in disease modeling and prospective regenerative medicine. Most studies evaluate neurons molecularly and only a handful of them use electrophysiological tools to directly indicate that these are genuine neurons. Therefore, the specific timing of development of intrinsic electrophysiological properties and synaptic capabilities remains poorly understood. Here we describe a systematic analysis of developing neurons derived in-vitro from human embryonic stem cells (hESCs). We show that hESCs differentiated in-vitro into early embryonic neurons, displaying basically mature morphological and electrical features as early as day 37. This early onset of action potential discharges suggests that first stages of neurogenesis in humans are already associated with electrical maturation. Spike frequency, amplitude, duration, threshold and after hyperpolarization were found to be the most predictive parameters for electrical maturity. Furthermore, we were able to detect spontaneous synaptic activity already at these early time-points, demonstrating that neuronal connectivity can develop concomitantly with the gradual process of electrical maturation. These results highlight the functional properties of hESCs in the process of their development into neurons. Moreover, our results provide practical tools for the direct measurement of functional maturity, which can be reproduced and implemented for stem cell research of neurogenesis in general, and neurodevelopmental disorders in particular.
      PubDate: 2014-10-01
      DOI: 10.12688/f1000research.4943.2
      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)
       
  • Case Report: Double lumen tube insertion in a morbidly obese patient
           through the non-channelled blade of the King Vision™
           videolaryngoscope [v4; indexed, http://f1000r.es/4g3]

    • Authors: Mohamed El-Tahan, D. John Doyle, Alaa M Khidr, Ahmed G Hassieb
      Abstract: We describe the insertion of the double lumen endobronchial tube (DLT) using a non-channeled standard blade of the King VisionTM videolaryngoscope for one lung ventilation (OLV) in a morbidly obese patient with a predicted difficult airway, severe restrictive pulmonary function, asthma, and hypertension. The patient was scheduled for a video-assisted thoracoscopic lung biopsy. The stylet of the DLT was bent to fit the natural curve of the #3 non-channeled blade of the King Vision™ videolaryngoscope. We conclude that the use of King Vision™ videolaryngoscope could offer an effective method of DLT placement for OLV.
      PubDate: 2014-09-29
      DOI: 10.12688/f1000research.4481.4
      Issue No: Vol. 3 (2014)
       
  • GASOLINE: a Cytoscape app for multiple local alignment of PPI networks
           [v2; indexed, http://f1000r.es/4f7]

    • Authors: Giovanni Micale, Andrea Continella, Alfredo Ferro, Rosalba Giugno, Alfredo Pulvirenti
      Abstract: Comparing protein interaction networks can reveal interesting patterns of interactions for a specific function or process in distantly related species. In this paper we present GASOLINE, a Cytoscape app for multiple local alignments of PPI (protein-protein interaction) networks. The app is based on the homonymous greedy and stochastic algorithm. GASOLINE starts with the identification of sets of similar nodes, called seeds of the alignment. Alignments are then extended in a greedy manner and finally refined. Both the identification of seeds and the extension of alignments are performed through an iterative Gibbs sampling strategy. GASOLINE is a Cytoscape app for computing and visualizing local alignments, without requiring any post-processing operations. GO terms can be easily attached to the aligned proteins for further functional analysis of alignments. GASOLINE can perform the alignment task in few minutes, even for a large number of input networks.
      PubDate: 2014-09-23
      DOI: 10.12688/f1000research.4537.2
      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)
       
  • Chile’s dilemma: how to reinsert scientists trained abroad [v1;
           indexed, http://f1000r.es/4cm]

    • Authors: Alexia Nunez-Parra, Maria-Paz Ramos
      Abstract: Chile is recognized worldwide as an emergent economy, with a great power in natural resource exploitation. Nonetheless, despite being one of the most developed countries in Latin America, Chile imports most of the knowledge and technology necessary to drive innovation in the country. The tight budget that the Chilean government assigned to research and development and the absence of a long-term scientific agenda contributed to a limited supply of scientists over the years. In an effort to reverse this scenario, Chile has created several fellowships, such as the Becas Chile Program (BCP) to encourage new generations to pursue graduate studies to ultimately advance research and development in situ. More than 6000 fellows are now being trained abroad, accumulating an incredible potential to transform the Chilean scientific environment as we know it.  Chile now faces a greater challenge: it has to offer infrastructure and job openings to the highly skilled professionals in whom it invested. Unfortunately no clear public policies to address this situation have been developed, partially due to the lack of a dedicated institution, such as a Ministry for Science and Technology which could focalize the necessary efforts to promote such policies. Therefore, in the meantime, Chilean scientist have been motivated to create different organizations, such as, Mas Ciencia para Chile and Nexos Chile-USA, to promote constructive discussion of the policies that could be implemented to improve the Chilean scientific situation. We hope that these and other organizations have a real impact on the generation of scientific guidelines that will finally contribute to the development of the country.
      PubDate: 2014-09-18
      DOI: 10.12688/f1000research.5287.1
      Issue No: Vol. 3 (2014)
       
  • Aging and energetics’ ‘Top 40’ future research
           opportunities 2010-2013 [v1; indexed, http://f1000r.es/4ae]

    • Authors: David B. Allison, Lisa H. Antoine, Scott W. Ballinger, Marcas M. Bamman, Peggy Biga, Victor M. Darley-Usmar, Gordon Fisher, Julia M. Gohlke, Ganesh V. Halade, John L. Hartman, Gary R. Hunter, Joseph L. Messina, Tim R. Nagy, Eric P. Plaisance, Kevin A. Roth, Michael W. Sandel, Tonia S. Schwartz, Daniel L. Smith, J. David Sweatt, Trygve O. Tollefsbol, Stephen A. Watts, Yongbin Yang, Jianhua Zhang, Steven N. Austad, Mickie L. Powell
      Abstract: Background: As part of a coordinated effort to expand our research activity at the interface of Aging and Energetics a team of investigators at The University of Alabama at Birmingham systematically assayed and catalogued the top research priorities identified in leading publications in that domain, believing the result would be useful to the scientific community at large. Objective: To identify research priorities and opportunities in the domain of aging and energetics as advocated in the 40 most cited papers related to aging and energetics in the last 4 years. Design: The investigators conducted a search for papers on aging and energetics in Scopus, ranked the resulting papers by number of times they were cited, and selected the ten most-cited papers in each of the four years that include 2010 to 2013, inclusive. Results:   Ten research categories were identified from the 40 papers.  These included: (1) Calorie restriction (CR) longevity response, (2) role of mTOR (mechanistic target of Rapamycin) and related factors in lifespan extension, (3) nutrient effects beyond energy (especially resveratrol, omega-3 fatty acids, and selected amino acids), 4) autophagy and increased longevity and health, (5) aging-associated predictors of chronic disease, (6) use and effects of mesenchymal stem cells (MSCs), (7) telomeres relative to aging and energetics, (8) accretion and effects of body fat, (9) the aging heart,  and (10) mitochondria, reactive oxygen species, and cellular energetics. Conclusion: The field is rich with exciting opportunities to build upon our existing knowledge about the relations among aspects of aging and aspects of energetics and to better understand the mechanisms which connect them.
      PubDate: 2014-09-12
      DOI: 10.12688/f1000research.5212.1
      Issue No: Vol. 3 (2014)
       
  • ReactomeFIViz: a Cytoscape app for pathway and network-based data analysis
           [v2; indexed, http://f1000r.es/4cf]

    • Authors: Guanming Wu, Eric Dawson, Adrian Duong, Robin Haw, Lincoln Stein
      Abstract: High-throughput experiments are routinely performed in modern biological studies. However, extracting meaningful results from massive experimental data sets is a challenging task for biologists. Projecting data onto pathway and network contexts is a powerful way to unravel patterns embedded in seemingly scattered large data sets and assist knowledge discovery related to cancer and other complex diseases. We have developed a Cytoscape app called “ReactomeFIViz”, which utilizes a highly reliable gene functional interaction network combined with human curated pathways derived from Reactome and other pathway databases. This app provides a suite of features to assist biologists in performing pathway- and network-based data analysis in a biologically intuitive and user-friendly way. Biologists can use this app to uncover network and pathway patterns related to their studies, search for gene signatures from gene expression data sets, reveal pathways significantly enriched by genes in a list, and integrate multiple genomic data types into a pathway context using probabilistic graphical models. We believe our app will give researchers substantial power to analyze intrinsically noisy high-throughput experimental data to find biologically relevant information.
      PubDate: 2014-09-12
      DOI: 10.12688/f1000research.4431.2
      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)
       
  • Cost for the treatment of actinic keratosis on the rise in Australia [v2;
           indexed, http://f1000r.es/48f]

    • Authors: Eshini Perera, Sean McGuigan, Rodney Sinclair
      Abstract: Objectives: To report the burden and cost of actinic keratosis (AK) treatment in Australia and to forecast the number of AK treatments and the associated costs to 2020. Design and setting: A retrospective study of data obtained from medicare Australia for AK treated by cryotherapy between 1 January 1994 and 31 December 2012, by year and by state or territory. Results: The total number of AK cryotherapy treatments increased from 247,515 in 1994 to 643,622 in 2012, and we estimate that the number of treatments will increase to 831,952 (95% CI 676,919 to 986,987) by 2020. The total Medicare Benefits Schedule (MBS) benefits paid out for AK in 2012 was $19.6 million and we forecast that this will increase to $24.7 million by 2020 (without inflation). Conclusion: The number of AK cryotherapy treatments increased by 160% between 1994 and 2012. we forecast that the number of treatments will increase by 30% between 2012 and 2020. The rates of non-melanoma skin cancer (NMSC) and AK appear to be increasing at the same rate. During the period 2010 to 2015 AK is anticipated to increase by 17.8% which follows a similar trend to published data that forecasts an increase in NMSC treatments of 22.3%.
      PubDate: 2014-08-20
      DOI: 10.12688/f1000research.4671.2
      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)
       
  • 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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