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Journal Cover   F1000Research
  [SJR: 0.219]   [H-I: 3]   [5 followers]  Follow
  This is an Open Access Journal Open Access journal
   ISSN (Online) 2046-1402
   Published by Faculty of 1000 Homepage  [1 journal]
  • FDA approved drugs as potential Ebola treatments [v2; indexed,

    • Authors: Sean Ekins, Megan Coffee
      Abstract: In the search for treatments for the Ebola Virus, multiple screens of FDA drugs have led to the identification of several with promising in vitro activity. These compounds were not originally developed as antivirals and some have been further tested in mouse in vivo models. We put forward the opinion that some of these drugs could be evaluated further and move into the clinic as they are already FDA approved and in many cases readily available. This may be important if there is a further outbreak in future and no other therapeutic is available.
      PubDate: 2015-03-10T14:43:40Z
      DOI: 10.12688/f1000research.6164.2
      Issue No: Vol. 4 (2015)
  • Guiding Ebola patients to suitable health facilities: an SMS-based
           approach [v1; indexed,]

    • Authors: Mohamad-Ali Trad, Raja Jurdak, Rajib Rana
      Abstract: Access to appropriate health services is a fundamental problem in developing countries, where patients do not have access to information and to the nearest health service facility. We propose building a recommendation system based on simple SMS text messaging to help Ebola patients readily find the closest health service with available and appropriate resources. The system will map people’s reported symptoms to likely Ebola case definitions and suitable health service locations. In addition to providing a valuable individual service to people with curable diseases, the proposed system will also predict population-level disease spread risk for infectious diseases using crowd-sourced symptoms from the population. Health workers will be able to better plan and anticipate responses to the current Ebola outbreak in West Africa. Patients will have improved access to appropriate health care. This system could also be applied in other resource poor or rich settings.
      PubDate: 2015-02-12T16:41:53Z
      DOI: 10.12688/f1000research.6105.1
      Issue No: Vol. 4 (2015)
  • Small molecules with antiviral activity against the Ebola virus [v1;

    • Authors: Nadia Litterman, Christopher Lipinski, Sean Ekins
      Abstract: The recent outbreak of the Ebola virus in West Africa has highlighted the clear shortage of broad-spectrum antiviral drugs for emerging viruses. There are numerous FDA approved drugs and other small molecules described in the literature that could be further evaluated for their potential as antiviral compounds. These molecules are in addition to the few new antivirals that have been tested in Ebola patients but were not originally developed against the Ebola virus, and may play an important role as we await an effective vaccine. The balance between using FDA approved drugs versus novel antivirals with minimal safety and no efficacy data in humans should be considered. We have evaluated 55 molecules from the perspective of an experienced medicinal chemist as well as using simple molecular properties and have highlighted 16 compounds that have desirable qualities as well as those that may be less desirable. In addition we propose that a collaborative database for sharing such published and novel information on small molecules is needed for the research community studying the Ebola virus.
      PubDate: 2015-02-09T15:10:45Z
      DOI: 10.12688/f1000research.6120.1
      Issue No: Vol. 4 (2015)
  • Enhancement of COPD biological networks using a web-based collaboration
           interface [v1; indexed,]

    • Authors: The sbv IMPROVER project team (in alphabetical order), Stephanie Boue, Brett Fields, Julia Hoeng, Jennifer Park, Manuel C. Peitsch, Walter K. Schlage, Marja Talikka, The Challenge Best Performers (in alphabetical order), Ilona Binenbaum, Vladimir Bondarenko, Oleg V. Bulgakov, Vera Cherkasova, Norberto Diaz-Diaz, Larisa Fedorova, Svetlana Guryanova, Julia Guzova, Galina Igorevna Koroleva, Elena Kozhemyakina, Rahul Kumar, Noa Lavid, Qingxian Lu, Swapna Menon, Yael Ouliel, Samantha C. Peterson, Alexander Prokhorov, Edward Sanders, Sarah Schrier, Golan Schwaitzer Neta, Irina Shvydchenko, Aravind Tallam, Gema Villa-Fombuena, John Wu, Ilya Yudkevich, Mariya Zelikman
      Abstract: The construction and application of biological network models is an approach that offers a holistic way to understand biological processes involved in disease. Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease of the airways for which therapeutic options currently are limited after diagnosis, even in its earliest stage. COPD network models are important tools to better understand the biological components and processes underlying initial disease development. With the increasing amounts of literature that are now available, crowdsourcing approaches offer new forms of collaboration for researchers to review biological findings, which can be applied to the construction and verification of complex biological networks. We report the construction of 50 biological network models relevant to lung biology and early COPD using an integrative systems biology and collaborative crowd-verification approach. By combining traditional literature curation with a data-driven approach that predicts molecular activities from transcriptomics data, we constructed an initial COPD network model set based on a previously published non-diseased lung-relevant model set. The crowd was given the opportunity to enhance and refine the networks on a website ( and to add mechanistic detail, as well as critically review existing evidence and evidence added by other users, so as to enhance the accuracy of the biological representation of the processes captured in the networks. Finally, scientists and experts in the field discussed and refined the networks during an in-person jamboree meeting. Here, we describe examples of the changes made to three of these networks: Neutrophil Signaling, Macrophage Signaling, and Th1-Th2 Signaling. We describe an innovative approach to biological network construction that combines literature and data mining and a crowdsourcing approach to generate a comprehensive set of COPD-relevant models that can be used to help understand the mechanisms related to lung pathobiology. Registered users of the website can freely browse and download the networks.
      PubDate: 2015-01-29T11:31:28Z
      DOI: 10.12688/f1000research.5984.1
      Issue No: Vol. 4 (2015)
  • Strain-specific and pooled genome sequences for populations of Drosophila
           melanogaster from three continents. [v1; indexed,]

    • Authors: Casey M. Bergman, Penelope R. Haddrill
      Abstract: To contribute to our general understanding of the evolutionary forces that shape variation in genome sequences in nature, we have sequenced genomes from 50 isofemale lines and six pooled samples from populations of Drosophila melanogaster on three continents. Analysis of raw and reference-mapped reads indicates the quality of these genomic sequence data is very high. Comparison of the predicted and experimentally-determined Wolbachia infection status of these samples suggests that strain or sample swaps are unlikely to have occurred in the generation of these data. Genome sequences are freely available in the European Nucleotide Archive under accession ERP009059. Isofemale lines can be obtained from the Drosophila Species Stock Center.
      PubDate: 2015-01-29T11:29:37Z
      DOI: 10.12688/f1000research.6090.1
      Issue No: Vol. 4 (2015)
  • Every scientist is a memory researcher: Suggestions for making
           research more memorable [v1; indexed,]

    • Authors: Christopher R. Madan
      Abstract: Independent of the actual results, some scientific articles are more memorable than others. As anyone who has written an article collaboratively knows, there are numerous ways a manuscript can be written to convey the same general ideas. To aid with this, many scientific writing books and editorials provide advice, often anecdotal, on how to make articles more memorable. Here I ground these suggestions with empirical support from memory research. Specifically, I suggest that researchers consider how to emphasize their work’s novelty, strive to describe their work using concrete, easy-to-understand terms, and use caution when attempting to evoke an emotional response in the reader. I also discuss considerations in title selections and conference presentations.
      PubDate: 2015-01-22T10:53:20Z
      DOI: 10.12688/f1000research.6053.1
      Issue No: Vol. 4 (2015)
  • Ketamine infusion for patients receiving extracorporeal membrane
           oxygenation support: a case series [v1; indexed,]

    • Authors: Bethany Tellor, Nicole Shin, Thomas J. Graetz, Michael S. Avidan
      Abstract: The use of ketamine infusion for sedation/analgesia in patients receiving extracorporeal membrane oxygenation (ECMO) therapy has not been described. The aims of this retrospective cohort study were to explore whether ketamine infusion for patients requiring ECMO therapy was associated with altered RASS scores, decreased concurrent sedative or opioid use, or with changes in vasopressor requirements.  All patients on ECMO who received ketamine infusions in addition to sedative and/or opioid infusions between December 2013 and October 2014 at Barnes-Jewish Hospital in St. Louis were retrospectively identified. Patient characteristics and process of care data were collected. A total of 26 ECMO patients receiving ketamine infusion were identified. The median (inter quartile range [range]) age was 40 years (30-52 [25-66]) with 62% male. The median starting infusion rate of ketamine was 50 mg/hr (30-50 [6-150]) and it was continued for a median duration of 9 days (4-14 [0.2-21]). Prior to ketamine, 14/26 patients were receiving vasopressor infusions to maintain hemodynamic stability. Ketamine initiation was associated with a decrease in vasopressor requirement in 11/26  patients within two hours, and 0/26 required an increase (p
      PubDate: 2015-01-16T16:29:25Z
      DOI: 10.12688/f1000research.6006.1
      Issue No: Vol. 4 (2015)
  • Case Report: Persistent erectile dysfunction in a man with prolactinoma
           [v1; indexed,]

    • Authors: Justin Badal, Ranjith Ramasamy, Tariq Hakky, Aravind Chandrashekar, Larry Lipshultz
      Abstract: Erectile dysfunction has been explored as a condition secondary to elevated prolactin; however, the mechanisms by which elevated prolactin levels cause erectile dysfunction have not yet been clearly established. We here present a patient with a history of prolactinoma who suffered from persistent erectile dysfunction despite testosterone supplementation and pharmacological and surgical treatment for the prolactinoma.  Patients who have had both prolactinemia and erectile dysfunction have been reported in the literature, but we find no report of a patient with persistent erectile dysfunction in the setting of testosterone supplementation and persistent hyperprolactinemia refractory to treatment. This case provides evidence supporting the idea that suppression of erectile function occurs in both the central and peripheral nervous systems independent of the hypothalamic-pituitary-gonadal axis.
      PubDate: 2015-01-15T16:52:59Z
      DOI: 10.12688/f1000research.5743.1
      Issue No: Vol. 4 (2015)
  • Association between obesity and depression in patients with diabetes
           mellitus type 2; a study protocol [v1; indexed,]

    • Authors: Eduardo De la Cruz-Cano, Carlos Alfonso Tovilla-Zarate, Emilio Reyes-Ramos, Thelma Beatriz Gonzalez-Castro, Isela Juarez-Castro, Maria Lilia López-Narváez, Ana Fresan
      Abstract: Background: Diabetes mellitus and depression are highly prevalent conditions throughout the world and have significant impact on health outcomes. It has been estimated that diabetes mellitus type 2 affects about 246 million people in the world; nevertheless, incidence varies among countries. There is evidence that depression is associated with a poor metabolic control in patients with type 2 diabetes mellitus that present other health problems (such as hypertension and obesity). The aim of this study protocol is to determine if obesity increases the risk for depression in patient with diabetes type 2. Methods: The analysis will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).The studies suitable for inclusion will be assessed by the Newcastle-Ottawa Scale (NOS) to determine their methodological quality. To identify the studies of interest, we will search on PubMed and EBSCO databases. We will use the following keyword combinations: "Diabetes Mellitus type 2 AND obesity AND depression", "depression AND Diabetes Mellitus type 2", "Diabetes Mellitus type 2 AND body mass index cross sectional study", "depression AND obesity cross-sectional study". Causes for exclusion will be publications that studied patients diagnosed with diabetes mellitus type 1; articles that focused on the treatment and complications of diabetes mellitus type 2; publications that have studied other clinical or psychiatric conditions (for instance, seizure disorder or history of schizophrenia, bipolar disorder, psychotic symptoms or dementia). Conclusion: The results of this study will form the basis for a better understanding of the association between obesity and depression in patients with diabetes mellitus type 2, and will allow development of prediction tools and better interventions. It is evident that several modifiable and non-modifiable risk factors play an important role in the pathogenesis of diabetes among population. Currently, evidence for the deleterious effects of diabetes mellitus type 2 are based on cross-sectional or other observational designs. Therefore, this study will have important implications for future research and public health guidance.
      PubDate: 2015-01-09T17:00:59Z
      DOI: 10.12688/f1000research.5995.1
      Issue No: Vol. 4 (2015)
  • Open peer review at four STEM journals: an observational overview [v1;

    • Authors: Emily Ford
      Abstract: Open peer review, peer review where authors' and reviewers' identities are disclosed to one another, is a growing trend in scholarly publishing. Through observation of four journals in STEM disciplines, PLoS One, Atmospheric Chemistry & Physics, PeerJ, and F1000Research, an observational overview is conducted. The overview relies on defined characteristics of open peer review. Results show that despite differing open peer review implementations, each journal retains editorial involvement in scholarly publishing. Further, the analysis shows that only one of these implementations is fully transparent in its peer review and decision making process. Finally, the overview contends that journals should clearly outline peer review and editorial processes in order to allow for open peer review to be better understood and adopted by authors, reviewers, editors, and readers of science communications.
      PubDate: 2015-01-09T16:59:14Z
      DOI: 10.12688/f1000research.6005.1
      Issue No: Vol. 4 (2015)
  • Case Report: Bilateral reexpansion pulmonary edema following treatment of
           a unilateral hemothorax [v1; indexed,]

    • Authors: Steven P de Wolf, Jaap Deunk, Alexander D Cornet, Paul WG Elbers
      Abstract: Bilateral re-expansion pulmonary edema (RPE) is an extremely rare entity. We report the unique case of bilateral RPE following a traumatic, unilateral hemopneumothorax in a young healthy male. Bilateral RPE occurred only one hour after drainage of a unilateral hemopneumothorax. The patient was treated with diuretics and supplemental oxygen. Diagnosis was confirmed by excluding other causes, using laboratory findings, chest radiography, pulmonary and cardiac ultrasound and high resolution computed tomography. His recovery was uneventful. The pathophysiology of bilateral RPE is not well known. Treatment is mainly supportive and consists of diuretics, mechanical ventilation, inotropes and steroids. In case of a pulmonary deterioration after the drainage of a traumatic pneumothorax, bilateral RPE should be considered after exclusion of more common causes of dyspnea.
      PubDate: 2014-12-30T17:10:03Z
      DOI: 10.12688/f1000research.6000.1
      Issue No: Vol. 3 (2014)
  • Subdivisions of the adult zebrafish pallium based on molecular marker
           analysis [v1; indexed,]

    • Authors: Julia Ganz, Volker Kroehne, Dorian Freudenreich, Anja Machate, Michaela Geffarth, Ingo Braasch, Jan Kaslin, Michael Brand
      Abstract: Background: The telencephalon shows a remarkable structural diversity among vertebrates. In particular, the everted telencephalon of ray-finned fishes has a markedly different morphology compared to the evaginated telencephalon of all other vertebrates. This difference in development has hampered the comparison between different areas of the pallium of ray-finned fishes and the pallial nuclei of all other vertebrates. Various models of homology between pallial subdivisions in ray-finned fishes and the pallial nuclei in tetrapods have been proposed based on connectional, neurochemical, gene expression and functional data. However, no consensus has been reached so far. In recent years, the analysis of conserved developmental marker genes has assisted the identification of homologies for different parts of the telencephalon among several tetrapod species. Results: We have investigated the gene expression pattern of conserved marker genes in the adult zebrafish (Danio rerio) pallium to identify pallial subdivisions and their homology to pallial nuclei in tetrapods. Combinatorial expression analysis of ascl1a, eomesa, emx1, emx2, emx3, and Prox1 identifies four main divisions in the adult zebrafish pallium. Within these subdivisions, we propose that Dm is homologous to the pallial amygdala in tetrapods and that the dorsal subdivision of Dl is homologous to part of the hippocampal formation in mouse. We have complemented this analysis be examining the gene expression of emx1, emx2 and emx3 in the zebrafish larval brain. Conclusions: Based on our gene expression data, we propose a new model of subdivisions in the adult zebrafish pallium and their putative homologies to pallial nuclei in tetrapods. Pallial nuclei control sensory, motor, and cognitive functions, like memory, learning and emotion. The identification of pallial subdivisions in the adult zebrafish and their homologies to pallial nuclei in tetrapods will contribute to the use of the zebrafish system as a model for neurobiological research and human neurodegenerative diseases.
      PubDate: 2014-12-17T16:21:22Z
      DOI: 10.12688/f1000research.5595.1
      Issue No: Vol. 3 (2014)
  • Case Report: A case report of Moyamoya disease in a 36 year old African
           American woman [v1; indexed,]

    • Authors: Rohit Kumar Gudepu, Mohtashim A. Qureshi, Ihtesham A. Qureshi, Lakshman Rao
      Abstract: Moyamoya is a rare idiopathic progressive vaso-occlusive disease characterized by irreversible condition of main blood vessels to the brain as they enter into the skull. We present a case of 36 year old African American female presenting to the Out Patient Clinic with headache which were on and off for 4-6 months and did not relieve on routine medical therapy. It was associated with weakness on right side for last few days. The patient was investigated with CT Angiogram, diagnosed as Moyamoya disease and operated. She has been followed up for the last 5 years and the patient has not complained of any headaches or focal neurological symptoms.
      PubDate: 2014-12-08T17:12:45Z
      DOI: 10.12688/f1000research.5859.1
      Issue No: Vol. 3 (2014)
  • Interaction of growth hormone receptor/binding protein gene disruption and
           caloric restriction for insulin sensitivity and attenuated aging [v1;

    • Authors: Oge Arum, Jamal Saleh, Ravneet Boparai, Jeremy Turner, John Kopchick, Romesh Khardori, Andrzej Bartke
      Abstract: The correlation of physiological sensitivity to insulin (vis-à-vis glycemic regulation) and longevity is extensively established, creating a justifiable gerontological interest on whether insulin sensitivity is causative, or even predictive, of some or all phenotypes of slowed senescence (including longevity). The growth hormone receptor/ binding protein gene-disrupted (GHR-KO) mouse is the most extensively investigated insulin-sensitive, attenuated aging model. It was reported that, in a manner divergent from similar mutants, GHR-KO mice fail to respond to caloric restriction (CR) by altering their insulin sensitivity. We hypothesized that maximized insulin responsiveness is what causes GHR-KO mice to exhibit a suppressed survivorship response to dietary (including caloric) restriction; and attempted to refute this hypothesis by assessing the effects of CR on GHR-KO mice for varied slow-aging-associated phenotypes. In contrast to previous reports, we found GHR-KO mice on CR to be less responsive than their ad libitum (A.L.) counterparts to the hypoglycemia-inducing effects of insulin. Further, CR had negligible effects on the metabolism or cognition of GHR-KO mice. Therefore, our data suggest that the effects of CR on the insulin sensitivity of GHR-KO mice do not concur with the effects of CR on the aging of GHR-KO mice.
      PubDate: 2014-10-28T15:21:28Z
      DOI: 10.12688/f1000research.5378.1
      Issue No: Vol. 3 (2014)
  • Case Report: Paroxysmal nocturnal hemoglobinuria in a woman heterozygous
           for G6PD A- [v2; indexed,]

    • Authors: Nieves Perdigones, Mariela Morales, Philip Mason, Monica Bessler
      Abstract: We describe a case of paroxysmal nocturnal hemoglobinuria (PNH) in a woman who is heterozygous for the glucose-6-phosphate dehydrogenase A-   (G6PDA-) allele. PNH is associated with one or more clones of cells that lack complement inhibition due to loss of function somatic mutations in the PIGA gene.  PIGA encodes the enzyme phosphatidylinositol glycan anchor biosynthesis, class A, which catalyses the first step of glycosylphosphatidylinisotol (GPI)  anchor synthesis. Two GPI anchored red cell surface antigens regulate complement lysis. G6PD catalyses the first step of the pentose phosphate pathway and enzyme variants, frequent in some populations have been selected because they confer resistance to malaria, are associated with hemolysis in the presence of oxidizing agents including several drugs. The patient had suffered a hemolytic attack after taking co-trimoxazole, a drug that precipitates hemolysis in G6PD deficient individuals. Since both G6PD and PIGA are X-linked we hypothesized that the PIGA mutation was on the X-chromosome carrying the G6PDA- allele. Investigations showed that in fact the PIGA mutation was on the X-chromosome carrying the normal G6PD B allele. We speculate that complement activation on G6PD A- red cells exposed to Bactrim might have triggered complement activation inducing the lysis of G6PD B PNH Type II red blood cells or that the patient may have had a PNH clone expressing G6PDA- at the time of the hemolytic episode.
      PubDate: 2014-10-21T15:12:41Z
      DOI: 10.12688/f1000research.4980.2
      Issue No: Vol. 3 (2014)
  • Directed evolution induces tributyrin hydrolysis in a virulence factor of
           Xylella fastidiosa using a duplicated gene as a template [v1; indexed,

    • Authors: Hossein Gouran, Sandeep Chakraborty, Basuthkar J. Rao, Bjarni Asgeirsson, Abhaya Dandekar
      Abstract: Duplication of genes is one of the preferred ways for natural selection to add advantageous functionality to the genome without having to reinvent the wheel with respect to catalytic efficiency and protein stability. The duplicated secretory virulence factors of Xylella fastidiosa (LesA, LesB and LesC), implicated in Pierce's disease of grape and citrus variegated chlorosis of citrus species, epitomizes the positive selection pressures exerted on advantageous genes in such pathogens. A deeper insight into the evolution of these lipases/esterases is essential to develop resistance mechanisms in transgenic plants. Directed evolution, an attempt to accelerate the evolutionary steps in the laboratory, is inherently simple when targeted for loss of function. A bigger challenge is to specify mutations that endow a new function, such as a lost functionality in a duplicated gene. Previously, we have proposed a method for enumerating candidates for mutations intended to transfer the functionality of one protein into another related protein based on the spatial and electrostatic properties of the active site residues (DECAAF). In the current work, we present in vivo validation of DECAAF by inducing tributyrin hydrolysis in LesB based on the active site similarity to LesA. The structures of these proteins have been modeled using RaptorX based on the closely related LipA protein from Xanthomonas oryzae. These mutations replicate the spatial and electrostatic conformation of LesA in the modeled structure of the mutant LesB as well, providing in silico validation before proceeding to the laborious in vivo work. Such focused mutations allows one to dissect the relevance of the duplicated genes in finer detail as compared to gene knockouts, since they do not interfere with other moonlighting functions, protein expression levels or protein-protein interaction.
      PubDate: 2014-09-09T09:47:05Z
      DOI: 10.12688/f1000research.5147.1
      Issue No: Vol. 3 (2014)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
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