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https://www.readbyqxmd.com/read/29652050/long-term-c-elegans-immobilization-enables-high-resolution-developmental-studies-in-vivo
#1
Simon Berger, Evelyn Lattmann, Tinri Aegerter-Wilmsen, Michael Hengartner, Alex Hajnal, Andrew deMello, Xavier Casadevall I Solvas
Live-imaging of C. elegans is essential for the study of conserved cellular pathways (e.g. EGFR/Wnt signaling) and morphogenesis in vivo. However, the usefulness of live imaging as a research tool has been severely limited by the need to immobilize worms prior to and during imaging. Conventionally, immobilization is achieved by employing both physical and chemical interventions. These are known to significantly affect many physiological processes, and thus limit our understanding of dynamic developmental processes...
April 13, 2018: Lab on a Chip
https://www.readbyqxmd.com/read/29650539/a-call-for-more-science-in-forensic-science
#2
Suzanne Bell, Sunita Sah, Thomas D Albright, S James Gates, M Bonner Denton, Arturo Casadevall
Forensic science is critical to the administration of justice. The discipline of forensic science is remarkably complex and includes methodologies ranging from DNA analysis to chemical composition to pattern recognition. Many forensic practices developed under the auspices of law enforcement and were vetted primarily by the legal system rather than being subjected to scientific scrutiny and empirical testing. Beginning in the 1990s, exonerations based on DNA-related methods revealed problems with some forensic disciplines, leading to calls for major reforms...
April 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29648516/the-phosphodiesterase-4-inhibitor-roflumilast-reverts-proteolysis-in-skeletal-muscle-cells-of-patients-with-copd-cachexia
#3
Esther Barreiro, Ester Puig-Vilanova, Anna Salazar-Degracia, Sergi Pascual-Guardia, Carme Casadevall, Joaquim Gea
Peripheral muscle weakness and mass loss are characteristic features in severe COPD. We hypothesized that the phosphodiesterase-4 inhibitor roflumilast-induced cAMP may ameliorate proteolysis and metabolism in skeletal muscles of COPD patients with severe muscle wasting. In myogenic precursor cells (isolated from muscle biopsies and cultured up to obtain differentiated myotubes) from 10 severe COPD patients and 10 healthy controls, which were treated with 1 microM roflumilast N-oxide (RNO) for three time-cohorts (1h, 6h, and 24h), genes of antioxidant defense and oxidative stress marker, myogenesis and muscle metabolism, proteolysis (tyrosine release assay) and ubiquitin-proteasome system markers, autophagy, and myosin isoforms were analyzed using RT-PCR and immunoblotting...
April 12, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29615812/structure-function-analysis-and-therapeutic-efficacy-of-antibodies-to-fungal-melanin-for-melanoma-radioimmunotherapy
#4
J D Nosanchuk, A Jeyakumar, A Ray, E Revskaya, Z Jiang, R A Bryan, K J H Allen, R Jiao, M E Malo, B L Gómez, A Morgenstern, F Bruchertseifer, D Rickles, G B Thornton, A Bowen, A Casadevall, E Dadachova
Metastatic melanoma remains difficult to treat despite recent approvals of several new drugs. Recently we reported encouraging results of Phase I clinical trial of radiolabeled with188 Re murine monoclonal IgM 6D2 to melanin in patients with Stage III/IV melanoma. Subsequently we generated a novel murine IgG 8C3 to melanin. IgGs are more amenable to humanization and cGMP (current Good Manufacturing Practice) manufacturing than IgMs. We performed comparative structural analysis of melanin-binding IgM 6D2 and IgG 8C3...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29615505/using-preprints-for-journal-clubs
#5
EDITORIAL
Arturo Casadevall, Neil Gow
Journal clubs are important mechanisms for teaching how to approach the scientific literature critically and for disseminating findings. Papers from high-impact journals often dominate journal club selections, a practice that reinforces the unscientific emphasis of placing high value on publishing venue rather than scientific content and critical analysis of the publications. We suggest improving journal clubs by including preprints rather than focusing completely on published papers. This change in practice might benefit the scientific enterprise in numerous ways, including by providing direct criticisms to preprint authors before publication, deemphasizing publishing venue, teaching students the art of reviewing papers, and making journal clubs more current by discussing unpublished data...
April 3, 2018: MBio
https://www.readbyqxmd.com/read/29568736/a-new-approach-to-evaluating-the-risk-benefit-equation-for-dual-use-and-gain-of-function-research-of-concern
#6
Michael J Imperiale, Arturo Casadevall
In the twenty-first century, biology faces a problem that has previously vexed other disciplines such as physics, namely the prospect that its knowledge domain could be used to generate biological agents with altered properties that enhanced their weapon potential. Biological weapons bring the additional dimension that these could be self-replicating, easy to manufacture and synthesized with commonly available expertise. This resulted in increasing concern about the type of research done and communicated, despite the fact that such research often has direct societal benefits, bringing the dual-use dilemma to biology...
2018: Frontiers in Bioengineering and Biotechnology
https://www.readbyqxmd.com/read/29564402/novel-antifungal-compounds-discovered-in-medicines-for-malaria-venture-s-malaria-box
#7
Eric H Jung, David J Meyers, Jürgen Bosch, Arturo Casadevall
Similarities in fungal and animal cells make antifungal discovery efforts more difficult than those for other classes of antimicrobial drugs. Currently, there are only three major classes of antifungal drugs used for the treatment of systemic fungal diseases: polyenes, azoles, and echinocandins. Even in situations where the offending fungal organism is susceptible to the available drugs, treatment courses can be lengthy and unsatisfactory, since eradication of infection is often very difficult, especially in individuals with impaired immunity...
March 2018: MSphere
https://www.readbyqxmd.com/read/29560793/extracellular-vesicles-and-vesicle-free-secretome-of-the-protozoa-acanthamoeba-castellanii-under-homeostasis-and-nutritional-stress-and-their-damaging-potential-to-host-cells
#8
Diego de Souza Gonçalves, Marina da Silva Ferreira, Susie Coutinho Liedke, Kamilla Xavier Gomes, Gabriel Afonso de Oliveira, Pedro Ernesto Lopes Leão, Gabriele Vargas Cesar, Sergio H Seabra, Juliana Reis Cortines, Arturo Casadevall, Leonardo Nimrichter, Gilberto Barbosa Domont, Magno Rodrigues Junqueira, Jose Mauro Peralta, Allan J Guimaraes
Acanthamoeba castellanii (Ac) are ubiquitously distributed in nature, and by contaminating medical devices such as heart valves and contact lenses, they cause a broad range of clinical presentations to humans. Although several molecules have been described to play a role in Ac pathogenesis, including parasite host-tissue invasion and escaping of host-defense, little information is available on their mechanisms of secretion. Herein, we describe the molecular components secreted by Ac, under different protein availability conditions to simulate host niches...
March 21, 2018: Virulence
https://www.readbyqxmd.com/read/29542711/melanin-triggers-antifungal-defences
#9
Arturo Casadevall
No abstract text is available yet for this article.
March 15, 2018: Nature
https://www.readbyqxmd.com/read/29463650/elegant-science
#10
EDITORIAL
Arturo Casadevall, Ferric C Fang
Elegance is a prized quality in science that is associated with simplicity and explanatory power. This essay considers the qualities that make a scientific model, experiment, method, or theory "elegant," with a focus on the life sciences. We propose a definition of elegance that includes clarity, cleverness, correctness, explanatory power, parsimony, and beauty. The pursuit of elegance can improve the quality of science, but elegance must be pursued with caution, as the truth is sometimes inelegant...
February 20, 2018: MBio
https://www.readbyqxmd.com/read/29460082/testing-hypotheses-on-risk-factors-for-scientific-misconduct-via-matched-control-analysis-of-papers-containing-problematic-image-duplications
#11
Daniele Fanelli, Rodrigo Costas, Ferric C Fang, Arturo Casadevall, Elisabeth M Bik
It is commonly hypothesized that scientists are more likely to engage in data falsification and fabrication when they are subject to pressures to publish, when they are not restrained by forms of social control, when they work in countries lacking policies to tackle scientific misconduct, and when they are male. Evidence to test these hypotheses, however, is inconclusive due to the difficulties of obtaining unbiased data. Here we report a pre-registered test of these four hypotheses, conducted on papers that were identified in a previous study as containing problematic image duplications through a systematic screening of the journal PLoS ONE...
February 19, 2018: Science and Engineering Ethics
https://www.readbyqxmd.com/read/29437927/the-viscoelastic-properties-of-the-fungal-cell-wall-allow-traffic-of-ambisome-as-intact-liposome-vesicles
#12
Louise Walker, Prashant Sood, Megan D Lenardon, Gillian Milne, Jon Olson, Gerard Jensen, Julie Wolf, Arturo Casadevall, Jill Adler-Moore, Neil A R Gow
The fungal cell wall is a critically important structure that represents a permeability barrier and protective shield. We probed Candida albicans and Cryptococcus neoformans with liposomes containing amphotericin B (AmBisome), with or without 15-nm colloidal gold particles. The liposomes have a diameter of 60 to 80 nm, and yet their mode of action requires them to penetrate the fungal cell wall to deliver amphotericin B to the cell membrane, where it binds to ergosterol. Surprisingly, using cryofixation techniques with electron microscopy, we observed that the liposomes remained intact during transit through the cell wall of both yeast species, even though the predicted porosity of the cell wall (pore size, ~5...
February 6, 2018: MBio
https://www.readbyqxmd.com/read/29436899/the-capsule-of-cryptococcus-neoformans
#13
Arturo Casadevall, Carolina Coelho, Radames J B Cordero, Quigly Dragotakes, Eric Jung, Raghav Vij, Maggie P Wear
The capsule of Cryptococcus neoformans is its dominant virulence factor and plays a key role in the biology of this fungus. In this essay, we focus on the capsule as a cellular structure and note the limitations inherent in the current methodologies available for its study. Given that no single method can provide the structure of the capsule, our notions of what is the cryptococcal capsule must be arrived at by synthesizing information gathered from very different methodological approaches including microscopy, polysaccharide chemistry and physical chemistry of macromolecules...
February 13, 2018: Virulence
https://www.readbyqxmd.com/read/29420889/hydrodynamics-in-cell-studies
#14
Deborah Huber, Ali Oskooei, Xavier Casadevall I Solvas, Andrew deMello, Govind V Kaigala
Hydrodynamic phenomena are ubiquitous in living organisms and can be used to manipulate cells or emulate physiological microenvironments experienced in vivo. Hydrodynamic effects influence multiple cellular properties and processes, including cell morphology, intracellular processes, cell-cell signaling cascades and reaction kinetics, and play an important role at the single-cell, multicellular, and organ level. Selected hydrodynamic effects can also be leveraged to control mechanical stresses, analyte transport, as well as local temperature within cellular microenvironments...
February 8, 2018: Chemical Reviews
https://www.readbyqxmd.com/read/29384960/dabrafenib-plus-trametinib-for-compassionate-use-in-metastatic-melanoma-a-strobe-compliant-retrospective-observational-postauthorization-study
#15
Salvador Martín Algarra, Virtudes Soriano, Luis Fernández-Morales, Miguel-Ángel Berciano-Guerrero, Karmele Mujika, José Luis Manzano, Teresa Puértolas Hernández, Ainara Soria, Delvys Rodríguez-Abreu, Enrique Espinosa Arranz, Javier Medina Martínez, Ivan Márquez-Rodas, Jordi Rubió-Casadevall, María Eugenia Ortega, José Miguel Jurado García, María José Lecumberri Biurrun, Isabel Palacio, María Rodríguez de la Borbolla Artacho, Javier Pérez Altozano, Victoria Eugenia Castellón Rubio, Almudena García, Pablo Luna, Anabel Ballesteros, Ovidio Fernández, Jose Antonio López Martín, Alfonso Berrocal, Ana Arance
The main objective of the study was to evaluate the efficacy and safety of dabrafenib alone or combined with trametinib for compassionate use in patients with metastatic melanoma.This retrospective, observational study involved 135 patients with unresectable stage IIIC or stage IV melanoma from an expanded-access program at 30 Spanish centers.Forty-eight patients received dabrafenib monotherapy and 87 received combination dabrafenib and trametinib; 4.4% and 95.6% of the patients had stage IIIC and IV melanoma, respectively...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29364243/automated-measurement-of-cryptococcal-species-polysaccharide-capsule-and-cell-body
#16
Quigly Dragotakes, Arturo Casadevall
The purpose of this technique is to provide a consistent, accurate, and manageable process for large numbers of polysaccharide capsule measurements. First, a threshold image is generated based on intensity values uniquely calculated for each image. Then, circles are detected based on contrast between the object and background using the well-established Circle Hough Transformation (CHT) algorithm. Finally, the detected cell capsules and bodies are matched according to center coordinates and radius size, and data is exported to the user in a manageable spreadsheet...
January 11, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29259091/reply-to-arg%C3%A3-elles-and-arg%C3%A3-elles-prieto-are-the-editors-responsible-for-our-obsession-with-the-impact-factor
#17
Arturo Casadevall, Ferric C Fang
No abstract text is available yet for this article.
December 19, 2017: MBio
https://www.readbyqxmd.com/read/29259084/graduate-biomedical-science-education-needs-a-new-philosophy
#18
Gundula Bosch, Arturo Casadevall
There is a growing realization that graduate education in the biomedical sciences is successful at teaching students how to conduct research but falls short in preparing them for a diverse job market, communicating with the public, and remaining versatile scientists throughout their careers. Major problems with graduate level education today include overspecialization in a narrow area of science without a proper grounding in essential critical thinking skills. Shortcomings in education may also contribute to some of the problems of the biomedical sciences, such as poor reproducibility, shoddy literature, and the rise in retracted publications...
December 19, 2017: MBio
https://www.readbyqxmd.com/read/29233901/immune-mediated-damage-completes-the-parabola-cryptococcus-neoformans-pathogenesis-can-reflect-the-outcome-of-a-weak-or-strong-immune-response
#19
Liise-Anne Pirofski, Arturo Casadevall
Cryptococcosis occurs most frequently in immunocompromised individuals. This has led to the prevailing view that this disease is the result of weak immune responses that cannot control the fungus. However, increasingly, clinical and experimental studies have revealed that the host immune response can contribute to cryptococcal pathogenesis, including the recent study of L. M. Neal et al. (mBio 8:e01415-17, 2017, https://doi.org/10.1128/mBio.01415-17) that reports that CD4+ T cells mediate tissue damage in experimental murine cryptococcosis...
December 12, 2017: MBio
https://www.readbyqxmd.com/read/29213074/galectin-3-impacts-cryptococcus-neoformans-infection-through-direct-antifungal-effects
#20
Fausto Almeida, Julie M Wolf, Thiago Aparecido da Silva, Carlos M DeLeon-Rodriguez, Caroline Patini Rezende, André Moreira Pessoni, Fabrício Freitas Fernandes, Rafael Silva-Rocha, Roberto Martinez, Marcio L Rodrigues, Maria Cristina Roque-Barreira, Arturo Casadevall
Cryptococcus neoformans is an encapsulated fungal pathogen that causes cryptococcosis, which is a major opportunistic infection in immunosuppressed individuals. Mammalian β-galactoside-binding protein Galectin-3 (Gal-3) modulates the host innate and adaptive immunity, and plays significant roles during microbial infections including some fungal diseases. Here we show that this protein plays a role also in C. neoformans infection. We find augmented Gal-3 serum levels in human and experimental infections, as well as in spleen, lung, and brain tissues of infected mice...
December 6, 2017: Nature Communications
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