Journal Articles

  • Discovering Anti-platelet Drug Combinations with an Integrated Model of Activator-Inhibitor Relationships, Activator-Activator Synergies and Inhibitor-Inhibitor Synergies
    [Apr 2015]

    by Federica Lombardi, Kalyan Golla, Darren J. Fitzpatrick, Fergal P. Casey, Niamh Moran, Denis C. Shields

    Identifying effective therapeutic drug combinations that modulate complex signaling pathways in platelets is central to the advancement of effective anti-thrombotic therapies. However, there is no systems model of the platelet that predicts responses to different inhibitor combinations. We developed an approach which goes beyond current inhibitor-inhibitor combination screening to efficiently consider other signaling aspects that may give insights into the behaviour of the platelet as a system. We investigated combinations of platelet inhibitors and activators. We evaluated three distinct strands of information, namely: activator-inhibitor combination screens (testing a panel of inhibitors against a panel of activators); inhibitor-inhibitor synergy screens; and activator-activator synergy screens. We demonstrated how these analyses may be efficiently performed, both experimentally and computationally, to identify particular combinations of most interest. Robust tests of activator-activator synergy and of inhibitor-inhibitor synergy required combinations to show significant excesses over the double doses of each component. Modeling identified multiple effects of an inhibitor of the P2Y12 ADP receptor, and complementarity between inhibitor-inhibitor synergy effects and activator-inhibitor combination effects. This approach accelerates the mapping of combination effects of compounds to develop combinations that may be therapeutically beneficial. We integrated the three information sources into a unified model that predicted the benefits of a triple drug combination targeting ADP, thromboxane and thrombin signaling.
    Categories: Journal Articles
  • The printed organs coming to a body near you
    [Apr 2015]

    Nature -

    The printed organs coming to a body near you

    Nature 520, 7547 (2015). http://www.nature.com/doifinder/10.1038/520273a

    Author: Heidi Ledford

    From kidneys to hands, 3D printers can now churn out made-to-order organs and bones using cells as ‘ink’.

    Categories: Journal Articles
  • Biography of a space telescope: Voices of Hubble
    [Apr 2015]

    Nature -

    Biography of a space telescope: Voices of Hubble

    Nature 520, 7547 (2015). http://www.nature.com/doifinder/10.1038/520282a

    Author: Alexandra Witze

    As the venerable space telescope turns 25 this month, key scientists and engineers recount the highs and lows of its stellar career.

    Categories: Journal Articles
  • Dual Element Intercalation into 2D Layered Bi2Se3 Nanoribbons
    [Apr 2015]

    Journal of the American Chemical SocietyDOI: 10.1021/jacs.5b00666
    Categories: Journal Articles
  • Numbers matter
    [Apr 2015]

    Nature -

    Numbers matter

    Nature 520, 7547 (2015). doi:10.1038/520263b

    Researchers need help in making the statistical power of animal experiments clear.

    Categories: Journal Articles
  • Announcement: Time to tackle cells’ mistaken identity
    [Apr 2015]

    Nature -

    Announcement: Time to tackle cells’ mistaken identity

    Nature 520, 7547 (2015). doi:10.1038/520264a

    The differences between a cow and a monkey are clear. It is easy to tell a moth from a mosquito. So why are there still scientific studies that mix them up? The answer is simple: hundreds of cell lines stored and used by modern laboratories

    Categories: Journal Articles
  • Scientists must speak up on fossil-fuel divestment
    [Apr 2015]

    Nature -

    Scientists must speak up on fossil-fuel divestment

    Nature 520, 7547 (2015). http://www.nature.com/doifinder/10.1038/520265a

    Author: Alan Rusbridger

    Alan Rusbridger wants researchers to help convince powerful philanthropic organizations to set an example and stop propelling carbon emissions.

    Categories: Journal Articles
  • Imaging: A 3D map of skin microbes and molecules
    [Apr 2015]

    Nature -

    Imaging: A 3D map of skin microbes and molecules

    Nature 520, 7547 (2015). doi:10.1038/520266a

    Researchers have glimpsed the complexities of human skin by creating a three-dimensional (3D) map of the chemicals and microbes found on the body's largest organ.Pieter Dorrestein of the University of California in San Diego and his colleagues swabbed 400 locations on the skin of

    Categories: Journal Articles
  • Astrophysics: Neutrinos from a galaxy far away
    [Apr 2015]

    Nature -

    Astrophysics: Neutrinos from a galaxy far away

    Nature 520, 7547 (2015). doi:10.1038/520266b

    Two of the most energetic neutrinos detected by a telescope in the Antarctic may have come from the cores of distant galaxies.Neutrinos are stable and can travel far in space, so they could shed light on distant astrophysical and galactic objects. The Antarctic telescope

    Categories: Journal Articles
  • Neuroscience: Brain zap stops electrical fault
    [Apr 2015]

    Nature -

    Neuroscience: Brain zap stops electrical fault

    Nature 520, 7547 (2015). doi:10.1038/520266c

    Deep-brain stimulation may improve movement in people with Parkinson's disease by reducing abnormally strong coupling of electrical activity in the brain.Implanted electrodes are used to treat some brain disorders, particularly Parkinson's disease. Coralie de Hemptinne at the University of California, San Francisco, and her

    Categories: Journal Articles
  • Marine science: Fishing drives population decline
    [Apr 2015]

    Nature -

    Marine science: Fishing drives population decline

    Nature 520, 7547 (2015). doi:10.1038/520266d

    Fishing magnifies natural variations in numbers of fish, increasing the risk of population collapses.Timothy Essington and his colleagues at the University of Washington in Seattle analysed at least 25 years' worth of data on 55 stocks of small fish such as sardines, herrings and

    Categories: Journal Articles
  • Seismology: San Francisco's quake hazard rises
    [Apr 2015]

    Nature -

    Seismology: San Francisco's quake hazard rises

    Nature 520, 7547 (2015). doi:10.1038/520267a

    Two geological faults in northern California are linked, meaning that the risk of a large earthquake in the eastern San Francisco Bay Area is greater than was thought.A team led by Estelle Chaussard of the University of California, Berkeley, used satellite radar to study

    Categories: Journal Articles
  • Atmospheric science: Asian pollution hitchhikes south
    [Apr 2015]

    Nature -

    Atmospheric science: Asian pollution hitchhikes south

    Nature 520, 7547 (2015). doi:10.1038/520267b

    Pollution from East Asia affects air quality in the distant tropics.A team led by Matthew Ashfold at the University of Cambridge, UK, detected elevated levels of a chlorine-containing gas at two remote sites in tropical Borneo during the Northern Hemisphere winter of 2008–09. The

    Categories: Journal Articles
  • Microbiology: Downsides of low-dose antibiotics
    [Apr 2015]

    Nature -

    Microbiology: Downsides of low-dose antibiotics

    Nature 520, 7547 (2015). doi:10.1038/520267c

    Taking low doses of antibiotics to prevent recurring bladder infections could make the illness worse than taking no antibiotic at all.Lee Goneau of the University of Toronto in Canada and his colleagues studied mice previously infected with urinary tract bacteria, and treated the animals

    Categories: Journal Articles
  • Molecular pathology: Cancer spreads among clams
    [Apr 2015]

    Nature -

    Molecular pathology: Cancer spreads among clams

    Nature 520, 7547 (2015). doi:10.1038/520267d

    Outbreaks of leukaemia-like cancer in soft-shell clams may have originated in a single clam.Mysterious cancers have been affecting clams and other marine bivalves in the United States and Europe since at least the 1970s. Stephen Goff at Columbia University in New York and his

    Categories: Journal Articles
  • Physics: Hot fluids act strangely in space
    [Apr 2015]

    Nature -

    Physics: Hot fluids act strangely in space

    Nature 520, 7547 (2015). doi:10.1038/520267e

    Boiling fluids behave differently in space and on Earth, suggesting that new approaches are needed to cool spacecraft in orbit.Heat pipes suck excess heat away from laptop computers and other devices, and consist of a tube filled with liquid that evaporates at one end

    Categories: Journal Articles
  • Seven days: 10–16 April 2015
    [Apr 2015]

    Nature -

    Seven days: 10–16 April 2015

    Nature 520, 7547 (2015). http://www.nature.com/doifinder/10.1038/520268a

    The week in science: Protests delay telescope construction, Brazil approves GM eucalyptus; and African Centres for Disease Control and Prevention takes shape.

    Categories: Journal Articles
  • UK funders demand strong statistics for animal studies
    [Apr 2015]

    Nature -

    UK funders demand strong statistics for animal studies

    Nature 520, 7547 (2015). http://www.nature.com/doifinder/10.1038/520271a

    Author: Daniel Cressey

    Move addresses concerns that some experiments are not using enough animals.

    Categories: Journal Articles
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