184 research outputs found
Directed Evolution of Protein-Based Neurotransmitter Sensors for MRI
The production of contrast agents sensitive to neuronal signaling events is a rate-limiting step in the development of molecular-level functional magnetic resonance imaging (molecular fMRI) approaches for studying the brain. High-throughput generation and evaluation of potential probes are possible using techniques for macromolecular engineering of protein-based contrast agents. In an initial exploration of this strategy, we used the method of directed evolution to identify mutants of a bacterial heme protein that allowed detection of the neurotransmitter dopamine in vitro and in living animals. The directed evolution method involves successive cycles of mutagenesis and screening that could be generalized to produce contrast agents sensitive to a variety of molecular targets in the nervous system
Measurements on the reality of the wavefunction
Quantum mechanics is an outstandingly successful description of nature,
underpinning fields from biology through chemistry to physics. At its heart is
the quantum wavefunction, the central tool for describing quantum systems. Yet
it is still unclear what the wavefunction actually is: does it merely represent
our limited knowledge of a system, or is it an element of reality? Recent no-go
theorems argued that if there was any underlying reality to start with, the
wavefunction must be real. However, that conclusion relied on debatable
assumptions, without which a partial knowledge interpretation can be maintained
to some extent. A different approach is to impose bounds on the degree to which
knowledge interpretations can explain quantum phenomena, such as why we cannot
perfectly distinguish non-orthogonal quantum states. Here we experimentally
test this approach with single photons. We find that no knowledge
interpretation can fully explain the indistinguishability of non-orthogonal
quantum states in three and four dimensions. Assuming that some underlying
reality exists, our results strengthen the view that the entire wavefunction
should be real. The only alternative is to adopt more unorthodox concepts such
as backwards-in-time causation, or to completely abandon any notion of
objective reality.Comment: 7 pages, 4 figure
Low potency toxins reveal dense interaction networks in metabolism
Background
The chemicals of metabolism are constructed of a small set of atoms and bonds. This may be because chemical structures outside the chemical space in which life operates are incompatible with biochemistry, or because mechanisms to make or utilize such excluded structures has not evolved. In this paper I address the extent to which biochemistry is restricted to a small fraction of the chemical space of possible chemicals, a restricted subset that I call Biochemical Space. I explore evidence that this restriction is at least in part due to selection again specific structures, and suggest a mechanism by which this occurs.
Results
Chemicals that contain structures that our outside Biochemical Space (UnBiological groups) are more likely to be toxic to a wide range of organisms, even though they have no specifically toxic groups and no obvious mechanism of toxicity. This correlation of UnBiological with toxicity is stronger for low potency (millimolar) toxins. I relate this to the observation that most chemicals interact with many biological structures at low millimolar toxicity. I hypothesise that life has to select its components not only to have a specific set of functions but also to avoid interactions with all the other components of life that might degrade their function.
Conclusions
The chemistry of life has to form a dense, self-consistent network of chemical structures, and cannot easily be arbitrarily extended. The toxicity of arbitrary chemicals is a reflection of the disruption to that network occasioned by trying to insert a chemical into it without also selecting all the other components to tolerate that chemical. This suggests new ways to test for the toxicity of chemicals, and that engineering organisms to make high concentrations of materials such as chemical precursors or fuels may require more substantial engineering than just of the synthetic pathways involved
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