DNA-based self-assembly of chiral plasmonic nanostructures with tailored optical response

Matter structured on a length scale comparable to or smaller than the wavelength of light can exhibit unusual optical properties. Particularly promising components for such materials are metal nanostructures, where structural alterations provide a straightforward means of tailoring their surface plasmon resonances and hence their interaction with light. But the top-down fabrication of plasmonic materials with controlled optical responses in the visible spectral range remains challenging, because lithographic methods are limited in resolution and in their ability to generate genuinely three-dimensional architectures. Molecular self-assembly provides an alternative bottom-up fabrication route not restricted by these limitations, and DNA- and peptide-directed assembly have proved to be viable methods for the controlled arrangement of metal nanoparticles in complex and also chiral geometries. Here we show that DNA origami enables the high-yield production of plasmonic structures that contain nanoparticles arranged in nanometre-scale helices. We find, in agreement with theoretical predictions, that the structures in solution exhibit defined circular dichroism and optical rotatory dispersion effects at visible wavelengths that originate from the collective plasmon-plasmon interactions of the nanoparticles positioned with an accuracy better than two nanometres. Circular dichroism effects in the visible part of the spectrum have been achieved by exploiting the chiral morphology of organic molecules and the plasmonic properties of nanoparticles, or even without precise control over the spatial configuration of the nanoparticles. In contrast, the optical response of our nanoparticle assemblies is rationally designed and tunable in handedness, colour and intensity-in accordance with our theoretical model.     

Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting

Cancer immunoediting, the process by which the immune system controls tumour outgrowth and shapes tumour immunogenicity, is comprised of three phases: elimination, equilibrium and escape. Although many immune components that participate in this process are known, its underlying mechanisms remain poorly defined. A central tenet of cancer immunoediting is that T-cell recognition of tumour antigens drives the immunological destruction or sculpting of a developing cancer. However, our current understanding of tumour antigens comes largely from analyses of cancers that develop in immunocompetent hosts and thus may have already been edited. Little is known about the antigens expressed in nascent tumour cells, whether they are sufficient to induce protective antitumour immune responses or whether their expression is modulated by the immune system. Here, using massively parallel sequencing, we characterize expressed mutations in highly immunogenic methylcholanthrene-induced sarcomas derived from immunodeficient Rag2(-/-) mice that phenotypically resemble nascent primary tumour cells. Using class I prediction algorithms, we identify mutant spectrin-β2 as a potential rejection antigen of the d42m1 sarcoma and validate this prediction by conventional antigen expression cloning and detection. We also demonstrate that cancer immunoediting of d42m1 occurs via a T-cell-dependent immunoselection process that promotes outgrowth of pre-existing tumour cell clones lacking highly antigenic mutant spectrin-β2 and other potential strong antigens. These results demonstrate that the strong immunogenicity of an unedited tumour can be ascribed to expression of highly antigenic mutant proteins and show that outgrowth of tumour cells that lack these strong antigens via a T-cell-dependent immunoselection process represents one mechanism of cancer immunoediting.     

Magnetic tornadoes as energy channels into the solar corona

Heating the outer layers of the magnetically quiet solar atmosphere to more than one million kelvin and accelerating the solar wind requires an energy flux of approximately 100 to 300?watts per square metre, but how this energy is transferred and dissipated there is a puzzle and several alternative solutions have been proposed. Braiding and twisting of magnetic field structures, which is caused by the convective flows at the solar surface, was suggested as an efficient mechanism for atmospheric heating. Convectively driven vortex flows that harbour magnetic fields are observed to be abundant in the photosphere (the visible surface of the Sun). Recently, corresponding swirling motions have been discovered in the chromosphere, the atmospheric layer sandwiched between the photosphere and the corona. Here we report the imprints of these chromospheric swirls in the transition region and low corona, and identify them as observational signatures of rapidly rotating magnetic structures. These ubiquitous structures, which resemble super-tornadoes under solar conditions, reach from the convection zone into the upper solar atmosphere and provide an alternative mechanism for channelling energy from the lower into the upper solar atmosphere.     

Anhedonia requires MC4R-mediated synaptic adaptations in nucleus accumbens

Chronic stress is a strong diathesis for depression in humans and is used to generate animal models of depression. It commonly leads to several major symptoms of depression, including dysregulated feeding behaviour, anhedonia and behavioural despair. Although hypotheses defining the neural pathophysiology of depression have been proposed, the critical synaptic adaptations in key brain circuits that mediate stress-induced depressive symptoms remain poorly understood. Here we show that chronic stress in mice decreases the strength of excitatory synapses on D1 dopamine receptor-expressing nucleus accumbens medium spiny neurons owing to activation of the melanocortin 4 receptor. Stress-elicited increases in behavioural measurements of anhedonia, but not increases in measurements of behavioural despair, are prevented by blocking these melanocortin 4 receptor-mediated synaptic changes in vivo. These results establish that stress-elicited anhedonia requires a neuropeptide-triggered, cell-type-specific synaptic adaptation in the nucleus accumbens and that distinct circuit adaptations mediate other major symptoms of stress-elicited depression.     

Skin infection generates non-migratory memory CD8+ T(RM) cells providing global skin immunity

Protective T-cell memory has long been thought to reside in blood and lymph nodes, but recently the concept of immune memory in peripheral tissues mediated by resident memory T (T(RM)) cells has been proposed. Here we show in mice that localized vaccinia virus (VACV) skin infection generates long-lived non-recirculating CD8(+) skin T(RM) cells that reside within the entire skin. These skin T(RM) cells are potent effector cells, and are superior to circulating central memory T (T(CM)) cells at providing rapid long-term protection against cutaneous re-infection. We find that CD8(+) T cells are rapidly recruited to skin after acute VACV infection. CD8(+) T-cell recruitment to skin is independent of CD4(+) T cells and interferon-γ, but requires the expression of E- and P-selectin ligands by CD8(+) T cells. Using parabiotic mice, we further show that circulating CD8(+) T(CM) and CD8(+) skin T(RM) cells are both generated after skin infection; however, CD8(+) T(CM) cells recirculate between blood and lymph nodes whereas T(RM) cells remain in the skin. Cutaneous CD8(+) T(RM) cells produce effector cytokines and persist for at least 6 months after infection. Mice with CD8(+) skin T(RM) cells rapidly cleared a subsequent re-infection with VACV whereas mice with circulating T(CM) but no skin T(RM) cells showed greatly impaired viral clearance, indicating that T(RM) cells provide superior protection. Finally, we show that T(RM) cells generated as a result of localized VACV skin infection reside not only in the site of infection, but also populate the entire skin surface and remain present for many months. Repeated re-infections lead to progressive accumulation of highly protective T(RM) cells in non-involved skin. These findings have important implications for our understanding of protective immune memory at epithelial interfaces with the environment, and suggest novel strategies for vaccines that protect against tissue tropic organisms.     

No meridional plasma flow in the heliosheath transition region

Over a two-year period, Voyager 1 observed a gradual slowing-down of radial plasma flow in the heliosheath to near-zero velocity after April 2010 at a distance of 113.5 astronomical units from the Sun (1 astronomical unit equals 1.5?×?10(8) kilometres). Voyager 1 was then about 20 astronomical units beyond the shock that terminates the free expansion of the solar wind and was immersed in the heated non-thermal plasma region called the heliosheath. The expectation from contemporary simulations was that the heliosheath plasma would be deflected from radial flow to meridional flow (in solar heliospheric coordinates), which at Voyager?1 would lie mainly on the (locally spherical) surface called the heliopause. This surface is supposed to separate the heliosheath plasma, which is of solar origin, from the interstellar plasma, which is of local Galactic origin. In 2011, the Voyager project began occasional temporary re-orientations of the spacecraft (totalling about 10-25 hours every 2 months) to re-align the Low-Energy Charged Particle instrument on board Voyager?1 so that it could measure meridional flow. Here we report that, contrary to expectations, these observations yielded a meridional flow velocity of +3?±?11?km?s(-1), that is, one consistent with zero within statistical uncertainties.