Micro-engineered local field control for high-sensitivity multispectral MRI

In recent years, biotechnology and biomedical research have benefited from the introduction of a variety of specialized nanoparticles whose well-defined, optically distinguishable signatures enable simultaneous tracking of numerous biological indicators. Unfortunately, equivalent multiplexing capabilities are largely absent in the field of magnetic resonance imaging (MRI). Comparable magnetic-resonance labels have generally been limited to relatively simple chemically synthesized superparamagnetic microparticles that are, to a large extent, indistinguishable from one another. Here we show how it is instead possible to use a top-down microfabrication approach to effectively encode distinguishable spectral signatures into the geometry of magnetic microstructures. Although based on different physical principles from those of optically probed nanoparticles, these geometrically defined magnetic microstructures permit a multiplexing functionality in the magnetic resonance radio-frequency spectrum that is in many ways analogous to that permitted by quantum dots in the optical spectrum. Additionally, in situ modification of particle geometries may facilitate radio-frequency probing of various local physiological variables.     

Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis

The ability to cross host barriers is an essential virulence determinant of invasive microbial pathogens. Listeria monocytogenes is a model microorganism that crosses human intestinal and placental barriers, and causes severe maternofetal infections by an unknown mechanism. Several studies have helped to characterize the bacterial invasion proteins InlA and InlB. However, their respective species specificity has complicated investigations on their in vivo role. Here we describe two novel and complementary animal models for human listeriosis: the gerbil, a natural host for L. monocytogenes, and a knock-in mouse line ubiquitously expressing humanized E-cadherin. Using these two models, we uncover the essential and interdependent roles of InlA and InlB in fetoplacental listeriosis, and thereby decipher the molecular mechanism underlying the ability of a microbe to target and cross the placental barrier.     

Observed and modelled stability of overflow across the Greenland-Scotland ridge

Across the Greenland-Scotland ridge there is a continuous flow of cold dense water, termed 'overflow', from the Nordic seas to the Atlantic Ocean. This is a main contributor to the production of North Atlantic Deep Water that feeds the lower limb of the Atlantic meridional overturning circulation, which has been predicted to weaken as a consequence of climate change. The two main overflow branches pass the Denmark Strait and the Faroe Bank channel. Here we combine results from direct current measurements in the Faroe Bank channel for 1995-2005 with an ensemble hindcast experiment for 1948-2005 using an ocean general circulation model. For the overlapping period we find a convincing agreement between model simulations and observations on monthly to interannual timescales. Both observations and model data show no significant trend in volume transport. In addition, for the whole 1948-2005 period, the model indicates no persistent trend in the Faroe Bank channel overflow or in the total overflow transport, in agreement with the few available historical observations. Deepening isopycnals in the Norwegian Sea have tended to decrease the pressure difference across the Greenland-Scotland ridge, but this has been compensated for by the effect of changes in sea level. In contrast with earlier studies, we therefore conclude that the Faroe Bank channel overflow, and also the total overflow, did not decrease consistently from 1950 to 2005, although the model does show a weakening total Atlantic meridional overturning circulation as a result of changes south of the Greenland-Scotland ridge.     

Reversal of pathological pain through specific spinal GABAA receptor subtypes

Inflammatory diseases and neuropathic insults are frequently accompanied by severe and debilitating pain, which can become chronic and often unresponsive to conventional analgesic treatment. A loss of synaptic inhibition in the spinal dorsal horn is considered to contribute significantly to this pain pathology. Facilitation of spinal gamma-aminobutyric acid (GABA)ergic neurotransmission through modulation of GABA(A) receptors should be able to compensate for this loss. With the use of GABA(A)-receptor point-mutated knock-in mice in which specific GABA(A) receptor subtypes have been selectively rendered insensitive to benzodiazepine-site ligands, we show here that pronounced analgesia can be achieved by specifically targeting spinal GABA(A) receptors containing the alpha2 and/or alpha3 subunits. We show that their selective activation by the non-sedative ('alpha1-sparing') benzodiazepine-site ligand L-838,417 (ref. 13) is highly effective against inflammatory and neuropathic pain yet devoid of unwanted sedation, motor impairment and tolerance development. L-838,417 not only diminished the nociceptive input to the brain but also reduced the activity of brain areas related to the associative-emotional components of pain, as shown by functional magnetic resonance imaging in rats. These results provide a rational basis for the development of subtype-selective GABAergic drugs for the treatment of chronic pain, which is often refractory to classical analgesics.     

Quantum oscillations in a molecular magnet

The term 'molecular magnet' generally refers to a molecular entity containing several magnetic ions whose coupled spins generate a collective spin, S (ref. 1). Such complex multi-spin systems provide attractive targets for the study of quantum effects at the mesoscopic scale. In these molecules, the large energy barriers between collective spin states can be crossed by thermal activation or quantum tunnelling, depending on the temperature or an applied magnetic field. There is the hope that these mesoscopic spin states can be harnessed for the realization of quantum bits--'qubits', the basic building blocks of a quantum computer--based on molecular magnets. But strong decoherence must be overcome if the envisaged applications are to become practical. Here we report the observation and analysis of Rabi oscillations (quantum oscillations resulting from the coherent absorption and emission of photons driven by an electromagnetic wave) of a molecular magnet in a hybrid system, in which discrete and well-separated magnetic clusters are embedded in a self-organized non-magnetic environment. Each cluster contains 15 antiferromagnetically coupled S = 1/2 spins, leading to an S = 1/2 collective ground state. When this system is placed into a resonant cavity, the microwave field induces oscillatory transitions between the ground and excited collective spin states, indicative of long-lived quantum coherence. The present observation of quantum oscillations suggests that low-dimension self-organized qubit networks having coherence times of the order of 100 micros (at liquid helium temperatures) are a realistic prospect.