A sphingosine-1-phosphate receptor regulates cell migration during vertebrate heart development

Coordinated cell migration is essential in many fundamental biological processes including embryonic development, organogenesis, wound healing and the immune response. During organogenesis, groups of cells are directed to specific locations within the embryo. Here we show that the zebrafish miles apart (mil) mutation specifically affects the migration of the heart precursors to the midline. We found that mutant cells transplanted into a wild-type embryo migrate normally and that wild-type cells in a mutant embryo fail to migrate, suggesting that mil may be involved in generating an environment permissive for migration. We isolated mil by positional cloning and show that it encodes a member of the lysosphingolipid G-protein-coupled receptor family. We also show that sphingosine-1-phosphate is a ligand for Mil, and that it activates several downstream signalling events that are not activated by the mutant alleles. These data reveal a new role for lysosphingolipids in regulating cell migration during vertebrate development and provide the first molecular clues into the fusion of the bilateral heart primordia during organogenesis of the heart.     

Crystal structure of enteropathogenic Escherichia coli intimin-receptor complex

Intimin and its translocated intimin receptor (Tir) are bacterial proteins that mediate adhesion between mammalian cells and attaching and effacing (A/E) pathogens. Enteropathogenic Escherichia coli (EPEC) causes significant paediatric morbidity and mortality world-wide. A related A/E pathogen, enterohaemorrhagic E. coli (EHEC; O157:H7) is one of the most important food-borne pathogens in North America, Europe and Japan. A unique and essential feature of A/E bacterial pathogens is the formation of actin-rich pedestals beneath the intimately adherent bacteria and localized destruction of the intestinal brush border. The bacterial outer membrane adhesin, intimin, is necessary for the production of the A/E lesion and diarrhoea. The A/E bacteria translocate their own receptor for intimin, Tir, into the membrane of mammalian cells using the type III secretion system. The translocated Tir triggers additional host signalling events and actin nucleation, which are essential for lesion formation. Here we describe the the crystal structures of an EPEC intimin carboxy-terminal fragment alone and in complex with the EPEC Tir intimin-binding domain, giving insight into the molecular mechanisms of adhesion of A/E pathogens.     

Transformation from temporal to rate coding in a somatosensory thalamocortical pathway

The anatomical connections from the whiskers to the rodent somatosensory (barrel) cortex form two parallel (lemniscal and paralemniscal) pathways. It is unclear whether the paralemniscal pathway is directly involved in tactile processing, because paralemniscal neuronal responses show poor spatial resolution, labile latencies and strong dependence on cortical feedback. Here we show that the paralemniscal system can transform temporally encoded vibrissal information into a rate code. We recorded the representations of the frequency of whisker movement along the two pathways in anaesthetized rats. In response to varying stimulus frequencies, the lemniscal neurons exhibited amplitude modulations and constant latencies. In contrast, paralemniscal neurons in both thalamus and cortex coded the input frequency as changes in latency. Because the onset latencies increased and the offset latencies remained constant, the latency increments were translated into a rate code: increasing onset latencies led to lower spike counts. A thalamocortical loop that includes cortical oscillations and thalamic gating can account for these results. Thus, variable latencies and effective cortical feedback in the paralemniscal system can serve the processing of temporal sensory cues, such as those that encode object location during whisking. In contrast, fixed time locking in the lemniscal system is crucial for reliable spatial processing.     

The mammalian sodium channel BNC1 is required for normal touch sensation

Of the vertebrate senses, touch is the least understood at the molecular level The ion channels that form the core of the mechanosensory complex and confer touch sensitivity remain unknown. However, the similarity of the brain sodium channel 1 (BNC1) to nematode proteins involved in mechanotransduction indicated that it might be a part of such a mechanosensor. Here we show that disrupting the mouse BNC1 gene markedly reduces the sensitivity of a specific component of mechanosensation: low-threshold rapidly adapting mechanoreceptors. In rodent hairy skin these mechanoreceptors are excited by hair movement. Consistent with this function, we found BNC1 in the lanceolate nerve endings that lie adjacent to and surround the hair follicle. Although BNC1 has been proposed to have a role in pH sensing, the acid-evoked current in cultured sensory neurons and the response of acid-stimulated nociceptors were normal in BNC1 null mice. These data identify the BNC1 channel as essential for the normal detection of light touch and indicate that BNC1 may be a central component of a mechanosensory complex.     

Geochemical evidence for terrestrial ecosystems 2.6 billion years ago

Microorganisms have flourished in the oceans since at least 3.8 billion years (3.8 Gyr) ago, but it is not at present clear when they first colonized the land. Organic matter in some Au/U-rich conglomerates and ancient soils of 2.3-2.7 Gyr age has been suggested as remnants of terrestrial organisms. Some 2.7-Gyr-old stromatolites have also been suggested as structures created by terrestrial organisms. However, it has been disputed whether this organic matter is indigenous or exogenic, and whether these stromatolites formed in marine or fresh water. Consequently, the oldest undisputed remnants of terrestrial organisms are currently the 1.2-Gyr-old microfossils from Arizona, USA. Unusually carbonaceous ancient soils--palaeosols--have been found in the Mpumalanga Province (Eastern Transvaal) of South Africa. Here we report the occurrences, elemental ratios (C, H, N, P) and isotopic compositions of this organic matter and its host rocks. These data show that the organic matter very probably represents remnants of microbial mats that developed on the soil surface between 2.6 and 2.7 Gyr ago. This places the development of terrestrial biomass more than 1.4 billion years earlier than previously reported.     

Coenzyme Q is an obligatory cofactor for uncoupling protein function

Uncoupling proteins (UCPs) are thought to be intricately controlled uncouplers that are responsible for the futile dissipation of mitochondrial chemiosmotic gradients, producing heat rather than ATP. They occur in many animal and plant cells and form a subfamily of the mitochondrial carrier family. Physiological uncoupling of oxidative phosphorylation must be strongly regulated to avoid deterioration of the energy supply and cell death, which is caused by toxic uncouplers. However, an H+ transporting uncoupling function is well established only for UCP1 from brown adipose tissue, and the regulation of UCP1 by fatty acids, nucleotides and pH remains controversial. The failure of UCP1 expressed in Escherichia coli inclusion bodies to carry out fatty-acid-dependent H+ transport activity inclusion bodies made us seek a native UCP cofactor. Here we report the identification of coenzyme Q (ubiquinone) as such a cofactor. On addition of CoQ10 to reconstituted UCP1 from inclusion bodies, fatty-acid-dependent H+ transport reached the same rate as with native UCP1. The H+ transport was highly sensitive to purine nucleotides, and activated only by oxidized but not reduced CoQ. H+ transport of native UCP1 correlated with the endogenous CoQ content.     

Strain effects and phase transitions in photonic resonator crystals

Optical structures with periodic variations of the dielectric constant in one or more directions (photonic crystals) have been employed extensively for studying optical diffraction phenomena. Practical interest in such structures arises from the possibilities they offer for tailoring photon modes, and thereby the characteristics of light propagation and light-matter interactions. Photonic resonator crystals comprising two-dimensional arrays of coupled optical microcavities have been fabricated using vertical-cavity surface-emitting laser wafers. In such structures, the light propagates mostly normal to the periodic plane. Therefore, the corresponding lateral Bragg-periodicities are larger, a feature that is advantageous for device manufacture as it allows for larger lattice constants in the lateral direction. Here we investigate strain effects in a photonic resonator crystal by shifting neighbouring lattice rows of microcavities in opposite directions, thereby introducing an alternating square or quasi-hexagonal pattern of shear strain. We find that, for strain values below a critical threshold, the lasing photon mode is virtually locked to the corresponding mode supported by the unstrained photonic crystal. At the critical strain value, we observe a phase-transition-like switching between the square and quasi-hexagonal lattice modes. The tolerance of subcritical strains suggests that the resonator crystal may be useful for applications requiring high spatial coherence across the lattice, while the mode switching could potentially be exploited in free-space optical communications.     

Kondo physics in carbon nanotubes

The connection of electrical leads to wire-like molecules is a logical step in the development of molecular electronics, but also allows studies of fundamental physics. For example, metallic carbon nanotubes are quantum wires that have been found to act as one-dimensional quantum dots, Luttinger liquids, proximity-induced superconductors and ballistic and diffusive one-dimensional metals. Here we report that electrically contacted single-walled carbon nanotubes can serve as powerful probes of Kondo physics, demonstrating the universality of the Kondo effect. Arising in the prototypical case from the interaction between a localized impurity magnetic moment and delocalized electrons in a metallic host, the Kondo effect has been used to explain enhanced low-temperature scattering from magnetic impurities in metals, and also occurs in transport through semiconductor quantum dots. The far greater tunability of dots (in our case, nanotubes) compared with atomic impurities renders new classes of Kondo-like effects accessible. Our nanotube devices differ from previous systems in which Kondo effects have been observed, in that they are one-dimensional quantum dots with three-dimensional metal (gold) reservoirs. This allows us to observe Kondo resonances for very large electron numbers (N) in the dot, and approaching the unitary limit (where the transmission reaches its maximum possible value). Moreover, we detect a previously unobserved Kondo effect, occurring for even values of N in a magnetic field.