Regulation of immunity by self-reactive T cells

A basic principle of immunology is that lymphocytes respond to foreign antigens but tolerate self tissues. For developing T cells, the ability to distinguish self from non-self is acquired in the thymus, where the majority of self-reactive cells are eliminated. Recently, however, it has become apparent that some self-reactive T cells avoid being destroyed and instead differentiate into specialized regulatory cells. This appears to be beneficial. Subpopulations of self-reactive T cells have a strong influence on self tolerance and may represent targets for therapeutic intervention to control a variety of autoimmune diseases, tumour growth and infection.     

Protein kinase Cdelta controls self-antigen-induced B-cell tolerance

Interaction of a B cell expressing self-specific B-cell antigen receptor (BCR) with an auto-antigen results in either clonal deletion or functional inactivation. Both of these processes lead to B-cell tolerance and are essential for the prevention of auto-immune diseases. Whereas clonal deletion results in the death of developing autoreactive B cells, functional inactivation of self-reactive B lymphocytes leads to complex changes in the phenotype of peripheral B cells, described collectively as anergy. Here we demonstrate that deficiency in protein kinase Cdelta (PKC-delta) prevents B-cell tolerance, and allows maturation and terminal differentiation of self-reactive B cells in the presence of the tolerizing antigen. The importance of PKC-delta in B-cell tolerance is further underscored by the appearance of autoreactive anti-DNA and anti-nuclear antibodies in the serum of PKC-delta-deficient mice. As deficiency of PKC-delta does not affect BCR-mediated B-cell activation in vitro and in vivo, our data suggest a selective and essential role of PKC-delta in tolerogenic, but not immunogenic, B-cell responses.     

Muted climate variations in continental Siberia during the mid-Pleistocene epoch

The large difference in carbon and oxygen isotope data from the marine record between marine oxygen isotope stage 12 (MIS 12) and MIS 11, spanning the interval between about 480 and 380 kyr ago, has been interpreted as a transition between an extremely cold glacial period and an unusually warm interglacial period, with consequences for global ice volume, sea level and the global carbon cycle. The extent of the change is intriguing, because orbital forcing is predicted to have been relatively weak at that time. Here we analyse a continuous sediment record from Lake Baikal, Siberia, which reveals a virtually continuous interglacial diatom assemblage, a stable littoral benthic diatom assemblage and lithogenic sediments with 'interglacial' characteristics for the period from MIS 15a to MIS 11 (from about 580 to 380 kyr ago). From these data, we infer significantly weaker climate contrasts between MIS 12 and 11 than during more recent glacial-interglacial transitions in the late Pleistocene epoch (about 130 to 10 kyr ago). For the period from MIS 15a to MIS 11, we also infer an apparent lack of extensive mountain glaciation.     

Evolutionary biology: hedgehog crosses the snail's midline

According to the dorsoventral axis-inversion theory, protostomes (such as insects, snails and worms) are organized upside-down by comparison with deuterostomes (vertebrates), in which case their respective ventrally (belly-side) and dorsally (back-side) located nervous systems, as well as their midline regions, should all be derived from a common ancestor. Here we provide experimental evidence for such homology by showing that an orthologue of hedgehog, an important gene in midline patterning in vertebrates, is expressed along the belly of the larva of the limpet Patella vulgata. This finding supports the existence of a similar mechanism for the development of the midline of the nervous system in protostomes and deuterostomes.     

The spring in the arch of the human foot

Large mammals, including humans, save much of the energy needed for running by means of elastic structures in their legs and feet. Kinetic and potential energy removed from the body in the first half of the stance phase is stored briefly as elastic strain energy and then returned in the second half by elastic recoil. Thus the animal runs in an analogous fashion to a rubber ball bouncing along. Among the elastic structures involved, the tendons of distal leg muscles have been shown to be important. Here we show that the elastic properties of the arch of the human foot are also important.     

A continuous-wave Raman silicon laser

Achieving optical gain and/or lasing in silicon has been one of the most challenging goals in silicon-based photonics because bulk silicon is an indirect bandgap semiconductor and therefore has a very low light emission efficiency. Recently, stimulated Raman scattering has been used to demonstrate light amplification and lasing in silicon. However, because of the nonlinear optical loss associated with two-photon absorption (TPA)-induced free carrier absorption (FCA), until now lasing has been limited to pulsed operation. Here we demonstrate a continuous-wave silicon Raman laser. Specifically, we show that TPA-induced FCA in silicon can be significantly reduced by introducing a reverse-biased p-i-n diode embedded in a silicon waveguide. The laser cavity is formed by coating the facets of the silicon waveguide with multilayer dielectric films. We have demonstrated stable single mode laser output with side-mode suppression of over 55 dB and linewidth of less than 80 MHz. The lasing threshold depends on the p-i-n reverse bias voltage and the laser wavelength can be tuned by adjusting the wavelength of the pump laser. The demonstration of a continuous-wave silicon laser represents a significant milestone for silicon-based optoelectronic devices.