Gridlock signalling pathway fashions the first embryonic artery.

Arteries and veins are morphologically, functionally and molecularly very different, but how this distinction is established during vasculogenesis is unknown. Here we show, by lineage tracking in zebrafish embryos, that angioblast precursors for the trunk artery and vein are spatially mixed in the lateral posterior mesoderm. Progeny of each angioblast, however, are restricted to one of the vessels. This arterial-venous decision is guided by gridlock (grl), an artery-restricted gene that is expressed in the lateral posterior mesoderm. Graded reduction of grl expression, by mutation or morpholino antisense, progressively ablates regions of the artery, and expands contiguous regions of the vein, preceded by an increase in expression of the venous marker EphB4 receptor (ephb4) and diminution of expression of the arterial marker ephrin-B2 (efnb2). grl is downstream of notch, and interference with notch signalling, by blocking Su(H), similarly reduces the artery and increases the vein. Thus, a notch-grl pathway controls assembly of the first embryonic artery, apparently by adjudicating an arterial versus venous cell fate decision.     

Atomic structure holography using thermal neutrons.

The idea of atomic-resolution holography has its roots in the X-ray work of Bragg and in Gabor's electron interference microscope. Gabor's lensless microscope was not realized in his time, but over the past twelve years there has been a steady increase in the number of reports on atomic-resolution holography. All of this work involves the use of electrons or hard X-rays to produce the hologram. Neutrons are often unique among scattering probes in their interaction with materials: for example, the relative visibility of hydrogen and its isotopes is a great advantage in the study of polymers and biologically relevant materials. Recent work proposed that atomic-resolution holography could be achieved with thermal neutrons. Here we use monochromatic thermal neutrons, adopting the inside-source concept of Sz?ke, to image planes of oxygen atoms located above and below a single hydrogen atom in the oxide mineral simpsonite.     

Leadership and Power in Fostering a Collaborative Community in a Non-Profit Professional Organization

This article provides an account of first-person action research used for organization development in an all-volunteer professional organization. During a 12-month period, members sought to build a collaborative community out of a formerly defunct group. As part of this project, the group’s leader conducted a self-study by examining his role in exercising power while leading the group in building a collaborative community. Although the goals to collaborate and explore power relations originate in different philosophical perspectives, they were combined with moderate success in this project. An ongoing theoretical analysis of the challenges in using this approach illustrates the complications of combining collaborative approaches with the exploration of power.     

Horses damp the spring in their step.

The muscular work of galloping in horses is halved by storing and returning elastic strain energy in spring-like muscle-tendon units.These make the legs act like a child's pogo stick that is tuned to stretch and recoil at 2.5 strides per second. This mechanism is optimized by unique musculoskeletal adaptations: the digital flexor muscles have extremely short fibres and significant passive properties, whereas the tendons are very long and span several joints. Length change occurs by a stretching of the spring-like digital flexor tendons rather than through energetically expensive length changes in the muscle. Despite being apparently redundant for such a mechanism, the muscle fibres in the digital flexors are well developed. Here we show that the mechanical arrangement of the elastic leg permits it to vibrate at a higher frequency of 30-40 Hz that could cause fatigue damage to tendon and bone. Furthermore, we show that the digital flexor muscles have minimal ability to contribute to or regulate significantly the 2.5-Hz cycle of movement, but are ideally arranged to damp these high-frequency oscillations in the limb.     

Vaccination against and treatment of tuberculosis, the leishmaniases and AIDS: perspectives from basic immunology and immunity to chronic intracellular infections

The occurrence of infectious disease represents a failure of the immune system, a failure that must be prevented by effective vaccination or remedied by treatment. Vaccination against acute diseases such as smallpox and polio are very effective, due to the rapid and increased immune response of vaccinated individuals upon natural infection. In contrast, effective vaccination against intracellular pathogens that cause chronic diseases, such as the leishmaniases, tuberculosis and AIDS, has not been achieved. Clinical observations suggest cell-mediated, Th1 responses, exclusive of antibody production and the generation of Th2 cells, are optimally protective against these intracellular pathogens. Effective vaccination must ensure the generation of such a protective response. We explore here whether understanding very broad features of the regulation of the immune response can accommodate modern findings on the immunological features of these diseases, and provide a perspective within which strategies for effective vaccination and treatment can be developed.     

通信电子战信号反演处理——I：概论

通信电子战信号处理迫切需要一个具有宏观指导意义的方法论。反演方法既是地球物理学中的基本处理方法，又是人类两大基本推理方法的一个子方法。讨论了反演方法及其理论的一般定义。指出在电子学与通信及其信号处理领域，将问题统一到信号反演的框架下，不仅有利于对处理方法的理论研究，而且有利于吸收那些在非电子学领域已经建立的反演方法及其理论。给出了关于通信电子战信号反演处理的定义，并提出其概念模型和目标参数。     

On the complexity of self.

Self peptides bound to self major histocompatibility complex (MHC) molecules have been implicated both in positive and in negative selection of T cells during intrathymic development. We report here that the novel MHC-restricted monoclonal antibody Y-Ae detects the MHC class II bound form of a major self peptide. Y-Ae binds approximately 12% of the relevant MHC class II molecules on self antigen presenting cells. The peptide detected by Y-Ae is one of several major peptides eluted from the MHC molecule. These data suggest that self peptides presented by self MHC class II molecules at densities sufficient to signal a CD4 T cell are of very limited complexity. Furthermore, as Y-Ae stains antigen presenting cells that mediate negative selection but not thymic cortical epithelial cells that drive positive selection, differential expression of self peptide:self MHC class II complexes may be a key feature of intrathymic selection.     

Acceleration of activation and inactivation by the beta subunit of the skeletal muscle calcium channel.

The L-type voltage-dependent calcium channel is an important link in excitation-contraction coupling of muscle cells (reviewed in refs 2 and 3). The channel has two functional characteristics: calcium permeation and receptor sites for calcium antagonists. In skeletal muscle the channel is a complex of five subunits, alpha 1, alpha 2, beta, gamma and delta. Complementary DNAs to these subunits have been cloned and their amino-acid sequences deduced. The skeletal muscle alpha 1 subunit cDNA expressed in L cells manifests as specific calcium-ion permeation, as well as sensitivity to the three classes of organic calcium-channel blockers. We report here that coexpression of the alpha 1 subunit with other subunits results in significant changes in dihydropyridine binding and gating properties. The available number of drug receptor sites increases 10-fold with an alpha 1 beta combination, whereas the affinity of the dihydropyridine binding site remains unchanged. Also, the presence of the beta subunit accelerates activation and inactivation kinetics of the calcium-channel current.     

Cloning of cDNA for the glutamate-binding subunit of an NMDA receptor complex.

The amino acids L-glutamic and L-aspartic acids form the most widespread excitatory transmitter network in mammalian brain. The excitation produced by L-glutamic acid is important in the early development of the nervous system, synaptic plasticity and memory formation, seizures and neuronal degeneration. The receptors activated by L-glutamic acid are a target for therapeutic intervention in neurodegenerative diseases, brain ischaemia and epilepsy. There are two types of receptors for the excitatory amino acids, those that lead to the opening of cation-selective channels and those that activate phospholipase C (ref. 11). The receptors activating ion channels are NMDA (N-methyl-D-aspartate) and kainate/AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)-sensitive receptors. The complementary DNAs for the kainate/AMPA receptor and for the metabotropic receptor have been cloned. We report here on the isolation and characterization of a protein complex of four major proteins that represents an intact complex of the NMDA receptor ion channel and on the cloning of the cDNA for one of the subunits of this receptor complex, the glutamate-binding protein.