Functional specificity of local synaptic connections in neocortical networks

Neuronal connectivity is fundamental to information processing in the brain. Therefore, understanding the mechanisms of sensory processing requires uncovering how connection patterns between neurons relate to their function. On a coarse scale, long-range projections can preferentially link cortical regions with similar responses to sensory stimuli. But on the local scale, where dendrites and axons overlap substantially, the functional specificity of connections remains unknown. Here we determine synaptic connectivity between nearby layer 2/3 pyramidal neurons in vitro, the response properties of which were first characterized in mouse visual cortex in vivo. We found that connection probability was related to the similarity of visually driven neuronal activity. Neurons with the same preference for oriented stimuli connected at twice the rate of neurons with orthogonal orientation preferences. Neurons responding similarly to naturalistic stimuli formed connections at much higher rates than those with uncorrelated responses. Bidirectional synaptic connections were found more frequently between neuronal pairs with strongly correlated visual responses. Our results reveal the degree of functional specificity of local synaptic connections in the visual cortex, and point to the existence of fine-scale subnetworks dedicated to processing related sensory information.     

Involvement of chemokine receptors in breast cancer metastasis

Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1alpha and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells.     

Genes for the major protein antigens of the leprosy parasite Mycobacterium leprae

Leprosy, a chronic infectious disease afflicting between 10 and 15 million people, is caused by the obligate intracellular parasite Mycobacterium leprae. Although M. leprae was the first identified bacterial pathogen of man, basic biochemical, immunological, diagnostic and therapeutic investigations have been severely limited because it remains one of the few human pathogens that have not been cultured in vitro. An M. leprae recombinant DNA expression library was constructed to provide a source of genes encoding proteins relevant for such studies. Monoclonal antibodies directed against M. leprae specific antigens have been used to isolate the genes encoding the five most immunogenic protein antigens of the leprosy bacillus. We report here that M. leprae specific epitopes recognized by all of 13 monoclonal antibodies tested were produced by recombinant phage in Escherichia coli.     

Revised checklist of the vascular plants of Bryce Canyon National Park, Utah

Prior to 1960, when the senior author wrote a dissertation on the plant ecology of the Paunsaugunt Plateau forests of Bryce Canyon National Park, relatively little plant taxonomic work had been done in the area. A checklist was prepared in 1971 that included 218 species of higher plants. During the field seasons 1978, 1979, and 1980, additional plants were collected during a second plant community study of the forests. The junior author spent the summer of 1980 at the park collecting plants in additional plant communities and organizing the herbarium collection. This checklist includes the additional species collected and updates the nomenclature of the vascular plants presently known to occur within the boundaries of Bryce Canyon National Park.     

Widespread magma oceans on asteroidal bodies in the early Solar System

Immediately following the formation of the Solar System, small planetary bodies accreted, some of which melted to produce igneous rocks. Over a longer timescale (15-33 Myr), the inner planets grew by incorporation of these smaller objects through collisions. Processes operating on such asteroids strongly influenced the final composition of these planets, including Earth. Currently there is little agreement about the nature of asteroidal igneous activity: proposals range from small-scale melting, to near total fusion and the formation of deep magma oceans. Here we report a study of oxygen isotopes in two basaltic meteorite suites, the HEDs (howardites, eucrites and diogenites, which are thought to sample the asteroid 4 Vesta) and the angrites (from an unidentified asteroidal source). Our results demonstrate that these meteorite suites formed during early, global-scale melting (> or = 50 per cent) events. We show that magma oceans were present on all the differentiated Solar System bodies so far sampled. Magma oceans produced compositionally layered planetesimals; the modification of such bodies before incorporation into larger objects can explain some anomalous planetary features, such as Earth's high Mg/Si ratio.     

Syndrome du jour: The historiography and moral implications of Diagnosing Darwin

Diagnosing Darwin's health problems has a long history. Innumerable diagnoses have been proffered in letters, articles, and a handful of dedicated books. Diagnostic speculation has exhibited contrasting somatogenic or psychogenic preferences. Psychogenic accounts dominated mid-century but were soon challenged by somatic explanations citing specific infectious or toxic aetiologies. This tension remains, although psychogenic accounts have tended to be swamped by an array of somatogenic diagnoses championed by biomedical specialists. As a whole, this parade of diagnoses has a striking syndrome du jour quality. Successive conjectures speak of the preoccupations and diagnostic fads of their particular age. Moreover, for many participants in this diagnostic game, unconscious presentism combined with self-serving projection, turning the question of what ailed Darwin into something of a Rorschach test. Never far from the surface was a sometimes-fraught tussle over the man's reputation, animated by the moral valences of the conjectures in play. In a broader sense, this diagnostic game has shaped biographical accounts of Darwin and his career in some significant ways.