Some aspects of succession in the spruce-fir forest zone of northern Utah

A site in the Rocky Mountain subalpine forest zone with which a series of hypotheses concerning ecosystem succession was tested is characterized. Succession from herb-dominated meadows to climax forests of Engelmann spruce and subalpine fir can follow at least four identified pathways. After fire, spruce and fir may reinvade a site directly, follow invasion by aspen, or follow invasion by lodgepole pine, the pathway depending on a combination of physical and biotic factors. In other cases, succession begins with long-established meadows which do not owe their existence to fire. In this latter pathway, aspen invades meadows by suckering and changes the environment near the soil surface so as to facilitate establishment of the climax tree species. The biota and soils of four characteristic seral stages (meadow, aspen, fir, spruce-fir) in this latter pathway are described.     

Subcellular trafficking of the substrate transporters GLUT4 and CD36 in cardiomyocytes

Cardiomyocytes use glucose as well as fatty acids for ATP production. These substrates are transported into the cell by glucose transporter 4 (GLUT4) and the fatty acid transporter CD36. Besides being located at the sarcolemma, GLUT4 and CD36 are stored in intracellular compartments. Raised plasma insulin concentrations and increased cardiac work will stimulate GLUT4 as well as CD36 to translocate to the sarcolemma. As so far studied, signaling pathways that regulate GLUT4 translocation similarly affect CD36 translocation. During the development of insulin resistance and type 2 diabetes, CD36 becomes permanently localized at the sarcolemma, whereas GLUT4 internalizes. This juxtaposed positioning of GLUT4 and CD36 is important for aberrant substrate uptake in the diabetic heart: chronically increased fatty acid uptake at the expense of glucose. To explain the differences in subcellular localization of GLUT4 and CD36 in type 2 diabetes, recent research has focused on the role of proteins involved in trafficking of cargo between subcellular compartments. Several of these proteins appear to be similarly involved in both GLUT4 and CD36 translocation. Others, however, have different roles in either GLUT4 or CD36 translocation. These trafficking components, which are differently involved in GLUT4 or CD36 translocation, may be considered novel targets for the development of therapies to restore the imbalanced substrate utilization that occurs in obesity, insulin resistance and diabetic cardiomyopathy.     

Cloning of a probable potassium channel gene from mouse brain

Potassium channels comprise a diverse class of ion channels important for neuronal excitability and plasticity. The recent cloning of the Shaker locus from Drosophila melanogaster has provided a starting point for molecular studies of potassium channels. Predicted Shaker proteins appear to be integral membrane proteins and have a sequence similar to the sequence of the S4 segment of the vertebrate sodium channel, where the S4 segment has been proposed to be the voltage sensor. Expression studies in frog oocytes confirm that Shaker encodes a component of a potassium channel (the A channel) that conducts a fast transient potassium current. Here we report the isolation of complementary DNA clones from the mouse brain, the nucleotide sequences of which predict a protein remarkably similar to the Shaker protein. The strong conservation of the predicted protein sequence in flies and mammals suggests that these mouse clones encode a potassium channel component and that the conserved amino acids may be essential to some aspect of potassium channel function.     

Cadherin 23 is a component of the tip link in hair-cell stereocilia

Mechanoelectrical transduction, the conversion of mechanical force into electrochemical signals, underlies a range of sensory phenomena, including touch, hearing and balance. Hair cells of the vertebrate inner ear are specialized mechanosensors that transduce mechanical forces arising from sound waves and head movement to provide our senses of hearing and balance; however, the mechanotransduction channel of hair cells and the molecules that regulate channel activity have remained elusive. One molecule that might participate in mechanoelectrical transduction is cadherin 23 (CDH23), as mutations in its gene cause deafness and age-related hearing loss. Furthermore, CDH23 is large enough to be the tip link, the extracellular filament proposed to gate the mechanotransduction channel. Here we show that antibodies against CDH23 label the tip link, and that CDH23 has biochemical properties similar to those of the tip link. Moreover, CDH23 forms a complex with myosin-1c, the only known component of the mechanotransduction apparatus, suggesting that CDH23 and myosin-1c cooperate to regulate the activity of mechanically gated ion channels in hair cells.     

Subtractive proteomic mapping of the endothelial surface in lung and solid tumours for tissue-specific therapy

The molecular complexity of tissues and the inaccessibility of most cells within a tissue limit the discovery of key targets for tissue-specific delivery of therapeutic and imaging agents in vivo. Here, we describe a hypothesis-driven, systems biology approach to identifying a small subset of proteins induced at the tissue-blood interface that are inherently accessible to antibodies injected intravenously. We use subcellular fractionation, subtractive proteomics and bioinformatics to identify endothelial cell surface proteins exhibiting restricted tissue distribution and apparent tissue modulation. Expression profiling and gamma-scintigraphic imaging with antibodies establishes two of these proteins, aminopeptidase-P and annexin A1, as selective in vivo targets for antibodies in lungs and solid tumours, respectively. Radio-immunotherapy to annexin A1 destroys tumours and increases animal survival. This analytical strategy can map tissue- and disease-specific expression of endothelial cell surface proteins to uncover novel accessible targets useful for imaging and therapy.     

Iron corrosion by novel anaerobic microorganisms

Corrosion of iron presents a serious economic problem. Whereas aerobic corrosion is a chemical process, anaerobic corrosion is frequently linked to the activity of sulphate-reducing bacteria (SRB). SRB are supposed to act upon iron primarily by produced hydrogen sulphide as a corrosive agent and by consumption of 'cathodic hydrogen' formed on iron in contact with water. Among SRB, Desulfovibrio species--with their capacity to consume hydrogen effectively--are conventionally regarded as the main culprits of anaerobic corrosion; however, the underlying mechanisms are complex and insufficiently understood. Here we describe novel marine, corrosive types of SRB obtained via an isolation approach with metallic iron as the only electron donor. In particular, a Desulfobacterium-like isolate reduced sulphate with metallic iron much faster than conventional hydrogen-scavenging Desulfovibrio species, suggesting that the novel surface-attached cell type obtained electrons from metallic iron in a more direct manner than via free hydrogen. Similarly, a newly isolated Methanobacterium-like archaeon produced methane with iron faster than do known hydrogen-using methanogens, again suggesting a more direct access to electrons from iron than via hydrogen consumption.     

Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis

Osteopoikilosis, Buschke-Ollendorff syndrome (BOS) and melorheostosis are disorders characterized by increased bone density. The occurrence of one or more of these phenotypes in the same individual or family suggests that these entities might be allelic. We collected data from three families in which affected individuals had osteopoikilosis with or without manifestations of BOS or melorheostosis. A genome-wide linkage analysis in these families, followed by the identification of a microdeletion in an unrelated individual with these diseases, allowed us to map the gene that is mutated in osteopoikilosis. All the affected individuals that we investigated were heterozygous with respect to a loss-of-function mutation in LEMD3 (also called MAN1), which encodes an inner nuclear membrane protein. A somatic mutation in the second allele of LEMD3 could not be identified in fibroblasts from affected skin of an individual with BOS and an individual with melorheostosis. XMAN1, the Xenopus laevis ortholog, antagonizes BMP signaling during embryogenesis. In this study, LEMD3 interacted with BMP and activin-TGFbeta receptor-activated Smads and antagonized both signaling pathways in human cells.     

The knockout mouse project

Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain.