Structure and mechanism of the chromatin remodelling factor ISW1a

Site-specific recognition of DNA in eukaryotic organisms depends on the arrangement of nucleosomes in chromatin. In the yeast Saccharomyces cerevisiae, ISW1a and related chromatin remodelling factors are implicated in establishing the nucleosome repeat during replication and altering nucleosome position to affect gene activity. Here we have solved the crystal structures of S. cerevisiae ISW1a lacking its ATPase domain both alone and with DNA bound at resolutions of 3.25?? and 3.60??, respectively, and we have visualized two different nucleosome-containing remodelling complexes using cryo-electron microscopy. The composite X-ray and electron microscopy structures combined with site-directed photocrosslinking analyses of these complexes suggest that ISW1a uses a dinucleosome substrate for chromatin remodelling. Results from a remodelling assay corroborate the dinucleosome model. We show how a chromatin remodelling factor could set the spacing between two adjacent nucleosomes acting as a 'protein ruler'.     

HIV-1 adaptation to NK-cell-mediated immune pressure

Natural killer (NK) cells have an important role in the control of viral infections, recognizing virally infected cells through a variety of activating and inhibitory receptors. Epidemiological and functional studies have recently suggested that NK cells can also contribute to the control of HIV-1 infection through recognition of virally infected cells by both activating and inhibitory killer immunoglobulin-like receptors (KIRs). However, it remains unknown whether NK cells can directly mediate antiviral immune pressure in vivo in humans. Here we describe KIR-associated amino-acid polymorphisms in the HIV-1 sequence of chronically infected individuals, on a population level. We show that these KIR-associated HIV-1 sequence polymorphisms can enhance the binding of inhibitory KIRs to HIV-1-infected CD4(+) T cells, and reduce the antiviral activity of KIR-positive NK cells. These data demonstrate that KIR-positive NK cells can place immunological pressure on HIV-1, and that the virus can evade such NK-cell-mediated immune pressure by selecting for sequence polymorphisms, as was previously described for virus-specific T cells and neutralizing antibodies. NK cells might therefore have a previously underappreciated role in contributing to viral evolution.     

Distribution and abundance of the Black-billed Magpie ( Pica pica ) in North America

Analysis of Audubon Society Christmas bird count data and certain environmental variables shows the degree to which the Black - billed Magpie is a bird of cool arid regions in North America. The abundance and distribution of this species appear to be limited by two major climatic barriers: increasing summer temperatures in the Southwest and increasing summer humidity and precipitation on the central plains.       

Virtual Reality As a New Tool in the City Planning Process

The introduction of virtual reality (VR)-models in the city planning process will cause changes in the traditional roles of the involved parties. In order to better understand some of these changes, the events involving the use of VR-models in an architectural competition concerning rebuilding-proposals for the city library in a Swedish city were analyzed. The study shows that VR was introduced into the competition as an extra add-on and that the VR-presentation was experienced as useful by the jury. The transformation of the architects’ contributions into VR was experienced as problematic by the architects, partly because they lost full control over the presentation. In the future architects are likely to have to produce the VR-models for their proposals themselves. This may make it more difficult for smaller architectural firms to enter the market but their proposals will be more accessible to a wider group of stakeholders.     

Cardiomyocyte proliferation in zebrafish and mammals: lessons for human disease

Cardiomyocytes proliferate profusely during early development and for a brief period after birth in mammals. Within a month after birth, this proliferative capability is dramatically reduced in mammals unlike lower vertebrates where it persists into adult life. The zebrafish, for example, retains the ability to regenerate the apex of the heart following resection by a mechanism predominantly driven by cardiomyocyte proliferation. Differences in proliferative capacity of cardiomyocytes in adulthood between mammals and lower vertebrates are closely liked to ontogenetic or phylogenetic factors. Elucidation of these factors has the potential to provide enormous benefits if they lead to the development of therapeutic strategies that facilitate cardiomyocyte proliferation. In this review, we highlight the differences between Mammalian and Zebrafish cardiomyocytes, which could explain at least in part the different proliferative capacities in these two species. We discuss the advantages of the zebrafish as a model of cardiomyocyte proliferation, particularly at the embryonic stage. We also identify a number of key molecular pathways with potential to reveal key steps in switching cardiomyocytes from a quiescent to a proliferative phenotype.     

Determination of proliferative compartments in human tumors

Summary Extracorporeal normothermic perfusion with radioactive thymidine allows a cytological, histological and structural analysis of proliferative compartments of human kidney carcinomas in whole-tumor autoradiograms.Supported by a grant from Bundesministerium für Jugend, Familie und Gesundheit, Bonn.     

A structural state of the myosin V motor without bound nucleotide

The myosin superfamily of molecular motors use ATP hydrolysis and actin-activated product release to produce directed movement and force. Although this is generally thought to involve movement of a mechanical lever arm attached to a motor core, the structural details of the rearrangement in myosin that drive the lever arm motion on actin attachment are unknown. Motivated by kinetic evidence that the processive unconventional myosin, myosin V, populates a unique state in the absence of nucleotide and actin, we obtained a 2.0 A structure of a myosin V fragment. Here we reveal a conformation of myosin without bound nucleotide. The nucleotide-binding site has adopted new conformations of the nucleotide-binding elements that reduce the affinity for the nucleotide. The major cleft in the molecule has closed, and the lever arm has assumed a position consistent with that in an actomyosin rigor complex. These changes have been accomplished by relative movements of the subdomains of the molecule, and reveal elements of the structural communication between the actin-binding interface and nucleotide-binding site of myosin that underlie the mechanism of chemo-mechanical transduction.     

Atom-molecule coherence in a Bose-Einstein condensate

Recent advances in the precise control of ultracold atomic systems have led to the realisation of Bose Einstein condensates (BECs) and degenerate Fermi gases. An important challenge is to extend this level of control to more complicated molecular systems. One route for producing ultracold molecules is to form them from the atoms in a BEC. For example, a two-photon stimulated Raman transition in a (87)Rb BEC has been used to produce (87)Rb(2) molecules in a single rotational-vibrational state, and ultracold molecules have also been formed through photoassociation of a sodium BEC. Although the coherence properties of such systems have not hitherto been probed, the prospect of creating a superposition of atomic and molecular condensates has initiated much theoretical work. Here we make use of a time-varying magnetic field near a Feshbach resonance to produce coherent coupling between atoms and molecules in a (85)Rb BEC. A mixture of atomic and molecular states is created and probed by sudden changes in the magnetic field, which lead to oscillations in the number of atoms that remain in the condensate. The oscillation frequency, measured over a large range of magnetic fields, is in excellent agreement with the theoretical molecular binding energy, indicating that we have created a quantum superposition of atoms and diatomic molecules two chemically different species.     

Modulation of an RNA-binding protein by abscisic-acid-activated protein kinase

Protein kinases are involved in stress signalling in both plant and animal systems. The hormone abscisic acid mediates the responses of plants to stresses such as drought, salinity and cold. Abscisic-acid-activated protein kinase (AAPK -- found in guard cells, which control stomatal pores -- has been shown to regulate plasma membrane ion channels. Here we show that AAPK-interacting protein 1 (AKIP1), with sequence homology to heterogeneous nuclear RNA-binding protein A/B, is a substrate of AAPK. AAPK-dependent phosphorylation is required for the interaction of AKIP1 with messenger RNA that encodes dehydrin, a protein implicated in cell protection under stress conditions. AAPK and AKIP1 are present in the guard-cell nucleus, and in vivo treatment of such cells with abscisic acid enhances the partitioning of AKIP1 into subnuclear foci which are reminiscent of nuclear speckles. These results show that phosphorylation-regulated RNA target discrimination by heterogeneous nuclear RNA-binding proteins may be a general phenomenon in eukaryotes, and implicate a plant hormone in the regulation of protein dynamics during rapid subnuclear reorganization.