Molecular analysis of the association of HLA-B53 and resistance to severe malaria.

The protective association between the human leukocyte antigen HLA-B53 and severe malaria was investigated by sequencing of peptides eluted from this molecule followed by screening of candidate epitopes from pre-erythrocytic-stage antigens of Plasmodium falciparum in biochemical and cellular assays. Among malaria-immune Africans, HLA-B53-restricted cytotoxic T lymphocytes recognized a conserved nonamer peptide from liver-stage-specific antigen-1 (LSA-1), but no HLA-B53-restricted epitopes were identified in other antigens. These findings indicate a possible molecular basis for this HLA-disease association and support the candidacy of liver-stage-specific antigen-1 as a malaria vaccine component.     

On the participation of the zona glomerulosa on the adrenal response to stress

Zusammenfassung Zwei Serien Ratten wurden durch Formalininjektion belastet. Die Zona glomerulosa der Nebennierenrinde reagierte durch Lipoidausscheidung nur in jener Serie, die durch hohe Lymphozytenzahl des Blutes, hohen Lipoidgehalt der Fasciculata, kleinere Aktivität der Lymphknötchen der Milz und auffallend intensive Stressreaktion der Fasciculata charakterisiert war. Bei Ratten, deren Glomerulosa ihre Lipoide ausgeschieden hatte, trat weder Schwellung noch Desintegration des lymphatischen Gewebes der Milz auf.     

Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2

The actions of corticotropin-releasing hormone (Crh), a mediator of endocrine and behavioural responses to stress, and the related hormone urocortin (Ucn) are coordinated by two receptors, Crhr1 (encoded by Crhr) and Crhr2. These receptors may exhibit distinct functions due to unique tissue distribution and pharmacology. Crhr-null mice have defined central functions for Crhr1 in anxiety and neuroendocrine stress responses. Here we generate Crhr2-/- mice and show that Crhr2 supplies regulatory features to the hypothalamic-pituitary-adrenal axis (HPA) stress response. Although initiation of the stress response appears to be normal, Crhr2-/- mice show early termination of adrenocorticotropic hormone (Acth) release, suggesting that Crhr2 is involved in maintaining HPA drive. Crhr2 also appears to modify the recovery phase of the HPA response, as corticosterone levels remain elevated 90 minutes after stress in Crhr2-/- mice. In addition, stress-coping behaviours associated with dearousal are reduced in Crhr2-/- mice. We also demonstrate that Crhr2 is essential for sustained feeding suppression (hypophagia) induced by Ucn. Feeding is initially suppressed in Crhr2-/- mice following Ucn, but Crhr2-/- mice recover more rapidly and completely than do wild-type mice. In addition to central nervous system effects, we found that, in contrast to wild-type mice, Crhr2-/- mice fail to show the enhanced cardiac performance or reduced blood pressure associated with systemic Ucn, suggesting that Crhr2 mediates these peripheral haemodynamic effects. Moreover, Crhr2-/- mice have elevated basal blood pressure, demonstrating that Crhr2 participates in cardiovascular homeostasis. Our results identify specific responses in the brain and periphery that involve Crhr2.     

Epistasis analysis with global transcriptional phenotypes

Classical epistasis analysis can determine the order of function of genes in pathways using morphological, biochemical and other phenotypes. It requires knowledge of the pathway's phenotypic output and a variety of experimental expertise and so is unsuitable for genome-scale analysis. Here we used microarray profiles of mutants as phenotypes for epistasis analysis. Considering genes that regulate activity of protein kinase A in Dictyostelium, we identified known and unknown epistatic relationships and reconstructed a genetic network with microarray phenotypes alone. This work shows that microarray data can provide a uniform, quantitative tool for large-scale genetic network analysis.     

Contractility cycle of an isolated gastropod ventricle

Zusammenfassung Plötzliche Dehnungen oder Entspannungen während des Eigenrhythmus der Herzkammer vonBusycon canaliculatum wurden dazu benützt, um den Verlauf des Aktivitätszustandes zu untersuchen. Sowohl Anstieg, wie auch Abfall des «active state» waren entsprechend langsam wie bei Wirbeltier-Herzmuskeln. Das tetanisierbare Schneckenherz stellt somit ein gutes Versuchsobjekt für die Aktivierung des Herzmuskels dar, da die maximale Kraft unabhängig von der Zeit ist.

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Research supported by National Science Foundation grant No. GB-1001.     

Mediation of the solar wind termination shock by non-thermal ions

Broad regions on both sides of the solar wind termination shock are populated by high intensities of non-thermal ions and electrons. The pre-shock particles in the solar wind have been measured by the spacecraft Voyager 1 (refs 1-5) and Voyager 2 (refs 3, 6). The post-shock particles in the heliosheath have also been measured by Voyager 1 (refs 3-5). It was not clear, however, what effect these particles might have on the physics of the shock transition until Voyager 2 crossed the shock on 31 August-1 September 2007 (refs 7-9). Unlike Voyager 1, Voyager 2 is making plasma measurements. Data from the plasma and magnetic field instruments on Voyager 2 indicate that non-thermal ion distributions probably have key roles in mediating dynamical processes at the termination shock and in the heliosheath. Here we report that intensities of low-energy ions measured by Voyager 2 produce non-thermal partial ion pressures in the heliosheath that are comparable to (or exceed) both the thermal plasma pressures and the scalar magnetic field pressures. We conclude that these ions are the >0.028 MeV portion of the non-thermal ion distribution that determines the termination shock structure and the acceleration of which extracts a large fraction of bulk-flow kinetic energy from the incident solar wind.     

Some comments on ‘forming new physics communities: Australia and Japan, 1914–1950’, by R. W. Home and M. Watanabe

The broad analysis made by Home and Watanabe of the development of physics in Australia during the period from 1914 to 1945 is generally accepted; however, details relating to the backgrounds of certain of these developments are questioned.     

A major susceptibility locus for leprosy in India maps to chromosome 10p13

Leprosy, a chronic infectious disease caused by Mycobacterium leprae, is prevalent in India, where about half of the world's estimated 800,000 cases occur. A role for the genetics of the host in variable susceptibility to leprosy has been indicated by familial clustering, twin studies, complex segregation analyses and human leukocyte antigen (HLA) association studies. We report here a genetic linkage scan of the genomes of 224 families from South India, containing 245 independent affected sibpairs with leprosy, mainly of the paucibacillary type. In a two-stage genome screen using 396 microsatellite markers, we found significant linkage (maximum lod score (MLS) = 4.09, P < 2x10-5) on chromosome 10p13 for a series of neighboring microsatellite markers, providing evidence for a major locus for this prevalent infectious disease. Thus, despite the polygenic nature of infectious disease susceptibility, some major, non-HLA-linked loci exist that may be mapped through obtainable numbers of affected sibling pairs.     

The RNA-binding protein FCA is an abscisic acid receptor

The phytohormone abscisic acid (ABA) regulates various physiological processes in plants. The molecular mechanisms by which this is achieved are not fully understood. Genetic approaches have characterized several downstream components of ABA signalling, but a receptor for ABA has remained elusive. Although studies indicate that several ABA response genes encode RNA-binding or RNA-processing proteins, none has been found to be functional in binding ABA. Here we show that FCA, an RNA-binding protein involved in flowering, binds ABA with high affinity in an interaction that is stereospecific and follows receptor kinetics. The interaction between FCA and ABA has molecular effects on downstream events in the autonomous floral pathway and, consequently, on the ability of the plant to undergo transition to flowering. We further show that ABA binding exerts a direct control on the FCA-mediated processing of precursor messenger RNA. Our results indicate that FCA is an ABA receptor involved in RNA metabolism and in controlling flowering time.     

Breakdown of Fermi-liquid theory in a copper-oxide superconductor.

The behaviour of electrons in solids is well described by Landau's Fermi-liquid theory, which predicts that although electrons in a metal interact, they can still be treated as well defined fermions, which are called 'quasiparticles'. At low temperatures, the ability of quasiparticles to transport heat is given strictly by their ability to transport charge, as described by a universal relation known as the Wiedemann-Franz law, which hitherto no material has been known to violate. High-temperature superconductors have long been thought to fall outside the realm of Fermi-liquid theory, as suggested by several anomalous properties, but this has yet to be shown conclusively. Here we report an experimental test of the Wiedemann-Franz law in the normal state of a copper-oxide superconductor, (Pr,Ce)2CuO4, which reveals that the elementary excitations that carry heat in this material are not fermions. This is compelling evidence for the breakdown of Fermi-liquid theory in high-temperature superconductors.