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<jats:p>The carboxyl-terminal domain, residues 146 to 231, of the human immunodeficiency virus–1 (HIV-1) capsid protein [CA(146–231)] is required for capsid dimerization and viral assembly. This domain contains a stretch of 20 residues, called the major homology region (MHR), which is conserved across retroviruses and is essential for viral assembly, maturation, and infectivity. The crystal structures of CA(146–231) and CA(151–231) reveal that the globular domain is composed of four helices and an extended amino-terminal strand. CA(146–231) dimerizes through parallel packing of helix 2 across a dyad. The MHR is distinct from the dimer interface and instead forms an intricate hydrogen-bonding network that interconnects strand 1 and helices 1 and 2. Alignment of the CA(146–231) dimer with the crystal structure of the capsid amino-terminal domain provides a model for the intact protein and extends models for assembly of the central conical core of HIV-1.</jats:p>

<jats:p>Reactive and potentially toxic cofactors such as copper ions are imported into eukaryotic cells and incorporated into target proteins by unknown mechanisms. Atx1, a prototypical copper chaperone protein from yeast, has now been shown to act as a soluble cytoplasmic copper(I) receptor that can adopt either a two- or three-coordinate metal center in the active site. Atx1 also associated directly with the Atx1-like cytosolic domains of Ccc2, a vesicular protein defined in genetic studies as a member of the copper-trafficking pathway. The unusual structure and dynamics of Atx1 suggest a copper exchange function for this protein and related domains in the Menkes and Wilson disease proteins.</jats:p>

<jats:p>Forces generated by protein polymerization are important for various forms of cellular motility. Assembling microtubules, for instance, are believed to exert pushing forces on chromosomes during mitosis. The force that a single microtubule can generate was measured by attaching microtubules to a substrate at one end and causing them to push against a microfabricated rigid barrier at the other end. The subsequent buckling of the microtubules was analyzed to determine both the force on each microtubule end and the growth velocity. The growth velocity decreased from 1.2 micrometers per minute at zero force to 0.2 micrometer per minute at forces of 3 to 4 piconewtons. The force-velocity relation fits well to a decaying exponential, in agreement with theoretical models, but the rate of decay is faster than predicted.</jats:p>

<jats:p>Activation of the transcription factor nuclear factor kappa B (NF-κB) is controlled by sequential phosphorylation, ubiquitination, and degradation of its inhibitory subunit IκB. A large multiprotein complex, the IκB kinase (IKK) signalsome, was purified from HeLa cells and found to contain a cytokine-inducible IκB kinase activity that phosphorylates IκB-α and IκB-β. Two components of the IKK signalsome, IKK-1 and IKK-2, were identified as closely related protein serine kinases containing leucine zipper and helix-loop-helix protein interaction motifs. Mutant versions of IKK-2 had pronounced effects on RelA nuclear translocation and NF-κB–dependent reporter activity, consistent with a critical role for the IKK kinases in the NF-κB signaling pathway.</jats:p>

<jats:p>Activation of the transcription factor nuclear factor kappa B (NF-κB) by inflammatory cytokines requires the successive action of NF-κB–inducing kinase (NIK) and IκB kinase–α (IKK-α). A widely expressed protein kinase was identified that is 52 percent identical to IKK-α. IκB kinase–β (IKK-β) activated NF-κB when overexpressed and phosphorylated serine residues 32 and 36 of IκB-α and serines 19 and 23 of IκB-β. The activity of IKK-β was stimulated by tumor necrosis factor and interleukin-1 treatment. IKK-α and IKK-β formed heterodimers that interacted with NIK. Overexpression of a catalytically inactive form of IKK-β blocked cytokine-induced NF-κB activation. Thus, an active IκB kinase complex may require three distinct protein kinases.</jats:p>

<jats:p>Measurements of atmospheric carbon dioxide and satellite-derived measurements of temperature and the vegetation index were used to investigate relationships among climate, carbon dioxide, and ecosystems. At the global scale, lagged correlations between temperature and carbon dioxide growth rate were found, indicating modulation by biogeochemical feedbacks. Spatial analysis of the temperature and vegetation index data suggests that the global correlations are a composite of individualistic responses of different ecosystems. The existence of biome-specific time scales of response implies that changes in global ecosystem distributions could indirectly alter the relationships between climate and carbon storage.</jats:p>

<jats:p>When transgenic mice that expressed human sickle hemoglobin were mated with mice having knockout mutations of the mouse α- and β-globin genes, animals were produced that synthesized only human hemoglobin in adult red blood cells. Similar to many human patients with sickle cell disease, the mice developed a severe hemolytic anemia and extensive organ pathology. Numerous sickled erythrocytes were observed in peripheral blood. Although chronically anemic, most animals survived for 2 to 9 months and were fertile. Drug and genetic therapies can now be tested in this mouse model of sickle cell disease.</jats:p>

<jats:p> To create mice expressing exclusively human sickle hemoglobin (HbS), transgenic mice expressing human α-, γ-, and β <jats:sup>S</jats:sup> -globin were generated and bred with knockout mice that had deletions of the murine α- and β-globin genes. These sickle cell mice have the major features (irreversibly sickled red cells, anemia, multiorgan pathology) found in humans with sickle cell disease and, as such, represent a useful in vivo system to accelerate the development of improved therapies for this common genetic disease. </jats:p>