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<jats:p> Although differences among species in enzyme maximal activity or concentration are often interpreted as adaptive and important for regulating metabolism, these differences may simply reflect phylogenetic divergence. Phylogenetic analysis of the expression of the glycolytic enzymes among 15 taxa of a North American fish genus ( <jats:italic>Fundulus)</jats:italic> indicated that most variation in enzyme concentration is due to evolutionary distance and may be nonadaptive. However, three enzymes’ maximal activities covary with environmental temperature and have adaptive value. Additionally, two pairs of enzymes covary, indicating coevolution. Thus, metabolic flux may be modulated by many different enzymes rather than by a single rate-limiting enzyme. </jats:p>

<jats:p>The proline-rich COOH-terminal region of dynamin binds various Src homology 3 (SH3) domain–containing proteins, but the physiological role of these interactions is unknown. In living nerve terminals, the function of the interaction with SH3 domains was examined. Amphiphysin contains an SH3 domain and is a major dynamin binding partner at the synapse. Microinjection of amphiphysin’s SH3 domain or of a dynamin peptide containing the SH3 binding site inhibited synaptic vesicle endocytosis at the stage of invaginated clathrin-coated pits, which resulted in an activity-dependent distortion of the synaptic architecture and a depression of transmitter release. These findings demonstrate that SH3-mediated interactions are required for dynamin function and support an essential role of clathrin-mediated endocytosis in synaptic vesicle recycling.</jats:p>

<jats:p>The participation of medial temporal-lobe structures in memory performance was examined by functional magnetic resonance imaging of local blood oxygenation level–dependent signals. Signals were measured during encoding into memory complex scenes or line drawings and during retrieval from memory of previously studied line drawings or words. Encoding tasks yielded increased signals for unfamiliar information in a posterior medial-temporal region that were focused in the parahippocampal cortex. Retrieval tasks yielded increased signals for successfully remembered information in an anterior medial-temporal region that were focused in the subiculum. These results indicate that separate components of the human medial temporal-lobe memory system are active during distinct memory processes.</jats:p>

<jats:p>An intracellular pathway for proteins liberated from mineralized matrix during resorption was identified in osteoclasts. Analysis by confocal microscopy of sites of active bone resorption showed that released matrix proteins, including degraded type I collagen, were endocytosed along the ruffled border within the resorption compartment and transcytosed through the osteoclast to the basolateral membrane. Intracellular trafficking of degraded collagen, as typified by the resorbing osteoclast, may provide the cell with a regulatory mechanism for the control of tissue degradation.</jats:p>

<jats:p>Osteoclasts are multinucleated cells responsible for bone resorption. During the resorption cycle, osteoclasts undergo dramatic changes in their polarity, and resorbing cells reveal four functionally and structurally different membrane domains. Bone degradation products, both organic and inorganic, were endocytosed from the ruffled border membrane. They were then found to be transported in vesicles through the cell to the plasma membrane domain, located in the middle of the basal membrane, where they were liberated into the extracellular space. These results explain how resorbing osteoclasts can simultaneously remove large amounts of matrix degradation products and penetrate into bone.</jats:p>

<jats:p> Activation of CD4 <jats:sup>+</jats:sup> T lymphocytes from human immunodeficiency virus–type 1 (HIV-1)–infected donors with immobilized antibodies to CD3 and CD28 induces a virus-resistant state. This effect is specific for macrophage-tropic HIV-1. Transcripts encoding CXCR4/Fusin, the fusion cofactor used by T cell line–tropic isolates, were abundant in CD3/CD28-stimulated cells, but transcripts encoding CCR5, the fusion cofactor used by macrophage-tropic viruses, were not detectable. Thus, CD3/CD28 costimulation induces an HIV-1–resistant phenotype similar to that seen in some highly exposed and HIV-uninfected individuals. </jats:p>

<jats:p>The chemokine receptors CXCR4 and CCR5 have recently been shown to act as coreceptors, in concert with CD4, for human immunodeficiency virus–type 1 (HIV-1) infection. RANTES and other chemokines that interact with CCR5 and block infection of peripheral blood mononuclear cell cultures inhibit infection of primary macrophages inefficiently at best. If used to treat HIV-1–infected individuals, these chemokines could fail to influence HIV replication in nonlymphocyte compartments while promoting unwanted inflammatory side effects. A derivative of RANTES that was created by chemical modification of the amino terminus, aminooxypentane (AOP)–RANTES, did not induce chemotaxis and was a subnanomolar antagonist of CCR5 function in monocytes. It potently inhibited infection of diverse cell types (including macrophages and lymphocytes) by nonsyncytium-inducing, macrophage-tropic HIV-1 strains. Thus, activation of cells by chemokines is not a prerequisite for the inhibition of viral uptake and replication. Chemokine receptor antagonists like AOP-RANTES that achieve full receptor occupancy at nanomolar concentrations are strong candidates for the therapy of HIV-1–infected individuals.</jats:p>