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<jats:p>A scanning tunneling microscope (STM) was used to explore the local electrical characteristics of single-wall carbon nanotubes. As the STM tip was moved along the length of the nanotubes, well-defined positions were found where the transport current changes abruptly from a graphitic-like response to one that is highly nonlinear and asymmetrical, including near-perfect rectification. The observations are consistent with the existence of localized, on-tube nanodevices of a type proposed theoretically.</jats:p>

<jats:p> Ste5 is a scaffold for the mitogen-activated protein kinase (MAPK) cascade components in a yeast pheromone response pathway. Ste5 also associates with Ste4, the β subunit of a heterotrimeric guanine nucleotide–binding protein, potentially linking receptor activation to stimulation of the MAPK cascade. A RING-H2 motif at the Ste5 amino terminus is apparently essential for function because Ste5(C177S) and Ste5(C177A C180A) mutants did not rescue the mating defect of a <jats:italic>ste5Δ</jats:italic> cell. In vitro Ste5(C177A C180A) bound each component of the MAPK cascade, but not Ste4. Unlike wild-type Ste5, the mutant did not appear to oligomerize; however, when fused to a heterologous dimerization domain (glutathione S-transferase), the chimeric protein restored mating in an <jats:italic>ste5Δ</jats:italic> cell and an <jats:italic>ste4Δ ste5Δ</jats:italic> double mutant. Thus, the RING-H2 domain mediates Ste4-Ste5 interaction, which is a prerequisite for Ste5-Ste5 self-association and signaling. </jats:p>

<jats:p> HLA-DM is a major histocompatibility complex (MHC) class II–like molecule that facilitates antigen processing by catalyzing the exchange of invariant chain–derived peptides (CLIP) from class II molecules for antigenic peptides. HLA-DO is a second class II–like molecule that physically associates with HLA-DM in B cells. HLA-DO was shown to block HLA-DM function. Purified HLA-DM-DO complexes could not promote peptide exchange in vitro. Expression of HLA-DO in a class II <jats:sup>+</jats:sup> and DM <jats:sup>+</jats:sup> , DO <jats:sup>−</jats:sup> human T cell line caused the accumulation of class II–CLIP complexes, indicating that HLA-DO blocked DM function in vivo and suggesting that HLA-DO is an important modulator of class II–restricted antigen processing. </jats:p>

<jats:p>Cyclic nucleotide–gated (CNG) ion channels are multimeric proteins that activate in response to the binding of cyclic nucleotide to intracellular domains. Here, an intramolecular protein–protein interaction between the amino-terminal domain and the carboxyl-terminal ligand-binding domain of the rat olfactory CNG channel was shown to exert an autoexcitatory effect on channel activation. Calcium-calmodulin, which modulates CNG channel activity during odorant adaptation, blocked this interaction. A specific deletion within the amino-terminal domain disrupted the interdomain interaction in vitro and altered the gating properties and calmodulin sensitivity of expressed channels. Thus, the amino-terminal domain may promote channel opening by directly interacting with the carboxyl-terminal gating machinery; calmodulin regulates channel activity by targeting this interaction.</jats:p>

<jats:p> Apoptosis of mouse neocortical neurons induced by serum deprivation or by staurosporine was associated with an early enhancement of delayed rectifier ( <jats:italic>I</jats:italic> <jats:sub>K</jats:sub> ) current and loss of total intracellular K <jats:sup>+</jats:sup> . This <jats:italic>I</jats:italic> <jats:sub>K</jats:sub> augmentation was not seen in neurons undergoing excitotoxic necrosis or in older neurons resistant to staurosporine-induced apoptosis. Attenuating outward K <jats:sup>+</jats:sup> current with tetraethylammonium or elevated extracellular K <jats:sup>+</jats:sup> , but not blockers of Ca <jats:sup>2+</jats:sup> , Cl <jats:sup>−</jats:sup> , or other K <jats:sup>+</jats:sup> channels, reduced apoptosis, even if associated increases in intracellular Ca <jats:sup>2+</jats:sup> concentration were prevented. Furthermore, exposure to the K <jats:sup>+</jats:sup> ionophore valinomycin or the K <jats:sup>+</jats:sup> -channel opener cromakalim induced apoptosis. Enhanced K <jats:sup>+</jats:sup> efflux may mediate certain forms of neuronal apoptosis. </jats:p>

<jats:p>Immunotherapy of mice with preexisting cancers with heat shock protein preparations derived from autologous cancer resulted in retarded progression of the primary cancer, a reduced metastatic load, and prolongation of life-span. Treatment with heat shock protein preparations derived from cancers other than the autologous cancer did not provide significant protection. Spontaneous cancers (lung cancer and melanoma), chemically induced cancers (fibrosarcoma and colon carcinoma), and an ultraviolet radiation-induced spindle cell carcinoma were tested, and the results support the efficacy of autologous cancer–derived heat shock protein–peptide complexes in immunotherapy of cancers without the need to identify specific tumor antigenic epitopes.</jats:p>

<jats:p> Familial adenomatous polyposis coli (FAP) is a disease characterized by the development of multiple colorectal adenomas, and affected individuals carry germline mutations in the <jats:italic>APC</jats:italic> gene. With the use of a conditional gene targeting system, a mouse model of FAP was created that circumvents the embryonic lethality of Apc deficiency and directs <jats:italic>Apc</jats:italic> inactivation specifically to the colorectal epithelium. <jats:italic>loxP</jats:italic> sites were inserted into the introns around <jats:italic>Apc</jats:italic> exon 14, and the resultant mutant allele ( <jats:italic>Apc</jats:italic> <jats:sup> <jats:italic>580S</jats:italic> </jats:sup> ) was introduced into the mouse germline. Mice homozygous for <jats:italic>Apc</jats:italic> <jats:sup> <jats:italic>580S</jats:italic> </jats:sup> were normal; however, upon infection of the colorectal region with an adenovirus encoding the Cre recombinase, the mice developed adenomas within 4 weeks. The adenomas showed deletion of <jats:italic>Apc</jats:italic> exon 14, indicating that the loss of Apc function was caused by Cre- <jats:italic>loxP–</jats:italic> mediated recombination. </jats:p>

<jats:p>In the absence of costimulation, T cells activated through their antigen receptor become unresponsive (anergic) and do not transcribe the gene encoding interleukin-2 (IL-2) when restimulated with antigen. Anergic alloantigen-specific human T cells contained phosphorylated Cbl that coimmunoprecipitated with Fyn. The adapter protein CrkL was associated with both phosphorylated Cbl and the guanidine nucleotide–releasing factor C3G, which catalyzes guanosine triphosphate (GTP) exchange on Rap1. Active Rap1 (GTP-bound form) was present in anergic cells. Forced expression of low amounts of Rap1-GTP in Jurkat T cells recapitulated the anergic defect and blocked T cell antigen receptor (TCR)– and CD28-mediated IL-2 gene transcription. Therefore, Rap1 functions as a negative regulator of TCR-mediated IL-2 gene transcription and may be responsible for the specific defect in IL-2 production in T cell anergy.</jats:p>

<jats:p> Oxidized guanine (8-oxo-7,8-dihydroguanine; 8-oxo-G) is a potent mutagen because of its ambiguous pairing with cytosine and adenine. The <jats:italic>Escherichia coli</jats:italic> MutT protein specifically hydrolyzes both 8-oxo-deoxyguanosine triphosphate (8-oxo-dGTP) and 8-oxo-guanosine triphosphate (8-oxo-rGTP), which are otherwise incorporated in DNA and RNA opposite template A. In vivo, this cleaning of the nucleotide pools decreases both DNA replication and transcription errors. The effect of <jats:italic>mutT</jats:italic> mutation on transcription fidelity was shown to depend on oxidative metabolism. Such control of transcriptional fidelity by the ubiquitous MutT function has implications for evolution of RNA-based life, phenotypic expression, adaptive mutagenesis, and functional maintenance of nondividing cells. </jats:p>

<jats:p> The inhibitory γ-aminobutyric acid–containing (GABAergic) neurons of the thalamic reticular and perigeniculate nuclei are involved in the generation of normal and abnormal synchronized activity in thalamocortical networks. An important factor controlling the generation of activity in this system is the amplitude and duration of inhibitory postsynaptic potentials (IPSPs) in thalamocortical cells, which depend on the pattern of activity generated in thalamic reticular and perigeniculate cells. Activation of single ferret perigeniculate neurons generated three distinct patterns of GABAergic IPSPs in thalamocortical neurons of the dorsal lateral geniculate nucleus: Low-frequency tonic discharge resulted in small-amplitude IPSPs mediated by GABA <jats:sub>A</jats:sub> receptors, burst firing resulted in large-amplitude GABA <jats:sub>A</jats:sub> IPSPs, and prolonged burst firing activated IPSPs mediated by GABA <jats:sub>A</jats:sub> and GABA <jats:sub>B</jats:sub> receptors. These functional properties of GABAergic inhibition can reconfigure the operations of thalamocortical networks into patterns of activity associated with waking, slow-wave sleep, and generalized seizures. </jats:p>