Polymers are usually considered thermal insulators, because the amorphous arrangement of the molecular chains reduces the mean free path of heat-conducting phonons. The most common method to increase thermal conductivity is to draw polymeric fibres, which increases chain alignment and crystallinity, but creates a material that currently has limited thermal applications. Here we show that pure polythiophene nanofibres can have a thermal conductivity up to ∼ 4.4 W m(-1) K(-1) (more than 20 times higher than the bulk polymer value) while remaining amorphous. This enhancement results from significant molecular chain orientation along the fibre axis that is obtained during electropolymerization using nanoscale templates. Thermal conductivity data suggest that, unlike in drawn crystalline fibres, in our fibres the dominant phonon-scattering process at room temperature is still related to structural disorder. Using vertically aligned arrays of nanofibres, we demonstrate effective heat transfer at critical contacts in electronic devices operating under high-power conditions at 200 °C over numerous cycles.

Formation of the immunological synapse (IS) in T cells involves large scale molecular movements that are mediated, at least in part, by reorganization of the actin cytoskeleton. Various signaling proteins accumulate at the IS and are localized in specialized membrane microdomains, known as lipid rafts. We have shown previously that lipid rafts cluster and localize at the IS in antigen-stimulated T cells. Here, we provide evidence that lipid raft polarization to the IS depends on an intracellular pathway that involves Vav1, Rac, and actin cytoskeleton reorganization. Thus, lipid rafts did not translocate to the IS in Vav1-deficient (Vav1 − /−) T cells upon antigen stimulation. Similarly, T cell receptor transgenic Jurkat T cells also failed to translocate lipid rafts to the IS when transfected with dominant negative Vav1 mutants. Raft polarization induced by membrane-bound cholera toxin cross-linking was also abolished in Jurkat T cells expressing dominant negative Vav1 or Rac mutants and in cells treated with inhibitors of actin polymerization. However, Vav overexpression that induced F-actin polymerization failed to induce lipid rafts clustering. Therefore, Vav is necessary, but not sufficient, to regulate lipid rafts clustering and polarization at the IS, suggesting that additional signals are required.

Protein kinase C-(PKC ) is a Ca 2؉ -independent PKC isoform that is selectively expressed in T lymphocytes (and muscle), and is thought to play an important role in T cell receptor-induced activation. To gain a better understanding of the function and regulation of PKC , we have employed the yeast two-hybrid system to identify PKC -interacting proteins. We report the isolation and characterization of a cDNA encoding a novel 335-amino acid (37.5-kDa) PKC -interacting protein termed PICOT (for PKC-interacting cousin of thioredoxin). PICOT is expressed in various tissues, including in T cells, where it colocalizes with PKC . PICOT displays an N-terminal thioredoxin homology domain, which is required for the interaction with PKC. Comparison of the unique C-terminal region of PICOT with expressed sequence tag data bases revealed two tandem repeats of a novel domain that is highly conserved from plants to mammals. Transient overexpression of full-length PICOT (but not its N-or C-terminal fragments) in T cells inhibited the activation of c-Jun N-terminal kinase (but not extracellular signal-regulated kinase), and the transcription factors AP-1 or NF-B. These findings suggest that PICOT and its evolutionary conserved homologues may interact with PKC-related kinases in multiple organisms and, second, that it plays a role in regulating the function of the thioredoxin system.Members of the protein kinase C (PKC) 1 family of intracellular serine/threonine kinases play critical roles in the regulation of cellular differentiation and proliferation in many cell types and in response to diverse stimuli, including hormones, neurotransmitters, and growth factors (1-3). The PKC family consists of 11 known mammalian members that are expressed in a wide variety of tissues and cell types. Based on sequence similarities, domain structures, and cofactor requirements, PKC isoenzymes can be grouped into three subfamilies. 1) The Ca 2ϩ -dependent conventional enzymes, consisting of PKC-␣, -␤I, -␤II, and -␥, contain three conserved domains, namely the diacylglycerol/phorbol ester binding C1 domain, which contains two repeats of a cysteine-rich zinc finger, the phospholipid-and calcium-binding C2 domain, and the catalytic C3 and C4 domains.2) The Ca 2ϩ -independent enzymes (PKC-␦, -⑀, -, -and -) are termed novel PKCs. The C2-like N-terminal domain of these enzymes can bind acidic phospholipids but not Ca 2ϩ . 3) A third PKC subfamily, termed atypical PKCs, includes PKCand -/ that possess a single cysteine-rich domain, lacking the ability to bind phospholipids or phorbol esters. PKC activity is regulated by defined cofactors that interact with specific regions of the regulatory domain as well as transphosphorylation by serine/threonine kinases and autophosphorylation. The activation is accompanied by a conformational change that releases the basic pseudosubstrate region from the catalytic cleft of the kinase domain. In addition, interaction with specific proteins, termed receptors for activated PKC, that function as selective scaffolds for a...

PKCθ plays an essential role in activation of mature T cells via stimulation of AP-1 and NF-κB, and is known to selectively translocate to the immunological synapse in antigen-stimulated T cells. Recently, we reported that a Vav/Rac pathway which depends on actin cytoskeleton reorganization mediates selective recruitment of PKCθ to the membrane or cytoskeleton and its catalytic activation by anti-CD3/CD28 costimulation. Because this pathway acted selectively on PKCθ, we addressed here the question of whether the translocation and activation of PKCθ in T cells is regulated by a unique pathway distinct from the conventional mechanism for PKC activation, i.e., PLC-mediated production of DAG. Using three independent approaches, i.e., a selective PLC inhibitor, a PLCγ1-deficient T cell line, or a dominant negative PLCγ1 mutant, we demonstrate that CD3/CD28-induced membrane recruitment and COOH-terminal phosphorylation of PKCθ are largely independent of PLC. In contrast, the same inhibitory strategies blocked the membrane translocation of PKCα. Membrane or lipid raft recruitment of PKCθ (but not PKCα) was absent in T cells treated with phosphatidylinositol 3-kinase (PI3-K) inhibitors or in Vav-deficient T cells, and was enhanced by constitutively active PI3-K. 3-phosphoinositide-dependent kinase-1 (PDK1) also upregulated the membrane translocation of PKCθ, but did not associate with it. These results provide evidence that a nonconventional PI3-K– and Vav-dependent pathway mediates the selective membrane recruitment and, possibly, activation of PKCθ in T cells.

We suggest that the earliest site of regulation of membrane transport by PLD is within the intermediate compartment between the endoplasmic reticulum and the Golgi complex.

We describe the isolation of a protein, SWAP-70-like adapter of T cells (SLAT), which is expressed at high levels in thymocytes and differentiated Th2 cells. SLAT expression was upregulated in differentiating Th2 cells and downregulated in Th1 cells. Ectopic SLAT expression exerted positive or negative effects on IL-4 versus IFNgamma induction, respectively. TCR signaling induced translocation of SLAT to the immunological synapse and its association with ZAP-70 kinase. SLAT reduced the association of ZAP-70 with TCR-zeta and interfered with ZAP-70 but not Lck signaling. Consistent with these results, pharmacological inhibition of ZAP-70 also induced Th2 skewing. Thus, SLAT is a protein which plays a role in Th2 development and/or activation, perhaps by interfering with ZAP-70 signaling.

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