The proin¯ammatory cytokine interleukin 17 is the founding member of a family of secreted proteins that elicit potent cellular responses. We report a novel human IL-17 homolog, IL-17F, and show that it is expressed by activated T cells, can stimulate production of other cytokines such as IL-6, IL-8 and granulocyte colony-stimulating factor, and can regulate cartilage matrix turnover. Unexpectedly, the crystal structure of IL-17F reveals that IL-17 family members adopt a monomer fold typical of cystine knot growth factors, despite lacking the disul®de responsible for de®ning the canonical`knot' structure. IL-17F dimerizes in a parallel manner like neurotrophins, and features an unusually large cavity on its surface. Remarkably, this cavity is located in precisely the same position where nerve growth factor binds its high af®nity receptor, TrkA, suggesting further parallels between IL-17s and neurotrophins with respect to receptor recognition.

In situ polymerized PEDOT is used as hole-transporting material to fabricate dye-sensitized solar cells (DSSCs) with an average efficiency of 6.1% (under 100 mW cm−2 AM1.5 illumination) using organic D149 dye as the sensitizer. By comparing with Z907-based devices, the excellent light response of D149-sensitized DSSCs is attributed to the broad light absorption, low photoelectron recombination, and good polymer penetration

Cationic poly[9,9-bis(6′-N,N,N-trimethylammonium)hexyl)fluorene-alt-4,7-(2,1,3-benzothiadiazole) dibromide] (PFBT) and poly[9,9-bis(6′-( N,N,N-trimethylammonium)hexyl)fluorenyldivinylene-alt-4,7-(2,1,3-benzothiadiazole) dibromide] (PFVBT) are designed and synthesized to serve as multicolor light-up probes for biomolecular quantification. Because of the charge-transfer electronic states of the polymers, they exhibit weak fluorescence in aqueous media which can be significantly enhanced by increasing the hydrophobicity of polymeric microenvironment. Molecular orbital simulations further reveal that the presence of vinyl bonds endows PFVBT with a stronger charge-transfer character relative to that of PFBT. Both PFBT and PFVBT exhibit linear fluorescence enhancement as a function of bovine serum albumin (BSA) or DNA concentration in buffer solution, allowing effective biomolecular quantification. Of particular interest is that the light-up responses of PFBT or PFVBT in the presence of BSA and DNA are different, featuring biomolecule-dependent yellow-to-golden and orange-to-red light-up signatures, respectively. With a more sensitive light-up response, PFVBT can quantify biomolecules more effectively than PFBT does, which highlights the crucial role of charge transfer in determining the microenvironment-responsive fluorescence of conjugated polyelectrolytes for chemical and biological sensing.

Triphenylamine derivatives bridged by methylene units afford a near planar molecular platform in a series of one dimer and two oligomers exhibiting increased structural rigidity compared to that of their parent triphenylamines. This series of dendrimers show significantly enhanced two-photon absorptions that are up to 3-fold that of triphenylamines with similar molecular size and structure.

ERK(1/2) phosphorylation was abolished by SB204741, a universal 5-HT(2) receptor antagonist, and in 5-HT(2B) receptor-depleted cells, but unaffected by 5-HT(2A) or 5-HT(2C) receptor antagonists (M100907 and SB242084). Phosphorylation of ERK(1/2) and EGFRs was abolished by AG 1478, an inhibitor of EGFR tyrosine kinases, and GM 6001, an inhibitor of Zn-dependent metalloproteinases, suggesting growth factor "shedding" and transactivation of EGFRs. Chelation of [Ca(2+)](i) or PKC inhibition with GF 109203X abrogated ERK(1/2) phosphorylation. Up-regulated mRNA and protein expression of c-fos and fosB was abolished by SB204741, AG1478, and by U0126, an inhibitor of ERK phosphorylation by MAP kinase/ERK kinase.

Castration of adult male rats reduces by half the penile erectile response to electrical field stimulation (EFS) of the cavernosal nerve, and the activity of penile nitric oxide synthase (NOS). Both changes are prevented by androgen administration. We have now investigated whether other strategies of androgen ablation or competition may act as stronger inhibitors, and, if so, whether the stronger inhibition is due to the depletion of penile NOS content. Rats were castrated or left intact and were treated daily as follows: 1) intact, with the antiandrogen flutamide (25 mg/kg/day, i.p.); 2) castrated, with similar treatment; 3) castrated, with 17 beta-estradiol 3-benzoate (estradiol; via silastic tubing, s.c.). Additional groups of intact rats received injections of a GnRH antagonist (GnRHA, 1.25 mg/kg, s.c.), or were hypophysectomized and left untreated. Controls were untreated intact and castrated animals. After 7 days, rats were subjected to EFS, and the ratios between maximal intracavernosal pressure (MIP) and mean arterial pressure (MAP) were measured. Penile NOS activity and the contents of neuronal NOS (nNOS) and endothelial NOS (eNOS) were determined. Castration reduced the MIP:MAP ratio and penile NOS activity. Androgen receptor blockade with flutamide induced a similar response in intact rats. When flutamide treatment was combined with castration, the erectile response was nearly abolished, but NOS activity was not decreased below the values in castrated rats. Estradiol given to castrated rats and hypophysectomy or GnRHA treatment in intact rats diminished the erectile response below the level in castrated animals. In hypophysectomized rats, penile NOS activity fell below levels in castrated animals. contents of nNOS and eNOS were not significantly reduced by any treatment. These data suggest that penile erection in the rat is completely dependent on androgens, presumably because of their role in the maintenance of penile NOS activity and of other ancillary factors. However, only the complete blockade of residual androgen effects at the tissue level or a total androgen depletion can abolish the erectile response.

A phalloidin-functionalized hyperbranched conjugated polyelectrolyte (HCPE-phalloidin) is synthesized and used for direct filamentous actin (F-actin) imaging in living Hela cells. Different from commercially available organic dye-phalloidin conjugates, which require sophisticated techniques to be delivered into living cells, simple incubation of living cells with HCPE-phalloidin leads to efficient internalization of the probe and clear visualization of F-actin due to high brightness of HCPE and good specificity between phalloidin and actin. In addition, HCPE-phalloidin possesses improved photostability as compared to that for commercially available Alexa Fluor 488-phalloidin conjugates, suggesting that the new probe is promising for long-term F-actin imaging in living cells. Further fine-tuning the fluorescent property and targeting ability of HCPE-based probes could lead to more complicated imaging applications and subcellular target detection.

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