Characterisation of two distinctly different processes associated with the electrocrystallization of microcrystals of phase I CuTCNQ (TCNQ= 7, 7, 8, 8-tetracyanoquinodimethane)

Semi-conducting phase I CuTCNQ (TCNQ = 7,7,8,8-tetracyanoquinodimethane), which is of considerable interest as a switching device for memory storage materials, can be electrocrystallized from CH3CN via two distinctly different pathways when TCNQ is reduced to TCNQ˙− in the presence of [Cu(MeCN)4]+. The first pathway, identified in earlier studies, occurs at potentials where TCNQ is reduced to TCNQ˙− and involves a nucleation–growth mechanism at preferred sites on the electrode to produce arrays of well separated large branched needle-shaped phase I CuTCNQ crystals. The second pathway, now identified at more negative potentials, generates much smaller needle-shaped phase I CuTCNQ crystals. These electrocrystallize on parts of the surface not occupied in the initial process and give rise to film-like characteristics. This process is attributed to the reduction of Cu+[(TCNQ˙−)(TCNQ)] or a stabilised film of TCNQ via a solid–solid conversion process, which also involves ingress of Cu+via a nucleation–growth mechanism. The CuTCNQ surface area coverage is extensive since it occurs at all areas of the electrode and not just at defect sites that dominate the crystal formation sites for the first pathway. Infrared spectra, X-ray diffraction, surface plasmon resonance, quartz crystal microbalance, scanning electron microscopy and optical image data all confirm that two distinctly different pathways are available to produce the kinetically-favoured and more highly conducting phase I CuTCNQ solid, rather than the phase II material.

Electrochemically-induced TCNQ/Mn TCNQ 2 (H2O) 2 (TCNQ= 7, 7, 8, 8-Tetracyanoquinodimethane) solid-solid interconversion : two voltammetrically distinct processes that allow selective generation of nanofiber or nanorod network morphologies

Unlike the case with other divalent transition metal M\[TCNQ](2)(H(2)O)(2) (M = Fe, Co, Ni) analogues, the electrochemically induced solid-solid phase interconversion of TCNQ microcrystals (TCNQ = 7,7,8,8-tetracyanoquinodimethane) to Mn\[TCNQ](2)(H(2)O)(2) occurs via two voltammetrically distinct, time dependent processes that generate the coordination polymer in nanofiber or rod-like morphologies. Careful manipulation of the voltammetric scan rate, electrolysis time, Mn(2+)((aq)) concentration, and the method of electrode modification with solid TCNQ allows selective generation of either morphology. Detailed ex situ spectroscopic (IR, Raman), scanning electron microscopy (SEM), and X-ray powder diffraction (XRD) characterization clearly establish that differences in the electrochemically synthesized Mn-TCNQ material are confined to morphology. Generation of the nanofiber form is proposed to take place rapidly via formation and reduction of a Mn-stabilized anionic dimer intermediate, \[(Mn(2+))(TCNQ-TCNQ)(2)(*-)], formed as a result of radical-substrate coupling between TCNQ(*-) and neutral TCNQ, accompanied by ingress of Mn(2+) ions from the aqueous solution at the triple phase TCNQ/electrode/electrolyte boundary. In contrast, formation of the nanorod form is much slower and is postulated to arise from disproportionation of the \[(Mn(2+))(TCNQ-TCNQ)(*-)(2)] intermediate. Thus, identification of the time dependent pathways via the solid-solid state electrochemical approach allows the crystal size of the Mn\[TCNQ](2)(H(2)O)(2) material to be tuned and provides new mechanistic insights into the formation of different morphologies.

Electrochemical formation of porous copper 7, 7, 8, 8-tetracyanoquinodimethane and copper 2, 3, 5, 6-tetrafluoro-7, 7, 8, 8-tetracyanoquinodimethane honeycomb surfaces with superhydrophobic properties

The electrochemical formation of highly porous CuTCNQ (TCNQ = 7,7,8,8-tetracyanoquinodimethane) and CuTCNQF4 (TCNQF4 = 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane) materials was undertaken via the spontaneous redox reaction between a porous copper template, created using a hydrogen bubbling template technique, and an acetonitrile solution containing TCNQ or TCNQF4. It was found that activation of the surface via vigorous hydrogen evolution that occurs during porous copper deposition and TCNQ mass transport being hindered through the porous network of the copper template influenced the growth of CuTCNQ and CuTCNQF4. This approach resulted in the fabrication of a honeycomb layered type structure where the internal walls consist of very fine crystalline needles or spikes. This combination of microscopic and nanoscopic roughness was found to be extremely beneficial for anti-wetting properties where superhydrophobic materials with contact angles as high as 177° were created. Given that CuTCNQ and CuTCNQF4 have shown potential as molecular based electronic materials in the area of switching and field emission, the creation of a surface that is moisture resistant may be of applied interest.

Effect of Imidazolium-based Ionic Liquids on the nanoscale morphology of CuTCNQ (TCNQ= 7, 7, 8, 8-tetracyanoquinodimethane) metal-organic semiconductors

We demonstrate for the first time the ionic-liquid-mediated synthesis of nanostructured CuTCNQ by the simple immersion of copper in a solution of TCNQ where the viscosity of the medium significantly impacts the corrosion–crystallization process and the final morphology of the material.

Vorinostat/SAHA-induced apoptosis in malignant mesothelioma is FLIP/caspase 8-dependent and HR23B-independent

Introduction: Malignant pleural mesothelioma (MPM) is a rapidly fatal malignancy that is increasing in incidence. The caspase 8 inhibitor FLIP is an anti-apoptotic protein over-expressed in several cancer types including MPM. The histone deacetylase (HDAC) inhibitor Vorinostat (SAHA) is currently being evaluated in relapsed mesothelioma. We examined the roles of FLIP and caspase 8 in regulating SAHA-induced apoptosis in MPM. Methods: The mechanism of SAHA-induced apoptosis was assessed in 7 MPM cell lines and in a multicellular spheroid model. SiRNA and overexpression approaches were used, and cell death was assessed by flow cytometry, Western blotting and clonogenic assays. Results: RNAi-mediated FLIP silencing resulted in caspase 8-dependent apoptosis in MPM cell line models. SAHA potently down-regulated FLIP protein expression in all 7 MPM cell lines and in a multicellular spheroid model of MPM. In 6/7 MPM cell lines, SAHA treatment resulted in significant levels of apoptosis induction. Moreover, this apoptosis was caspase 8-dependent in all six sensitive cell lines. SAHA-induced apoptosis was also inhibited by stable FLIP overexpression. In contrast, down-regulation of HR23B, a candidate predictive biomarker for HDAC inhibitors, significantly inhibited SAHA-induced apoptosis in only 1/6 SAHA-sensitive MPM cell lines. Analysis of MPM patient samples demonstrated significant inter-patient variations in FLIP and caspase 8 expressions. In addition, SAHA enhanced cisplatin-induced apoptosis in a FLIP-dependent manner. Conclusions: These results indicate that FLIP is a major target for SAHA in MPM and identifies FLIP, caspase 8 and associated signalling molecules as candidate biomarkers for SAHA in this disease. © 2011 Elsevier Ltd. All rights reserved.

Procaspase 8 overexpression in non-small-cell lung cancer promotes apoptosis induced by FLIP silencing

We found that procaspase 8 was overexpressed in non-small-cell lung cancers (NSCLCs) compared with matched normal tissues. The caspase 8 inhibitor FLICE-inhibitory protein (FLIP) was also overexpressed in the majority of NSCLCs. Silencing FLIP induced caspase 8 activation and apoptosis in NSCLC cell lines, but not in normal lung cell lines. Apoptosis induced by FLIP silencing was mediated by the TRAIL death receptors DR4 and DR5, but was not dependent on ligation of the receptors by TRAIL. Furthermore, the apoptosis induced by FLIP silencing was dependent on the overexpression of procaspase 8 in NSCLC cells. Moreover, in NSCLC cells, but not in normal cells, FLIP silencing induced co-localization of DR5 and ceramide, and disruption of this co-localization abrogated apoptosis. FLIP silencing supra-additively increased TRAIL-induced apoptosis of NSCLC cells; however, normal lung cells were resistant to TRAIL, even when FLIP was silenced. Importantly, FLIP silencing sensitized NSCLC cells but not normal cells to chemotherapy in vitro, and silencing FLIP in vivo retarded NSCLC xenograft growth and enhanced the anti-tumour effects of cisplatin. Collectively, our results suggest that due to frequent procaspase 8 overexpression, NSCLCs may be particularly sensitive to FLIP-targeted therapies.

The M(r) 43K major capsid protein of rice ragged stunt oryzavirus is a post-translationally processed product of a M(r) 67 348 polypeptide encoded by genome segment 8

The nucleotide sequence of DNA complementary to rice ragged stunt oryzavirus (RRSV) genome segment 8 (S8) of an isolate from Thailand was determined. RRSV S8 is 1 914 bp in size and contains a single large open reading frame (ORF) spanning nucleotides 23 to 1 810 which is capable of encoding a protein of M(r) 67 348. The N-terminal amino acid sequence of a ~43K virion polypeptide matched to that inferred for an internal region of the S8 coding sequence. These data suggest that the 43K protein is encoded by S8 and is derived by a proteolytic cleavage. Predicted polypeptide sizes from this possible cleavage of S8 protein are 26K and 42K. Polyclonal antibodies raised against a maltose binding protein (MBP)-S8 fusion polypeptide (expressed in Escherichia coli) recognised four RRSV particle associated polypeptides of M(r) 67K, 46K, 43K and 26K and all except the 26K polypeptide were also highly immunoreactive to polyclonal antibodies raised against purified RRSV particles. Cleavage of the MBP-S8 fusion polypeptide with protease Factor X produced the expected 40K MBP and two polypeptides of apparent M(r) 46K and 26K. Antibodies to purified RRSV particles reacted strongly with the intact fusion protein and the 46K cleavage product but weakly to the 26K product. Furthermore, in vitro transcription and translation of the S8 coding region revealed a post-translational self cleavage of the 67K polypeptide to 46K and 26K products. These data indicate that S8 encodes a structural polypeptide, the majority of which is auto- catalytically cleaved to 26K and 46K proteins. The data also suggest that the 26K protein is the self cleaving protease and that the 46K product is further processed or undergoes stable conformational changes to a ~43K major capsid protein.

Why Australian and Indian researchers should collaborate to advance wound management innovation

In 2011, 366 million people suffered from diabetes worldwide, resulting in 4.6 million deaths at a cost of US$465 billion in direct healthcare expenditures1. India has the world’s second largest diabetic population at 61.8 million (8.3% of total population)1, while in Australia 8.1% of the population have been diagnosed with diabetes1. Diabetic foot ulcers (DFUs) affect up to 25% of diabetic patients, precipitating 85% of all diabetic amputations2,3. DFUs have significant social and economic impacts associated with increased hospitalisation rates, cost of care, and the reduced capacity of patients and carers to work. In isolated regions of Australia and India the incidence of DFU and associated infection is substantially increased, resulting in hospitalisation rates up to 4- fold that of major cities...

Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer

Failure to efficiently induce apoptosis contributes to cisplatin resistance in non-small-cell lung cancer (NSCLC). Although BCL-2-associated X protein (BAX) and BCL-2 antagonist killer (BAK) are critical regulators of the mitochondrial apoptosis pathway, their requirement has not been robustly established in relation to cisplatin. Here, we show that cisplatin can efficiently bypass mitochondrial apoptosis block caused by loss of BAX and BAK, via activation of the extrinsic death receptor pathway in some model cell lines. Apoptosis resistance following cisplatin can only be observed when both extrinsic and intrinsic pathways are blocked, consistent with redundancy between mitochondrial and death receptor pathways in cisplatin-induced apoptosis. In H460 NSCLC cells, caspase-8 cleavage was shown to be induced by cisplatin and is dependent on death receptor 4, death receptor 5, Fas-associated protein with death domain, acid sphingomyelinase and ceramide synthesis. In contrast, cisplatin-resistant cells fail to activate caspase-8 via this pathway despite conserving sensitivity to death ligand-driven activation. Accordingly, caspase-8 activation block acquired during cisplatin resistance, can be bypassed by death receptor agonism.

Prognostic and therapeutic relevance of FLIP and procaspase-8 overexpression in non-small cell lung cancer

Non-small cell lung carcinoma remains by far the leading cause of cancer-related deaths worldwide. Overexpression of FLIP, which blocks the extrinsic apoptotic pathway by inhibiting caspase-8 activation, has been identified in various cancers. We investigated FLIP and procaspase-8 expression in NSCLC and the effect of HDAC inhibitors on FLIP expression, activation of caspase-8 and drug resistance in NSCLC and normal lung cell line models. Immunohistochemical analysis of cytoplasmic and nuclear FLIP and procaspase-8 protein expression was carried out using a novel digital pathology approach. Both FLIP and procaspase-8 were found to be significantly overexpressed in tumours, and importantly, high cytoplasmic expression of FLIP significantly correlated with shorter overall survival. Treatment with HDAC inhibitors targeting HDAC1-3 downregulated FLIP expression predominantly via post-transcriptional mechanisms, and this resulted in death receptor- and caspase-8-dependent apoptosis in NSCLC cells, but not normal lung cells. In addition, HDAC inhibitors synergized with TRAIL and cisplatin in NSCLC cells in a FLIP- and caspase-8-dependent manner. Thus, FLIP and procaspase-8 are overexpressed in NSCLC, and high cytoplasmic FLIP expression is indicative of poor prognosis. Targeting high FLIP expression using HDAC1-3 selective inhibitors such as entinostat to exploit high procaspase-8 expression in NSCLC has promising therapeutic potential, particularly when used in combination with TRAIL receptor-targeted agents.

Voltammetric, spectroscopic, and microscopic investigations of electrocrystallized forms of semiconducting AgTCNQ (TCNQ=7,7,8,8-tetracyanoquinodimethane) exhibiting different morphologies and colors

Chemically synthesized AgTCNQ exists in two forms that differ in their morphologies (needles and microcrystals) and colors (red and blue). It is now shown that both forms exhibit essentially indistinguishable X-ray diffraction, spectroscopic, and thermochemical data, implying that they are not separate phases, as implied in some literature. Electrochemical reduction of TCNQ((MeCN)) in the presence of Ag+((MeCN)) generates both red and blue AgTCNQ. On glassy carbon, platinum, or indium tin oxide electrodes and at relatively positive deposition potentials, slow growth of high aspect ratio, red needle AgTCNQ crystals occurs. After longer times and at more negative deposition potentials, blue microcrystalline AgTCNQ thin films are favored. Blue AgTCNQ is postulated to be generated via reduction of a Ag+\[(TCNQ(center dot-))(TCNQ)]((MeCN)) intermediate. At even more negative potentials, Ag-(metal) formation inhibits further growth of AgTCNQ. On a gold electrode, Ag-(metal)) deposition occurs at more positive potentials than on the other electrode materials examined. However, surface plasmon resonance data indicate (hat a small potential region is available between the stripping of Ag-(metal)) and the oxidation of TCNQ(center dot-)(MeCN) back to TCNQ(MeCN) where AgTCNQ may form. AgTCNQ in both the red and blue forms also can be prepared electrochemically on a TCNQ((s)) modified electrode in -0.1 M AgNO3(aq) where deposition of Ag(m,,,I) onto the TCNQ((s)) crystals allows a charge transfer process to occur. However, the morphology formed in this solid-solid phase transformation is more difficult to control.

Where are all the female participants in sports and exercise medicine research?

The aim of this study is to estimate the ratio of male and female participants in Sports and Exercise Medicine research. Original research articles published in three major Sports and Exercise Medicine journals (Medicine and Science in Sport and Exercise, British Journal of Sports Medicine and American Journal of Sports Medicine) over a three year period were examined. Each article was screened to determine the following: total number of participants, the number of female participants and the number of male participants. The percentage of females and males per article in each of the journals was also calculated. Cross tabulations and Chi square analysis were used to compare the gender representation of participants within each of the journals. Data were extracted from 1, 382 articles involving a total of 6, 076, 705 participants. 2, 366, 998 (39%) participants were female and 3, 709, 707 (61%) male. The average percentage of female participants per article across the journals ranged from 35-37%. Females were significantly under-represented across all of the journals (X2 =23566, df=2, p<0.00001). There were no significant differences between the three journals. In conclusion, Sports and Exercise Medicine practitioners should be cognisant of sexual dimorphism and gender disparity in the current literature.

Solid-state structure of some substituted hexahydro-1,4:5,8-diepoxy­naphthalenes

The structure of several carboxy-substituted hexahydro-1,4:5,8-diepoxynaphthalenes have been solved with X-ray crystallography, in some cases confirming previously contentious structures. The compounds of interest are constructed in efficient one-step 2 × [4+2] cycloaddition reactions from furan and acetylene carboxylate derivatives.

Competitive charge-remote and anion-induced fragmentations of the non-8-enoate anion. A charge-remote reaction which co-occurs with hydrogen scrambling

The non-8-enoate anion undergoes losses of the elements of C3H6, C4H8 and C6H12 on collisional activation, The mechanisms of these processes have been elucidated by a combination of product ion and labelling (H-2 and C-13) studies, together with a neutralisation reionisation mass spectrometric study. These studies allow the following conclusions to be made. (i) The loss of C3H6 involves cyclisation of the enolate anion of non-8-enoic acid to yield the cyclopentyl carboxylate anion and propene. (ii) The loss of 'C4H8' is a charge-remote process (one which proceeds remote from the charged centre) which yields the pent-4-enoate anion, butadiene and dihydrogen. This process co-occurs and competes with complex H scrambling. (iii) The major loss of 'C6H12' occurs primarily by a charge-remote process yielding the acrylate anion, hexa-1,5-diene and dihydrogen, but in this case no H scrambling accompanies the process. (iv) It is argued that the major reason why the two charge-remote processes occur in preference to anion-induced losses of but-l-ene and hex-l-ene from the respective 4- and 2-anions is that although these anions are formed, they have alternative and lower energy fragmentation pathways than those involving the losses of but-l-ene and hex-l-ene; viz. the transient 4-anion undergoes facile proton transfer to yield a more stable anion, whereas the 2-(enolate) anion undergoes preferential cyclisation followed by elimination of propene [see (i) above].