Relative abundance of full-length and truncated FOXP1 isoforms is associated with differential NFκB activity in Follicular Lymphoma

FOXP1 is a transcriptional repressor that has been proposed to repress the expression of some NFκB-responsive genes. Furthermore, truncated forms of FOXP1 have been associated with a subtype of Diffuse Large B-cell Lymphoma characterised by constitutive NFκB activity, indicating that they may inhibit this repression. We have shown that FL tumors have increased relative abundance of truncated FOXP1 isoforms and this is associated with increased expression of NFκB-associated genes. Our results provide strong evidence that relative FOXP1 isoform abundance is associated with NFκB activity in FL, and could potentially be used as a marker for this gene signature.

Differential gene expression in breast cancer cell lines and stroma-tumor differences in microdissected breast cancer biopsies revealed by display array analysis

To examine gene-expression patterning in late-stage breast cancer biopsies, we used a microdissection technique to separate tumor from the surrounding breast tissue or stroma. A DD-PCR protocol was then used to amplify expressed products, which were resolved using PAGE and used as probe to hybridize with representative human arrays and cDNA libraries. The probe derived from the tumor–stroma comparison was hybridized with a gene array and an arrayed cDNA library derived from a GCT of bone; 21 known genes or expressed sequence tags were detected, of which 17 showed differential expression. These included factors associated with epithelial to mesenchymal transition (vimentin), the cargo selection protein (TIP47) and the signal transducer and activator of transcription (STAT3). Northern blot analysis was used to confirm those genes also expressed by representative breast cancer cell lines. Notably, 6 genes of unknown function were restricted to tumor while the majority of stroma-associated genes were known. When applied to transformed breast cancer cell lines (MDA-MB-435 and T47D) that are known to have different metastatic potential, DD array analysis revealed a further 20 genes; 17 of these genes showed differential expression. Use of microdissection and the DD-PCR array protocol allowed us to identify factors whose localized expression within the breast may play a role in abnormal breast development or breast carcinogenesis.

Differential entrainment of neuroelectric delta oscillations in developmental dyslexia

Oscillatory entrainment to the speech signal is important for language processing, but has not yet been studied in developmental disorders of language. Developmental dyslexia, a difficulty in acquiring efficient reading skills linked to difficulties with phonology (the sound structure of language), has been associated with behavioural entrainment deficits. It has been proposed that the phonological ‘deficit’ that characterises dyslexia across languages is related to impaired auditory entrainment to speech at lower frequencies via neuroelectric oscillations (<10 Hz, ‘temporal sampling theory’). Impaired entrainment to temporal modulations at lower frequencies would affect the recovery of the prosodic and syllabic structure of speech. Here we investigated event-related oscillatory EEG activity and contingent negative variation (CNV) to auditory rhythmic tone streams delivered at frequencies within the delta band (2 Hz, 1.5 Hz), relevant to sampling stressed syllables in speech. Given prior behavioural entrainment findings at these rates, we predicted functionally atypical entrainment of delta oscillations in dyslexia. Participants performed a rhythmic expectancy task, detecting occasional white noise targets interspersed with tones occurring regularly at rates of 2 Hz or 1.5 Hz. Both groups showed significant entrainment of delta oscillations to the rhythmic stimulus stream, however the strength of inter-trial delta phase coherence (ITC, ‘phase locking’) and the CNV were both significantly weaker in dyslexics, suggestive of weaker entrainment and less preparatory brain activity. Both ITC strength and CNV amplitude were significantly related to individual differences in language processing and reading. Additionally, the instantaneous phase of prestimulus delta oscillation predicted behavioural responding (response time) for control participants only.

System level tests of transformer differential protection using an IEC 61850 process bus

The IEC 61850 family of standards for substation communication systems were released in the early 2000s, and include IEC 61850-8-1 and IEC 61850-9-2 that enable Ethernet to be used for process-level connections between transmission substation switchyards and control rooms. This paper presents an investigation of process bus protection performance, as the in-service behavior of multi-function process buses is largely unknown. An experimental approach was adopted that used a Real Time Digital Simulator and 'live' substation automation devices. The effect of sampling synchronization error and network traffic on transformer differential protection performance was assessed and compared to conventional hard-wired connections. Ethernet was used for all sampled value measurements, circuit breaker tripping, transformer tap-changer position reports and Precision Time Protocol synchronization of sampled value merging unit sampling. Test results showed that the protection relay under investigation operated correctly with process bus network traffic approaching 100% capacity. The protection system was not adversely affected by synchronizing errors significantly larger than the standards permit, suggesting these requirements may be overly conservative. This 'closed loop' approach, using substation automation hardware, validated the operation of protection relays under extreme conditions. Digital connections using a single shared Ethernet network outperformed conventional hard-wired solutions.

Spreading peak demand for urban rail transit through differential fare policy : a review of empirical evidence

More evenly spread demand for public transport throughout a day can reduce transit service provider‟s total asset and labour costs. A plausible peak spreading strategy is to increase peak fare and/or to reduce off-peak fare. This paper reviews relevant empirical studies for urban rail systems, as rail transit plays a key role in Australian urban passenger transport and experiences severe peak loading variability. The literature is categorised into four groups: a) passenger opinions on willingness to change time for travel, b) valuations of displacement time using stated preference technique, c) simulations of peak spreading based on trip scheduling models, and: d) real-world cases of peak spreading using differential fare. Policy prescription is advised to take into account impacts of traveller‟s time flexibility and joint effects of mode shifting and peak spreading. Although focusing on urban rail, arguments in this paper are relevant to public transport in general with values to researchers and practitioners.

Investigating the association between sun exposure and folate degradation in the human body

This thesis is the first study to investigate the associations between sun exposure and folate degradation in a group of childbearing age women in a high UV environment. It examined whether the degree of sun exposure experienced by women influenced blood folate levels following a period of folic acid supplementation and found a strong significant relationship between increased sun exposure and folate degradation. This relationship has strong implications for public health and the thesis has provided a foundation for further research in this area.

Differential pathologic variables and outcomes across the spectrum of adenocarcinoma of the esophagogastric junction

Background Adenocarcinoma of the esophagogastric junction (AEG) as described by Siewert et al. is classified as one entity in the latest (7th Edition) American Joint Cancer Committee/International Union Against Cancer (AJCC/UICC) manual, compared with the previous mix of esophageal and gastric staging systems. The origin of AEG tumors, esophageal or gastric, and their biology remain controversial, particularly for AEG type II (cardia) tumors. Methods We adapted a large prospective database (n = 520: 180 type I, 182 type II, 158 type III) to compare AEG tumors under the new TNM system Pathological variables associated with prognosis were compared (pT, pN, stage, differentiation, R status, lymphovascular invasion, perineural involvement, number of positive nodes, percent of positive nodes, and tumor length), as well as overall survival. Results Compared with AEG type I tumors, type II and type III tumors had significantly (p\0.05) more advanced pN stages, greater number and percentage of positive nodes, poorer differentiation, more radial margin involvement, and more perineural invasion. In AEG type I, 14/180 patients (8%) had[6 involved nodes (pN3), compared with 16 and 30% of patients classified type II and III, respectively. Median survival was significantly (p = 0.03) improved for type I patients (38 months) compared with those with tumors classified as type II (28 months) and type III (24 months). In multivariate analysis node positivity and pN staging but not AEG site had an impact on survival. Conclusions In this series AEG type I is associated with more favorable pathologic features and improved outcomes compared with AEG type II and III. This may reflect earlier diagnosis, but an alternative possibility, that type I may be a unique paradigm with more favorable biology, requires further study. © Société Internationale de Chirurgie 2010.

Degradation of simazine from aqueous solutions by diatomite-supported nanosized zero-valent iron composite materials

A novel composite material based on deposition of nanosized zero-valent iron (nZVI) particles on acid-leached diatomite was synthesised for the removal of a chlorinated contaminant in water. The nZVI /diatomite composites were characterized by X-ray diffraction, scanning electron microscopy, elemental analysis, transmission electron microscopy and X-ray photoelectron spectroscopy. Compared with the pure nZVI particles, better dispersion of nZVI particles on the surface or inside the pores of diatom shells was observed. The herbicide simazine was selected as the model chlorinated contaminant and the removal efficiency by nZVI /diatomite composite was compared with that of the pristine nZVI and commercial iron powder. It was found that the diatomite supported nZVI composite material prepared by centrifugation exhibits relatively better efficient activity in decomposition of simazine than commercial Fe, lab synthesized nZVI and composite material prepared via rotary evaporation, and the optimum experimental conditions were obtained based on a series of batch experiments. This study on immobilizing nZVI particles onto diatomite opens a new avenue for the practical application of nZVI and the diatomite-supported nanosized zero-valent iron composite materials have potential applications in environmental remediation.

The Enamovirus P0 protein is a silencing suppressor which inhibits local and systemic RNA silencing through AGO1 degradation

The P0 protein of poleroviruses and P1 protein of sobemoviruses suppress the plant's RNA silencing machinery. Here we identified a silencing suppressor protein (SSP), P0PE, in the Enamovirus Pea enation mosaic virus-1 (PEMV-1) and showed that it and the P0s of poleroviruses Potato leaf roll virus and Cereal yellow dwarf virus have strong local and systemic SSP activity, while the P1 of Sobemovirus Southern bean mosaic virus supresses systemic silencing. The nuclear localized P0PE has no discernable sequence conservation with known SSPs, but proved to be a strong suppressor of local silencing and a moderate suppressor of systemic silencing. Like the P0s from poleroviruses, P0PE destabilizes AGO1 and this action is mediated by an F-box-like domain. Therefore, despite the lack of any sequence similarity, the poleroviral and enamoviral SSPs have a conserved mode of action upon the RNA silencing machinery. © 2012 Elsevier Inc.

Differential Regulation of Clusterin Isoforms by the Androgen Receptor

Clusterin (CLU) was initially reported as an androgen-repressed gene which is now shown to be an androgen-regulated ATP-independent cytoprotective molecular chaperone. CLU binds to a wide variety of client proteins to potently inhibit stress-induced protein aggregation and chaperone or stabilise conformations of proteins at times of cell stress. CLU is an enigmatic protein, being ascribed both pro- and anti-apoptotic roles. Recent evidence has shown that both secreted (sCLU) and nuclear (nCLU) isoforms can be produced, and that protein function is dependent on the sub-cellular localisation. We and others have shown that sCLU is cytoprotective, while nCLU is pro-apoptotic. It now seems likely that the apparently dichotomous functions of CLU result from the expression of different but related CLU isoforms and splice variants, and that cell survival depends in part on the relative expression of pro- versus anti-apoptotic CLU proteins. In cancer cells, increased sCLU expression is associated with increased resistance to apoptotic triggers and treatment resistance. CLU is a stress-induced protein upregulated after apoptotic triggers like androgen ablation and chemotherapy. Treatment strategies targeting stress-associated increases in sCLU expression enhance treatment-induced apoptosis and delay the emergence of androgen independence. Differential regulation of CLU isoforms and splice variants by androgens may be a pathway whereby cancer cells develop treatment resistance and evade apoptosis.

The IL-6 response to Chlamydia from primary reproductive epithelial cells is highly variable and may be involved in differential susceptibility to the immunopathological consequences of chlamydial infection

Background Chlamydia trachomatis infection results in reproductive damage in some women. The process and factors involved in this immunopathology are not well understood. This study aimed to investigate the role of primary human cellular responses to chlamydial stress response proteases and chlamydial infection to further identify the immune processes involved in serious disease sequelae. Results Laboratory cell cultures and primary human reproductive epithelial cultures produced IL-6 in response to chlamydial stress response proteases (CtHtrA and CtTsp), UV inactivated Chlamydia, and live Chlamydia. The magnitude of the IL-6 response varied considerably (up to 1000 pg ml-1) across different primary human reproductive cultures. Thus different levels of IL-6 production by reproductive epithelia may be a determinant in disease outcome. Interestingly, co-culture models with either THP-1 cells or autologous primary human PBMC generally resulted in increased levels of IL-6, except in the case of live Chlamydia where the level of IL-6 was decreased compared to the epithelial cell culture only, suggesting this pathway may be able to be modulated by live Chlamydia. PBMC responses to the stress response proteases (CtTsp and CtHtrA) did not significantly vary for the different participant cohorts. Therefore, these proteases may possess conserved innate PAMPs. MAP kinases appeared to be involved in this IL-6 induction from human cells. Finally, we also demonstrated that IL-6 was induced by these proteins and Chlamydia from mouse primary reproductive cell cultures (BALB/C mice) and mouse laboratory cell models. Conclusions We have demonstrated that IL-6 may be a key factor for the chlamydial disease outcome in humans, given that primary human reproductive epithelial cell culture showed considerable variation in IL-6 response to Chlamydia or chlamydial proteins, and that the presence of live Chlamydia (but not UV killed) during co-culture resulted in a reduced IL-6 response suggesting this response may be moderated by the presence of the organism.

Differential expression of VEGF ligands and receptors in prostate cancer

BACKGROUND Prostate cancer disseminates to regional lymph nodes, however the molecular mechanisms responsible for lymph node metastasis are poorly understood. The vascular endothelial growth factor (VEGF) ligand and receptor family have been implicated in the growth and spread of prostate cancer via activation of the blood vasculature and lymphatic systems. The purpose of this study was to comprehensively examine the expression pattern of VEGF ligands and receptors in the glandular epithelium, stroma, lymphatic vasculature and blood vessels in prostate cancer. METHODS The localization of VEGF-A, VEGF-C, VEGF-D, VEGF receptor (VEGFR)-1, VEGFR-2, and VEGFR-3 was examined in cancerous and adjacent benign prostate tissue from 52 subjects representing various grades of prostate cancer. RESULTS Except for VEGFR-2, extensive staining was observed for all ligands and receptors in the prostate specimens. In epithelial cells, VEGF-A and VEGFR-1 expression was higher in tumor tissue compared to benign tissue. VEGF-D and VEGFR-3 expression was significantly higher in benign tissue compared to tumor in the stroma and the endothelium of lymphatic and blood vessels. In addition, the frequency of lymphatic vessels, but not blood vessels, was lower in tumor tissue compared with benign tissue. CONCLUSIONS These results suggest that activation of VEGFR-1 by VEGF-A within the carcinoma, and activation of lymphatic endothelial cell VEGFR-3 by VEGF-D within the adjacent benign stroma may be important signaling mechanisms involved in the progression and subsequent metastatic spread of prostate cancer. Thus inhibition of these pathways may contribute to therapeutic strategies for the management of prostate cancer.

Tuning the surface structure of nitrogen-doped TiO2Nanofibres : an effective method to rnhance photocatalytic activities of visible-light-driven green synthesis and degradation

Nitrogen-doped TiO2 nanofibres of anatase and TiO2(B) phases were synthesised by a reaction between titanate nanofibres of a layered structure and gaseous NH3 at 400–700 °C, following a different mechanism than that for the direct nitrogen doping from TiO2. The surface of the N-doped TiO2 nanofibres can be tuned by facial calcination in air to remove the surface-bonded N species, whereas the core remains N doped. N-Doped TiO2 nanofibres, only after calcination in air, became effective photocatalysts for the decomposition of sulforhodamine B under visible-light irradiation. The surface-oxidised surface layer was proven to be very effective for organic molecule adsorption, and the activation of oxygen molecules, whereas the remaining N-doped interior of the fibres strongly absorbed visible light, resulting in the generation of electrons and holes. The N-doped nanofibres were also used as supports of gold nanoparticle (Au NP) photocatalysts for visible-light-driven hydroamination of phenylacetylene with aniline. Phenylacetylene was activated on the N-doped surface of the nanofibres and aniline on the Au NPs. The Au NPs adsorbed on N-doped TiO2(B) nanofibres exhibited much better conversion (80 % of phenylacetylene) than when adsorbed on undoped fibres (46 %) at 40 °C and 95 % of the product is the desired imine. The surface N species can prevent the adsorption of O2 that is unfavourable for the hydroamination reaction, and thus, improve the photocatalytic activity. Removal of the surface N species resulted in a sharp decrease of the photocatalytic activity. These photocatalysts are feasible for practical applications, because they can be easily dispersed into solution and separated from a liquid by filtration, sedimentation or centrifugation due to their fibril morphology.

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.

The influence of school science teachers : the differential importance attributed by males and females to encouragement from science teachers

Research on the achievement and retention of female students in science and mathematics is located within a context of falling levels of participation in physical science and mathematics courses in Australian schools, and underrepresentation of females in some science, technology, engineering and mathematics (STEM) courses. The Interests and Recruitment in Science (IRIS) project is an international project that aims to contribute to understanding and improving recruitment, retention and gender equity in STEM higher education. Nearly 3500 first year students in 30 Australian universities responded to the IRIS survey of 5-point Likert items and open responses. This paper explores gender differences in first year university students’ responses to three questions about important influences on their course choice. The IRIS study found good teachers were rated highly by both males and females as influential in choosing STEM courses, and significantly higher numbers of females rated personal encouragement from senior high school science teacher as very important. In suggestions for addressing sex disparities in male-dominated STEM courses, more females indicated the importance of good teaching/encouragement and more females said (unspecified) encouragement. This study relates to the influence of school science teachers and results are discussed in relation to implications for science education.