Overexpression of proto-oncogene FBI-1 activates membrane type 1-matrix metalloproteinase in association with adverse outcome in ovarian cancers

<p>Abstract</p> <p>Background</p> <p>FBI-1 (factor that binds to the inducer of short transcripts of human immunodeficiency virus-1) is a member of the POK (POZ and Kruppel) family of transcription factors and play important roles in cellular differentiation and oncogenesis. Recent evidence suggests that FBI-1 is expressed at high levels in a subset of human lymphomas and some epithelial solid tumors. However, the function of FBI-1 in human ovarian cancers remains elusive.</p> <p>Results</p> <p>In this study, we investigated the role of FBI-1 in human ovarian cancers, in particularly, its function in cancer cell invasion via modulating membrane type 1-matrix metalloproteinase (MT1-MMP). Significantly higher FBI-1 protein and mRNA expression levels were demonstrated in ovarian cancers samples and cell lines compared with borderline tumors and benign cystadenomas. Increased FBI-1 mRNA expression was correlated significantly with gene amplification (P = 0.037). Moreover, higher FBI-1 expression was found in metastatic foci (P = 0.036) and malignant ascites (P = 0.021), and was significantly associated with advanced stage (P = 0.012), shorter overall survival (P = 0.032) and disease-free survival (P = 0.016). <it>In vitro</it>, overexpressed FBI-1 significantly enhanced cell migration and invasion both in OVCA 420 and SKOV-3 ovarian carcinoma cells, irrespective of <it>p53 </it>status, accompanied with elevated expression of MT1-MMP, but not MMP-2 or TIMP-2. Moreover, knockdown of MT1-MMP abolished FBI-1-mediated cell migration and invasion. Conversely, stable knockdown of FBI-1 remarkably reduced the motility of these cells with decreased expression of MT1-MMP. Promoter assay and chromatin immunoprecipitation study indicated that FBI-1 could directly interact with the promoter spanning ~600bp of the 5'-flanking sequence of MT1-MMP and enhanced its expression in a dose-dependent manner. Furthermore, stable knockdown and ectopic expression of FBI-1 decreased and increased cell proliferation respectively in OVCA 420, but not in the p53 null SKOV-3 cells.</p> <p>Conclusions</p> <p>Our results suggested an important role of FBI-1 in ovarian cancer cell proliferation, cell mobility, and invasiveness, and that FBI-1 can be a potential target of chemotherapy.</p

Pseudofam: the pseudogene families database

Pseudofam (http://pseudofam.pseudogene.org) is a database of pseudogene families based on the protein families from the Pfam database. It provides resources for analyzing the family structure of pseudogenes including query tools, statistical summaries and sequence alignments. The current version of Pseudofam contains more than 125 000 pseudogenes identified from 10 eukaryotic genomes and aligned within nearly 3000 families (approximately one-third of the total families in PfamA). Pseudofam uses a large-scale parallelized homology search algorithm (implemented as an extension of the PseudoPipe pipeline) to identify pseudogenes. Each identified pseudogene is assigned to its parent protein family and subsequently aligned to each other by transferring the parent domain alignments from the Pfam family. Pseudogenes are also given additional annotation based on an ontology, reflecting their mode of creation and subsequent history. In particular, our annotation highlights the association of pseudogene families with genomic features, such as segmental duplications. In addition, pseudogene families are associated with key statistics, which identify outlier families with an unusual degree of pseudogenization. The statistics also show how the number of genes and pseudogenes in families correlates across different species. Overall, they highlight the fact that housekeeping families tend to be enriched with a large number of pseudogenes

Towards a global partnership model in interprofessional education for cross-sector problem-solving

Objectives A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. Methods This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students’ data. Results We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest–posttest differences in students’ readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students’ social interaction anxiety after the IPE simulation. Conclusions The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

FBI-1 amplification in gestational trophoblastic disease

Gestational Trophoblastic Disease (GTD) encompasses a spectrum of disease that involves abnormal trophoblastic proliferation. It includes hydatidiform mole (HM), placental site trophoblastic tumor (PSTT), epithelioid trophoblastic tumor (ETT) and choriocarcinoma (CCA). While HMs are abnormal pregnancies with limited invasive potential, CCAs are true malignancies requiring chemotherapy. Although the majority of HM is resolved by surgical intervention, approximately 8-30% of them would develop into persistent GTD. In addition to that, being the most aggressive neoplasm in GTD, choriocarcinoma is a frankly malignant gestational trophoblastic neoplasm (GTN) that could be arisen from HM and could be fetal when widespread metastasis is developed. However, the underlying mechanisms of this disease progression are still unclear. FBI-1 (Factor that Binds to Inducer of Short Transcripts (IST) protein 1) is a transcription factor that has been observed to be overexpressed in various types of human cancers. Recently, overexpression of FBI-1 is also reported in GTD and also in association with GTN development. However, the causes of FBI-1 overexpression in GTD are still unclear. This study aims to investigate gene amplification as a possible cause of FBI-1 overexpression in GTD. A quantitative real time PCR (qPCR) assay was established and was used to investigate ZBTB7A (the gene encoding FBI-1) amplification in GTD cell lines and clinical samples. Using our qPCR assay, we demonstrated that ZBTB7A is not amplified in the CCA cell lines JEG-3 and JAR, in comparison with an immortalized trophoblast cell line HTR-8/SVneo. Testing ZBTB7A amplification in clinical samples also obtained similar findings although overexpression of FBI-1 was demonstrated in our previous studies. This is the first report illustrating absence of ZBTB7A amplification in cells with FBI-1 overexpression. There are other techniques that can detect gene amplification and/or other genetic and epigenetic mechanisms that may govern FBI-1 expression in GTD. Further studies will be worthwhile to pursue as FBI-1 is a potential target for cancer therapy.published_or_final_versionPathologyMasterMaster of Medical Science

Organic Optical Sensor Based on Monolithic Integration of Organic Electronic Devices

A novel organic optical sensor that integrates a front organic light-emitting diode (OLED) and an organic photodiode (OPD) is demonstrated. The stripe-shaped cathode is used in the OLED components to create light signals, while the space between the stripe-shaped cathodes serves as the detection window for integrated OPD units. A MoO3 (5 nm)/Ag (15 nm) bi-layer inter-electrode is interposed between the vertically stacked OLED and OPD units, serving simultaneously as the cathode for the front OLED and an anode for the upper OPD units in the sensor. In the integrated sensor, the emission of the OLED units is confined by the area of the opaque stripe-shaped cathodes, optimized to maximize the reflected light passing through the window space for detection by the OPD components. This can ensure high OLED emission output, increasing the signal/noise ratio. The design and fabrication flexibility of an integrated OLED/OPD device also has low cost benefits, and is light weight and ultra-thin, making it possible for application in wearable units, finger print identification, image sensors, smart light sources, and compact information systems

Sub-Wavelength Imaging from Multilayer Superlens

Multilayer superlens has been reported that it had advantages over the original single slab superlens [1]. In this work, single silver layer and Ag-SiO2 multilayer superlens devices working at wavelength of 365 nm were fabricated using standard photolithography method. Grating object with sub-wavelength resolution could be resolved through both kinds of superlens with working distance up to 128nm. However, Ag-SiO2 multilayer superlens shows higher transmittance and image contrasts than the single silver layer one, this result verifies the theoretical results in Ref. [1]

The formation of a charge layer at the interface of GaMnAs and an organic material

The interface formed between the ferromagnetic semiconductor GaMnAs and the organic semiconductor N,N$^\prime$-diphenyl-N,N$^\prime$-bis(1-naphthyl)(1,1$^\prime$-biphenyl)-4,4$^\prime$-diamine (NPB) was investigated using current transport measurement and ultraviolet photoemission spectroscopy (UPS). The hole injection barrier at a GaMnAs and NPB interface was measured as 0.77 eV by modelling the measured current density-voltage (J-V) characteristics in a GaMnAs$/$NPB$/$Al structured device. The vacuum level shift at a GaMnAs$/$NPB interface was deduced to be 0.54 eV, indicating that a dipole layer exists at the interface. A UPS study gave a vacuum level shift of 0.53 eV and a band offset between the GaMnAs valence band and the highest occupied molecular orbital of NPB of 0.79 eV, in good agreement with the results of J-V measurements. We attribute the vacuum level shift to charge transfer across the interface

3,4,9,10-Perylenetetracarboxylicdiimide as an interlayer for ultraviolet organic light emitting diodes

Ultraviolet organic light emitting diodes with 3,4,9,10-perylenetetracarboxylicdiimide (PTCDI) interlayer have been achieved. The emission spectrum and intensity were strongly dependent on the thickness of PTCDI interlayer, in spite of the fact that PTCDI has neither much lower HOMO nor much higher LUMO level, which is considered necessary for efficient charge blocking layers. The influence of PTCDI layer was investigated in three different device configurations and obtained results are discussed. For optimal device configuration, OLED with emission centered at 370 nm and turn-on voltage of 4.5 V is obtained