The effect of hyperthermia on the phosphoinositide signalling system of tumour cells

The effect of heat on the phosphoinositide signalling pathway was investigated in CHO-K1 cells and WRK-1 cells. Heat caused a decrease in 1,2-diacylglycerol (1,2- DAG) levels but did not have any effect on monoacylglycerol (MAG) levels in both cell types. On the other hand, an increase in triacylglycerol (TAG) level was observed in both cell lines. This heat-induced decrease in 1,2-DAG level in WRK-1 cells was not due to an increase in turnover rate of 1,2-DAG to phosphatidic acid (PA) since the decrease in 1,2-DAG was not affected when cells were heated in the presence of die DAG kinase inhibitor, dioctanoylethylene glycol (diC(_8)EG). The increase in TAG level may be due to a rapid, he at-induced increase in TAG synthesis from 1,2-DAG, thus leading to decreased levels of 1,2-DAG. Heat also led to an increase in inositol bisphosphate (InsP(_2)) and inositol trisphosphate (InsP(_3)) but not inositol monophosphate (InsP(_1)) or higher inositol phosphate (InsP(_4/5/6)) levels in WRK-1 cells. The increase in InsP(_2) and InsP(_3) was both temperature and heating time-dependent. A transient increase in InsP(_3) was observed at 11 min, and did not require extracellular calcium nor did it depend on the heat-induced increase in cytosolic free calcium ([Ca(^2+)]i). The magnitude of the heat- induced increase in InsP(_3) was comparable to that obtained upon incubation in AIF(_4). Stimulation of WRK-1 cells with vasopressin at 45ºC distorted the pattern of inositol phosphate metabolism. However, the vasopressin-sensitive phosphoinositide signalling pathway remained intact after a severe heat shock, sufficient to lead to the death of greater than 95% of the cells. Heat also led to an increase in [Ca(^2+)]i in WRK-1 cells which came primarily (solely?) from calcium influx from the extracellular medium. This influx was unlikely to occur through voltage-gated calcium channels because calcium channel blockers, such as La(^3+) and nifedipine, did not inhibit the heat-induced elevation in [Ca(^2+)]i. This heat-induced increase in [Ca(^2+)]i may have a protective role in hyperthermic cell death

Adaptive reuse of heritage architecture and its external effects on sustainable built environment—Hedonic pricing model and case studies in Hong Kong

The integration of the sustainable development perspective into the discussion of heritage conservation by UNESCO in 2015 represents an acknowledgement of the values of heritage conservation in the agenda of sustainable development. This paper aims to provide empirical evidence regarding how heritage conservation fits into the overall sustainable development in Hong Kong by examining the external effects generated by architectural heritage conservation onto their adjacent neighborhood. By two adaptive reuse heritage case studies with respective hedonic pricing analysis on their adjacent property prices, this paper presents the results of how residential property prices have been increased as a result of heritage adaptive reuse. The analysis suggests that an established heritage grading mechanism along with a socially inclusive conservation approach with community stakeholders not only maintains the authenticity of the cultural heritage, but also brings substantial social and economic benefits to the neighboring communities. The research findings add new knowledge

Realization of Woodpile Structure Using Optical Interference Holography

We report the use of a (4+1)-beam optical interference holography technique to fabricate woodpile structures in photo-resists. The configuration consists of 4 linear polarized side beams arranged symmetrically around a circular polarized central beam with all the beams from the same half space, making it easily accessible experimentally. The fabricated woodpile structures are in good agreement with model simulations. Furthermore, woodpiles with the diamond symmetry are also obtained by exploiting the deformations of the photo-resists. Directional bandgaps in the visible range are also observed for the samples with and without the correct stacking of the woodpile structures.Comment: 9 pages and three figure

Chiral microstructures (spirals) fabrication by holographic lithography

We present an optical interference model to create chiral microstructures (spirals) and its realization in photoresist using holographic lithography. The model is based on the interference of six equally-spaced circumpolar linear polarized side beams and a circular polarized central beam. The pitch and separation of the spirals can be varied by changing the angle between the side beams and the central beam. The realization of the model is carried out using the 325 nm line of a He-Cd laser and spirals of sub-micron size are fabricated in photoresist.Comment: 6 page

The protection of Victoria Harbour in Hong Kong : an analysis of civic engagement strategies

published_or_final_versionPolitics and Public AdministrationMasterMaster of Public Administratio

Exogenous Expression of Human apoA-I Enhances Cardiac Differentiation of Pluripotent Stem Cells

The cardioprotective effects of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA-I) are well documented, but their effects in the direction of the cardiac differentiation of embryonic stem cells are unknown. We evaluated the effects of exogenous apoA-I expression on cardiac differentiation of ESCs and maturation of ESC-derived cardiomyocytes. We stably over-expressed full-length human apoA-I cDNA with lentivirus (LV)-mediated gene transfer in undifferentiated mouse ESCs and human induced pluripotent stem cells. Upon cardiac differentiation, we observed a significantly higher percentage of beating embryoid bodies, an increased number of cardiomyocytes as determined by flow cytometry, and expression of cardiac markers including α-myosin heavy chain, β-myosin heavy chain and myosin light chain 2 ventricular transcripts in LV-apoA-I transduced ESCs compared with control (LV-GFP). In the presence of noggin, a BMP4 antagonist, activation of BMP4-SMAD signaling cascade in apoA-I transduced ESCs completely abolished the apoA-I stimulated cardiac differentiation. Furthermore, co-application of recombinant apoA-I and BMP4 synergistically increased the percentage of beating EBs derived from untransduced D3 ESCs. These together suggests that that pro-cardiogenic apoA-I is mediated via the BMP4-SMAD signaling pathway. Functionally, cardiomyocytes derived from the apoA-I-transduced cells exhibited improved calcium handling properties in both non-caffeine and caffeine-induced calcium transient, suggesting that apoA-I plays a role in enhancing cardiac maturation. This increased cardiac differentiation and maturation has also been observed in human iPSCs, providing further evidence of the beneficial effects of apoA-I in promoting cardiac differentiation. In Conclusion, we present novel experimental evidence that apoA-I enhances cardiac differentiation of ESCs and iPSCs and promotes maturation of the calcium handling property of ESC-derived cardiomyocytes via the BMP4/SMAD signaling pathway

Enhanced progesterone support during stimulated cycles of transvaginal follicular aspiration improves bovine in vitro embryo production

The in vitro production (IVP) of cattle embryos requires that germinal-vesicle stage oocytes undergo a period of maturation in vitro prior to fertilization and culture to the blastocyst stage. Success of IVP in taurine cattle is enhanced following ovarian stimulation prior to oocyte retrieval (OPU), particularly if preceded by a short period of FSH withdrawal (‘coasting’). However, evidence regarding the importance of progesterone (P4) support during OPU-IVP is equivocal. The current study, therefore, determined the effects of increased peripheral P4 concentrations during FSH-stimulated (‘coasted’) cycles of OPU. Progesterone support was provided by either an active corpus luteum (CL) and/or one of two intravaginal P4 releasing devices (i.e., CIDR® [1.38g P4] or PRID® Delta [1.55g P4]). Expt. 1 established an initial estrus prior to OPU, allowing CL formation (single luteal phase) spanning the first two of five cycles of OPU; the remaining three cycles were supported by either a CIDR® or PRID® Delta. Expt. 2 commenced with two cycles of dominant follicle removal (including prostaglandin F2α) undertaken seven days apart prior to six cycles of OPU. The absence of a CL meant that these cycles were supported only by a CIDR® or PRID® Delta. As each experiment involved several sequential cycles of OPU, the cumulative effects of device use on vaginal discharges were also assessed. Each experiment involved 10 sexually mature Holstein heifers. In the absence of a CL, peak plasma P4 concentrations were greater (P = 0.002) for the PRID® Delta (4.3 ± 0.22) than for the CIDR® (2.9 ± 0.22). In Expt. 1 there was an interaction (P < 0.05) between CL presence at OPU and P4 device on Day 8 blastocyst yields, indicating an effect of P4 device only when the CL was absent. The percentage hatching/hatched blastocysts of matured oocytes for the CIDR® and PRID® Delta was 44.3 ± 5.04 and 41.0 ± 5.40 in the presence, and 17.1 ± 3.48 and 42.2 ± 3.76 in the absence, of a CL (P = 0.018). Combined analyses of data from Expt. 1 and 2, when no CL was present, confirmed that Day 8 blastocyst yields were greater (P = 0.022) for the PRID® Delta than the CIDR®. Vaginal discharge scores were higher (P < 0.001) for the PRID® Delta than the CIDR® in Expt. 1 but not in Expt 2; however scores were low, did not increase with repeated use, and thus were deemed of no clinical or welfare concern. In conclusion, enhanced P4 support during FSH-stimulated cycles of OPU-IVP can improve in vitro embryo development

Mindfulness-based cognitive therapy v. group psychoeducation for people with generalised anxiety disorder: randomised controlled trial

Background: Research suggests that an 8-week mindfulness-based cognitive therapy (MBCT) course may be effective for generalised anxiety disorder (GAD). Aims: To compare changes in anxiety levels among participants with GAD randomly assigned to MBCT, cognitive–behavioural therapy-based psychoeducation and usual care. Method: In total, 182 participants with GAD were recruited (trial registration number: CUHK_CCT00267) and assigned to the three groups and followed for 5 months after baseline assessment with the two intervention groups followed for an additional 6 months. Primary outcomes were anxiety and worry levels. Results: Linear mixed models demonstrated significant group × time interaction (F(4,148) = 5.10, P = 0.001) effects for decreased anxiety for both the intervention groups relative to usual care. Significant group × time interaction effects were observed for worry and depressive symptoms and mental health-related quality of life for the psychoeducation group only. Conclusions: These results suggest that both of the interventions appear to be superior to usual care for the reduction of anxiety symptoms

The predictive value of G8 and the Cancer and aging research group chemotherapy toxicity tool in treatment-related toxicity in older Chinese patients with cancer

Introduction: Older patients experience a higher risk of treatment-related toxicity (TRT). The G8 screening tool was developed to separate cancer older patients fit to receive standard treatment from those who are frail and experiencing functional decline due to reduced organ function and multiple comorbidities. The Cancer and Aging Research Group chemotherapy toxicity tool (CARG-tt) questionnaire was developed to predict chemotherapy toxicity in geriatric patients. This prospective observational study evaluated the performance of G8 and CARG-tt in predicting severe TRT in older Chinese cancer patients. Methods: Chinese patients aged ≥65 with a diagnosis of solid malignancy and scheduled to receive anti-cancer treatment (chemotherapy or targeted therapy) were enrolled from March 2016 to July 2017 at the Department of Clinical Oncology at Queen Mary Hospital in Hong Kong. All patients completed the G8 and CARG-tt screening and pre-treatment assessments before starting treatment. Patients were monitored for any severe TRT, which was defined by grades 3–5 using the National Cancer Institute's Common Terminology Criteria for Adverse Events v4.03, treatment discontinuation, or unexpected hospitalization from starting to 30 days after treatment. Results: A total of 259 patients (male: 154, 59.5%; median age: 73.4, age range: 65–93) were enrolled in the study. Two hundred and ten (81.1%) patients received chemotherapy while the rest (n = 49, 18.9%) received targeted therapy. Overall, 146 patients (56.8%) experienced severe TRT. The mean G8 score was 12.4 (SD: 2.8). The G8 score had a significant association with unexpected admission (cutoff: 14, 41.3% vs. 26.5%, p = 0.03) but not significant in other types of TRTs. The mean CARG-tt score was 7.67 (SD: 3.7); it was not associated with severe TRTs. Conclusions: The G8 and CARG-tt demonstrated a weak prediction of severe TRT in older Chinese cancer patients. Future studies need to develop predictive tools for TRT in patients receiving novel antineoplastic therapies, with a focus on subgroup analysis for different populations

Developmental, cytogenetic and epigenetic consequences of removing complex proteins and adding melatonin during in vitro maturation of bovine oocytes

BackgroundIn vitro maturation (IVM) of germinal vesicle intact oocytes prior to in vitro fertilization (IVF) is practiced widely in animals. In human assisted reproduction it is generally reserved for fertility preservation or where ovarian stimulation is contraindicated. Standard practice incorporates complex proteins (CP), in the form of serum and/or albumin, into IVM media to mimic the ovarian follicle environment. However, the undefined nature of CP, together with batch variation and ethical concerns regarding their origin, necessitate the development of more defined formulations. A known component of follicular fluid, melatonin, has multifaceted roles including that of a metabolic regulator and antioxidant. In certain circumstances it can enhance oocyte maturation. At this stage in development, the germinal-vesicle intact oocyte is prone to aneuploidy and epigenetic dysregulation.ObjectivesTo determine the developmental, cytogenetic and epigenetic consequences of removing CP and including melatonin during bovine IVM.Materials and methodsThe study comprised a 2 x 2 factorial arrangement comparing (i) the inclusion or exclusion of CP, and (ii) the addition (100 nM) or omission of melatonin, during IVM. Cumulus-oocyte complexes (COCs) were retrieved from stimulated cycles. Following IVM and IVF, putative zygotes were cultured to Day 8 in standard media. RNAseq was performed on isolated cumulus cells, cytogenetic analyses (SNP-based algorithms) on isolated trophectoderm cells, and DNA methylation analysis (reduced representation bisulfite sequencing) on isolated cells of the inner-cell mass.ResultsRemoval of CP during IVM led to modest reductions in blastocyst development, whilst added melatonin was beneficial in the presence but detrimental in the absence of CP. The composition of IVM media did not affect the nature or incidence of chromosomal abnormalities but cumulus-cell transcript expression indicated altered metabolism (primarily lipid) in COCs. These effects preceded the establishment of distinct metabolic and epigenetic signatures several days later in expanded and hatching blastocysts.ConclusionsThese findings highlight the importance of lipid, particularly sterol, metabolism by the COC during IVM. They lay the foundation for future studies that seek to develop chemically defined systems of IVM for the generation of transferrable embryos that are both cytogenetically and epigenetically normal