Different cis-regulatory DNA elements mediate developmental stage- and tissue-specific expression of the human COL2A1 gene in transgenic mice

Expression of the type II collagen gene (human COL2A1, mouse Col2a1) heralds the differentiation of chondrocytes. It is also expressed in progenitor cells of some nonchondrogenic tissues during embryogenesis. DNA sequences in the 5' flanking region and intron 1 are known to control tissue- specific expression in vitro, but the regulation of COL2A1 expression in vivo is not clearly understood. We have tested the regulatory activity of DNA sequences from COL2A1 on the expression of a lacZ reporter gene in transgenic mice. We have found that type II collagen characteristic expression of the transgene requires the enhancer activity of a 309-bp fragment (+2,388 to +2,696) in intron 1 in conjunction with 6.1-kb 5' sequences. Different regulatory elements were found in the 1.6-kb region (+701 to +2,387) of intron 1 which only needs 90-bp 5' sequences for tissue-specific expression in different components of the developing cartilaginous skeleton. Distinct positive and negative regulatory elements act together to control tissue- specific transgene expression in the developing midbrain neuroepithelium. Positive elements affecting expression in the midbrain were found in the region from -90 to -1,500 and from +701 to +2,387, whereas negatively acting elements were detected in the regions from -1,500 to -6,100 and +2,388 to +2,855.published_or_final_versio

Pericardial effusion after open heart surgery for congenital heart disease

Objectives: To determine the prevalence and time course of pericardial effusion after open heart surgery for congenital heart diseases and to identify predisposing risk factors. Design and patients: Prospective assessment of development of pericardial effusion in 336 patients (163 males) undergoing open heart surgery for congenital heart disease by serial echocardiography on days 5, 7, 14, 21, and 28 postoperatively. Setting: Tertiary paediatric cardiac centre. Results: The prevalence of pericardial effusion was 23% (77 of 336). Of the 77 patients who developed effusion, 43 (56%) had moderate to large effusions and 18 (23%) were symptomatic. Patients who had a large amount of effusion were more likely to be symptomatic than those with only a small to moderate amount (47.4% v 15.5%, p = 0.01). The mean (SD) onset of pericardial effusion was 11 (7) days after surgery, with 97% (75 of 77) of cases being diagnosed on or before day 28 after surgery. The prevalence of effusion after Fontan-type procedures (60%, 6 of 10) was significantly higher than that after other types of cardiac surgery: repair of left to right shunts (22.1%, 43 of 125), repair of lesions with right ventricular outflow tract obstruction (22.6%, 19 of 84), arterial switch operation (6.7%, 1 of 15), and miscellaneous procedures (25%, 8 of 32) (p = 0.037). Univariate analyses showed that female patients (p = 0.009) and those receiving warfarin (p = 0.002) had increased risk of postoperative pericardial effusion. A greater pericardial drain output in the first four hours after surgery also tended to be significant (p = 0.056). Multivariate logistic regression similarly identified warfarin treatment (β = 1.73, p = 0.009) and female sex (β for male = -0.63, p = 0.037) as significant determinants. Conclusions: Pericardial effusion occurs commonly after open heart surgery for congenital heart disease. Serial echocardiographic monitoring up to 28 days postoperatively is indicated in selected high risk patients such as those with symptoms of postpericardiotomy syndrome and those given warfarin.published_or_final_versio

Asymmetric-detection time-stretch optical microscopy (ATOM) for high-contrast and high-speed microfluidic cellular imaging

High-throughput cellular imaging is acclaimed as captivating yet challenging in biomedical diagnostics. We have demonstrated a new imaging modality, asymmetric-detection time-stretch optical microscopy (ATOM), by incorporating a simple detection scheme which is a further advancement in time-stretch microscopy - a viable solution to achieve high-speed and high-throughput cellular imaging. Through the asymmetric-detection scheme in ATOM, the time-stretch image contrast is enhanced through accessing to the phase-gradient information. With the operation in the 1 μm wavelength range, we demonstrate high-resolution and high-contrast cellular imaging in ultrafast microfluidic flow (up to 10 m/s) by ATOM - achieving an imaging throughput equivalent to 100,000 cells/sec. © 2014 SPIE.published_or_final_versio

Adiponectin is protective against oxidative stress-induced cytotoxicity in amyloid-beta neurotoxicity

Oral PresentationBeta-amyloid (Aβ) neurotoxicity is important in Alzheimer’s disease (AD) pathogenesis. Aβ neurotoxicity causes oxidative stress, inflammation, and mitochondrial damage resulting in neuronal degeneration and death. Oxidative stress, inflammation, and mitochondrial failure are also pathophysiological mechanisms of type 2 diabetes mellitus (T2DM) which is characterised by insulin resistance. Interestingly, T2DM increases risk to develop AD which is associated with reduced neuronal insulin sensitivity (central insulin resistance). We studied the potential protective effect of adipon…published_or_final_versio

A Novel Liver-targeted Testosterone Therapy for Sarcopenia in Androgen Deprived Men With Prostate Cancer.

Objective: Androgen deprivation therapy (ADT) reduces muscle and bone mass, increasing frailty in men with prostate cancer. The liver mediates the whole body anabolic effects of testosterone. Based on first-pass metabolism, liver-targeted testosterone treatment (LTTT) entails oral delivery of a small dose of testosterone that does not raise peripheral blood testosterone levels. LTTT reduces blood urea and stimulates protein anabolism in hypogonadal men and postmenopausal women. We investigated whether LTTT prevents loss of lean and bone mass during ADT. Method: A 6-month, double-blind, placebo-controlled study of testosterone 40 mg/day in 50 men. Primary outcome measures were lean mass and bone mineral content (BMC). Testosterone, urea and prostate-specific antigen (PSA) were monitored. Patients were withdrawn if PSA exceeded 4 ng/mL. Results: 42 patients completed the study. Mean (95% CI) testosterone rose during LTTT but not placebo treatment [∆ 2.2 (1.3-3.0) vs -0.7 (-1.5 to 0.2) nmol/L; P < 0.01]. Mean PSA level did not change significantly during either treatment. Blood urea fell [∆ -0.4 (-0.9 to -0.1) mmol/L] during LTTT but not placebo [∆ 0.05 (-0.8 to 0.9) mmol/L]. BMC [∆ 49 (5 to 93) g; P < 0.02] and lean mass [∆ 0.8 (-0.1 to 1.7) kg; P = 0.04) increased compared to placebo. Five patients on LTTT withdrew from increased PSA levels, all returning to baseline levels. Conclusion: LTTT shows promise as a simple therapy for preventing sarcopenia and bone loss during ADT. LTTT may induce reversible PSA rise in some patients. Further studies are required to optimize LTTT dose in ADT. LTTT has potential application in other catabolic states in men and women

Interferometric time-stretch microscopy for ultrafast quantitative cellular and tissue imaging at 1 μm

Quantitative phase imaging (QPI) has been proven to be a powerful tool for label-free characterization of biological specimens. However, the imaging speed, largely limited by the image sensor technology, impedes its utility in applications where high-throughput screening and efficient big-data analysis are mandated. We here demonstrate interferometric time-stretch (iTS) microscopy for delivering ultrafast quantitative phase cellular and tissue imaging at an imaging line-scan rate >20 MHz-orders-of-magnitude faster than conventional QPI. Enabling an efficient time-stretch operation in the 1-mum wavelength window, we present an iTS microscope system for practical ultrafast QPI of fixed cells and tissue sections, as well as ultrafast flowing cells (at a flow speed of up to 8 ms). To the best of our knowledge, this is the first time that time-stretch imaging could reveal quantitative morphological information of cells and tissues with nanometer precision. As many parameters can be further extracted from the phase and can serve as the intrinsic biomarkers for disease diagnosis, iTS microscopy could find its niche in high-throughput and high-content cellular assays (e.g., imaging flow cytometry) as well as tissue refractometric imaging (e.g., whole-slide imaging for digital pathology).published_or_final_versio

Cognitive impairment in adiponectin-knockout mice

Oral Presentationpublished_or_final_versio

Large-Scale Surface Shape Sensing with Learning-Based Computational Mechanics

Proprioception, the ability to perceive one's own configuration and movement in space, enables organisms to safely and accurately interact with their environment and each other. The underlying sensory nerves that make this possible are highly dense and use sophisticated communication pathways to propagate signals from nerves in muscle, skin, and joints to the central nervous system wherein the organism can process and react to stimuli. In a step forward to realize robots with such perceptive capability, a flexible sensor framework that incorporates a novel modeling strategy, taking advantage of computational mechanics and machine learning, is proposed. The sensor framework on a large flexible sensor that transforms sparsely distributed strains into continuous surface is implemented. Finite element (FE) analysis is utilized to determine design parameters, while an FE model is built to enrich the morphological data used in the supervised training to achieve continuous surface reconstruction. A mapping between the local strain data and the enriched surface data is subsequently trained using ensemble learning. This hybrid approach enables real time, robust, and high‐order surface reconstruction. The sensing performance is evaluated in terms of accuracy, repeatability, and feasibility with numerous scenarios, which has not been demonstrated on such a large‐scale sensor before

Asymmetric-detection time-stretch optical microscopy (ATOM) for ultrafast high-contrast cellular imaging in flow

published_or_final_versio

Population dynamics of the Mantis Shrimp Oratosquilla oratoria before and after the Trawling Ban in Hong Kong's Coastal Waters

Poster presentation: P-53Fisheries & Marine Resources ManagementThrough studying population dynamics of marine benthic species, we can reveal the changes of their population size and structure in relation to environmental changes due to management intervention such as prohibition of trawling based fisheries. The results of population dynamics studies can also provide baseline information for stock assessment and sustainable management of the species. Due to the overexploitation of fishery resources, a territory-wide trawling ban has been implemented in Hong Kong waters ...postprin