Stringent requirement for spatial arrangement of extracellular matrix in supporting cell morphogenesis and differentiation

BACKGROUND: In vitro experiments on the functional roles of extracellular matrix (ECM) components usually involve the culture of cells on surfaces coated with purified ECM components. These experiments can seldom recuperate the spatial arrangement of ECM found in vivo. In this study, we have overcome this obstacle by using histological sections of bovine Achilles tendon as cell culture substrates. RESULTS: We found that tendon sections can be viewed as a pre-formed block of ECM in which the collagen fibrils exhibited a spatial regularity unraveled in any artificially constructed scaffold. By carving the tendon at different angles relative to its main axis, we created different surfaces with distinct spatial arrangements of collagen fibrils. To assess the cellular responses to these surfaces, human mesenchymal stem cells (MSCs) were directly cultured on these sections, hence exposed to the collagen with different spatial orientations. Cells seeded on longitudinal tendon sections adopted a highly elongated and aligned morphology, and expressed an increased level of tenomodulin, suggesting that the collagen fibrils present in this section provide a microenvironment that facilitates cell morphogenesis and differentiation. However, MSC elongation, alignment and induction of tenomodulin diminished dramatically even as the sectioned angle changed slightly. CONCLUSION: Our results suggest that cell functions are influenced not only by the type or concentration of ECM components, but also by the precise spatial arrangements of these molecules. The method developed in this study offers a simple and robust way for the studying of cell-ECM interactions, and opens many research avenues in the field of matrix biology.published_or_final_versio

Systemic lupus erythematosus (SLE) is associated with telomerase activation

published_or_final_versio

Berberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: The cellular mechanism

Extensive studies have revealed that berberine, a small molecule derived from Coptidis rhizoma (Huanglian in Chinese) and many other plants, has strong anti-tumor properties. To better understand berberine-induced cell death and its underlying mechanisms in cancer, we examined autophagy and apoptosis in the human hepatic carcinoma cell lines HepG2 and MHCC97-L. The results of this study indicate that berberine can induce both autophagy and apoptosis in hepatocellular carcinoma cells. Berberine-induced cell death in human hepatic carcinoma cells was diminished in the presence of the cell death inhibitor 3-methyladenine, or following interference with the essential autophagy gene Atg5. Mechanistic studies showed that berberine may activate mitochondrial apoptosis in HepG2 and MHCC97-L cells by increasing Bax expression, the formation of permeable transition pores, cytochrome C release to cytosol, and subsequent activation of the caspases 3 and 9 execution pathway. Berberine may also induce autophagic cell death in HepG2 and MHCC97-L cells through activation of Beclin-1 and inhibition of the mTOR-signaling pathway by suppressing the activity of Akt and up-regulating P38 MAPK signaling. This is the first study to describe the role of Beclin-1 activation and mTOR inhibition in berberine-induced autophagic cell death. These results further demonstrate the potential of berberine as a therapeutic agent in the emerging list of cancer therapies with novel mechanisms. © 2010 Wiley-Liss, Inc.postprin

Anode modification of polyfluorene-based polymer light-emitting devices

A glycerol-modified poly(3,4-ethylene dioxythiophene) (PEDOT): poly(styrene sulfonate) (PSS) layer was used as an anode buffer layer in polymer light-emitting devices using poly(9,9-dioctylfluorene) (F8) as the emitter. Devices with a configuration of indium tin oxide/PEDOT:PSS (with or without glycerol)/F8/CsF/Al were fabricated. It was found that the glycerol-modified device showed a much larger current density than the unmodified device. At an operating voltage of 6 V, the glycerol-modified device showed a luminance of 1300Cd/m 2 and a current efficiency of 1.7 Cd/A compared to the corresponding values of 500Cd/m 2 and 1.3 Cd/A in the unmodified device. Analysis by ultraviolet spectroscopy suggests that the two devices have the same energy level structure and the performance improvement should not be due to change in the PEDOT/polymer interface. It was further found that incorporating a suitable amount of glycerol into the PEDOT:PSS layer can increase its conductivity by six times. This leads to a better balance in the hole and electron currents and thus improved device efficiency. © 2002 American Institute of Physics.published_or_final_versio

Associations of apolipoprotein E exon 4 and lipoprotein lipase S447X polymorphisms with acute ischemic stroke and myocardial infarction

Background: Because apolipoprotein E (apoE) and lipopoprotein lipase (LPL) polymorphisms interact with each other and with other factors to affect lipid metabolism, we sought to determine their separate and combined effects in association with ischemic vascular disease. Methods: We performed a case-control study of 816 subjects: 246 acute ischemic stroke patients, 234 acute myocardial infarction patients, and 336 controls. APOE exon 4 and LPL S447X genotypes were determined. Results: APOE ε2 and ε4 homozygotes were increased in stroke (4.5% vs. 1.0%, p = 0.008), while in myocardial infarction the ε4 allele was increased (12.6% vs. 9.5%, p = 0.006) but ε2 was decreased (3.7% vs. 12.1%, p = 0.000006). For subjects with either APOE ε2 or ε4 alleles, LPL X alleles were increased in vascular disease (OR = 2.2, p = 0.01). LPL X alleles displayed opposite tendencies toward association with disease when subjects were divided by sex, smoking, or APOE genotype. Meta-analysis and regression analysis of previous studies supported the sex and smoking dichotomies. Conclusion: This is the first report of an association of vascular disease with an interaction of APOE exon 4 and LPL S447X genotypes. Therefore, APOE genotypes and LPL S447X interactions with apoE, sex, and smoking may affect the risk of myocardial infarction and ischemic stroke. © 2006 by Walter de Gruyter.published_or_final_versio

Foveated image processing for faster object detection and recognition in embedded systems using deep convolutional neural networks

Object detection and recognition algorithms using deep convolutional neural networks (CNNs) tend to be computationally intensive to implement. This presents a particular challenge for embedded systems, such as mobile robots, where the computational resources tend to be far less than for workstations. As an alternative to standard, uniformly sampled images, we propose the use of foveated image sampling here to reduce the size of images, which are faster to process in a CNN due to the reduced number of convolution operations. We evaluate object detection and recognition on the Microsoft COCO database, using foveated image sampling at different image sizes, ranging from 416×416 to 96×96 pixels, on an embedded GPU – an NVIDIA Jetson TX2 with 256 CUDA cores. The results show that it is possible to achieve a 4× speed-up in frame rates, from 3.59 FPS to 15.24 FPS, using 416×416 and 128×128 pixel images respectively. For foveated sampling, this image size reduction led to just a small decrease in recall performance in the foveal region, to 92.0% of the baseline performance with full-sized images, compared to a significant decrease to 50.1% of baseline recall performance in uniformly sampled images, demonstrating the advantage of foveated sampling

Fluorescence lifetime imaging of optically levitated aerosol: a technique to quantitatively map the viscosity of suspended aerosol particles

We describe a technique to measure the viscosity of stably levitated single micron-sized aerosol particles. Particle levitation allows the aerosol phase to be probed in the absence of potentially artefact-causing surfaces. To achieve this feat, we combined two laser based techniques: optical trapping for aerosol particle levitation, using a counter-propagating laser beam configuration, and fluorescent lifetime imaging microscopy (FLIM) of molecular rotors for the measurement of viscosity within the particle. Unlike other techniques used to measure aerosol particle viscosity, this allows for the non-destructive probing of viscosity of aerosol particles without interference from surfaces. The well-described viscosity of sucrose aerosol, under a range of relative humidity conditions, is used to validate the technique. Furthermore we investigate a pharmaceutically-relevant mixture of sodium chloride and salbutamol sulphate under humidities representative of $\textit{in vivo}$ drug inhalation. Finally, we provide a methodology for incorporating molecular rotors into already levitated particles, thereby making the FLIM/optical trapping technique applicable to real world aerosol systems, such as atmospheric aerosols and those generated by pharmaceutical inhalers.European Research Council (Grant ID: 279405), Science and Technology Facilities Council (Central Laser Facility, Grant ID: LSF1207), Engineering and Physical Sciences Research Council (Grant ID: EP/I003983/1), Natural Environmental Research Council (Grant ID: NE/J500070/1

Endogenous cholinergic inputs and local circuit mechanisms govern the phasic mesolimbic dopamine response to nicotine

Nicotine exerts its reinforcing action by stimulating nicotinic acetylcholine receptors (nAChRs) and boosting dopamine (DA) output from the ventral tegmental area (VTA). Recent data have led to a debate about the principal pathway of nicotine action: direct stimulation of the DAergic cells through nAChR activation, or disinhibition mediated through desensitization of nAChRs on GABAergic interneurons. We use a computational model of the VTA circuitry and nAChR function to shed light on this issue. Our model illustrates that the α4β2-containing nAChRs either on DA or GABA cells can mediate the acute effects of nicotine. We account for in vitro as well as in vivo data, and predict the conditions necessary for either direct stimulation or disinhibition to be at the origin of DA activity increases. We propose key experiments to disentangle the contribution of both mechanisms. We show that the rate of endogenous acetylcholine input crucially determines the evoked DA response for both mechanisms. Together our results delineate the mechanisms by which the VTA mediates the acute rewarding properties of nicotine and suggest an acetylcholine dependence hypothesis for nicotine reinforcement.Peer reviewe

Towards strange metallic holography

We initiate a holographic model building approach to `strange metallic' phenomenology. Our model couples a neutral Lifshitz-invariant quantum critical theory, dual to a bulk gravitational background, to a finite density of gapped probe charge carriers, dually described by D-branes. In the physical regime of temperature much lower than the charge density and gap, we exhibit anomalous scalings of the temperature and frequency dependent conductivity. Choosing the dynamical critical exponent $z$ appropriately we can match the non-Fermi liquid scalings, such as linear resistivity, observed in strange metal regimes. As part of our investigation we outline three distinct string theory realizations of Lifshitz geometries: from F theory, from polarised branes, and from a gravitating charged Fermi gas. We also identify general features of renormalisation group flow in Lifshitz theories, such as the appearance of relevant charge-charge interactions when $z \geq 2$. We outline a program to extend this model building approach to other anomalous observables of interest such as the Hall conductivity.Comment: 71 pages, 8 figure

One-year delayed effect of fog on malaria transmission: a time-series analysis in the rain forest area of Mengla County, south-west China

Background: Malaria is a major public health burden in the tropics with the potential to significantly increase in response to climate change. Analyses of data from the recent past can elucidate how short-term variations in weather factors affect malaria transmission. This study explored the impact of climate variability on the transmission of malaria in the tropical rain forest area of Mengla County, south-west China. Methods: Ecological time-series analysis was performed on data collected between 1971 and 1999. Auto-regressive integrated moving average (ARIMA) models were used to evaluate the relationship between weather factors and malaria incidence. Results: At the time scale of months, the predictors for malaria incidence included: minimum temperature, maximum temperature, and fog day frequency. The effect of minimum temperature on malaria incidence was greater in the cool months than in the hot months. The fog day frequency in October had a positive effect on malaria incidence in May of the following year. At the time scale of years, the annual fog day frequency was the only weather predictor of the annual incidence of malaria. Conclusion: Fog day frequency was for the first time found to be a predictor of malaria incidence in a rain forest area. The one-year delayed effect of fog on malaria transmission may involve providing water input and maintaining aquatic breeding sites for mosquitoes in vulnerable times when there is little rainfall in the 6-month dry seasons. These findings should be considered in the prediction of future patterns of malaria for similar tropical rain forest areas worldwide