Collagen scaffold remodeling by human mesenchymal stem cells

DMM 2011 entitled: Re-engineering Regenerative MedicinePoster Session - Tissue Engineering: no. 82Type I collagen has been widely used as scaffold for tissue engineering because of its excellent biocompatibility and negligible immunogenicity. We previously have developed a collagen microencapsulation technology entrapping many cells including human mesenchymal stem cells (hMSCs) in microspheres made of nanofibrous collagen meshwork. Nevertheless, little is understood about how stem cells interact with and remodel the collagen meshwork. This study aims to investigate collagen remodeling by human mesenchymal stem cells (hMSCs) in terms of degradation, new matrix synthesis, and re‐organization. We …postprin

Perinatal Gene Transfer to the Liver

The liver acts as a host to many functions hence raising the possibility that any one may be compromised by a single gene defect. Inherited or de novo mutations in these genes may result in relatively mild diseases or be so devastating that death within the first weeks or months of life is inevitable. Some diseases can be managed using conventional medicines whereas others are, as yet, untreatable. In this review we consider the application of early intervention gene therapy in neonatal and fetal preclinical studies. We appraise the tools of this technology, including lentivirus, adenovirus and adeno-associated virus (AAV)-based vectors. We highlight the application of these for a range of diseases including hemophilia, urea cycle disorders such as ornithine transcarbamylase deficiency, organic acidemias, lysosomal storage diseases including mucopolysaccharidoses, glycogen storage diseases and bile metabolism. We conclude by assessing the advantages and disadvantages associated with fetal and neonatal liver gene transfer

Taurine change in visual cortex of neonatal monocular enucleated rat: a proton MRS study

Posters - MRS of Animal Brain: 4530Neonatal monocular enucleation has been used to study developmental mechanisms underlying visual perception and the cross-modal changes in the central nervous system caused by early loss of the visual input. In this study, we demonstrated that alteration in the metabolism of taurine in visual cortex accompanied with neonatal monocular enucleation could be monitored using 1H MRS at 7 T. The change in taurine signal with respect to creatine signal may possibly due to the increased taurine signal in the right control visual cortex, likely caused by the plasticity resulted from recruitment of resources to the remaining left eye for adaptation.postprin

Comprehension of Subject and Object Relative Clauses in a Trilingual Acquisition Context

Chinese relative clauses (RCs) have word order properties that are distinctly rare across languages of the world; such properties provide a good testing ground to tease apart predictions regarding the relative complexity of subject and object RCs in acquisition and processing. This study considers these special word order properties in a multilingual acquisition context, examining how Cantonese(L1)-English(L2)-Mandarin(L3) trilingual children process RCs in two Chinese languages differing in exposure conditions. Studying in an English immersion international school, these trilinguals are also under intensive exposure to English. Comparisons of the trilinguals with their monolingual counterparts are made with a focus on the directionality of cross-linguistic influence. The study considers how various factors such as language exposure, structural overlaps in the target languages, typological distance, and language dominance can account for the linguistic abilities and vulnerabilities exhibited by a group of children in a trilingual acquisition context. Twenty-one trilingual 5- to 6-year-olds completed tests of subject- and object- RC comprehension in all three languages. Twenty-four age-matched Cantonese monolinguals and 24 age-matched Mandarin monolinguals served as comparison groups. Despite limited exposure to Mandarin, the trilinguals performed comparable to the monolinguals. Their Cantonese performance uniquely predicts their Mandarin performance, suggesting positive transfer from L1 Cantonese to L3 Mandarin. In Cantonese, however, despite extensive exposure from birth, the trilinguals comprehended object RCs significantly worse than the monolinguals. Error analyses suggested an English-based head-initial analysis, implying negative transfer from L2 English to L1 Cantonese. Overall, we identified a specific case of bi-directional influence between the first and second/third languages. The trilinguals experience facilitation in processing Mandarin RCs, because parallels and overlaps in both form and function provide a transparent basis for positive transfer from L1 Cantonese to L3 Mandarin. On the other hand, they experience more difficulty in processing object RCs in Cantonese compared to their monolingual peers, because structural overlaps with competing structures from English plus intensive exposure to English lead to negative transfer from L2 English to L1 Cantonese. The findings provide further evidence that head noun assignment in object RCs is especially vulnerable in multilingual Cantonese children when they are under intensive exposure to English.published_or_final_versio

Modelling the binding mode of macrocycles: Docking and conformational sampling

Drug discovery is increasingly tackling challenging protein binding sites regarding molecular recognition and druggability, including shallow and solvent-exposed protein-protein interaction interfaces. Macrocycles are emerging as promising chemotypes to modulate such sites. Despite their chemical complexity, macrocycles comprise important drugs and offer advantages compared to non-cyclic analogs, hence the recent impetus in the medicinal chemistry of macrocycles. Elaboration of macrocycles, or constituent fragments, can strongly benefit from knowledge of their binding mode to a target. When such information from X-ray crystallography is elusive, computational docking can provide working models. However, few studies have explored docking protocols for macrocycles, since conventional docking methods struggle with the conformational complexity of macrocycles, and also potentially with the shallower topology of their binding sites. Indeed, macrocycle binding mode prediction with the mainstream docking software GOLD has hardly been explored. Here, we present an in-depth study of macrocycle docking with GOLD and the ChemPLP scores. First, we summarize the thorough curation of a test set of 41 protein-macrocycle X-ray structures, raising the issue of lattice contacts with such systems. Rigid docking of the known bioactive conformers was successful (three top ranked poses) for 92.7% of the systems, in absence of crystallographic waters. Thus, without conformational search issues, scoring performed well. However, docking success dropped to 29.3% with the GOLD built-in conformational search. Yet, the success rate doubled to 58.5% when GOLD was supplied with extensive conformer ensembles docked rigidly. The reasons for failure, sampling or scoring, were analyzed, exemplified with particular cases. Overall, binding mode prediction of macrocycles remains challenging, but can be much improved with tailored protocols. The analysis of the interplay between conformational sampling and docking will be relevant to the prospective modelling of macrocycles in general

Left ventricular myocardial deformation and mechanical dyssynchrony in children with normal ventricular shortening fraction after anthracycline therapy

Objective: The M-mode-derived left ventricular shortening fraction is incorporated into most of the paediatric oncology protocols for monitoring of cardiotoxicity. This study tested the hypothesis that alteration of left ventricular myocardial deformation and mechanical dyssynchrony may occur in asymptomatic children after anthracycline therapy despite having left ventricular shortening fractions within the limits of normal. Design: Cross-sectional study. Setting: Tertiary paediatric cardiac centre. Methods: Left ventricular longitudinal, circumferential and radial myocardial deformation was determined using speckle tracking echocardiography in 45 patients aged 15.3±5.8 years. Real-time three-dimensional echocardiographic data were acquired for the measurement of left ventricular volumes and systolic dyssynchrony index (SDI), the latter derived from the dispersion of time-to-minimum regional volume using a 16-segment model. The results were compared with those of 44 controls. Results: Compared with controls, patients had reduced left ventricular global systolic longitudinal strain (p=0.012), circumferential strain (p4.96%) in patients was 16% (95% CI 6% to 29%). In patients, SDI correlated negatively with left ventricular ejection fraction (r=-0.52, p<0.001), radial strain (r=-0.35, p=0.021), circumferential strain (r=-0.37, p=0.015) and circumferential SR (r=-0.43, p=0.004), but not with the cumulative anthracycline dose (p=0.82). Conclusions: Impaired left ventricular myocardial deformation and mechanical dyssynchrony may exist in children after anthracycline therapy despite having normal left ventricular shortening fractions.published_or_final_versio

Temperature-dependent photoluminescence of GaInP/AlGaInP multiple quantum well laser structure grown by metalorganic chemical vapor deposition with tertiarybutylarsine and tertiarybutylphosphine

A GaInP/AlGaInP multiple quantum well laser structure was grown by low-pressure metalorganic chemical vapor deposition with tertiarybutylarsine and tertiarybutylphosphine. Laser diodes fabricated from this structure lased at room temperature. Photoluminescence ~PL! measurements were performed from 10 to 230 K. The PL energy increased with temperature from 10 to 70 K and decreased above 70 K. The former was attributed to thermal activation of trapped carriers due to localization in the quantum wells, while the latter was attributed to temperature-induced band-gap shrinkage. The PL intensity as a function of temperature was fitted by employing two nonradiative recombination mechanisms with good agreement, resulting in two activation energies that correspond to losses of photogenerated carriers to nonradiative centers. © 2003 American Institute of Physics.published_or_final_versio

Do temperature changes cause eczema flares? An English cohort study.

BACKGROUND: It is unclear if ambient temperature changes affect eczema. It is also unclear if people with worse disease are more susceptible to weather-related flares, or specific types of emollient offer protection. Substantiating these links may help inform action plans and patients self-management. OBJECTIVE: To investigate the effect of short-term temperature variations on eczema symptoms in children. METHODS: Data from a UK cohort of 519 children (6 months-12 years) with at least mild eczema, participating in a randomised trial comparing four types of emollients on eczema symptoms, were combined with observed temperature data from the Hadley Centre's Integrated Surface Database.Hot & cold weeks were defined by average regional temperature >75th or <25th percentile, January 2018-February 2020. Eczema flares were defined as ≥3 point change in patient-oriented eczema measure (POEM). Random effects logistic regression models were used to estimate the odds ratios of flares in hot & cold weeks (reference group: temperate weeks). The likelihood ratio test assessed for evidence of effect modification by disease severity and emollient type. RESULTS: The baseline mean age was 4.9 years (SD 3.2) and POEM score was 9.2 (SD 5.5), indicating moderate eczema. 90% of participants lived within 20 km of their nearest weather station. From the 519 participants there were 6,796 consecutively paired POEMs and 1,082 flares.Seasonal variation in POEM scores was observed, suggesting symptoms worsening with colder weather in winter and improving with warmer weather in summer. Odds ratios of flares were: 1.15 (p = 0.136, 95%CI 0.96-1.39) in cold weeks, 0.85 (p = 0.045, 95%CI 0.72-1.00) in hot weeks. Likelihood ratio test showed no evidence of this differing by disease severity (p = 0.53) or emollient type used (p = 0.55). CONCLUSIONS: Our findings are consistent with previous studies demonstrating either improvements in eczema symptoms or reduced flares in hot weather. Worse disease and different emollient types did not increase susceptibility or provide protection against temperature changes. Further work should investigate the role of sunlight, humidity, air pollution and other environmental factors

A novel process for preparing PZT thick films

2000-2001 > Academic research: refereed > Refereed conference paperVersion of RecordPublishe