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

Profiling biomolecules at cell-biomaterial interface by quantitative proteomics

Session: Controlling Microenvironment and Cell Fate: abstract no. 789INTRODUCTION: Implant surface structure and chemistry determines the contacting cell’s fate. Therefore, the fate of those cells directly affect bone-implant incorporation in clinical practice1-5. However, how these chemical and mechanical signals translating to cellular responses are not yet known. The major drawback is a lack of systematic study of cellbiomaterial interaction in terms of protein expression, specifically, at the attachment interface between the cell and biomaterial (adherence surface, AS). Therefore, we have proposed to unbiasedly identify the biomolecules at the interface by proteomics. This method combines the use of a subcellular fractionation with quantitative mass …postprintThe 2010 North America Conference of the Tissue Engineering and Regenerative Medicine International Society (TERMIS-NA 2010), Orlando, FL., 5-8 December 2010

Population Factors Affecting Initial Diffusion Patterns of H1N1

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Effects of geographic scale on population factors in acute disease diffusion analysis

Objective To explore socio-demographic data of the population as proxies for risk factors in disease transmission modeling at different geographic scales. Methods Patient records of confirmed H1N1 influenza were analyzed at three geographic aggregation levels together with population census statistics. Results The study confirmed that four population factors were related in different degrees to disease incidence, but the results varied according to spatial resolution. The degree of association actually decreased when data of a higher spatial resolution were used. Conclusions We concluded that variables at suitable spatial resolution may be useful in improving the predictive powers of models for disease outbreaks.published_or_final_versio

An Early Warning System for Detecting H1N1 Disease Outbreak - A Spatio-temporal Approach

The outbreaks of new and emerging infectious diseases in recent decades have caused widespread social and economic disruptions in the global economy. Various guidelines for pandemic influenza planning are based upon traditional infection control, best practice and evidence. This article describes the development of an early warning system for detecting disease outbreaks in the urban setting of Hong Kong, using 216 confirmed cases of H1N1 influenza from 1 May 2009 to 20 June 2009. The prediction model uses two variables – daily influenza cases and population numbers – as input to the spatio-temporal and stochastic SEIR model to forecast impending disease cases. The fairly encouraging forecast accuracy metrics for the 1- and 2-day advance prediction suggest that the number of impending cases could be estimated with some degree of certainty. Much like a weather forecast system, the procedure combines technical and scientific skills using empirical data but the interpretation requires experience and intuitive reasoning.postprin

Ge quantum dot arrays grown by ultrahigh vacuum molecular beam epitaxy on the Si(001) surface: nucleation, morphology and CMOS compatibility

Issues of morphology, nucleation and growth of Ge cluster arrays deposited by ultrahigh vacuum molecular beam epitaxy on the Si(001) surface are considered. Difference in nucleation of quantum dots during Ge deposition at low (<600 deg C) and high (>600 deg. C) temperatures is studied by high resolution scanning tunneling microscopy. The atomic models of growth of both species of Ge huts---pyramids and wedges---are proposed. The growth cycle of Ge QD arrays at low temperatures is explored. A problem of lowering of the array formation temperature is discussed with the focus on CMOS compatibility of the entire process; a special attention is paid upon approaches to reduction of treatment temperature during the Si(001) surface pre-growth cleaning, which is at once a key and the highest-temperature phase of the Ge/Si(001) quantum dot dense array formation process. The temperature of the Si clean surface preparation, the final high-temperature step of which is, as a rule, carried out directly in the MBE chamber just before the structure deposition, determines the compatibility of formation process of Ge-QD-array based devices with the CMOS manufacturing cycle. Silicon surface hydrogenation at the final stage of its wet chemical etching during the preliminary cleaning is proposed as a possible way of efficient reduction of the Si wafer pre-growth annealing temperature.Comment: 30 pages, 11 figure

CMOS-compatible dense arrays of Ge quantum dots on the Si(001) surface: hut cluster nucleation, atomic structure and array life cycle during UHV MBE growth

We report a direct observation of Ge hut nucleation on Si(001) during UHV molecular beam epitaxy at 360°C. Nuclei of pyramids and wedges were observed on the wetting layer (WL) (M × N) patches starting from the coverage of 5.1 Å and found to have different structures. Atomic models of nuclei of both hut species have been built as well as models of the growing clusters. The growth of huts of each species has been demonstrated to follow generic scenarios. The formation of the second atomic layer of a wedge results in rearrangement of its first layer. Its ridge structure does not repeat the nucleus. A pyramid grows without phase transitions. A structure of its vertex copies the nucleus. Transitions between hut species turned out to be impossible. The wedges contain point defects in the upper corners of the triangular faces and have preferential growth directions along the ridges. The derived structure of the {105} facet follows the paired dimer model. Further growth of hut arrays results in domination of wedges, and the density of pyramids exponentially drops. The second generation of huts arises at coverages >10 Å; new huts occupy the whole WL at coverages ~14 Å. Nanocrystalline Ge 2D layer begins forming at coverages >14 Å

Identification of novel candidate target genes, including EPHB3, MASP1 and SST at 3q26.2–q29 in squamous cell carcinoma of the lung

<p>Abstract</p> <p>Background</p> <p>The underlying genetic alterations for squamous cell carcinoma (SCC) and adenocarcinoma (AC) carcinogenesis are largely unknown.</p> <p>Methods</p> <p>High-resolution array- CGH was performed to identify the differences in the patterns of genomic imbalances between SCC and AC of non-small cell lung cancer (NSCLC).</p> <p>Results</p> <p>On a genome-wide profile, SCCs showed higher frequency of gains than ACs (<it>p </it>= 0.067). More specifically, statistically significant differences were observed across the histologic subtypes for gains at 2q14.2, 3q26.2–q29, 12p13.2–p13.33, and 19p13.3, as well as losses at 3p26.2–p26.3, 16p13.11, and 17p11.2 in SCC, and gains at 7q22.1 and losses at 15q22.2–q25.2 occurred in AC (<it>P </it>< 0.05). The most striking difference between SCC and AC was gains at the 3q26.2–q29, occurring in 86% (19/22) of SCCs, but in only 21% (3/14) of ACs. Many significant genes at the 3q26.2–q29 regions previously linked to a specific histology, such as EVI1,<it>MDS1, PIK3CA </it>and <it>TP73L</it>, were observed in SCC (<it>P </it>< 0.05). In addition, we identified the following possible target genes (> 30% of patients) at 3q26.2–q29: <it>LOC389174 </it>(3q26.2),<it>KCNMB3 </it>(3q26.32),<it>EPHB3 </it>(3q27.1), <it>MASP1 </it>and <it>SST </it>(3q27.3), <it>LPP </it>and <it>FGF12 </it>(3q28), and <it>OPA1</it>,<it>KIAA022</it>,<it>LOC220729</it>, <it>LOC440996</it>,<it>LOC440997</it>, and <it>LOC440998 </it>(3q29), all of which were significantly targeted in SCC (<it>P </it>< 0.05). Among these same genes, high-level amplifications were detected for the gene, <it>EPHB3</it>, at 3q27.1, and <it>MASP1 </it>and <it>SST</it>, at 3q27.3 (18, 18, and 14%, respectively). Quantitative real time PCR demonstrated array CGH detected potential candidate genes that were over expressed in SCCs.</p> <p>Conclusion</p> <p>Using whole-genome array CGH, we have successfully identified significant differences and unique information of chromosomal signatures prevalent between the SCC and AC subtypes of NSCLC. The newly identified candidate target genes may prove to be highly attractive candidate molecular markers for the classification of NSCLC histologic subtypes, and could potentially contribute to the pathogenesis of the squamous cell carcinoma of the lung.</p

Hospitalizations for varicella in children and adolescents in a referral hospital in Hong Kong, 2004 to 2008: A time series study

Background: Varicella accounts for significant morbidities and remains a public health issue worldwide. Climatic factors have been shown to associate with the incidence and transmission of various infectious diseases. We describe the epidemiology of varicella in paediatric patients hospitalized at a tertiary referral hospital in Hong Kong from 2004 to 2008, and to explore the possible association between the occurrence of varicella infection and various climatic factors. Methods. The hospital discharge database of Princess Margaret Hospital was retrospectively analyzed for admissions associated with varicella from 2004 to 2008. Meteorological data were obtained from the monthly meteorological reports from the Hong Kong Observatory website. Time series analysis was performed with Poisson regression using a Generalized Estimating Equation (GEE) approach. Results: During the study period, 598 children were hospitalized for varicella. The mean age on admission was 57.6 months, and the mean duration of hospitalization was 3.7 days. The overall complication rate was 47%. The mean monthly relative humidity, especially in cool seasons, was inversely correlated with the monthly varicella cases of the same month. Conclusions: Varicella can lead to serious complications and prolonged hospitalization, even in previously healthy children. Lower relative humidity in cool seasons is associated with higher number of paediatric varicella hospital admissions. These findings are useful for a better understanding of the pattern of paediatric varicella hospitalization in Hong Kong. © 2011 Chan et al; licensee BioMed Central Ltd.link_to_subscribed_fulltex