Dynamic Phase Transitions in Cell Spreading

We monitored isotropic spreading of mouse embryonic fibroblasts on fibronectin-coated substrates. Cell adhesion area versus time was measured via total internal reflection fluorescence microscopy. Spreading proceeds in well-defined phases. We found a power-law area growth with distinct exponents a_i in three sequential phases, which we denote basal (a_1=0.4+-0.2), continous (a_2=1.6+-0.9) and contractile (a_3=0.3+-0.2) spreading. High resolution differential interference contrast microscopy was used to characterize local membrane dynamics at the spreading front. Fourier power spectra of membrane velocity reveal the sudden development of periodic membrane retractions at the transition from continous to contractile spreading. We propose that the classification of cell spreading into phases with distinct functional characteristics and protein activity patterns serves as a paradigm for a general program of a phase classification of cellular phenotype. Biological variability is drastically reduced when only the corresponding phases are used for comparison across species/different cell lines.Comment: 4 pages, 5 figure

A Compact Fiber Optic Eye Diagnostic System

A new fiber optic probe developed for determining transport properties of sub-micron particles in fluid experiments in a microgravity environment has been applied to study different parts of an eye. The probe positioned in front of an eye, delivers a low power (approximately few microW) light from a laser diode into the eye and guides the light which is back scattered by different components (aqueous humor, lens, and vitreous humor) of the eye through a receiving optical fiber to a photo detector. The probe provides rapid determination of macromolecular diffusivities and their respective size distributions in the eye lens and the gel-like materials in the vitreous humor. In a clinical setting, the probe can be mounted on a standard slit-lamp apparatus simply using a Hruby lens holder. The capability of detecting cataracts, both nuclear and cortical, in their early stages of formation, in a non invasive and quantitative fashion, has the potential in patient monitoring and in developing and testing new drugs or diet therapies to 'dissolve' or slow down the cataract formation before the surgery becomes necessary. The ability to detect biochemical and macromolecular changes in the vitreous structure can be very useful in identifying certain diseases of the posterior chamber and their complications, e.g., posterior vitreous detachment and diabetic retinopathy

Periodic Lamellipodial Contractions Correlate with Rearward Actin Waves

AbstractCellular lamellipodia bind to the matrix and probe its rigidity through forces generated by rearward F-actin transport. Cells respond to matrix rigidity by moving toward more rigid matrices using an unknown mechanism. In spreading and migrating cells we find local periodic contractions of lamellipodia that depend on matrix rigidity, fibronectin binding and myosin light chain kinase (MLCK). These contractions leave periodic rows of matrix bound β3-integrin and paxillin while generating waves of rearward moving actin bound α-actinin and MLCK. The period between contractions corresponds to the time for F-actin to move across the lamellipodia. Shortening lamellipodial width by activating cofilin decreased this period proportionally. Increasing lamellipodial width by Rac signaling activation increased this period. We propose that an actin bound, contraction-activated signaling complex is transported locally from the tip to the base of the lamellipodium, activating the next contraction/extension cycle

A Compact Fiber Optic Eye Diagnostics System

A new fiber optic probe development for determining transport properties of sub-micron particles in fluids experiments in a microgravity environment has been applied to study different parts of the eye. The probe positioned in front of an eye, delivers a low power (approximately a few mu W) light from a laser diode into the eye and guides the light which is back scattered by different components (aqueous humor, lens, and vitreous humor) of the eye through a receiving optical fiber to a photo detector. The probe provides rapid determination of macromolecular diffusivities and their respective size distributions in the eye lens and the gel-like material in the vitreous humor. For a clinical use, the probe is mounted on a standard slit-lamp apparatus simply using Hruby lens holder. The capability of detecting cataracts, both nuclear and cortical, in their early stages of formation, in a non invasive and quantitative fashion, has the potential in patient monitoring and in developing and testing new drugs or diet therapies to 'dissolve' or slow down the cataract formation before the surgery becomes necessary. The ability to detect biochemical and macromolecular changes in the vitreous structure can be very useful in identifying certain diseases of the posterior chamber and their complications, e.g., posterior vitreous detachment and diabetic retinopathy

Primary myxoid liposarcoma of the supraglottic larynx

Sarcomas are a rare occurrence accounting for roughly 1% of all cancer cases reported. Of these, 9–18% will be identified as liposarcoma. Overall, only 4–9% of all liposarcomas occur in the head and neck region. As such, it is a rare event to see a primary liposarcoma of the aerodigestive tract. These tumors are typically misdiagnosed secondary to their indolent, asymptomatic course and similarities in appearance to other benign lesions. An understanding of these lesions will help clinicians appropriately manage their patients. We present a case of a 60-year male with a primary supraglottic myxoid liposarcoma, and provide relevant information about liposarcomas

Generation tourism: towards a common identity

The purpose of this article is to highlight the implications of the indiscipline of tourism academia for a new generation of tourism academics. Generation Tourism is characterised by scholars with a multi-disciplinary education associated with a broad field of study and commonly considered to lack the advantages of a discipline-focused education with its strong theoretical and methodological foundations. The problem this article addresses relates to how new generations of scholars and their views on knowledge creation achieve ascendancy in ways that move on from existing paradigms and earlier cohorts of scholars. Our main argument is that Generation Tourism scholars would benefit from a more clearly developed and common academic identity. To begin the critical conversation around the identity of Generation Tourism we outline five possible points of departure. These points are: (1) learning from historical developments in parent disciplines; (2) spearheading inter-disciplinary scholarship; (3) working towards theoretical developments; (4) embracing mediating methodologies and (5) forming tourism nodes and networks. Recognising these as starting points rather than final statements, we hope that the conversation about Generation Tourism identity will continue in other forums

Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine.

OBJECTIVE: Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock. METHODS: The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575-590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit ? (2) Should we monitor preload and fluid responsiveness in shock ? (3) How and when should we monitor stroke volume or cardiac output in shock ? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock ? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock ? Four types of statements were used: definition, recommendation, best practice and statement of fact. RESULTS: Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring. CONCLUSIONS: This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock

Coalition Formation and the Ancillary Benefits of Climate Policy

Several studies found ancillary benefits of environmental policy to be of considerable size. These additional private benefits imply not only higher cooperative but also noncooperative abatement targets. However, beyond these largely undisputed important quantitative effects, there are qualitative and strategic implications associated with ancillary benefits: climate policy is no longer a pure but an impure public good. In this paper, we investigate these implications in a setting of non-cooperative coalition formation. In particular, we address the following questions. 1) Do ancillary benefits increase participation in international environmental agreements? 2) Do ancillary benefits raise the success of these treaties in welfare terms

On the Mechanism of Action of SJ-172550 in Inhibiting the Interaction of MDM4 and p53

SJ-172550 (1) was previously discovered in a biochemical high throughput screen for inhibitors of the interaction of MDMX and p53 and characterized as a reversible inhibitor (J. Biol. Chem. 2010; 285∶10786). Further study of the biochemical mode of action of 1 has shown that it acts through a complicated mechanism in which the compound forms a covalent but reversible complex with MDMX and locks MDMX into a conformation that is unable to bind p53. The relative stability of this complex is influenced by many factors including the reducing potential of the media, the presence of aggregates, and other factors that influence the conformational stability of the protein. This complex mechanism of action hinders the further development of compound 1 as a selective MDMX inhibitor

Correction: AGAPE (Automated Genome Analysis PipelinE) for Pan-Genome Analysis of Saccharomyces cerevisiae

The characterization and public release of genome sequences from thousands of organisms is expanding the scope for genetic variation studies. However, understanding the phenotypic consequences of genetic variation remains a challenge in eukaryotes due to the complexity of the genotype-phenotype map. One approach to this is the intensive study of model systems for which diverse sources of information can be accumulated and integrated. Saccharomyces cerevisiae is an extensively studied model organism, with well-known protein functions and thoroughly curated phenotype data. To develop and expand the available resources linking genomic variation with function in yeast, we aim to model the pan-genome of S. cerevisiae. To initiate the yeast pan-genome, we newly sequenced or re-sequenced the genomes of 25 strains that are commonly used in the yeast research community using advanced sequencing technology at high quality. We also developed a pipeline for automated pan-genome analysis, which integrates the steps of assembly, annotation, and variation calling. To assign strain-specific functional annotations, we identified genes that were not present in the reference genome. We classified these according to their presence or absence across strains and characterized each group of genes with known functional and phenotypic features. The functional roles of novel genes not found in the reference genome and associated with strains or groups of strains appear to be consistent with anticipated adaptations in specific lineages. As more S. cerevisiae strain genomes are released, our analysis can be used to collate genome data and relate it to lineage-specific patterns of genome evolution. Our new tool set will enhance our understanding of genomic and functional evolution in S. cerevisiae, and will be available to the yeast genetics and molecular biology community