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Cells exhibit propagating membrane waves which involve the actin cytoskeleton. One type of such membranal waves are Circular Dorsal Ruffles (CDR) which are related to endocytosis and receptor internalization. Experimentally, CDRs have been associated with membrane bound activators of actin polymerization of concave shape. We present experimental evidence for the localization of convex membrane proteins in these structures, and their insensitivity to inhibition of myosin II contractility in immortalized mouse embryo fibroblasts cell cultures. These observations lead us to propose a theoretical model which explains the formation of these waves due to the interplay between complexes that contain activators of actin polymerization and membrane-bound curved proteins of both types of curvature (concave and convex). Our model predicts that th...
Phylodynamics - the field aiming to quantitatively integrate the ecological and evolutionary dynamics of rapidly evolving populations like those of RNA viruses – increasingly relies upon coalescent approaches to infer past population dynamics from reconstructed genealogies. As sequence data have become more abundant, these approaches are beginning to be used on populations undergoing rapid and rather complex dynamics. In such cases, the simple demographic models that current phylodynamic methods employ can be limiting. First, these models are not ideal for yielding biological insight into the processes that drive the dynamics of the populations of interest. Second, these models differ in form from mechanistic and often stochastic population dynamic models that are currently widely used when fitting models to time series data. As such, ...
The 30-second television message, "Wings", aired June 23 - July 3, 2003 in strategic U.S. markets on primetime cable and network t.v. stations. "Wings" provides a whimsical glimpse into the scientific progress that could be made if research and discoveries were openly and freely shared.
Background To date, research on racial discrimination and health typically has employed explicit self-report measures, despite their potentially being affected by what people are able and willing to say. We accordingly employed an Implicit Association Test (IAT) for racial discrimination, first developed and used in two recent published studies, and measured associations of the explicit and implicit discrimination measures with each other, socioeconomic and psychosocial variables, and smoking. Methodology/Principal Findings Among the 504 black and 501 white US-born participants, age 35–64, randomly recruited in 2008–2010 from 4 community health centers in Boston, MA, black participants were over 1.5 times more likely (p<0.05) to be worse off economically (e.g., for poverty and low education) and have higher social desirability sco...
Background and Aims. Increasing evidence that a number of malignancies are characterised by tumour cell heterogeneity has recently been published, but there is still a lack of data concerning liver cancers. The aim of this study was to investigate and characterise tumour-propagating cell (TPC) compartments within human hepatocellular carcinoma (HCC). Methods. After long-term culture, we identified three morphologically different tumour cell populations in a single HCC specimen, and extensively characterised them by means of flow cytometry, fluorescence microscopy, karyotyping and microarray analyses, single cell cloning, and xenotransplantation in NOD/SCID/IL2Rγ−/− mice. Results. The primary cell populations (hcc-1, -2 and -3) and two clones generated by means of limiting dilutions from hcc-1 (clone-1/7 and -1/8) differently expressed ...
HIV/HCV coinfected individuals under highly active antiretroviral therapy (HAART) represent an interesting model for the investigation of the role played by the immune system in driving the evolution of the HCV quasispecies. We prospectively studied the intra-host evolution of the HCV heterogeneity in 8 coinfected subjects, selected from a cohort of 32 patients initiating HAART: 5 immunological responders (group A) and 3 immunological non-responders (group B), and in two HCV singly infected controls not assuming drugs (group C). For all these subjects at least two serial samples obtained at the first observation (before HAART) and more than 1 year later, underwent clonal sequence analysis of partial E1/E2 sequences, encompassing the whole HVR1. Evolutionary rates, dated phylogenies and population dynamics were co-estimated by using a B...
The organization of genes on chromosomes changes over evolutionary time. In some organisms, such as fruit flies and mosquitoes, inversions of chromosome regions are widespread. This has been associated with adaptation to environmental pressures and speciation. However, the mechanisms by which inversions are generated at the molecular level are poorly understood. The prevailing view involves the interactions of sequences that are moderately repeated in the genome. Here, we use molecular and computational methods to study 29 inversions that differentiate the chromosomes of three closely related fruit fly species. We find little support for a causal role of repetitive sequences in the origin of inversions and, instead, detect the presence of inverted duplications of ancestrally unique sequences (generally protein-coding genes) in the brea...
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