225 research outputs found
Uncoupling of EGFR–RAS signaling and nuclear localization of YBX1 in colorectal cancer
The transcription factor YBX1 can act as a mediator of signals transmitted via
the EGFR–RAS–MAPK axis. YBX1 expression has been associated with tumor
progression and prognosis in multiple types of cancer. Immunohistochemical
studies have revealed dependency between YBX1 expression and individual EGFR
family members. We analyzed YBX1 and EGFR family proteins in a colorectal
cancer (CRC) cohort and provide functional analyses of YBX1 in the context of
EGFR–RAS–MAPK signaling. Immunohistochemistry for YBX1 and EGFR family
receptors with two antibodies for YBX1 and EGFR were performed and related to
clinicopathological data. We employed Caco2 cells expressing an inducible
KRASV12 gene to determine effects on localization and levels of YBX1. Mouse
xenografts of Caco2-KRASV12 cells were used to determine YBX1 dynamics in a
tissue context. The two different antibodies against YBX1 showed discordant
immunohistochemical stainings in cell culture and clinical specimens.
Expression of YBX1 and EGFR family members were not correlated in CRC.
Analysis of Caco2 xenografts displayed again heterogeneity of YBX1 staining
with both antibodies. Our results suggest that YBX1 is controlled via complex
regulatory mechanisms involving tumor stroma interaction and signal
transduction processes. Our study highlights that YBX1 antibodies have
different specificities, advocating their use in a combined manner
Fluctuating magnetic moments in liquid metals
We re-analyze literature data on neutron scattering by liquid metals to show
that non-magnetic liquid metals possess a magnetic moment that fluctuates on a
picosecond time scale. This time scale follows the motion of the cage-diffusion
process in which an ion rattles around in the cage formed by its neighbors. We
find that these fluctuating magnetic moments are present in liquid Hg, Al, Ga
and Pb, and possibly also in the alkali metals.Comment: 17 pages, 5 figures, submitted to PR
MEDIPS: genome-wide differential coverage analysis of sequencing data derived from DNA enrichment experiments
MOTIVATION: DNA enrichment followed by sequencing is a versatile tool in molecular biology, with a wide variety of applications including genome-wide analysis of epigenetic marks and mechanisms. A common requirement of these diverse applications is a comparison of read coverage between experimental conditions. The amount of samples generated for such comparisons ranges from few replicates to hundreds of samples per condition for epigenome-wide association studies. Consequently, there is an urgent need for software that allows for fast and simple processing and comparison of sequencing data derived from enriched DNA. RESULTS: Here, we present a major update of the R/Bioconductor package MEDIPS, which allows for an arbitrary number of replicates per group and integrates sophisticated statistical methods for the detection of differential coverage between experimental conditions. Our approach can be applied to a diversity of quantitative sequencing data. In addition, our update adds novel functionality to MEDIPS, including correlation analysis between samples, and takes advantage of Bioconductor's annotation databases to facilitate annotation of specific genomic regions. AVAILABILITY AND IMPLEMENTATION: The latest version of MEDIPS is available as version 1.12.0 and part of Bioconductor 2.13. The package comes with a manual containing detailed description of its functionality and is available at http://www.bioconductor.org
Atomic Transport in Dense, Multi-Component Metallic Liquids
Pd43Ni10Cu27P0 has been investigated in its equilibrium liquid state with
incoherent, inelastic neutron scattering. As compared to simple liquids, liquid
PdNiCuP is characterized by a dense packing with a packing fraction above 0.5.
The intermediate scattering function exhibits a fast relaxation process that
precedes structural relaxation. Structural relaxation obeys a time-temperature
superposition that extends over a temperature range of 540K. The mode-coupling
theory of the liquid to glass transition (MCT) gives a consistent description
of the dynamics which governs the mass transport in liquid PdNiCuP alloys. MCT
scaling laws extrapolate to a critical temperature Tc at about 20% below the
liquidus temperature. Diffusivities derived from the mean relaxation times
compare well with Co diffusivities from recent tracer diffusion measurements
and diffsuivities calculated from viscosity via the Stokes-Einstein relation.
In contrast to simple metallic liquids, the atomic transport in dense, liquid
PdNiCuP is characterized by a drastical slowing down of dynamics on cooling, a
q^{-2} dependence of the mean relaxation times at intermediate q and a
vanishing isotope effect as a result of a highly collective transport
mechanism. At temperatures as high as 2Tc diffusion in liquid PdNiCuP is as
fast as in simple liquids at the melting point. However, the difference in the
underlying atomic transport mechanism indicates that the diffusion mechanism in
liquids is not controlled by the value of the diffusivity but rather by that of
the packing fraction
Density fluctuations and single-particle dynamics in liquid lithium
The single-particle and collective dynamical properties of liquid lithium
have been evaluated at several thermodynamic states near the triple point. This
is performed within the framework of mode-coupling theory, using a
self-consistent scheme which, starting from the known static structure of the
liquid, allows the theoretical calculation of several dynamical properties.
Special attention is devoted to several aspects of the single-particle
dynamics, which are discussed as a function of the thermodynamic state. The
results are compared with those of Molecular Dynamics simulations and other
theoretical approaches.Comment: 31 pages (in preprint format), 14 figures. Submitted to Phys. Rev.
Forest elephant movement and habitat use in a tropical forest-grassland mosaic in Gabon
Poaching of forest elephants (Loxodonta cyclotis) for ivory has decimated their populations in Central Africa. Studying elephant movement can provide insight into habitat and resource use to reveal where, when, and why they move and guide conservation efforts. We fitted 17 forest elephants with global positioning system (GPS) collars in 2015 and 2016 in the tropical forest-grassland mosaic of the Wonga Wongué Presidential Reserve (WW), Gabon. Using the location data, we quantified movement distances, home ranges, and habitat use to examine the environmental drivers of elephant movements and predict where elephants occur spatially and temporally. Forest elephants, on average, traveled 2,840 km annually and had home ranges of 713 km2, with males covering significantly larger home ranges than females. Forest elephants demonstrated both daily and seasonal movement patterns. Daily, they moved between forest and grassland at dawn and dusk. Seasonally, they spent proportionally more time in grassland than forest during the short-wet season when grasses recruit. Forest elephants also traveled faster during the short-wet season when fruit availability was greatest, likely reflecting long, direct movements to preferred fruiting tree species. Forest elephants tended to select areas with high tree and shrub density that afford cover and browse. When villages occurred in their home ranges elephants spent a disproportionate amount of time near them, particularly in the dry season, probably for access to agricultural crops and preferred habitat. Given the importance of the grassland habitat for elephants, maintenance of the forest-grassland matrix is a conservation priority in WW. Law enforcement, outreach, and education should focus on areas of potential human-elephant conflict near villages along the borders of the reserve. GPS-tracking should be extended into multi-use areas in the peripheries of protected areas to evaluate the effects of human disturbance on elephant movements and to maintain connectivity among elephant populations in Gabon
A census of cell types and paracrine interactions in colorectal cancer
In colorectal cancer, oncogenic mutations transform a hierarchically organized and homeostatic epithelium into invasive cancer tissue. To define differences in cellular composition between the normal colon and colorectal cancer, and to map potential cellular interactions between tumor cells and their microenvironment, we profiled transcriptomes of >50,000 single cells from tumors and matched normal tissues of eight colorectal cancer patients. We find that tumor formation is accompanied by changes in epithelial, immune and stromal cell compartments in all patients. In the epithelium, we identify a continuum of five tumor-specific stem cell and progenitor-like populations, and persistent multilineage differentiation. We find multiple stromal and immune cell types to be consistently expanded in tumor compared to the normal colon, including cancer-associated fibroblasts, pericytes, monocytes, macrophages and a subset of T cells. We identify epithelial tumor cells and cancer-associated fibroblasts as relevant for assigning colorectal cancer consensus molecular subtypes. Our survey of growth factors in the tumor microenvironment identifies cell types responsible for increased paracrine EGFR, MET and TGF-β signaling in tumor tissue compared to the normal colon. We show that matched colorectal cancer organoids retain cell type heterogeneity, allowing to define a distinct differentiation trajectory encompassing stem and progenitor-like tumor cells. In summary, our single-cell analyses provide insights into cell types and signals shaping colorectal cancer cell plasticity
PWD/Ph-encoded genetic variants modulate the cellular Wnt/β-Catenin response to suppress ApcMin-triggered intestinal tumor formation
Genetic predisposition affects the penetrance of tumor-initiating mutations, such as APC mutations that stabilize β-catenin and cause intestinal tumors in mice and humans. However, the mechanisms involved in genetically predisposed penetrance are not well understood. Here, we analyzed tumor multiplicity and gene expression in tumor-prone ApcMin/+ mice on highly variant C57BL/6J (B6) and PWD/Ph (PWD) genetic backgrounds. (B6 × PWD) F1 APCMin offspring mice were largely free of intestinal adenoma, and several chromosome substitution (consomic) strains carrying single PWD chromosomes on the B6 genetic background displayed reduced adenoma numbers. Multiple dosage-dependent modifier loci on PWD chromosome 5 each contributed to tumor suppression. Activation of β-catenin–driven and stem cell–specific gene expression in the presence of ApcMin or following APC loss remained moderate in intestines carrying PWD chromosome 5, suggesting that PWD variants restrict adenoma initiation by controlling stem cell homeostasis. Gene expression of modifier candidates and DNA methylation on chromosome 5 were predominantly cis controlled and largely reflected parental patterns, providing a genetic basis for inheritance of tumor susceptibility. Human SNP variants of several modifier candidates were depleted in colorectal cancer genomes, suggesting that similar mechanisms may also affect the penetrance of cancer driver mutations in humans. Overall, our analysis highlights the strong impact that multiple genetic variants acting in networks can exert on tumor development
Evidence of short time dynamical correlations in simple liquids
We report a molecular dynamics (MD) study of the collective dynamics of a
simple monatomic liquid -interacting through a two body potential that mimics
that of lithium- across the liquid-glass transition. In the glassy phase we
find evidences of a fast relaxation process similar to that recently found in
Lennard-Jones glasses. The origin of this process is ascribed to the
topological disorder, i.e. to the dephasing of the different momentum
Fourier components of the actual normal modes of vibration of the disordered
structure. More important, we find that the fast relaxation persists in the
liquid phase with almost no temperature dependence of its characteristic
parameters (strength and relaxation time). We conclude, therefore, that in the
liquid phase well above the melting point, at variance with the usual
assumption of {\it un-correlated} binary collisions, the short time particles
motion is strongly {\it correlated} and can be described via a normal mode
expansion of the atomic dynamics.Comment: 7 pages, 7 .eps figs. To appear in Phys. Rev.
- …