1,833 research outputs found
Emergent collective chemotaxis without single-cell gradient sensing
Many eukaryotic cells chemotax, sensing and following chemical gradients.
However, experiments have shown that even under conditions when single cells
cannot chemotax, small clusters may still follow a gradient. This behavior has
been observed in neural crest cells, in lymphocytes, and during border cell
migration in Drosophila, but its origin remains puzzling. Here, we propose a
new mechanism underlying this "collective guidance", and study a model based on
this mechanism both analytically and computationally. Our approach posits that
the contact inhibition of locomotion (CIL), where cells polarize away from
cell-cell contact, is regulated by the chemoattractant. Individual cells must
measure the mean attractant value, but need not measure its gradient, to give
rise to directional motility for a cell cluster. We present analytic formulas
for how cluster velocity and chemotactic index depend on the number and
organization of cells in the cluster. The presence of strong orientation
effects provides a simple test for our theory of collective guidance.Comment: Updated with additional simulations. Aspects of v1 of this paper
about adaptation and amplification have been extended and turned into a
separate paper, and removed from the current versio
Collective signal processing in cluster chemotaxis: roles of adaptation, amplification, and co-attraction in collective guidance
Single eukaryotic cells commonly sense and follow chemical gradients,
performing chemotaxis. Recent experiments and theories, however, show that even
when single cells do not chemotax, clusters of cells may, if their interactions
are regulated by the chemoattractant. We study this general mechanism of
"collective guidance" computationally with models that integrate stochastic
dynamics for individual cells with biochemical reactions within the cells, and
diffusion of chemical signals between the cells. We show that if clusters of
cells use the well-known local excitation, global inhibition (LEGI) mechanism
to sense chemoattractant gradients, the speed of the cell cluster becomes
non-monotonic in the cluster's size - clusters either larger or smaller than an
optimal size will have lower speed. We argue that the cell cluster speed is a
crucial readout of how the cluster processes chemotactic signal; both
amplification and adaptation will alter the behavior of cluster speed as a
function of size. We also show that, contrary to the assumptions of earlier
theories, collective guidance does not require persistent cell-cell contacts
and strong short range adhesion to function. If cell-cell adhesion is absent,
and the cluster cohesion is instead provided by a co-attraction mechanism, e.g.
chemotaxis toward a secreted molecule, collective guidance may still function.
However, new behaviors, such as cluster rotation, may also appear in this case.
Together, the combination of co-attraction and adaptation allows for collective
guidance that is robust to varying chemoattractant concentrations while not
requiring strong cell-cell adhesion.Comment: This article extends some results previously presented in
arXiv:1506.0669
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The E-NTPDase Family of Ectonucleotidases: Structure Function Relationships and Pathophysiological Significance
Ectonucleotidases are ectoenzymes that hydrolyze extracellular nucleotides to the respective nucleosides. Within the past decade, ectonucleotidases belonging to several enzyme families have been discovered, cloned and characterized. In this article, we specifically address the cell surface-located members of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase/CD39) family (NTPDase1,2,3, and 8). The molecular identification of individual NTPDase subtypes, genetic engineering, mutational analyses, and the generation of subtype-specific antibodies have resulted in considerable insights into enzyme structure and function. These advances also allow definition of physiological and patho-physiological implications of NTPDases in a considerable variety of tissues. Biological actions of NTPDases are a consequence (at least in part) of the regulated phosphohydrolytic activity on extracellular nucleotides and consequent effects on P2-receptor signaling. It further appears that the spatial and temporal expression of NTPDases by various cell types within the vasculature, the nervous tissues and other tissues impacts on several patho-physiological processes. Examples include acute effects on cellular metabolism, adhesion, activation and migration with other protracted impacts upon developmental responses, inclusive of cellular proliferation, differentiation and apoptosis, as seen with atherosclerosis, degenerative neurological diseases and immune rejection of transplanted organs and cells. Future clinical applications are expected to involve the development of new therapeutic strategies for transplantation and various inflammatory cardiovascular, gastrointestinal and neurological diseases
Cluster-induced crater formation
Using molecular-dynamics simulation, we study the crater volumes induced by
energetic impacts ( km/s) of projectiles containing up to N=1000
atoms. We find that for Lennard-Jones bonded material the crater volume depends
solely on the total impact energy . Above a threshold \Eth, the volume
rises linearly with . Similar results are obtained for metallic materials.
By scaling the impact energy to the target cohesive energy , the crater
volumes become independent of the target material. To a first approximation,
the crater volume increases in proportion with the available scaled energy,
. The proportionality factor is termed the cratering efficiency and
assumes values of around 0.5.Comment: 9 page
Generating and sustaining long-lived spin states in 15N,15NâČ-azobenzene
Long-Lived spin States (LLSs) hold a great promise for sustaining non-thermal spin order and investigating various slow processes by Nuclear Magnetic Resonance (NMR) spectroscopy. Of special interest for such application are molecules containing nearly equivalent magnetic nuclei, which possess LLSs even at high magnetic fields. In this work, we report an LLS in trans-15N,15NâČ-azobenzene. The singlet state of the 15N spin pair exhibits a long-lived character. We solve the challenging problem of generating and detecting this LLS and further increase the LLS population by converting the much higher magnetization of protons into the 15N singlet spin order. As far as the longevity of this spin order is concerned, various schemes have been tested for sustaining the LLS. Lifetimes of 17âminutes have been achieved at 16.4âT, a value about 250 times longer than the longitudinal relaxation time of 15N in this magnetic field. We believe that such extended relaxation times, along with the photochromic properties of azobenzene, which changes conformation upon light irradiation and can be hyperpolarized by using parahydrogen, are promising for designing new experiments with photo-switchable long-lived hyperpolarization
Coherent manipulation of non-thermal spin order in optical nuclear polarization experiments
Time resolved measurements of Optical Nuclear Polarization (ONP) have been
performed on hyperpolarized triplet states in molecular crystals created by
light excitation. Transfer of the initial electron polarization to nuclear
spins has been studied in the presence of radiofrequency excitation; the
experiments have been performed with different pulse sequences using different
doped molecular systems. The experimental results clearly demonstrate the
dominant role of coherent mechanisms of spin order transfer, which manifest
themselves in well pronounced oscillations. These oscillations are of two
types, precessions and nutations, having characteristic frequencies, which are
the same for the different molecular systems and the pulse sequences applied.
Hence, precessions and nutations constitute a general feature of polarization
transfer in ONP experiments. In general, coherent manipulation of spin order
transfer creates a powerful resource for improving the performance of the ONP
method, which paves the way to strong signal enhancement in nuclear magnetic
resonance
Chromosomal Localization of the Carcinoembryonic Antigen Gene Family and Differential Expression in Various Tumors
Carcinoembryonic antigen (CEA) is a glycoprotein which is important as a tumor marker for a number of human cancers. It is a member of a gene family comprising about 10 closely related genes. In order to characterize mUNAs transcribed from individual genes we have identified by DNA and RNA hybridization experiments, gene-specific sequences from the 3 ' noncoding regions of CEA, and of nonspecific cross-reacting antigen (NCA) mRNAs, which have been recently cloned. With these probes, CEA mRNAs with lengths of 3.5 and 3.0 kilobases and an NCA mRNA species of 2.5 kilobases were identified in various human tumors. A 2.2-kilobase mRNA species, however, could only be detected in leu kocytes of patients with chronic myeloid leukemia by hybridization with a probe from the immunoglobulin-like repeat domain of CEA. This region is known to be very similar among the various members of the CEA gene family, and indeed the probe hybridizes with all four mRNA species. In situ hybridization with a cross-hybridizing probe from the NCA gene localized the members of the CEA gene family to the short and to the long arm of chromosome 19. In addition, a CEA cDNA probe was found to hybridize to the long arm of chromosome 19 only
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