Directed cell migration in the presence of obstacles

BACKGROUND: Chemotactic movement is a common feature of many cells and microscopic organisms. In vivo, chemotactic cells have to follow a chemotactic gradient and simultaneously avoid the numerous obstacles present in their migratory path towards the chemotactic source. It is not clear how cells detect and avoid obstacles, in particular whether they need a specialized biological mechanism to do so. RESULTS: We propose that cells can sense the presence of obstacles and avoid them because obstacles interfere with the chemical field. We build a model to test this hypothesis and find that this naturally enables efficient at-a-distance sensing to be achieved with no need for a specific and active obstacle-sensing mechanism. We find that (i) the efficiency of obstacle avoidance depends strongly on whether the chemotactic chemical reacts or remains unabsorbed at the obstacle surface. In particular, it is found that chemotactic cells generally avoid absorbing barriers much more easily than non-absorbing ones. (ii) The typically low noise in a cell's motion hinders the ability to avoid obstacles. We also derive an expression estimating the typical distance traveled by chemotactic cells in a 3D random distribution of obstacles before capture; this is a measure of the distance over which chemotaxis is viable as a means of directing cells from one point to another in vivo. CONCLUSION: Chemotactic cells, in many cases, can avoid obstacles by simply following the spatially perturbed chemical gradients around obstacles. It is thus unlikely that they have developed specialized mechanisms to cope with environments having low to moderate concentrations of obstacles

The Mechanism of Abrupt Transition between Theta and Hyper-Excitable Spiking Activity in Medial Entorhinal Cortex Layer II Stellate Cells

Recent studies have shown that stellate cells (SCs) of the medial entorhinal cortex become hyper-excitable in animal models of temporal lobe epilepsy. These studies have also demonstrated the existence of recurrent connections among SCs, reduced levels of recurrent inhibition in epileptic networks as compared to control ones, and comparable levels of recurrent excitation among SCs in both network types. In this work, we investigate the biophysical and dynamic mechanism of generation of the fast time scale corresponding to hyper-excitable firing and the transition between theta and fast firing frequency activity in SCs. We show that recurrently connected minimal networks of SCs exhibit abrupt, threshold-like transition between theta and hyper-excitable firing frequencies as the result of small changes in the maximal synaptic (AMPAergic) conductance. The threshold required for this transition is modulated by synaptic inhibition. Similar abrupt transition between firing frequency regimes can be observed in single, self-coupled SCs, which represent a network of recurrently coupled neurons synchronized in phase, but not in synaptically isolated SCs as the result of changes in the levels of the tonic drive. Using dynamical systems tools (phase-space analysis), we explain the dynamic mechanism underlying the genesis of the fast time scale and the abrupt transition between firing frequency regimes, their dependence on the intrinsic SC's currents and synaptic excitation. This abrupt transition is mechanistically different from others observed in similar networks with different cell types. Most notably, there is no bistability involved. ‘In vitro’ experiments using single SCs self-coupled with dynamic clamp show the abrupt transition between firing frequency regimes, and demonstrate that our theoretical predictions are not an artifact of the model. In addition, these experiments show that high-frequency firing is burst-like with a duration modulated by an M-current

Proline-rich antimicrobial peptide, PR-39 gene transduction altered invasive activity and actin structure in human hepatocellular carcinoma cells

PR-39 is an endogenous proline-rich antimicrobial peptide which induces the synthesis of syndecan-1, a transmembrane heparan sulphate proteoglycan involved in cell-to-matrix interactions and wound healing. Previously, we revealed that the expression of syndecan-1 was reduced in human hepatocellular carcinomas with high metastatic potential and speculated that syndecan-1 played an important role in inhibition of invasion and metastasis. It is assumed that a modification of this process with PR-39 and syndecan-1 may result in a new strategy by which it can inhibit the invasion and metastasis. Therefore, we transduced a gene of PR-39 into human hepatocellular carcinoma cell line HLF, which shows a low expression of syndecan-1 and a high in vitro invasive activity, and examined whether this procedure could reduce the invasive activity of tumour cells. In two transfectants with PR-39 gene, the syndecan-1 expression was induced and the invasive activity in type I collagen-coated chamber was inhibited. Moreover, these transfectants showed the suppression of motile activity assayed by phagokinetic tracks in addition to the disorganization of actin filaments observed by a confocal imaging system. In contrast, five transfectants with syndecan-1 gene in the HLF cells revealed suppression of invasive activity but did not alter the motile activity and actin structures of the cell. These results suggest that PR-39 has functions involved in the suppression of motile activity and alteration of actin structure on human hepatocellular carcinoma cells in addition to the suppression of invasive activity which might result from the induction of syndecan-1 expression. © 1999 Cancer Research Campaig

Modeling visual-based pitch, lift and speed control strategies in hoverflies

<div><p>To avoid crashing onto the floor, a free falling fly needs to trigger its wingbeats quickly and control the orientation of its thrust accurately and swiftly to stabilize its pitch and hence its speed. Behavioural data have suggested that the vertical optic flow produced by the fall and crossing the visual field plays a key role in this anti-crash response. Free fall behavior analyses have also suggested that flying insect may not rely on graviception to stabilize their flight. Based on these two assumptions, we have developed a model which accounts for hoverflies´ position and pitch orientation recorded in 3D with a fast stereo camera during experimental free falls. Our dynamic model shows that optic flow-based control combined with closed-loop control of the pitch suffice to stabilize the flight properly. In addition, our model sheds a new light on the visual-based feedback control of fly´s pitch, lift and thrust. Since graviceptive cues are possibly not used by flying insects, the use of a vertical reference to control the pitch is discussed, based on the results obtained on a complete dynamic model of a virtual fly falling in a textured corridor. This model would provide a useful tool for understanding more clearly how insects may or not estimate their absolute attitude.</p></div

Photodisintegration of 4^4He into p+t

The two-body photodisintegration of $^4$He into a proton and a triton has been studied using the CEBAF Large-Acceptance Spectrometer (CLAS) at Jefferson Laboratory. Real photons produced with the Hall-B bremsstrahlung-tagging system in the energy range from 0.35 to 1.55 GeV were incident on a liquid $^4$He target. This is the first measurement of the photodisintegration of $^4$He above 0.4 GeV. The differential cross sections for the $\gamma$$^4$He$\to pt$ reaction have been measured as a function of photon-beam energy and proton-scattering angle, and are compared with the latest model calculations by J.-M. Laget. At 0.6-1.2 GeV, our data are in good agreement only with the calculations that include three-body mechanisms, thus confirming their importance. These results reinforce the conclusion of our previous study of the three-body breakup of $^3$He that demonstrated the great importance of three-body mechanisms in the energy region 0.5-0.8 GeV .Comment: 13 pages submitted in one tgz file containing 2 tex file and 22 postscrip figure

π0\pi^0 photoproduction on the proton for photon energies from 0.675 to 2.875 GeV

Differential cross sections for the reaction $\gamma p \to p \pi^0$ have been measured with the CEBAF Large Acceptance Spectrometer (CLAS) and a tagged photon beam with energies from 0.675 to 2.875 GeV. The results reported here possess greater accuracy in the absolute normalization than previous measurements. They disagree with recent CB-ELSA measurements for the process at forward scattering angles. Agreement with the SAID and MAID fits is found below 1 GeV. The present set of cross sections has been incorporated into the SAID database, and exploratory fits have been extended to 3 GeV. Resonance couplings have been extracted and compared to previous determinations.Comment: 18 pages, 48 figure

Exclusive ρ0\rho^0 electroproduction on the proton at CLAS

The $e p\to e^\prime p \rho^0$ reaction has been measured, using the 5.754 GeV electron beam of Jefferson Lab and the CLAS detector. This represents the largest ever set of data for this reaction in the valence region. Integrated and differential cross sections are presented. The $W$, $Q^2$ and $t$ dependences of the cross section are compared to theoretical calculations based on $t$-channel meson-exchange Regge theory on the one hand and on quark handbag diagrams related to Generalized Parton Distributions (GPDs) on the other hand. The Regge approach can describe at the $\approx$ 30% level most of the features of the present data while the two GPD calculations that are presented in this article which succesfully reproduce the high energy data strongly underestimate the present data. The question is then raised whether this discrepancy originates from an incomplete or inexact way of modelling the GPDs or the associated hard scattering amplitude or whether the GPD formalism is simply inapplicable in this region due to higher-twists contributions, incalculable at present.Comment: 29 pages, 29 figure

First Measurement of Beam-Recoil Observables Cx and Cz in Hyperon Photoproduction

Spin transfer from circularly polarized real photons to recoiling hyperons has been measured for the reactions $\vec\gamma + p \to K^+ + \vec\Lambda$ and $\vec\gamma + p \to K^+ + \vec\Sigma^0$. The data were obtained using the CLAS detector at Jefferson Lab for center-of-mass energies $W$ between 1.6 and 2.53 GeV, and for $-0.85<\cos\theta_{K^+}^{c.m.}< +0.95$. For the $\Lambda$, the polarization transfer coefficient along the photon momentum axis, $C_z$, was found to be near unity for a wide range of energy and kaon production angles. The associated transverse polarization coefficient, $C_x$, is smaller than $C_z$ by a roughly constant difference of unity. Most significantly, the {\it total} $\Lambda$ polarization vector, including the induced polarization $P$, has magnitude consistent with unity at all measured energies and production angles when the beam is fully polarized. For the $\Sigma^0$ this simple phenomenology does not hold. All existing hadrodynamic models are in poor agreement with these results.Comment: 28 pages, 18 figures, Submitted to Physical Review

Regional adaptation defines sensitivity to future ocean acidification

Physiological responses to temperature are known to be a major determinant of species distributions and can dictate the sensitivity of populations to global warming. In contrast, little is known about how other major global change drivers, such as ocean acidification (OA), will shape species distributions in the future. Here, by integrating population genetics with experimental data for growth and mineralization, physiology and metabolomics, we demonstrate that the sensitivity of populations of the gastropod Littorina littorea to future OA is shaped by regional adaptation. Individuals from populations towards the edges of the natural latitudinal range in the Northeast Atlantic exhibit greater shell dissolution and the inability to upregulate their metabolism when exposed to low pH, thus appearing most sensitive to low seawater pH. Our results suggest that future levels of OA could mediate temperature-driven shifts in species distributions, thereby influencing future biogeography and the functioning of marine ecosystems

Microbial Activities and Dissolved Organic Matter Dynamics in Oil-Contaminated Surface Seawater from the Deepwater Horizon Oil Spill Site

The Deepwater Horizon oil spill triggered a complex cascade of microbial responses that reshaped the dynamics of heterotrophic carbon degradation and the turnover of dissolved organic carbon (DOC) in oil contaminated waters. Our results from 21-day laboratory incubations in rotating glass bottles (roller bottles) demonstrate that microbial dynamics and carbon flux in oil-contaminated surface water sampled near the spill site two weeks after the onset of the blowout were greatly affected by activities of microbes associated with macroscopic oil aggregates. Roller bottles with oil-amended water showed rapid formation of oil aggregates that were similar in size and appearance compared to oil aggregates observed in surface waters near the spill site. Oil aggregates that formed in roller bottles were densely colonized by heterotrophic bacteria, exhibiting high rates of enzymatic activity (lipase hydrolysis) indicative of oil degradation. Ambient waters surrounding aggregates also showed enhanced microbial activities not directly associated with primary oil-degradation (β-glucosidase; peptidase), as well as a twofold increase in DOC. Concurrent changes in fluorescence properties of colored dissolved organic matter (CDOM) suggest an increase in oil-derived, aromatic hydrocarbons in the DOC pool. Thus our data indicate that oil aggregates mediate, by two distinct mechanisms, the transfer of hydrocarbons to the deep sea: a microbially-derived flux of oil-derived DOC from sinking oil aggregates into the ambient water column, and rapid sedimentation of the oil aggregates themselves, serving as vehicles for oily particulate matter as well as oil aggregate-associated microbial communities