Insulin-like growth factor-1 induces hyperproliferation of PKD1 cystic cells via a Ras/Raf dependent signalling pathway

Autosomal dominant polycystic kidney disease (ADPKD) largely results from mutations in the PKD1 gene leading to hyperproliferation of renal tubular epithelial cells and consequent cyst formation. Rodent models of PKD suggest that the multifunctional hormone insulin-like growth factor-1 (IGF-1) could play a pathogenic role in renal cyst formation. In order to test this possibility, conditionally immortalized renal epithelial cells were prepared from normal individuals and from ADPKD patients with known germline mutations in PKD1. All patient cell lines had a decreased or absence of polycystin-1 but not polycystin-2. These cells had an increased sensitivity to IGF-1 and to cyclic AMP, which required phosphatidylinositol-3 (PI3)-kinase and the mitogen-activated protein kinase, extracellular signal-regulated protein kinase (ERK) for enhanced growth. Inhibition of Ras or Raf abolished the stimulated cell proliferation. Our results suggest that haploinsufficiency of polycystin-1 lowers the activation threshold of the Ras/Raf signalling system leading to growth factor-induced hyperproliferation. Inhibition of Ras or Raf activity may be a therapeutic option for decreasing tubular cell proliferation in ADPKD

Star and cluster formation in extreme environments

Current empirical evidence on the star-formation processes in the extreme, high-pressure environments induced by galaxy encounters (mostly based on high-resolution Hubble Space Telescope observations) strongly suggests that star CLUSTER formation is an important and perhaps even the dominant mode of star formation in such starburst events. The sizes, luminosities, and mass estimates of the young massive star clusters (YMCs) are entirely consistent with what is expected for young Milky Way-type globular clusters (GCs). Recent evidence lends support to the scenario that GCs, which were once thought to be the oldest building blocks of galaxies, are still forming today. Here, I present a novel empirical approach to assess the shape of the initial-to-current YMC mass functions, and hence their possible survival chances for a Hubble time.Comment: 6 pages, LaTeX with Kluwer style files included; to appear in: "Starbursts - from 30 Doradus to Lyman break galaxies" (Cambridge UK, September 2004; talk summary), Astrophysics & Space Science Library, eds. de Grijs R., Gonzalez Delgado R.M., Kluwer: Dordrech

A Knob for Changing Light Propagation from Subluminal to Superluminal

We show how the application of a coupling field connecting the two lower metastable states of a lambda-system can produce a variety of new results on the propagation of a weak electromagnetic pulse. In principle the light propagation can be changed from subluminal to superluminal. The negative group index results from the regions of anomalous dispersion and gain in susceptibility.Comment: 6 pages,5 figures, typed in RevTeX, accepted in Phys. Rev.

Superluminal optical pulse propagation in nonlinear coherent media

The propagation of light-pulse with negative group-velocity in a nonlinear medium is studied theoretically. We show that the necessary conditions for these effects to be observable are realized in a three-level $\Lambda$-system interacting with a linearly polarized laser beam in the presence of a static magnetic field. In low power regime, when all other nonlinear processes are negligible, the light-induced Zeeman coherence cancels the resonant absorption of the medium almost completely, but preserves the dispersion anomalous and very high. As a result, a superluminal light pulse propagation can be observed in the sense that the peak of the transmitted pulse exits the medium before the peak of the incident pulse enters. There is no violation of causality and energy conservation. Moreover, the superluminal effects are prominently manifested in the reshaping of pulse, which is caused by the intensity-dependent pulse velocity. Unlike the shock wave formation in a nonlinear medium with normal dispersion, here, the self-steepening of the pulse trailing edge takes place due to the fact that the more intense parts of the pulse travel slower. The predicted effect can be easily observed in the well known schemes employed for studying of nonlinear magneto-optical rotation. The upper bound of sample length is found from the criterion that the pulse self-steepening and group-advance time are observable without pulse distortion caused by the group-velocity dispersion.Comment: 16 pages, 7 figure

Elastic interactions of active cells with soft materials

Anchorage-dependent cells collect information on the mechanical properties of the environment through their contractile machineries and use this information to position and orient themselves. Since the probing process is anisotropic, cellular force patterns during active mechanosensing can be modelled as anisotropic force contraction dipoles. Their build-up depends on the mechanical properties of the environment, including elastic rigidity and prestrain. In a finite sized sample, it also depends on sample geometry and boundary conditions through image strain fields. We discuss the interactions of active cells with an elastic environment and compare it to the case of physical force dipoles. Despite marked differences, both cases can be described in the same theoretical framework. We exactly solve the elastic equations for anisotropic force contraction dipoles in different geometries (full space, halfspace and sphere) and with different boundary conditions. These results are then used to predict optimal position and orientation of mechanosensing cells in soft material.Comment: Revtex, 38 pages, 8 Postscript files included; revised version, accepted for publication in Phys. Rev.

Quantum coherence in a degenerate two-level atomic ensemble: for a transition Fe=0↔Fg=1F_e=0\leftrightarrow F_g=1

For a transition $F_e=0\leftrightarrow F_g=1$ driven by a linearly polarized light and probed by a circularly light, quantum coherence effects are investigated. Due to the coherence between the drive Rabi frequency and Zeeman splitting, electromagnetically induced transparency, electromagnetically induced absorption, and the transition from positive to negative dispersion are obtained, as well as the populations coherently oscillating in a wide spectral region. At the zero pump-probe detuning, the subluminal and superluminal light propagation is predicted. Finally, coherent population trapping states are not highly sensitive to the refraction and absorption in such ensemble.Comment: 9 pages, 6 figure

Transverse Fresnel-Fizeau drag effects in strongly dispersive media

A light beam normally incident upon an uniformly moving dielectric medium is in general subject to bendings due to a transverse Fresnel-Fizeau light drag effect. In conventional dielectrics, the magnitude of this bending effect is very small and hard to detect. Yet, it can be dramatically enhanced in strongly dispersive media where slow group velocities in the m/s range have been recently observed taking advantage of the electromagnetically induced transparency (EIT) effect. In addition to the usual downstream drag that takes place for positive group velocities, we predict a significant anomalous upstream drag to occur for small and negative group velocities. Furthermore, for sufficiently fast speeds of the medium, higher order dispersion terms are found to play an important role and to be responsible for peculiar effects such as light propagation along curved paths and the restoration of the spatial coherence of an incident noisy beam. The physics underlying this new class of slow-light effects is thoroughly discussed

Evolutionary trait‐based approaches for predicting future global impacts of plant pathogens in the genus Phytophthora

Plant pathogens are introduced to new geographical regions ever more frequently as global connectivity increases. Predicting the threat they pose to plant health can be difficult without in‐depth knowledge of behaviour, distribution and spread. Here, we evaluate the potential for using biological traits and phylogeny to predict global threats from emerging pathogens. We use a species‐level trait database and phylogeny for 179 Phytophthora species: oomycete pathogens impacting natural, agricultural, horticultural and forestry settings. We compile host and distribution reports for Phytophthora species across 178 countries and evaluate the power of traits, phylogeny and time since description (reflecting species‐level knowledge) to explain and predict their international transport, maximum latitude and host breadth using Bayesian phylogenetic generalised linear mixed models. In the best‐performing models, traits, phylogeny and time since description together explained up to 90%, 97% and 87% of variance in number of countries reached, latitudinal limits and host range, respectively. Traits and phylogeny together explained up to 26%, 41% and 34% of variance in the number of countries reached, maximum latitude and host plant families affected, respectively, but time since description had the strongest effect. Root‐attacking species were reported in more countries, and on more host plant families than foliar‐attacking species. Host generalist pathogens had thicker‐walled resting structures (stress‐tolerant oospores) and faster growth rates at their optima. Cold‐tolerant species are reported in more countries and at higher latitudes, though more accurate interspecific empirical data are needed to confirm this finding. Policy implications. We evaluate the potential of an evolutionary trait‐based framework to support horizon‐scanning approaches for identifying pathogens with greater potential for global‐scale impacts. Potential future threats from Phytophthora include Phytophthora x heterohybrida, P. lactucae, P. glovera, P. x incrassata, P. amnicola and P. aquimorbida, which are recently described, possibly under‐reported species, with similar traits and/or phylogenetic proximity to other high‐impact species. Priority traits to measure for emerging species may be thermal minima, oospore wall index and growth rate at optimum temperature. Trait‐based horizon‐scanning approaches would benefit from the development of international and cross‐sectoral collaborations to deliver centralised databases incorporating pathogen distributions, traits and phylogeny

An autoinhibitory control element defines calcium-regulated isoforms of nitric oxide synthase

Nitric oxide synthases (NOSs) are classified functionally, based on whether calmodulin binding is Ca2+-dependent (cNOS) or Ca2+-independent (iNOS). This key dichotomy has not been defined at the molecular level. Here we show that cNOS isoforms contain a unique polypeptide insert in their FMN binding domains which is not shared with iNOS or other related flavoproteins. Previously identified autoinhibitory domains in calmodulin-regulated enzymes raise the possibility that the polypeptide insert is the autoinhibitory domain of cNOSs. Consistent with this possibility, three-dimensional molecular modeling suggested that the insert originates from a site immediately adjacent to the calmodulin binding sequence. Synthetic peptides derived from the 45-amino acid insert of endothelial NOS were found to potently inhibit binding of calmodulin and activation of cNOS isoforms. This inhibition was associated with peptide binding to NOS, rather than free calmodulin, and inhibition could be reversed by increasing calmodulin concentration. In contrast, insert-derived peptides did not interfere with the arginine site of cNOS, as assessed from [3H]NG-nitro-L-arginine binding, nor did they potently effect iNOS activity. Limited proteolysis studies showed that calmodulin's ability to gate electron flow through cNOSs is associated with displacement of the insert polypeptide; this is the first specific calmodulin-induced change in NOS conformation to be identified. Together, our findings strongly suggest that the insert is an autoinhibitory control element, docking with a site on cNOSs which impedes calmodulin binding and enzymatic activation. The autoinhibitory control element molecularly defines cNOSs and offers a unique target for developing novel NOS activators and inhibitors

Multiorder coherent Raman scattering of a quantum probe field

We study the multiorder coherent Raman scattering of a quantum probe field in a far-off-resonance medium with a prepared coherence. Under the conditions of negligible dispersion and limited bandwidth, we derive a Bessel-function solution for the sideband field operators. We analytically and numerically calculate various quantum statistical characteristics of the sideband fields. We show that the multiorder coherent Raman process can replicate the statistical properties of a single-mode quantum probe field into a broad comb of generated Raman sidebands. We also study the mixing and modulation of photon statistical properties in the case of two-mode input. We show that the prepared Raman coherence and the medium length can be used as control parameters to switch a sideband field from one type of photon statistics to another type, or from a non-squeezed state to a squeezed state and vice versa.Comment: 12 pages, 7 figures, to be published in Phys. Rev.