Determination of Rod and Cone Influence to the Early and Late Dynamic of the Pupillary Light Response.

PURPOSE: This study aims to identify which aspects of the pupil light reflex are most influenced by rods and cones independently by analyzing pupil recordings from different mouse models of photoreceptor deficiency. METHODS: One-month-old wild type (WT), rodless (Rho-/-), coneless (Cnga3-/-), or photoreceptor less (Cnga3-/-; Rho-/- or Gnat1-/-) mice were subjected to brief red and blue light stimuli of increasing intensity. To describe the initial dynamic response to light, the maximal pupillary constriction amplitudes and the derivative curve of the first 3 seconds were determined. To estimate the postillumination phase, the constriction amplitude at 9.5 seconds after light termination was related to the maximal constriction amplitude. RESULTS: Rho-/- mice showed decreased constriction amplitude but more prolonged pupilloconstriction to all blue and red light stimuli compared to wild type mice. Cnga3-/- mice had constriction amplitudes similar to WT however following maximal constriction, the early and rapid dilation to low intensity blue light was decreased. To high intensity blue light, the Cnga3-/- mice demonstrated marked prolongation of the pupillary constriction. Cnga3-/-; Rho-/- mice had no pupil response to red light of low and medium intensity. CONCLUSIONS: From specific gene defective mouse models which selectively voided the rod or cone function, we determined that mouse rod photoreceptors are highly contributing to the pupil response to blue light stimuli but also to low and medium red stimuli. We also observed that cone cells mainly drive the partial rapid dilation of the initial response to low blue light stimuli. Thus photoreceptor dysfunction can be derived from chromatic pupillometry in mouse models

Paramagnetic Meissner Effect in Multiply-Connected Superconductors

We have measured a paramagnetic Meissner effect in Nb-Al2O3-Nb Josephson junction arrays using a scanning SQUID microscope. The arrays exhibit diamagnetism for some cooling fields and paramagnetism for other cooling fields. The measured mean magnetization is always less than 0.3 flux quantum (in terms of flux per unit cell of the array) for the range of cooling fields investigated. We demonstrate that a new model of magnetic screening, valid for multiply-connected superconductors, reproduces all of the essential features of paramagnetism that we observe and that no exotic mechanism, such as d-wave superconductivity, is needed for paramagnetism.Comment: 4 pages, 3 figures, LaTe

Aging Effect in Ceramic Superconductors

A three-dimensional lattice of the Josephson junctions with a finite self-conductance is employed to model ceramic superconductors. Using Monte Carlo simulations it is shown that the aging disappears in the strong screening limit. In the weeak screening regime aging is present even at low temperatures. For intermediate values of the self-inductance aging occurs at intermediate temperatures interval but is suppressed entirely at high and low temperatures. Our results are in good agreement with experiments.Comment: 5 pages, 5 eps figures, to appear in Physical Review Letter

Multigenic lentiviral vectors for combined and tissue-specific expression of miRNA- and protein-based antiangiogenic factors.

Lentivirus-based gene delivery vectors carrying multiple gene cassettes are powerful tools in gene transfer studies and gene therapy, allowing coexpression of multiple therapeutic factors and, if desired, fluorescent reporters. Current strategies to express transgenes and microRNA (miRNA) clusters from a single vector have certain limitations that affect transgene expression levels and/or vector titers. In this study, we describe a novel vector design that facilitates combined expression of therapeutic RNA- and protein-based antiangiogenic factors as well as a fluorescent reporter from back-to-back RNApolII-driven expression cassettes. This configuration allows effective production of intron-embedded miRNAs that are released upon transduction of target cells. Exploiting such multigenic lentiviral vectors, we demonstrate robust miRNA-directed downregulation of vascular endothelial growth factor (VEGF) expression, leading to reduced angiogenesis, and parallel impairment of angiogenic pathways by codelivering the gene encoding pigment epithelium-derived factor (PEDF). Notably, subretinal injections of lentiviral vectors reveal efficient retinal pigment epithelium-specific gene expression driven by the VMD2 promoter, verifying that multigenic lentiviral vectors can be produced with high titers sufficient for in vivo applications. Altogether, our results suggest the potential applicability of combined miRNA- and protein-encoding lentiviral vectors in antiangiogenic gene therapy, including new combination therapies for amelioration of age-related macular degeneration

Induced paramagnetic states by localized π\pi -loops in grain boundaries

Recent experiments on high-temperature superconductors show paramagnetic behavior localized at grain boundaries (GB). This paramagnetism can be attributed to the presence unconventional d-wave induced $\pi$-junctions. By modeling the GB as an array of $\pi$ and conventional Josephson junction we determine the conditions of the occurrence of the paramagnetic behavior.Comment: 4 pages, 4 figures, submitted to Phys. Rev. Let

Non-Fermi liquid behavior of SrRuO_3 -- evidence from infrared conductivity

The reflectivity of the itinerant ferromagnet SrRuO_3 has been measured between 50 and 25,000 cm-1 at temperatures ranging from 40 to 300 K, and used to obtain conductivity, scattering rate, and effective mass as a function of frequency and temperature. We find that at low temperatures the conductivity falls unusually slowly as a function of frequency (proportional to \omega^{-1/2}), and at high temperatures it even appears to increase as a function of frequency in the far-infrared limit. The data suggest that the charge dynamics of SrRuO_3 are substantially different from those of Fermi-liquid metals.Comment: 4 pages, 3 postscript figure

Bmi1 loss produces an increase in astroglial cells and a decrease in neural stem cell population and proliferation

The polycomb transcriptional repressor Bmi1 promotes cell cycle progression, controls cell senescence, and is implicated in brain development. Loss of Bmi1 leads to a decreased brain size and causes progressive ataxia and epilepsy. Recently, Bmi1 was shown to control neural stem cell (NSC) renewal. However, the effect of Bmi1 loss on neural cell fate in vivo and the question whether the action of Bmi1 was intrinsic to the NSCs remained to be investigated. Here, we show that Bmi1 is expressed in the germinal zone in vivo and in NSCs as well as in progenitors proliferating in vitro, but not in differentiated cells. Loss of Bmi1 led to a decrease in proliferation in zones known to contain progenitors: the newborn cortex and the newborn and adult subventricular zone. This decrease was accentuated in vitro, where we observed a drastic reduction in NSC proliferation and renewal because of NSC-intrinsic effects of Bmi1 as shown by the means of RNA interference. Bmi1(-/-) mice also presented more astrocytes at birth, and a generalized gliosis at postnatal day 30. At both stages, colocalization of bromodeoxyuridine and GFAP demonstrated that Bmi1 loss did not prevent astrocyte precursor proliferation. Supporting these observations, Bmi1(-/-) neurospheres generate preferentially astrocytes probably attributable to a different responsiveness to environmental factors. Bmi1 is therefore necessary for NSC renewal in a cell-intrinsic mode, whereas the altered cell pattern of the Bmi1(-/-) brain shows that in vivo astrocyte precursors can proliferate in the absence of Bmi1

Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditions

Several clinical trials are exploring therapeutic effect of human CD34(+) cells in ischemic diseases, including myocardial infarction. Unfortunately, most of the cells die few days after delivery. Herein we show that lysophosphatidic acid (LPA)-treated human umbilical cord blood-derived CD34(+) cells cultured under hypoxic and serum-deprived conditions present 2.2-fold and 1.3-fold higher survival relatively to non-treated cells and prostaglandin E2-treated cells, respectively. The pro-survival effect of LPA is concentration- and time-dependent and it is mediated by the activation of peroxisome proliferator-activator receptor γ (PPARγ) and downstream, by the activation of pro-survival ERK and Akt signaling pathways and the inhibition of mitochondrial apoptotic pathway. In hypoxia and serum-deprived culture conditions, LPA induces CD34(+) cell proliferation without maintaining the their undifferentiating state, and enhances IL-8, IL-6 and G-CSF secretion during the first 12 h compared to non-treated cells. LPA-treated CD34(+) cells delivered in fibrin gels have enhanced survival and improved cardiac fractional shortening at 2 weeks on rat infarcted hearts as compared to hearts treated with placebo. We have developed a new platform to enhance the survival of CD34(+) cells using a natural and cost-effective ligand and demonstrated its utility in the preservation of the functionality of the heart after infarction.info:eu-repo/semantics/publishedVersio

Fate specification and tissue-specific cell cycle control of the <i>Caenorhabditis elegans</i> intestine

Coordination between cell fate specification and cell cycle control in multicellular organisms is essential to regulate cell numbers in tissues and organs during development, and its failure may lead to oncogenesis. In mammalian cells, as part of a general cell cycle checkpoint mechanism, the F-box protein β-transducin repeat-containing protein (β-TrCP) and the Skp1/Cul1/F-box complex control the periodic cell cycle fluctuations in abundance of the CDC25A and B phosphatases. Here, we find that the Caenorhabditis elegans β-TrCP orthologue LIN-23 regulates a progressive decline of CDC-25.1 abundance over several embryonic cell cycles and specifies cell number of one tissue, the embryonic intestine. The negative regulation of CDC-25.1 abundance by LIN-23 may be developmentally controlled because CDC-25.1 accumulates over time within the developing germline, where LIN-23 is also present. Concurrent with the destabilization of CDC-25.1, LIN-23 displays a spatially dynamic behavior in the embryo, periodically entering a nuclear compartment where CDC-25.1 is abundant

Non-Fermi liquid behavior and scaling of low frequency suppression in optical conductivity spectra of CaRuO3_3

Optical conductivity spectra $\sigma_1(\omega)$ of paramagnetic CaRuO$_3$ are investigated at various temperatures. At T=10 K, it shows a non-Fermi liquid behavior of $\sigma_1(\omega)\sim 1/{\omega}^{\frac 12}$, similar to the case of a ferromagnet SrRuO$_3$. As the temperature ($T$) is increased, on the other hand, $\sigma_1(\omega)$ in the low frequency region is progressively suppressed, deviating from the 1/{\omega}^{\frac 12%}-dependence. Interestingly, the suppression of $\sigma_1(\omega)$ is found to scale with $\omega /T$ at all temperatures. The origin of the $$ scaling behavior coupled with the non-Fermi liquid behavior is discussed.Comment: 4 pages, 3 figure