Galaxy evolution from strong lensing statistics: the differential evolution of the velocity dispersion function in concord with the LambdaCDM paradigm

We study galaxy evolution from z=1 to z=0 as a function of velocity dispersion sigma for galaxies with sigma > 95 km/s based on the measured and Monte Carlo realised local velocity dispersion functions (VDFs) of galaxies and the revised statistical properties of 30 strongly-lensed sources. We assume that the total (luminous plus dark) mass profile of a galaxy is isothermal in the optical region for 0 < z < 1 as suggested by mass modelling of lensing galaxies. For the evolutionary behaviours of the VDFs we find that: (1) the number density of massive (mostly early-type) galaxies with sigma > 200 km/s evolves differentially in the way that the number density evolution is greater at a higher velocity dispersion; (2) the number density of intermediate and low mass early-type galaxies (95 km/s < sigma < 200 km/s) is nearly constant; (3) the late-type VDF transformed from the Monte Carlo realised circular velocity function is consistent with no evolution in its shape or integrated number density consistent with galaxy survey results. These evolutionary behaviours of the VDFs are strikingly similar to those of the dark halo mass function (DMF) from N-body simulations and the stellar mass function (SMF) predicted by recent semi-analytic models of galaxy formation under the current LambdaCDM hierarchical structure formation paradigm. Interestingly, the VDF evolutions appear to be qualitatively different from ``stellar mass-downsizing'' evolutions obtained by many galaxy surveys. The coevolution of the DMF, the VDF and the SMF is investigated in quantitative detail in a following paper. We consider several possible systematic errors for the lensing analysis and find that they are not likely to alter the conclusions.(abridged)Comment: MNRAS, accepted (20 pages, 12 figures), parts of section 6 of v2 moved to a following wor

The coevolution of the velocity and mass functions of galaxies and dark haloes

We employ a bias-corrected abundance matching technique to investigate the coevolution of the LCDM dark halo mass function (HMF), the observationally derived velocity dispersion and stellar mass functions (VDF, SMF) of galaxies between z=1 and 0. We use for the first time the evolution of the VDF constrained through strong lensing statistics by Chae (2010) for galaxy-halo abundance matching studies. As a local benchmark we use a couple of z ~ 0 VDFs (a Monte-Carlo realised VDF based on SDSS DR5 and a directly measured VDF based on SDSS DR6). We then focus on connecting the VDF evolution to the HMF evolution predicted by N-body simulations and the SMF evolution constrained by galaxy surveys. On the VDF-HMF connection, we find that the local dark halo virial mass-central stellar velocity dispersion (Mvir-sigma) relation is in good agreement with the individual properties of well-studied low-redshift dark haloes, and the VDF evolution closely parallels the HMF evolution meaning little evolution in the Mvir-sigma relation. On the VDF-SMF connection, it is also likely that the stellar mass-stellar velocity dispersion (Mstar-sigma) relation evolves little taking the abundance matching results together with other independent observational results and hydrodynamic simulation results. Our results support the simple picture that as the halo grows hierarchically, the stellar mass and the central stellar velocity dispersion grow in parallel. We discuss possible implications of this parallel coevolution for galaxy formation and evolution under the LCDM paradigm.Comment: 15 pages, 12 figures, MNRAS, revised extensively after referee comment

Intra-Arterial Thrombolysis after Full-Dose Intravenous tPA via the "Drip and Ship" Approach in Patients with Acute Ischemic Stroke: Preliminary Report

According to the "drip and ship" concept, patients who are not responsive to intravenous tissue plasminogen activator (IV-tPA) at a community hospital may be candidates for subsequent intra-arterial (IA) thrombolysis at a comprehensive stroke center. We elucidated the efficacy and safety of combined IV/IA thrombolysis via the drip and ship approach. We retrospectively reviewed patients with acute ischemic stroke who underwent combined IV/IA thrombolysis between March 2006 and June 2009. The patients were divided into two groups (inside hospital IV-tPA vs. outside hospital IV-tPA). We compared the short- and long-term clinical outcome, recanalization rate, intracranial hemorrhage after the procedure, and onset to treatment time between the two groups. A total of 23 patients with inside hospital IV-tPA and 10 patients with outside hospital IV-tPA were included. The mean pre-treatment National Institutes of Health Stroke Scale (NIHSS) scores were 15.8 and 17.5, respectively. Baseline characteristics were not significantly different between the two groups. The NIHSS score at 1 week and favorable outcome rate (modified Rankin Scale ≤2) 3 months after the procedure were not significantly different (p=0.730 and p=0.141, respectively). The rate of recanalization and intracranial hemorrhage were not significantly different (p=0.560 and p=0.730, respectively). The onset to IA thrombolysis time was also not significantly different (222.7 vs. 239.3 minutes, p=0.455). Our results suggest that initiation of IV-tPA in a community hospital with rapid transfer to a comprehensive stroke center for subsequent IA thrombolysis can be a safe and feasible therapeutic option in acute stroke management

SAUR63 stimulates cell growth at the plasma membrane

In plants, regulated cell expansion determines organ size and shape. Several members of the family of redundantly acting Small Auxin Up RNA (SAUR) proteins can stimulate plasma membrane (PM) H+-ATPase proton pumping activity by inhibiting PM-associated PP2C.D phosphatases, thereby increasing the PM electrochemical potential, acidifying the apoplast, and stimulating cell expansion. Similarly, Arabidopsis thaliana SAUR63 was able to increase growth of various organs, antagonize PP2C.D5 phosphatase, and increase H+-ATPase activity. Using a gain-of-function approach to bypass genetic redundancy, we dissected structural requirements for SAUR63 growth-promoting activity. The divergent N-terminal domain of SAUR63 has a predicted basic amphipathic α-helix and was able to drive partial PM association. Deletion of the N-terminal domain decreased PM association of a SAUR63 fusion protein, as well as decreasing protein level and eliminating growth-promoting activity. Conversely, forced PM association restored ability to promote H+-ATPase activity and cell expansion, indicating that SAUR63 is active when PM-associated. Lipid binding assays and perturbations of PM lipid composition indicate that the N-terminal domain can interact with PM anionic lipids. Mutations in the conserved SAUR domain also reduced PM association in root cells. Thus, both the N-terminal domain and the SAUR domain may cooperatively mediate the SAUR63 PM association required to promote growth

Sl-IAA3, a tomato Aux/IAA at the crossroads of auxin and ethylene signalling involved in differential growth

Whereas the interplay of multiple hormones is essential for most plant developmental processes, the key integrating molecular players remain largely undiscovered or uncharacterized. It is shown here that a member of the tomato auxin/indole-3-acetic acid (Aux/IAA) gene family, Sl-IAA3, intersects the auxin and ethylene signal transduction pathways. Aux/IAA genes encode short-lived transcriptional regulators central to the control of auxin responses. Their functions have been defined primarily by dominant, gain-of-function mutant alleles in Arabidopsis. The Sl-IAA3 gene encodes a nuclear-targeted protein that can repress transcription from auxin-responsive promoters. Sl-IAA3 expression is auxin and ethylene dependent, is regulated on a tight tissue-specific basis, and is associated with tissues undergoing differential growth such as in epinastic petioles and apical hook. Antisense down-regulation of Sl-IAA3 results in auxin and ethylene-related phenotypes, including altered apical dominance, lower auxin sensitivity, exaggerated apical hook curvature in the dark and reduced petiole epinasty in the light. The results provide novel insights into the roles of Aux/IAAs and position the Sl-IAA3 protein at the crossroads of auxin and ethylene signalling in tomato

Cellular Mechanisms of Etrolizumab Treatment in Inflammatory Bowel Disease

Background: Anti-integrin therapy is a new frontline strategy in the treatment of inflammatory bowel diseases (IBD). The anti-β7 integrin antibody etrolizumab is currently being investigated for safety and efficacy in Crohn’s disease (CD) and ulcerative colitis (UC) in several phase III trials. Mechanistically, etrolizumab is known to block β7 integrin ligand binding and reduces intestinal trafficking of β7-expressing cells. Etrolizumab blocks β7 integrin ligand binding and reduces β7-positive lymphocyte migration and retention in the inflamed gut mucosa, but the exact mechanisms by which this inhibition occurs are not fully understood.Methods: Cellular effects of etrolizumab or etrolizumab surrogate antibody (etrolizumab-s) were investigated in cell culture models and analyzed by flow cytometry, fluorescence microscopy, ImageStream®, stimulated emission depletion (STED) microscopy and functional dynamic in vitro adhesion assays. Moreover, effects on α4β7 integrin were compared with the pharmacodynamically similar antibody vedolizumab.Results: As demonstrated by several different approaches, etrolizumab and etrolizumab-s treatment led to internalization of β7 integrin. This resulted in impaired dynamic adhesion to MAdCAM-1. Internalized β7 integrin localized in endosomes and re-expression of β7 was dependent on de novo protein synthesis. In vitro etrolizumab treatment did not lead to cellular activation or cytokine secretion and did not induce cytotoxicity. Internalization of α4β7 integrin was increased with etrolizumab compared with vedolizumab.Discussion: Our data suggest that etrolizumab does not elicit secondary effector functions on the single cell level. Integrin internalization may be an important mechanism of action of etrolizumab, which might explain some but not all immunological effects observed with etrolizumab

Characterization of the Arabidopsis thaliana 2-Cys peroxiredoxin interactome

This document is the Accepted Manuscript of the following article: Delphine Cerveau, et al, ‘Characterization of the Arabidopsis thaliana 2-Cys peroxiredoxin interactome’, Plant Science, Vol. 252, pp. 30-41, July 2016, doi: https://doi.org/10.1016/j.plantsci.2016.07.003. This manuscript version is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License CC BY NC-ND 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.Peroxiredoxins are ubiquitous thiol-dependent peroxidases for which chaperone and signaling roles havebeen reported in various types of organisms in recent years. In plants, the peroxidase function of thetwo typical plastidial 2-Cys peroxiredoxins (2-Cys PRX A and B) has been highlighted while the otherfunctions, particularly in ROS-dependent signaling pathways, are still elusive notably due to the lack ofknowledge of interacting partners. Using an ex vivo approach based on co-immunoprecipitation of leafextracts from Arabidopsis thaliana wild-type and mutant plants lacking 2-Cys PRX expression followedby mass spectrometry-based proteomics, 158 proteins were found associated with 2-Cys PRXs. Alreadyknown partners like thioredoxin-related electron donors (Chloroplastic Drought-induced Stress Proteinof 32 kDa, Atypical Cysteine Histidine-rich Thioredoxin 2) and enzymes involved in chlorophyll synthe-sis (Protochlorophyllide OxidoReductase B) or carbon metabolism (Fructose-1,6-BisPhosphatase) wereidentified, validating the relevance of the approach. Bioinformatic and bibliographic analyses allowedthe functional classification of the identified proteins and revealed that more than 40% are localized inplastids. The possible roles of plant 2-Cys PRXs in redox signaling pathways are discussed in relation withthe functions of the potential partners notably those involved in redox homeostasis, carbon and aminoacid metabolisms as well as chlorophyll biosynthesis.Peer reviewe

Cerebellum Abnormalities in Idiopathic Generalized Epilepsy with Generalized Tonic-Clonic Seizures Revealed by Diffusion Tensor Imaging

Although there is increasing evidence suggesting that there may be subtle abnormalities in idiopathic generalized epilepsy (IGE) patients using modern neuroimaging techniques, most of these previous studies focused on the brain grey matter, leaving the underlying white matter abnormalities in IGE largely unknown, which baffles the treatment as well as the understanding of IGE. In this work, we adopted multiple methods from different levels based on diffusion tensor imaging (DTI) to analyze the white matter abnormalities in 14 young male IGE patients with generalized tonic-clonic seizures (GTCS) only, comparing with 29 age-matched male healthy controls. First, we performed a voxel-based analysis (VBA) of the fractional anisotropy (FA) images derived from DTI. Second, we used a tract-based spatial statistics (TBSS) method to explore the alterations within the white matter skeleton of the patients. Third, we adopted region-of-interest (ROI) analyses based on the findings of VBA and TBSS to further confirm abnormal brain regions in the patients. At last, considering the convergent evidences we found by VBA, TBSS and ROI analyses, a subsequent probabilistic fiber tractography study was performed to investigate the abnormal white matter connectivity in the patients. Significantly decreased FA values were consistently observed in the cerebellum of patients, providing fresh evidence and new clues for the important role of cerebellum in IGE with GTCS

Simultaneous measurements of electronic conduction and Raman response in molecular junctions

Electronic conduction through single molecules is affected by the molecular electronic structure as well as by other information that is extremely difficult to assess, such as bonding geometry and chemical environment. The lack of an independent diagnostic technique has long hampered single-molecule conductance studies. We report simultaneous measurement of the conductance and the Raman spectra of nanoscale junctions used for single-molecule electronic experiments. Blinking and spectral diffusion in the Raman response of both para-mercaptoaniline and a fluorinated oligophenylyne ethynylene correlate in time with changes in the electronic conductance. Finite difference time domain calculations confirm that these correlations do not result from the conductance modifying the Raman enhancement. Therefore, these observations strongly imply that multimodal sensing of individual molecules is possible in these mass-producible nanostructures.Comment: 16 pages, 5 figures + supporting material of 15 pages, 10 figure

Allomorphy as a mechanism of post-translational control of enzyme activity

Enzyme regulation is vital for metabolic adaptability in living systems. Fine control of enzyme activity is often delivered through post-translational mechanisms, such as allostery or allokairy. β-phosphoglucomutase (βPGM) from Lactococcus lactis is a phosphoryl transfer enzyme required for complete catabolism of trehalose and maltose, through the isomerisation of β-glucose 1-phosphate to glucose 6-phosphate via β-glucose 1,6-bisphosphate. Surprisingly for a gatekeeper of glycolysis, no fine control mechanism of βPGM has yet been reported. Herein, we describe allomorphy, a post-translational control mechanism of enzyme activity. In βPGM, isomerisation of the K145-P146 peptide bond results in the population of two conformers that have different activities owing to repositioning of the K145 sidechain. In vivo phosphorylating agents, such as fructose 1,6-bisphosphate, generate phosphorylated forms of both conformers, leading to a lag phase in activity until the more active phosphorylated conformer dominates. In contrast, the reaction intermediate β-glucose 1,6-bisphosphate, whose concentration depends on the β-glucose 1-phosphate concentration, couples the conformational switch and the phosphorylation step, resulting in the rapid generation of the more active phosphorylated conformer. In enabling different behaviours for different allomorphic activators, allomorphy allows an organism to maximise its responsiveness to environmental changes while minimising the diversion of valuable metabolites