For the Love of Pete: An Orphan Train Story

Review of: "For the Love of Pete: An Orphan Train Story," by Ethel Barker

Prostaglandin D2 synthase induces apoptosis in pig kidney LLC-PK1 cells

Prostaglandin D2 synthase induces apoptosis in pig kidney LLC-PK1 cells.BackgroundProstaglandin D2 synthase (PGD2S), a unique member of the lipocalin family, is found at elevated levels in the serum of patients with renal impairment and has recently been implicated as a new biochemical marker of renal insufficiency. The aim of this study was to investigate the apoptotic effects of PGD2S on a pig kidney epithelial cell line (LLC-PK1) and to investigate the effects of prostaglandins and growth factors on this process.MethodsApoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL), annexin V staining, and electron microscopy.ResultsA four- to fivefold increase in apoptosis was observed in PGD2S-treated cells as compared with controls and the apoptosis appeared to act via caspase-3. A cyclooxygenase-2 inhibitor, anti-PGD2S antibody, and selenium all significantly inhibited the apoptosis induced by PGD2S; however, none had any effect on the apoptosis induced by the known apoptotic inducer camptothecin. Furthermore, prostaglandins E1 and E2, known to induce mitogen-activated protein (MAP) kinase phosphorylation and exhibit cytoprotective effects, both inhibited PGD2S-induced apoptosis, while prostaglandin H2 had no significant effect. Growth factors such as insulin, insulin-like growth factor-1, and platelet-derived growth factor also decreased PGD2S-induced apoptosis. In addition, PGD2S isolated from human serum seemed slightly more effective at inducing apoptosis than recombinantly expressed protein.ConclusionsWe report on the induction of apoptosis by PGD2S in LLC-PK1 pig kidney epithelial cells, and speculate that the accumulation of PGD2S in the serum of kidney failure patients may further exacerbate renal problems and is most likely regulated by other prostaglandins and growth factors

Rapid Cue-Specific Remodeling of the Nascent Axonal Proteome.

Axonal protein synthesis and degradation are rapidly regulated by extrinsic signals during neural wiring, but the full landscape of proteomic changes remains unknown due to limitations in axon sampling and sensitivity. By combining pulsed stable isotope labeling of amino acids in cell culture with single-pot solid-phase-enhanced sample preparation, we characterized the nascent proteome of isolated retinal axons on an unparalleled rapid timescale (5 min). Our analysis detects 350 basally translated axonal proteins on average, including several linked to neurological disease. Axons stimulated by different cues (Netrin-1, BDNF, Sema3A) show distinct signatures with more than 100 different nascent protein species up- or downregulated within the first 5 min followed by further dynamic remodeling. Switching repulsion to attraction triggers opposite regulation of a subset of common nascent proteins. Our findings thus reveal the rapid remodeling of the axonal proteomic landscape by extrinsic cues and uncover a logic underlying attraction versus repulsion

Dimensionality reduction for point feature SLAM problems with spherical covariance matrices

© 2014 Elsevier Ltd. All rights reserved. The main contribution of this paper is the dimensionality reduction for multiple-step 2D point feature based Simultaneous Localization and Mapping (SLAM), which is an extension of our previous work on one-step SLAM (Wang et al.; 2013). It has been proved that SLAM with multiple robot poses and a number of point feature positions as variables is equivalent to an optimization problem with only the robot orientations as variables, when the associated uncertainties can be described using spherical covariance matrices. This reduces the dimension of original problem from 3m+2n to m only (where m is the number of poses and n is the number of features). The optimization problem after dimensionality reduction can be solved numerically using the unconstrained optimization algorithms. While dimensionality reduction may not provide computational saving for all nonlinear optimization problems, for some SLAM problems we can achieve benefits such as improvement on time consumption and convergence. For the special case of two-step SLAM when the orientation information from odometry is not incorporated, an algorithm that can guarantee to obtain the globally optimal solution (in the maximum likelihood sense) is derived. Simulation and experimental datasets are used to verify the equivalence between the reduced nonlinear optimization problem and the original full optimization problem, as well as the proposed new algorithm for obtaining the globally optimal solution for two-step SLAM

JUMPING MODE ATOMIC FORCE MICROSCOPY ON GRANA MEMBRANES FROM SPINACH

FWN – Publicaties zonder aanstelling Universiteit Leide

A New Crucial Protein Interaction Element That Targets the Adenovirus E4-ORF1 Oncoprotein to Membrane Vesicles

Human adenovirus type 9 exclusively elicits mammary tumors in experimental animals, and the primary oncogenic determinant of this virus is the E4-ORF1 oncogene, as opposed to the well-known E1A and E1Boncogenes. The tumorigenic potential of E4-ORF1, as well as its ability to oncogenically stimulate phosphatidylinositol 3-kinase (PI3K), depends on a carboxyl-terminal PDZ domain-binding motif (PBM) that mediates interactions with several different membrane-associated cellular PDZ proteins, including MUPP1, PATJ, MAGI-1, ZO-2, and Dlg1. Nevertheless, because certain E4-ORF1 mutations that alter neither the sequence nor the function of the PBM abolish E4-ORF1-induced PI3K activation and cellular transformation, we reasoned that E4-ORF1 must possess an additional crucial protein element. In the present study, we identified seven E4-ORF1 amino acid residues that define this new element, designated domain 2, and showed that it mediates binding to a 70-kDa cellular phosphoprotein. We also discovered that domain 2 or the PBM independently promotes E4-ORF1 localization to cytoplasmic membrane vesicles and that this activity of domain 2 depends on E4-ORF1 trimerization. Consistent with the latter observation, molecular-modeling analyses predicted that E4-ORF1 trimerization brings together six out of seven domain 2 residues at each of the three subunit interfaces. These findings importantly demonstrate that PI3K activation and cellular transformation induced by E4-ORF1 require two separate protein interaction elements, domain 2 and the PBM, each of which targets E4-ORF1 to vesicle membranes in cells

A dynamic perspective on affect and creativity

10.5465/amj.2010.0894Academy of Management Journal562432-45

Reaction of Ph2C(X)(CO2H) (X = OH, NH2) with [VO(OR)3] (R = Et, nPr): Structure, magnetic susceptibility and ROP capability

Reaction of [VO(OR)3] (R = Et, nPr) with 2,2′-diphenylglycine afforded the alkoxide-bridged dimers {[VO(OR)(μ-OR)][Ph2C(NH2)(CO2)]}2, whereas use of benzilic acid, in the presence of alkali metals, afforded 16-membered metallocycles {V8(O)4M(OR)8[Ph2C(OH)(CO2)]12} (M = <1 Na, K). For the ring systems, magnetic susceptibility data is consistent with mixed-valence vanadium with an average oxidation state of 3.5. The dimer and ring systems are capable of the ring opening polymerisation (ROP) of ϵ-caprolactone under N2, air, or as melts affording mostly low to medium molecular weight cyclic and linear products

Type I and type II interferon responses in two human liver cell lines (Huh-7 and HuH6)

AbstractMost studies investigating the biology of Hepatitis C virus (HCV) have used the human hepatoma cell line Huh-7 or subclones thereof, as these are the most permissive cell lines for HCV infection and replication. Other cell lines also support replication of HCV, most notably the human hepatoblastoma cell line HuH6. HCV replication in cell culture is generally highly sensitive to interferons (IFNs) and differences in the IFN-mediated inhibition of virus replication may reflect alterations in the IFN-induced antiviral response inherent to different host cells. For example, HCV replication is highly sensitive to IFN-γ treatment in Huh-7, but not in HuH6 cells. In this study, we used microarray-based gene expression profiling to compare the response of Huh-7 and HuH6 cells to stimulation with IFN-α and IFN-γ. Furthermore, we determined whether the resistance of HCV replication in HuH6 cells can be linked to differences in the expression profile of IFN-regulated genes. Although both cells lines responded to IFNs with rapid changes in gene expression, thereby demonstrating functional type I and type II signaling pathways, differences were observed for a number of genes. Raw and normalized expression data have been deposited in GEO under accession number GSE68927

ACCOUNTING OF DAMPING IN THE EVALUATION AND SEISMIC STABILITY TASKS OF BUILDINGS AND STRUCTURES

It is proved that for the majority of building structures characterized by different damping elements. The goal of constructing matrix hysteretic damping that takes into account the internal friction in the material. The study is based on generalized hypothesis of E. S. Sorokin on the proportionality of the matrices of damping and stiffness elements of the structure. The methods of accounting for damping in the evaluation of the earthquake resistance of structures. The exact and approximate methods of decomposition of the motion equations for the mode shapes are considered. It is established that the empirical criterion of the approximate method applicability of accounting for damping and its refinement on the basis of the initial approximation can serve as the correlation coefficients of waveforms. It is shown that for non-proportional damping it is possible to approximate the decomposition of movements according to oscillations forms of non-damped system, if the forms are weakly correlated