A role for the cleaved cytoplasmic domain of E-cadherin in the nucleus

Cell-cell contacts play a vital role in intracellular signaling, although the molecular mechanisms of these signaling pathways are not fully understood. E-cadherin, an important mediator of cell-cell adhesions, has been shown to be cleaved by γ-secretase. This cleavage releases a fragment of E-cadherin, E-cadherin C-terminal fragment 2 (E-cad/CTF2), into the cytosol. Here, we study the fate and function of this fragment. First, we show that coexpression of the cadherin-binding protein, p120 catenin (p120), enhances the nuclear translocation of E-cad/CTF2. By knocking down p120 with short interfering RNA, we also demonstrate that p120 is necessary for the nuclear localization of E-cad/CTF2. Furthermore, p120 enhances and is required for the specific binding of E-cad/CTF2 to DNA. Finally, we show that E-cad/CTF2 can regulate the p120-Kaiso-mediated signaling pathway in the nucleus. These data indicate a novel role for cleaved E-cadherin in the nucleus

Continuous roadmapping in liver TACE procedures using 2D–3D catheter-based registration

PURPOSE: Fusion of pre/perioperative images and intra-operative images may add relevant information during image-guided procedures. In abdominal procedures, respiratory motion changes the position of organs, and thus accurate image guidance requires a continuous update of the spatial alignment of the (pre/perioperative) information with the organ position during the intervention. METHODS: In this paper, we propose a method to register in real time perioperative 3D rotational angiography images (3DRA) to intra-operative single-plane 2D fluoroscopic images for improved guidance in TACE interventions. The method uses the shape of 3D vessels extracted from the 3DRA and the 2D catheter shape extracted from fluoroscopy. First, the appropriate 3D vessel is selected from the complete vascular tree using a shape similarity metric. Subsequently, the catheter is registered to this vessel, and the 3DRA is visualized based on the registration results. The method is evaluated on simulated data and clinical data. RESULTS: The first selected vessel, ranked with the shape similarity metric, is used more than 39 % in the final registration and the second more than 21 %. The median of the closest corresponding points distance between 2D angiography vessels and projected 3D vessels is 4.7–5.4 mm when using the brute force optimizer and 5.2–6.6 mm when using the Powell optimizer. CONCLUSION: We present a catheter-based registration method to continuously fuse a 3DRA roadmap arterial tree onto 2D fluoroscopic images with an efficient shape similarity

Diabetes mellitus remission in three cats with hypersomatotropism after cabergoline treatment

Three diabetic cats presented with polyuria, polydipsia, polyphagia and poor glycemic control. Cat 1 displayed prognathia inferior and had a body condition score (BCS) of 4/5; cat 2 had a BCS of 5/5; and cat 3 had broad facial features. Serum insulin-like growth factor 1 concentrations were compatible with hypersomatotropism in cat 1 and cat 2 (>1500 ng/ml and 1200 ng/ml, respectively) and just below the cut-off of 1000 ng/ml (947 ng/ml) in cat 3; in this last cat diagnosis was further supported by the presence of pituitary enlargement on MRI. Oral cabergoline (10 μg/kg q48h) was initiated. Insulin requirements progressively reduced, as evidenced by daily blood glucose monitoring and weekly blood glucose curves. Diabetic remission occurred in all three cats between the second and third months of cabergoline treatment. At the time of writing, remission has persisted thus far (cat 1: 23 months; cat 2: 14 months; cat 3: 38 months). Relevance and novel information: To our knowledge, these are the first reported cases of diabetic remission in cats with hypersomatotropism after cabergoline treatment, despite previous reports of this being an ineffective treatment. Further work is indicated to determine why some cats do, and others do not, respond to this treatment.Fil: Miceli, Diego Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires; ArgentinaFil: Vidal, Patricia Noemi. Universidad de Buenos Aires; ArgentinaFil: Pompili, Gustavo A. Universidad de Buenos Aires; ArgentinaFil: Castillo, Víctor A. Universidad de Buenos Aires; ArgentinaFil: Soler Arias, Elber A. Universidad de Buenos Aires; ArgentinaFil: Niessen, Stijn JM. Royal Veterinary College University ; Reino Unid

Gender, style diversity and their effect on fund performance

© 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license(http://creativecommons.org/licenses/by/4.0/).This paper examines the performance of 358 European diversified equity mutual funds controlling for gender diversity. Fund performance is evaluated against funds’ designated market indices and representative style portfolios. Consistently with previous studies, proper statistical tests point to the absence of significant differences in performance and risk between female and male managed funds. However, perverse market timing manifests itself mainly in female managed funds and in the left tail of the returns distribution. Interestingly, at fund level there is evidence of significant overperformance that survives even after accounting for funds’ exposure to known risk factors. Employing a quantile regression approach reveals that fund performance is highly dependent on the selection of the specific quantile of the returns distribution; also, style consistency for male and female managers manifests itself across different quantiles. These results have important implications for fund management companies and for retail investors’ asset allocation strategies

The Rotterdam Scan Study: design update 2016 and main findings

Imaging plays an essential role in research on neurological diseases in the elderly. The Rotterdam Scan Study was initiated as part of the ongoing Rotterdam Study with the aim to elucidate the causes of neurological disease by performing imaging of the brain in a prospective population-based setting. Initially, in 1995 and 1999, random subsamples of participants from the Rotterdam Study underwent neuroimaging, whereas from 2005 onwards MRI has been implemented into the core protocol of the Rotterdam Study. In this paper, we discuss the background and rationale of the Rotterdam Scan Study. Moreover, we describe the imaging protocol, image post-processing techniques, and the main findings to date. Finally, we provide recommendations for future research, which will also be topics of investigation in the Rotterdam Scan Study

Heterochromatin-Driven Nuclear Softening Protects the Genome against Mechanical Stress-Induced Damage

Summary Tissue homeostasis requires maintenance of functional integrity under stress. A central source of stress is mechanical force that acts on cells, their nuclei, and chromatin, but how the genome is protected against mechanical stress is unclear. We show that mechanical stretch deforms the nucleus, which cells initially counteract via a calcium-dependent nuclear softening driven by loss of H3K9me3-marked heterochromatin. The resulting changes in chromatin rheology and architecture are required to insulate genetic material from mechanical force. Failure to mount this nuclear mechanoresponse results in DNA damage. Persistent, high-amplitude stretch induces supracellular alignment of tissue to redistribute mechanical energy before it reaches the nucleus. This tissue-scale mechanoadaptation functions through a separate pathway mediated by cell-cell contacts and allows cells/tissues to switch off nuclear mechanotransduction to restore initial chromatin state. Our work identifies an unconventional role of chromatin in altering its own mechanical state to maintain genome integrity in response to deformation.Peer reviewe

Search for Heavy Isosinglet Neutrino in e+e- Annihilation at LEP

We report on a search for the first generation heavy neutrino that is an isosinglet under the standard SU(2)_L gauge group. The data collected with the L3 detector at center-of-mass energies between 130 GeV and 208 GeV are used.The decay channel N_e --> eW is investigated and no evidence is found for a heavy neutrino, N_e, in a mass range between 80 GeV and 205 GeV. Upper limits on the mixing parameter between the heavy and light neutrino are derived

Search for a Higgs Boson Decaying into Two Photons at LEP

A Higgs particle produced in association with a Z boson and decaying into two photons is searched for in the data collected by the L3 experiment at LEP. All possible decay modes of the Z boson are investigated. No signal is observed in 447.5 pb^-1 of data recorded at centre-of-mass energies up to 209 GeV. Limits on the branching fraction of the Higgs boson decay into two photons as a function of the Higgs mass are derived. A lower limit on the mass of a fermiophobic Higgs boson is set at 105.4 GeV at 95% confidence level

The intramembrane protease Sppl2a is required for B cell and DC development and survival via cleavage of the invariant chain

The protease Sppl2a cleaves the N-terminal fragment of invariant chain (CD74) and is required for efficient B cell development and function.B cell development requires tight regulation to allow for the generation of a diverse repertoire while preventing the development of autoreactive cells. We report, using N-ethyl-N-nitrosourea (ENU)–induced mutagenesis, the identification of a mutant mouse (chompB) with a block in early B cell development. The blockade occurs after the transitional 1 (T1) stage and leads to a decrease in mature B cell subsets and deficits in T cell–dependent antibody responses. Additionally, chompB mice have decreases in myeloid dendritic cells (DCs). The mutation was mapped to the intramembrane protease signal peptide peptidase-like 2a (Sppl2a), a gene not previously implicated in immune cell development. Proteomic analysis identified the invariant chain (CD74) as a key substrate of Sppl2a and suggests that regulated intramembrane proteolysis of CD74 by Sppl2a contributes to B cell and DC survival. Moreover, these data suggest that modulation of Sppl2a may be a useful therapeutic strategy for treatment of B cell dependent autoimmune disorders