110 research outputs found
STAT1: A Novel Target of miR-150 and miR-223 Is Involved in the Proliferation of HTLV-IâTransformed and ATL Cells
AbstractWe have previously reported on the deregulation of cellular microRNAs involved in hematopoiesis and inflammation in human T-cell lymphotropic virus type 1 (HTLV-I)âtransformed cells. In this study, we demonstrate that miR-150 and miR-223 specifically target the signal transducer and activator of transcription 1 (STAT1) 3âČ untranslated region, reducing STAT1 expression and dampening STAT1-dependent signaling in human T cells. The effects of miR-150 and miR-223 on endogenous STAT1 were confirmed using inducible cell lines. Our studies also showed that miR-150 expression is upregulated by interleukin-2 signaling in adult T cell leukemia/lymphoma (ATL) cells. HTLV-Iâtransformed and ATL-derived cells have reduced levels of miR150 and miR223 expression, which coincide with increased STAT1 expression and STAT1-dependent signaling. Knockdown of STAT1 by short hairpin RNA demonstrated that the constitutive activation of STAT1 is required for the continuous proliferation of HTLV-Iâtransformed cells. Our studies further demonstrate that increased expression of STAT1 in ATL cells is associated with higher levels of major histocompatibility complex class I expression. Previous studies have demonstrated that the pressure exerted by natural killer (NK) cells in vivo can edit leukemic tumor cells by forcing an increased expression of major histocompatibility complex class I to escape immune clearance. STAT1-expressing tumor cells produce more aggressive tumors because they cannot be eliminated by NK cells. Our results suggest that therapeutic approaches using combined targeting of STAT1 and MHC class I may be an effective approach to activate NK cellâmediated clearance of ATL tumor cells
Jean-Noël Jeanneney, Clemenceau. DerniÚres nouvelles du Tigre
« Il y a des gens qui rĂ©trĂ©cissent par manque dâadmiration », nous rappelle Jean-NoĂ«l Jeanneney, en citant ces mots attribuĂ©s Ă Victor Hugo. Ce ne fut pas le cas de Clemenceau, pas plus que de ceux qui, aujourdâhui, sâintĂ©ressent Ă cette figure marquante de la vie politique française. Car son souvenir et par lui sa dĂ©fense, voire son modĂšle, restent dâune actualitĂ© toujours stimulante oĂč lâadmiration prend une place quâelle nâa pas toujours eue. Sur ce personnage central de la TroisiĂšme RĂ©pub..
Jean-Michel Guieu, Gagner la paix (1914-1929)
Le 11 novembre 1918, les AlliĂ©s, vainqueurs de la guerre, rĂ©agissent avec liesse Ă lâannonce de lâArmistice. La population lĂ©gitimement enjouĂ©e cĂ©lĂšbre alors la fin du premier conflit mondial. Mais la paix se substitue-t-elle pour autant Ă la guerre ? Rien nâest moins sĂ»r et les annĂ©es qui suivent vont montrer prĂ©cisĂ©ment les difficultĂ©s de sa mise en place. Clemenceau, clairvoyant bien quâheureux de se voir fĂȘtĂ© en « PĂšre la Victoire », ne dit pas autre chose : « Nous avons gagnĂ© la guerre, ..
Hyperspectral images segmentation: a proposal
Hyper-Spectral Imaging (HIS) also known as chemical or spectroscopic imaging is an emerging technique that combines
imaging and spectroscopy to capture both spectral and spatial information from an object. Hyperspectral images are
made up of contiguous wavebands in a given spectral band. These images provide information on the chemical
make-up profile of objects, thus allowing the differentiation of objects of the same colour but which possess make-up
profile. Yet, whatever the application field, most of the methods devoted to HIS processing conduct data analysis without
taking into account spatial information.Pixels are processed individually, as an array of spectral data without any spatial
structure. Standard classification approaches are thus widely used (k-means, fuzzy-c-means hierarchical
classification...). Linear modelling methods such as Partial Least Square analysis (PLS) or non linear approaches like
support vector machine (SVM) are also used at different scales (remote sensing or laboratory applications). However,
with the development of high resolution sensors, coupled exploitation of spectral and spatial information to process
complex images, would appear to be a very relevant approach. However, few methods are proposed in the litterature.
The most recent approaches can be broadly classified in two main categories. The first ones are related to a direct
extension of individual pixel classification methods using just the spectral dimension (k-means, fuzzy-c-means or FCM,
Support Vector Machine or SVM). Spatial dimension is integrated as an additionnal classification parameter (Markov
fields with local homogeneity constrainst [5], Support Vector Machine or SVM with spectral and spatial kernels
combination [2], geometrically guided fuzzy C-means [3]...). The second ones combine the two fields related to each
dimension (spectral and spatial), namely chemometric and image analysis. Various strategies have been attempted. The
first one is to rely on chemometrics methods (Principal Component Analysis or PCA, Independant Component Analysis or
ICA, Curvilinear Component Analysis...) to reduce the spectral dimension and then to apply standard images processing technics on the resulting score images i.e. data projection on a subspace. Another approach is to extend the definition
of basic image processing operators to this new dimensionality (morphological operators for example [1, 4]).
However, the approaches mentioned above tend to favour only one description either directly or indirectly (spectral or
spatial). The purpose of this paper is to propose a hyperspectral processing approach that strikes a better balance in the
treatment of both kinds of information....Cet article prĂ©sente une stratĂ©gie de segmentation dâimages hyperspectrales liant de façon symĂ©trique et
conjointe les aspects spectraux et spatiaux. Pour cela, nous proposons de construire des variables latentes
permettant de dĂ©finir un sous-espace reprĂ©sentant au mieux la topologie de lâimage. Dans cet article, nous
limiterons cette notion de topologie Ă la seule appartenance aux rĂ©gions. Pour ce faire, nous utilisons dâune
part les notions de lâanalyse discriminante (variance intra, inter) et les propriĂ©tĂ©s des algorithmes de
segmentation en région liées à celles-ci. Le principe générique théorique est exposé puis décliné sous la
forme dâun exemple dâimplĂ©mentation optimisĂ© utilisant un algorithme de segmentation en rĂ©gion type split
and merge. Les résultats obtenus sur une image de synthÚse puis réelle sont exposés et commentés
Hyperspectral image segmentation: the butterfly approach
International audienceFew methods are proposed in the litterature for coupling the spectral and the spatial dimension available on hyperspectral images. This paper proposes a generic segmentation scheme named butterfly based on an iterative process and a cross analysis of spectral and spatial information. Indeed, spatial and spatial structures are extracted in spatial and spectral space respectively both taking into account the other one. To apply this layout on hyperspectral imgages, we focus particulary on spatial and spectral structures i.e. topologic concepts and latent variable for the spatial and the spectral space respectively. Moreover, a cooperation scheme with these structures is proposed. Finally, results obtained on real hyperspectral images using this specific implementation of the butterfly approach are presented and discussed
Measurements of mechanical thermal noise and energy dissipation in optical dielectric coatings
In recent years an increasing number of devices and experiments are shown to
be limited by mechanical thermal noise. In particular sub-Hertz laser frequency
stabilization and gravitational wave detectors, that are able to measure
fluctuations of 1E-18 m/rtHz or less, are being limited by thermal noise in the
dielectric coatings deposited on mirrors. In this paper we present a new
measurement of thermal noise in low absorption dielectric coatings deposited on
micro-cantilevers and we compare it with the results obtained from the
mechanical loss measurements. The coating thermal noise is measured on the
widest range of frequencies with the highest signal to noise ratio ever
achieved. In addition we present a novel technique to deduce the coating
mechanical losses from the measurement of the mechanical quality factor which
does not rely on the knowledge of the coating and substrate Young moduli. The
dielectric coatings are deposited by ion beam sputtering. The results presented
here give a frequency independent loss angle of (4.70 0.2)x1E-4 with a
Young's modulus of 118 GPa for annealed tantala from 10 Hz to 20 kHz. For
as-deposited silica, a weak frequency dependence (~ f^{-0.025}) is observed in
this frequency range, with a Young's modulus of 70 GPa and an internal damping
of (6.0 0.3)x1E-4 at 16 kHz, but this value decreases by one order of
magnitude after annealing and the frequency dependence disappears.Comment: Accepted for publication in Phys. Rev.
Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases
Background: Human T cell Leukemia virus type 1 (HTLV-I) is etiologically linked to adult T cell leukemia/lymphoma (ATL) and an inflammatory neurodegenerative disease called HTLV-I-associated myelopathy or tropical spastic paraparesis (HAM/TSP). The exact genetic or epigenetic events and/or environmental factors that influence the development of ATL, or HAM/TSP diseases are largely unknown. The tumor suppressor gene, Fragile Histidine Triad Diadenosine Triphosphatase (FHIT), is frequently lost in cancer through epigenetic modifications and/or deletion. FHIT is a tumor suppressor acting as genome caretaker by regulating cellular DNA repair. Indeed, FHIT loss leads to replicative stress and accumulation of double DNA strand breaks. Therefore, loss of FHIT expression plays a key role in cellular transformation. Methods: Here, we studied over 400 samples from HTLV-I-infected individuals with ATL, TSP/HAM, or asymptomatic carriers (AC) for FHIT loss and expression. We examined the epigenetic status of FHIT through methylation specific PCR and bisulfite sequencing; and correlated these results to FHIT expression in patient samples. Results: We found that epigenetic alteration of FHIT is specifically found in chronic and acute ATL but is absent in asymptomatic HTLV-I carriers and TSP/HAM patients' samples. Furthermore, the extent of FHIT methylation in ATL patients was quantitatively comparable in virus-infected and virus non-infected cells. We also found that longitudinal HTLV-I carriers that progressed to smoldering ATL and descendants of ATL patients harbor FHIT methylation. Conclusions: These results suggest that germinal epigenetic mutation of FHIT represents a preexisting mark predisposing to the development of ATL diseases. These findings have important clinical implications as patients with acute ATL are rarely cured. Our study suggests an alternative strategy to the current "wait and see approach" in that early screening of HTLV-I-infected individuals for germinal epimutation of FHIT and early treatment may offer significant clinical benefits
Mutation of epigenetic regulators TET2 and MLL3 in patients with HTLV-I-induced acute adult T-cell leukemia
Small PARP inhibitor PJ-34 induces cell cycle arrest and apoptosis of adult T-cell leukemia cells
A grant from the One-University Open Access Fund at the University of Kansas was used to defray the authorâs publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background
HTLV-I is associated with the development of an aggressive form of lymphocytic leukemia known as adult T-cell leukemia/lymphoma (ATLL). A major obstacle for effective treatment of ATLL resides in the genetic diversity of tumor cells and their ability to acquire resistance to chemotherapy regimens. As a result, most patients relapse and current therapeutic approaches still have limited long-term survival benefits. Hence, the development of novel approaches is greatly needed.
Methods
In this study, we found that a small molecule inhibitor of poly (ADP-ribose) polymerase (PARP), PJ-34, is very effective in activating S/G2M cell cycle checkpoints, resulting in permanent cell cycle arrest and reactivation of p53 transcription functions and caspase-3-dependent apoptosis of HTLV-I-transformed and patient-derived ATLL tumor cells. We also found that HTLV-I-transformed MT-2 cells are resistant to PJ-34 therapy associated with reduced cleaved caspase-3 activation and increased expression of RelA/p65.
Conclusion
Since PJ-34 has been tested in clinical trials for the treatment of solid tumors, our results suggest that some ATLL patients may be good candidates to benefit from PJ-34 therapy
Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study
BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12âgâdl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (â„week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] gâdl-1 for neonates in week 1, 9.6 [7.7 to 10.4] gâdl-1 in week 2 and 8.0 [7.3 to 9.0] gâdl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] mlâkg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] gâdl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348
- âŠ