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Kyoko Ochiai, Haruka Kondo, Yasunobu Okamura, Hiroki Shima, Yuko Kurokochi, Kazumi Kimura, Ryo Funayama, Takeshi Nagashima, Keiko Nakayama, Katsuyuki Yui, Kengo Kinoshita, Kazuhiko Igarashi
The transcription factor (TF) interferon regulatory factor-4 (IRF4) promotes both germinal center (GC) reactions and plasma cell (PC) differentiation by binding to alternative DNA motifs including AP-1-IRF composite elements, Ets-IRF composite elements (EICEs), and interferon sequence response elements (ISREs). Although all of these motifs mediate transcriptional activation by IRF4, it is still unknown how some of the IRF4 target genes are downregulated upon PC differentiation. Here, we revealed a molecular mechanism of IRF4-mediated gene downregulation during PC differentiation...
April 24, 2018: Blood Advances
Dapeng Wang, Huitian Diao, Adam J Getzler, Walter Rogal, Megan A Frederick, Justin Milner, Bingfei Yu, Shane Crotty, Ananda W Goldrath, Matthew E Pipkin
T cell receptor (TCR) stimulation of naive CD8+ T cells initiates reprogramming of cis-regulatory landscapes that specify effector and memory cytotoxic T lymphocyte (CTL) differentiation. We mapped regions of hyper-accessible chromatin in naive cells during TCR stimulation and discovered that the transcription factor (TF) Runx3 promoted accessibility to memory CTL-specific cis-regulatory regions before the first cell division and was essential for memory CTL differentiation. Runx3 was specifically required for accessibility to regions highly enriched with IRF, bZIP and Prdm1-like TF motifs, upregulation of TFs Irf4 and Blimp1, and activation of fundamental CTL attributes in early effector and memory precursor cells...
April 17, 2018: Immunity
Riho Kurata, Asuka Kumagai, Xiaofeng Cui, Masamitsu Harada, Jun Nagai, Yasuhiro Yoshida, Kei-Ichi Ozaki, Yoshimasa Tanaka, Tomo Yonezawa
BACKGROUND: Transcriptional regulation is very important and pivotal function in myriad biological responses. Thus, methods to determine transcriptional activity are required in not only basic medical research but also drug discovery. We established novel reporter constructs using human secreted embryonic alkaline phosphatase (SEAP) and Epstein-Barr virus nuclear antigen (EBNA) 1, which can maintain constructs synchronized to host cell replication. METHODS: We established nuclear factor-kappa B (NFkB) or interferon regulatory factor (IRF) driven SEAP expression constructs and then, introduced them into culture cells...
April 17, 2018: Current Pharmaceutical Biotechnology
Hyungwoo Lee, Kyung Eun Kang, Hyewon Chung, Hyung Chan Kim
PURPOSE: To evaluate an automated segmentation algorithm with a convolutional neural network (CNN) to quantify and detect intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), and subretinal hyperreflective material (SHRM) through analyses of spectral domain optical coherence tomography (SD-OCT) images from patients with neovascular age-related macular degeneration (nAMD). DESIGN: Reliability and validity analysis of a diagnostic tool...
April 12, 2018: American Journal of Ophthalmology
Margaret A DiVita, Carl V Granger, Richard Goldstein, Paulette M Niewczyk, Jo L Freudenheim
OBJECTIVE: To examine the association between the Medicare pressure ulcer quality indicator (the development of new or worsened pressure ulcers), with rehabilitation outcomes among Medicare patients seen in an inpatient rehabilitation facility (IRF). Data collection on the pressure ulcer quality indicator began in October of 2012, however, the value of this indicator is not known. DESIGN: Retrospective descriptive study. SETTING: IRFs subscribed to the Uniform Data System for Medical Rehabilitation...
April 9, 2018: Archives of Physical Medicine and Rehabilitation
Jin Tian, Yongxiang Liu, Xiaoxiao Liu, Xue Sun, Jikai Zhang, Liandong Qu
As a prevalent agent in cats, feline herpesvirus 1 (FHV-1) infection contributes to feline respiratory disease and acute and chronic conjunctivitis. FHV-1 can successfully evade the host innate immune response and persist for the lifetime of the cat. Several mechanisms of immune evasion by human herpesviruses have been elucidated, but the mechanism by FHV-1 remains unknown. In this study, we screened for FHV-1 ORFs responsible for inhibiting type I interferon (IFN) pathway with an IFN-β promoter reporter and an analysis of IFN-β mRNA levels in HEK 293T cells and CRFK feline cell line, and we identified the Ser/Thr kinase US3 as the most powerful inhibitor...
April 4, 2018: Journal of Virology
Keizo Shinomori, Athanasios Panorgias, John S Werner
Impulse response functions for an incremental luminous pulse (ON flash) or a decremental luminous pulse (OFF flash) were derived for twelve young (19-24 years old) and ten old (65-84 years old) observers. Thresholds were measured for two pulses separated by stimulus-onset-asynchronies from 13.3 to 186.7 ms. The pulses had a spatial Gaussian shape and were presented as increments or decrements on a 15  cd/m2 equal-energy white background, having the same chromaticity as the pulse. A spatial four-alternative forced-choice method was combined with a staircase procedure...
April 1, 2018: Journal of the Optical Society of America. A, Optics, Image Science, and Vision
Susana F Silva, José Paulo Domingues, António Miguel Morgado
Time-gated fluorescence lifetime imaging microscopy (FLIM) is a powerful technique to assess the biochemistry of cells and tissues. When applied to living thick samples, it is hampered by the lack of optical sectioning and the need of acquiring many images for an accurate measurement of fluorescence lifetimes. Here, we report on the use of processing techniques to overcome these limitations, minimizing the acquisition time, while providing optical sectioning. We evaluated the application of the HiLo and the rapid lifetime determination (RLD) techniques for accurate measurement of fluorescence lifetimes with optical sectioning...
2018: Journal of Healthcare Engineering
Khaldoon Alsamman, Omar S El-Masry
Interferon regulatory factors (IRFs) are a group of closely related proteins collectively referred to as the IRF family. Members of this family were originally recognized for their roles in inflammatory responses; however, recent research has suggested that they are also involved in tumor biology. This review focuses on current knowledge of the roles of IRF-1 and IRF-2 in human cancer, with particular attention paid to the impact of IRF-1 inactivation. The different mechanisms underlying IRF-1 inactivation and their implications for human cancers and the potential importance of IRF-1 in immunotherapy are also summarized...
March 29, 2018: Bioscience Reports
Ickpyo Hong, Amol Karmarkar, Winston Chan, Yong-Fang Kuo, Trudy Mallinson, Kenneth J Ottenbacher, James Goodwin, Clark R Andersen, Timothy A Reistetter
OBJECTIVE: To explore variation in acute care use of inpatient (IRF) and skilled nursing (SNF) rehabilitation following ischemic and hemorrhagic stroke. DESIGN: A secondary analysis of Medicare claims data linked to IRF and SNF assessment files (2013-2014). RESULTS: The sample included 122,084 stroke patients discharged to IRF or SNF from 3,677 acute hospitals. Of the acute hospitals, 3,649 discharged patients with an ischemic stroke (range 1-402 patients/hospital, median=15) compared to 1,832 acute hospitals that discharged patients with hemorrhagic events (range 1-73 patients/hospital, median=4)...
March 28, 2018: American Journal of Physical Medicine & Rehabilitation
Nikolai Schleussner, Olaf Merkel, Mariantonia Costanza, Huan-Chang Liang, Franziska Hummel, Chiara Romagnani, Pawel Durek, Ioannis Anagnostopoulos, Michael Hummel, Korinna Jöhrens, Antonia Niedobitek, Patrick R Griffin, Roberto Piva, Henrike L Sczakiel, Wilhelm Woessmann, Christine Damm-Welk, Christian Hinze, Dagmar Stoiber, Bernd Gillissen, Suzanne D Turner, Eva Kaergel, Linda von Hoff, Michael Grau, Georg Lenz, Bernd Dörken, Claus Scheidereit, Lukas Kenner, Martin Janz, Stephan Mathas
Transcription factor AP-1 is constitutively activated and IRF4 drives growth and survival in ALK+ and ALK- anaplastic large cell lymphoma (ALCL). Here we demonstrate high-level BATF and BATF3 expression in ALCL. Both BATFs bind classical AP-1 motifs and interact with in ALCL deregulated AP-1 factors. Together with IRF4, they co-occupy AP-1-IRF composite elements, differentiating ALCL from non-ALCL. Gene-specific inactivation of BATFs, or global AP-1 inhibition results in ALCL growth retardation and/or cell death in vitro and in vivo...
March 28, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Yiming K Chang, Zheng Zuo, Gary D Stormo
BACKGROUND: BATF family transcription factors (BATF, BATF2 and BATF3) form hetero-trimers with JUNB and either IRF4 or IRF8 to regulate cell fate in T cells and dendritic cells in vivo. While each combination of the hetero-trimer has a distinct role, some degree of cross-compensation was observed. The basis for the differential actions of IRF4 and IRF8 with BATF factors and JUNB is still unknown. We propose that the differences in function between these hetero-trimers may be caused by differences in their DNA binding preferences...
March 27, 2018: BMC Molecular Biology
Gwansik Park, Jason Forman, Taewung Kim, Matthew B Panzer, Jeff R Crandall
OBJECTIVE: The goal of this study was to explore a framework for developing injury risk functions (IRFs) in a bottom-up approach based on responses of parametrically variable finite element (FE) models representing exemplar populations. METHODS: First, a parametric femur modeling tool was developed and validated using a subject-specific (SS)-FE modeling approach. Second, principal component analysis and regression were used to identify parametric geometric descriptors of the human femur and the distribution of those factors for 3 target occupant sizes (5th, 50th, and 95th percentile males)...
February 28, 2018: Traffic Injury Prevention
T Calderbank, M Bown, A Saratzis
BACKGROUND: Endovascular abdominal aortic aneurysm (AAA) repair (EVAR) is currently used routinely to treat AAA. Suprarenal fixation (SRF) of EVAR grafts can lead to renal dysfunction. A meta-analysis of studies using estimated glomerular filtration rate (eGFR) as a measure of renal injury to assess the effect of SRF on renal function was performed. METHODS: An electronic search was carried out to identify all articles that reported on renal injury following SRF versus infrarenal fixation (IRF) EVAR, and 24 studies were identified...
March 23, 2018: European Journal of Vascular and Endovascular Surgery
Yudha Manggala, Chayanin Angthong, Andri Primadhi, Supoj Kungwan
This study was to report the comparison of outcomes between Ilizarov ring fixator (IRF) and Taylor Spatial Frame® (Smith & Nephew, Memphis, Tenn.; TSF) in terms of the effectiveness of ankle-foot deformities correction, follow-up results, and complications. Fourteen patients with ankle-foot deformities were corrected using circular external fixation (IRF group = 7 patients; TSF group = 7 patients) and related procedures. Baseline data and treatment variables were recorded. The patients' mean age was 42...
December 14, 2017: Orthopedic Reviews
Hyungwoo Lee, Kyung Eun Kang, Hyewon Chung, Hyung Chan Kim
PURPOSE: To investigate the prognostic factors of visual and anatomic outcomes in patients with diabetic macular edema (DME) treated with intravitreal injection of dexamethasone implant. METHODS: We retrospectively studied 32 eyes of 31 patients with DME for best-corrected visual acuity (BCVA), central macular thickness, and height and width of both intraretinal fluid (IRF) and subretinal fluid. Logistic regression analysis was used to examine correlations between the baseline characteristics and outcomes at 3 and 6 months...
March 13, 2018: Korean Journal of Ophthalmology: KJO
Lorenza Tulli, Francesca Cattaneo, Juliette Vinot, Cosima T Baldari, Ugo D'Oro
Toll-like receptors (TLRs) play a key role in the activation of innate immune cells, in which their engagement leads to production of cytokines and co-stimulatory molecules. TLRs signaling requires recruitment of toll/IL-1R (TIR) domain-containing adaptors, such as MyD88 and/or TRIF, and leads to activation of several transcription factors, such as NF-κB, the AP1 complex, and various members of the interferon regulatory factor (IRF) family, which in turn results in triggering of several cellular functions associated with these receptors...
2018: Frontiers in Immunology
Peter Moritz Becher, Svenja Hinrichs, Nina Fluschnik, Jan K Hennigs, Karin Klingel, Stefan Blankenberg, Dirk Westermann, Diana Lindner
Heart failure (HF) is a leading cause of morbidity and mortality in the western world. Although optimal medical care and treatment is widely available, the prognosis of patients with HF is still poor. Toll-like receptors (TLRs) are important compartments of the innate immunity. Current studies have identified TLRs as critical mediators in cardiovascular diseases. In the present study, we investigated the involvement of TLRs and interferon (IFN) regulatory factors (IRFs) in different experimental HF models including viral myocarditis, myocardial ischemia, diabetes mellitus, and cardiac hypertrophy...
2018: PloS One
Megan A Schilling, Robab Katani, Sahar Memari, Meredith Cavanaugh, Joram Buza, Jessica Radzio-Basu, Fulgence N Mpenda, Melissa S Deist, Susan J Lamont, Vivek Kapur
Traditional approaches to assess the immune response of chickens to infection are through animal trials, which are expensive, require enhanced biosecurity, compromise welfare, and are frequently influenced by confounding variables. Since the chicken embryo becomes immunocompetent prior to hatch, we here characterized the transcriptional response of selected innate immune genes to Newcastle disease virus (NDV) infection in chicken embryos at days 10, 14, and 18 of embryonic development. The results suggest that the innate immune response 72 h after challenge of 18-day chicken embryo is both consistent and robust...
2018: Frontiers in Genetics
Zhengyuan Zhou, Satish K Chitneni, Nick Devoogdt, Michael R Zalutsky, Ganesan Vaidyanathan
In a previous study, we evaluated a HER2-specific single domain antibody fragment (sdAb) 2Rs15d labeled with18 F via conjugation of a residualizing prosthetic agent that was synthesized by copper-catalyzed azide-alkyne cycloaddition (CuAAC). In order to potentially increase overall efficiency and decrease the time required for labeling, we now investigate the use of a strain-promoted azide-alkyne cycloaddition (SPAAC) between the 2Rs15d sdAb, which had been pre-derivatized with an azide-containing residualizing moiety, and an18 F-labeled aza-dibenzocyclooctyne derivative...
March 10, 2018: Bioorganic & Medicinal Chemistry
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