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Franziska Rieche, Katia Carmine-Simmen, Burkhard Poeck, Doris Kretzschmar, Roland Strauss
The β-amyloid precursor protein (APP) plays a central role in the etiology of Alzheimer's disease (AD). However, its normal physiological functions are still unclear. APP is cleaved by various secretases whereby sequential processing by the β- and γ-secretases produces the β-amyloid peptide that is accumulating in plaques that typify AD. In addition, this produces secreted N-terminal sAPPβ fragments and the APP intracellular domain (AICD). Alternative cleavage by α-secretase results in slightly longer secreted sAPPα fragments and the identical AICD...
February 12, 2018: Current Biology: CB
Wei Du, Hemn Mohammadpour, Rachel E O'Neill, Sandeep Kumar, Chuan Chen, Michelle Qiu, Lin Mei, Jingxin Qiu, Philip L McCarthy, Kelvin P Lee, Xuefang Cao
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for hematologic malignancies. Donor T cells are able to eliminate residual tumor cells after allo-HCT, producing the beneficial graft-versus-tumor (GVT) effect, but can also cause graft-versus-host disease (GVHD) when attacking host normal tissues. We previously reported that granzyme B (GzmB) is involved in activation-induced cell death (AICD) of donor T cells and exerts differential impacts on GVHD and GVT effect. Serine protease inhibitor 6 (Spi6) is the sole endogenous inhibitor of GzmB that can protect immune and tissue cells against GzmB-mediated damage...
2018: Oncoimmunology
Matthew J Scheffel, Gina Scurti, Megan M Wyatt, Elizabeth Garrett-Mayer, Chrystal M Paulos, Michael I Nishimura, Christina Voelkel-Johnson
Therapeutic outcomes for adoptive cell transfer (ACT) therapy are constrained by the quality of the infused T cells. The rapid expansion necessary to obtain large numbers of cells results in a more terminally differentiated phenotype with decreased durability and functionality. N-acetyl cysteine (NAC) protects against activation-induced cell death (AICD) and improves anti-tumor efficacy of Pmel-1 T cells in vivo. Here, we show that these benefits of NAC can be extended to engineered T cells and significantly increases T-cell survival within the tumor microenvironment...
February 2, 2018: Cancer Immunology, Immunotherapy: CII
Raquel Coronel, Adela Bernabeu-Zornoza, Charlotte Palmer, Mar Muñiz-Moreno, Alberto Zambrano, Eva Cano, Isabel Liste
Amyloid precursor protein (APP) is a member of the APP family of proteins, and different enzymatic processing leads to the production of several derivatives that are shown to have distinct biological functions. APP is involved in the pathology of Alzheimer's disease (AD), the most common neurodegenerative disorder causing dementia. Furthermore, it is believed that individuals with Down syndrome (DS) have increased APP expression, due to an extra copy of chromosome 21 (Hsa21), that contains the gene for APP...
January 30, 2018: Molecular Neurobiology
Bader Abu Ghalyoun, Matthew Lempel, Hamid Shaaban, Fayez Shamoon
A 32-year-old woman with a past medical history of paroxysmal atrial fibrillation, long QT syndrome, and implantation of an automatic iimplantable cardioverter-defibrillator (AICD) following cardiac arrest presented with disabling symptoms of paroxysmal atrial fibrillation due to recurrent AICD shocks. Before curative ablation, transesophageal echocardiography was performed to assess for existing thrombi. This is a rare case of successful resolution with apixaban of a massive left atrial appendage thrombus due to non-rheumatic atrial fibrillation that was successfully treated with apixaban...
January 2018: Annals of Cardiac Anaesthesia
Wai Yin Vivien Chiu, Alex Chun Koon, Jacky Chi Ki Ngo, Ho Yin Edwin Chan, Kwok-Fai Lau
Amyloidogenic processing of APP by β- and γ-secretases leads to the generation of amyloid-β peptide (Aβ), and the accumulation of Aβ in senile plaques is a hallmark of Alzheimer's disease (AD). Understanding the mechanisms of APP processing is therefore paramount. Increasing evidence suggests that APP intracellular domain (AICD) interacting proteins influence APP processing. In this study, we characterized the overexpression of AICD interactor GULP1 in a Drosophila AD model expressing human BACE and APP695...
November 21, 2017: Oncotarget
Chao Liu, Cheng-Wu Zhang, Yi Zhou, Wan Qing Wong, Liying Corinne Lee, Wei Yi Ong, Sung Ok Yoon, Wanjin Hong, Xin-Yuan Fu, Tuck Wah Soong, Edward H Koo, Lawrence W Stanton, Kah-Leong Lim, Zhi-Cheng Xiao, Gavin S Dawe
Axonal injury is a common feature of central nervous system insults. Upregulation of amyloid precursor protein (APP) is observed following central nervous system neurotrauma and is regarded as a marker of central nervous system axonal injury. However, the underlying mechanism by which APP mediates neuronal death remains to be elucidated. Here, we used mouse optic nerve axotomy (ONA) to model central nervous system axonal injury replicating aspects of retinal ganglion cell (RGC) death in optic neuropathies. APP and APP intracellular domain (AICD) were upregulated in retina after ONA and APP knockout reduced Tuj1+ RGC loss...
December 13, 2017: Cell Death and Differentiation
Elli Mann, Robert Kluesener, Felix Boschann, Jana Ruppert, Franz P Armbruster, Andreas Meinitzer, Christoph Melzer, Thomas B Dschietzig
BACKGROUND: Homoarginine (hArg) is known to have an impact on nitric oxide (NO) metabolism. It seems to increase NO generation and/or availability, thereby enhancing endothelial function. In addition, hArg is connected to energy metabolism since the key enzyme, L-arginine-glycine amidinotransferase (AGAT) for hArg synthesis in the kidneys, is also involved in the synthesis of energy metabolites like guanidinoacetate. Former studies indicate that low levels of hArg are linked to cardiovascular disease and increased all-cause mortality...
November 1, 2017: Clinical Laboratory
Ravichandra Tagirasa, Shaifaly Parmar, Manas R Barik, Satish Devadas, Soumyava Basu
Purpose: Intraocular inflammation in tuberculosis-associated uveitis (TBU) is usually widespread, and responds unpredictably to treatment. Herein, we analyze the intraocular T-cell response in TBU for its surface phenotype, antigenic specificity, and functional characteristics to explain the above observations. Methods: We isolated T cells from vitreous humor samples of patients with TBU and non-TB uveitis (controls). These were directly stained for surface markers CD4, CD8, CD45RO, CD45RA, CCR7, as well as intracellular cytokines IFN-γ, TNF-α, and IL-17 and analyzed on flow cytometry...
November 1, 2017: Investigative Ophthalmology & Visual Science
Brendan Gongol, Traci L Marin, John D Jeppson, Karina Mayagoitia, Samuel Shin, Nicholas Sanchez, Wolff M Kirsch, Harry V Vinters, Christopher G Wilson, Othman Ghribi, Salvador Soriano
The function of the amyloid precursor protein (APP) in brain health remains unclear. This study elucidated a novel cytoprotective signaling pathway initiated by the APP transcriptionally active intracellular domain (AICD) in response to 27-hydroxycholesterol (27OHC), an oxidized cholesterol metabolite associated with neurodegeneration. The cellular response to 27OHC was hormetic, such that low, but not high, doses promoted AICD transactivation of microtubule associated serine/threonine kinase family member 4 (MAST4)...
October 24, 2017: Scientific Reports
Biju Basumatary, Jyoti Rai, R V Ramana Reddy, Jeyaraman Sankar
One-electron oxidation of a GaIII -corrole with N(4-BrC6 H4 )3 SbCl6 resulted in an air-stable non-innocent GaIII -corrole radical. The single-crystal X-ray crystallography of the 2,17-bis-formyl-5,10,15-tris(pentafluorophenyl)corrolato gallium(III)(chloride) radical ([3-Cl]. ) revealed delocalization of the unpaired electron, which was further confirmed by electron spin resonance (ESR) spectroscopy and spin density distribution plot. In addition, the nucleus-independent chemical shift (NICS), anisotropy-induced current density (AICD) and harmonic oscillator model of aromaticity (HOMA) supported a [17] π-electron-conjugated (or antiaromatic) radical...
December 11, 2017: Chemistry: a European Journal
Rajiv Juneja, Prajeesh M Nambiar
Cardiomyopathy is considered as a heart muscle disease of multiple aetiologies, unlike other cardiac diseases related to a definitive pathophysiology. With more and more research and with the advent of genetic analysis pin pointing the disease causing mutations, causative factors have been defined and classifications and definitions have changed over time. Patients with these conditions present to anaesthesiologists in elective and emergency situations, placement of automated internal cardioverter defibrillator (AICD) devices or biventricular pacing but may also be diagnosed at anaesthetic pre-assessment...
September 2017: Indian Journal of Anaesthesia
Meng Zhang, Jing Wang, Lingwei Jia, Jin Huang, Cheng He, Fuqing Hu, Lifei Yuan, Guihua Wang, Mingxia Yu, Zhuoya Li
Secretory tumor necrosis factor-alpha (sTNF-α) is known to mediate activation- induced cell death (AICD). However, the role of tmTNF-α in AICD is still obscure. Here, we demonstrated that tmTNF-α expression significantly increased accompanied with enhanced apoptosis during AICD in Jurkat and primary human T cells. Knockdown or enhancement of tmTNF-α expression in activated T cells suppressed or promoted AICD, respectively. Treatment of activated T cells with exogenous tmTNF-α significantly augmented AICD, indicating that tmTNF-α as an effector molecule mediates AICD...
September 8, 2017: Oncotarget
Xian-Sheng Ke, Yongseok Hong, Peiyu Tu, Qing He, Vincent M Lynch, Dongho Kim, Jonathan L Sessler
Bis-dicarbacorrole (bis-H3) with two adj-CCNN subunits was synthesized by incorporating a dibenzo[g,p]chrysene moiety into the macrocyclic structure. The two trianionic cores in bis-H3 can stabilize two Cu(III) ions (bis-Cu) or concurrently a Cu(III) cation and a Pd(II) ion in the form of a hetero bis-metal complex (mix-Cu/Pd). As prepared, mix-Cu/Pd displays organic π radical character, as confirmed by various techniques, including electron paramagnetic resonance spectroscopy, cyclic voltammetry, femtosecond transient absorption measurements, and DFT calculations...
October 12, 2017: Journal of the American Chemical Society
Karine Laulagnier, Charlotte Javalet, Fiona J Hemming, Mathilde Chivet, Gaëlle Lachenal, Béatrice Blot, Christine Chatellard, Rémy Sadoul
Amyloid beta peptide (Aβ), the main component of senile plaques of Alzheimer's disease brains, is produced by sequential cleavage of amyloid precursor protein (APP) and of its C-terminal fragments (CTFs). An unanswered question is how amyloidogenic peptides spread throughout the brain during the course of the disease. Here, we show that small lipid vesicles called exosomes, secreted in the extracellular milieu by cortical neurons, carry endogenous APP and are strikingly enriched in CTF-α and the newly characterized CTF-η...
February 2018: Cellular and Molecular Life Sciences: CMLS
Sandra Guidi, Fiorenza Stagni, Renata Bartesaghi
No abstract text is available yet for this article.
August 1, 2017: Oncotarget
Stacey A Maskarinec, Joshua T Thaden, Derek D Cyr, Felicia Ruffin, Maria Souli, Vance G Fowler
BACKGROUND: The species-specific risk of cardiac device-related infection (CDRI) among bacteremic patients is incompletely understood. METHODS: We conducted a prospective cohort study of hospitalized patients from October 2002 to December 2014 with a cardiac device (CD) and either Staphylococcus aureus bacteremia (SAB) or Gram-negative bacteremia (GNB). Cardiac devices were defined as either prosthetic heart valves (PHVs), including valvular support rings, permanent pacemakers (PPMs)/automatic implantable cardioverter defibrillators (AICDs), or left ventricular assist devices (LVADs)...
2017: Open Forum Infectious Diseases
Leah Alabanza, Melissa Pegues, Claudia Geldres, Victoria Shi, Jed J W Wiltzius, Stuart A Sievers, Shicheng Yang, James N Kochenderfer
Anti-CD19 chimeric antigen receptor (CAR) T cells have caused remissions of B cell malignancies, but problems including cytokine-mediated toxicity and short persistence of CAR T cells in vivo might limit the effectiveness of anti-CD19 CAR T cells. Anti-CD19 CARs that have been tested clinically had single-chain variable fragments (scFvs) derived from murine antibodies. We have designed and constructed novel anti-CD19 CARs containing a scFv with fully human variable regions. T cells expressing these CARs specifically recognized CD19(+) target cells and carried out functions including degranulation, cytokine release, and proliferation...
November 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
Hiroshi Matsumiya, Koji Kawata, Ryuta Kamekura, Chieko Tsubomatsu, Sumito Jitsukawa, Takamasa Asai, Syunsuke Akasaka, Motonari Kamei, Keiji Yamashita, Fumie Ito, Terufumi Kubo, Noriyuki Sato, Ken-Ichi Takano, Tetsuo Himi, Shingo Ichimiya
Florid reactive follicular hyperplasia (FRFH), which is characterized by large germinal centers (GCs) within normal lymphoid follicles, is often observed in benign lesions of lymph nodes and other tissues. Because of the histologic similarity of FRFH to tumorous lesions such as follicular lymphoma, careful pathological examination is required to evaluate such lesions; however, little is known about the mechanism underlying the development of FRFH. In this study, we investigated T follicular helper (Tfh) cells in hyperplastic tonsils of patients with obstructive sleep apnea syndrome (OSA), which frequently exhibits typical FRFH...
July 26, 2017: Immunology Letters
Meng Zhang, Jing Wang, Lingwei Jia, Jin Huang, Cheng He, Fuqing Hu, Lifei Yuan, Guihua Wang, Mingxia Yu, Zhuoya Li
Secretory tumor necrosis factor-alpha (sTNF-α) is known to mediate activation- induced cell death (AICD). However, the role of tmTNF-α in AICD is still obscure. Here, we demonstrated that tmTNF-α expression significantly increased accompanied with enhanced apoptosis during AICD in Jurkat and primary human T cells. Knockdown or enhancement of tmTNF-α expression in activated T cells suppressed or promoted AICD, respectively. Treatment of activated T cells with exogenous tmTNF-α significantly augmented AICD, indicating that tmTNF-α as an effector molecule mediates AICD...
July 10, 2017: Oncotarget
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