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Matthew J Scheffel, Gina Scurti, Patricia Simms, Elizabeth Garrett-Mayer, Shikhar Mehrotra, Michael I Nishimura, Christina Voelkel-Johnson
Although adoptive transfer of autologous tumor antigen-specific T-cell immunotherapy can produce remarkable clinical efficacy, most patients do not achieve durable complete responses. We hypothesized that reducing susceptibility of T cells to activation-induced cell death (AICD), which increases during the rapid in vitro expansion of therapeutic T cells before their infusion, might improve the persistence of adoptively transferred cells. Our investigations revealed that repetitive stimulation of the T-cell receptor (TCR) induced AICD, as a result of activating the DNA damage response pathway through ATM-mediated Ser15 phosphorylation of p53...
October 15, 2016: Cancer Research
Raghav Murthy, Matthew R Williams, James C Perry, Suzanne Shepard, Daniel DiBardino
The primary and secondary prevention of sudden cardiac death resulting from malignant arrhythmia, channelopathy, and hypertrophic cardiomyopathy often requires the implantation of automatic internal cardiac defibrillators (AICDs) in the pediatric population. In young patients, the small size of the systemic veins, complex anatomy of congenital heart disease, and body habitus often preclude safe and durable transvenous placement of the AICD coil, requiring innovative methods to circumvent this problem. This report describes the technique used at Rady Children's Hospital San Diego/UCSD for the epicardial placement of an ICD system with a transvenous ICD coil placed between the aorta and pulmonary artery, thereby producing a stable location and excellent coil-to-can vector for successful defibrillation...
October 2016: Annals of Thoracic Surgery
Corrado Mauro, Campello Silvia
Mitochondrial structural and functional changes and the autophagy pathway crosstalk under several stress conditions. However, their interplay under physiological cell death stimulation has been unclear. In our recent report, we show that during activation-induced cell death (AICD), the T-cell receptor (TCR)-dependent pathway that controls immune tolerance, autophagy is inhibited at an early stage. Further, we found that this inhibition is coupled with mitochondria fragmentation and cristae remodeling to unleash the apoptotic program...
September 14, 2016: Autophagy
Friedman Or, Zaretski Arik
We present a case of a silicone breast implant rupture after insertion of an automatic implantable cardioverter defibrillator (AICD). A 51-year-old woman presented to our plastic surgery clinic to exchange her silicone breast implants. The patient underwent cosmetic mastopexy and breast augmentation in 2008. Because of recurrent myocardial infarctions and chronic heart failure, she underwent an insertion of an AICD in 2014 in which the left breast implant was hit. In this report, we discuss the first case of an AICD insertion, disrupting a breast implant...
August 2016: Plastic and Reconstructive Surgery. Global Open
Sinyi Kong, Yi Yang, Yuanming Xu, Yajun Wang, Yusi Zhang, Johanna Melo-Cardenas, Xiangping Xu, Beixue Gao, Edward B Thorp, Donna D Zhang, Bin Zhang, Jianxun Song, Kezhong Zhang, Jianning Zhang, Jinping Zhang, Huabin Li, Deyu Fang
Humoral immunity involves multiple checkpoints during B-cell development, maturation, and activation. The cell death receptor CD95/Fas-mediated apoptosis plays a critical role in eliminating the unwanted activation of B cells by self-reactive antigens and in maintaining B-cell homeostasis through activation-induced B-cell death (AICD). The molecular mechanisms controlling AICD remain largely undefined. Herein, we show that the E3 ubiquitin ligase Hrd1 protected B cells from activation-induced cell death by degrading the death receptor Fas...
September 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
Hassan Bukhari, Katharina Kolbe, Gregor Leonhardt, Christina Loosse, Elisabeth Schröder, Shirley Knauer, Katrin Marcus, Thorsten Müller
A central molecular hallmark of Alzheimer's disease (AD) is the β- and γ-secretase-mediated cleavage of the amyloid precursor protein (APP), which causes the generation of different c-terminal fragments like C99, AICD57, or AICD50 that fully or in part contain the APP transmembrane domain. In this study, we demonstrate that membrane-tethered C99 is phosphorylated by JNK3A at residue T668 (APP695 numbering) to a higher extent than AICD57, whereas AICD50 is not capable of being phosphorylated. The modification decreases the turnover of APP, while the blockade of APP cleavage increases APP phosphorylation...
November 2016: Cellular Signalling
Amro Ilaiwy, Megan T Quintana, James R Bain, Michael J Muehlbauer, David I Brown, William E Stansfield, Monte S Willis
Studies of skeletal muscle disuse, either in patients on bed rest or experimentally in animals (immobilization), have demonstrated that decreased protein synthesis is common, with transient parallel increases in protein degradation. Muscle disuse atrophy involves a process of transition from slow to fast myosin fiber types. A shift toward glycolysis, decreased capacity for fat oxidation, and substrate accumulation in atrophied muscles have been reported, as has accommodation of the liver with an increased gluconeogenic capacity...
October 2016: International Journal of Biochemistry & Cell Biology
Doureradjou Peroumal, Thiruvaimozhi Abimannan, Ravichandra Tagirasa, Jyothi Ranjan Parida, Santosh Kumar Singh, Prasantha Padhan, Satish Devadas
Activation Induced Cell Death of T helper cells is central to maintaining immune homeostasis and a perturbation often manifests in aberrant T helper cells that is associated with immunopathologies. Significant presence of T cells positive for IL-17A (Th17) and dual positive for IFN-γ/IL-17A (Th1/Th17) in both effector (CD45RA+RO+) and memory (CD45RA-RO+) compartments with differential FasL protein in RA peripheral blood suggested their differential TCR AICD sensitivity. Lowered active caspase-3 in Th17 and Th1/Th17 over Th1 cells confirmed their capability to resist AICD and pointed to early upstream events...
July 28, 2016: Oncotarget
Jin Dai, Antti J Niemi, Jianfeng He
The Landau-Ginzburg-Wilson paradigm is proposed as a framework, to investigate the conformational landscape of intrinsically unstructured proteins. A universal Cα-trace Landau free energy is deduced from general symmetry considerations, with the ensuing all-atom structure modeled using publicly available reconstruction programs Pulchra and Scwrl. As an example, the conformational stability of an amyloid precursor protein intra-cellular domain (AICD) is inspected; the reference conformation is the crystallographic structure with code 3DXC in Protein Data Bank (PDB) that describes a heterodimer of AICD and a nuclear multi-domain adaptor protein Fe65...
July 28, 2016: Journal of Chemical Physics
S T Stephenson, V Bostik, P Bostik
Increased CD4+ T cell apoptosis and activation induced cell death (AICD) as a result of HIV infection in humans and SIV infection in Rhesus macaques (RM) is indicative of disease. Some non-human primate species naturally infected by SIV, such as African sooty mangabeys (SM), do not succumb to SIV despite high viral loads. Previously, we showed that mRNA levels of GSK-3β a kinase involved in T cell signaling, are significantly decreased in SIV+ RM compared to SIV+ SM. The current study confirms that expression of GSK-3β is decreased at the protein level in SIV+ RM...
2016: Epidemiologie, Mikrobiologie, Imunologie
Anirban Banerjee, Krishnamurthy Thyagarajan, Shilpak Chatterjee, Paramita Chakraborty, Pravin Kesarwani, Myroslawa Soloshchenko, Mazen Al-Hommrani, Kristina Andrijauskaite, Kelly Moxley, Harinarayanan Janakiraman, Matthew J Scheffel, Kristi Helke, Kent Armenson, Viswanathan Palanisamy, Mark P Rubinstein, Elizabeth-Garrett Mayer, David J Cole, Chrystal M Paulos, Christina Voelkel-Johnson, Michael I Nishimura, Shikhar Mehrotra
Repetitive stimulation of T-cell receptor (TCR) with cognate antigen results in robust proliferation and expansion of the T cells, and also imprints them with replicative senescence signatures. Our previous studies have shown that life-span and antitumor function of T cells can be enhanced by inhibiting reactive oxygen species (ROS) or intervening with ROS-dependent JNK activation that leads to its activation-induced cell death. Because tumor suppressor protein p53 is also a redox active transcription factor that regulates cellular ROS generation that triggers downstream factor-mediating apoptosis, we determined if p53 levels could influence persistence and function of tumor-reactive T cells...
September 15, 2016: Cancer Research
Kaushik Ghosal, Qingyuan Fan, Hana N Dawson, Sanjay W Pimplikar
Amyloid precursor protein (APP) is cleaved by gamma-secretase to simultaneously generate amyloid beta (Aβ) and APP Intracellular Domain (AICD) peptides. Aβ plays a pivotal role in Alzheimer's disease (AD) pathogenesis but recent studies suggest that amyloid-independent mechanisms also contribute to the disease. We previously showed that AICD transgenic mice (AICD-Tg) exhibit AD-like features such as tau pathology, aberrant neuronal activity, memory deficits and neurodegeneration in an age-dependent manner...
2016: PloS One
Hyundoo Hwang, Changsik Shin, Juhee Park, Enoch Kang, Bongseo Choi, Jae-A Han, Yoonkyung Do, Seongho Ryu, Yoon-Kyoung Cho
Breast cancer remains as a challenging disease with high mortality in women. Increasing evidence points the importance of understanding a crosstalk between breast cancers and immune cells, but little is known about the effect of breast cancer-derived factors on the migratory properties of dendritic cells (DCs) and their consequent capability in inducing T cell immune responses. Utilizing a unique 3D microfluidic device, we here showed that breast cancers (MCF-7, MDA-MB-231, MDA-MB-436 and SK-BR-3)-derived soluble factors increase the migration of DCs toward CCL19...
2016: Scientific Reports
John Sabu, Kalyani Regeti, Mary Mallappallil, John Kassotis, Hamidul Islam, Shoaib Zafar, Rafay Khan, Hiyam Ibrahim, Romana Kanta, Shuvendu Sen, Abdalla Yousif, Qiang Nai
It is important but difficult to distinguish convulsive syncope from epileptic seizure in many patients. We report a case of a man who presented to emergency department after several witnessed seizure-like episodes. He had a previous medical history of systolic heart failure and automated implantable converter defibrillator (AICD) in situ. The differential diagnoses raised were epileptic seizures and convulsive syncope secondary to cardiac arrhythmia. Subsequent AICD interrogation revealed ventricular tachycardia and fibrillation (v-tach/fib)...
August 2016: Journal of Clinical Medicine Research
Mauro Corrado, Francesca R Mariotti, Laura Trapani, Lucia Taraborrelli, Francesca Nazio, Valentina Cianfanelli, Maria Eugenia Soriano, Emilie Schrepfer, Francesco Cecconi, Luca Scorrano, Silvia Campello
Mitochondrial dynamics and functionality are linked to the autophagic degradative pathway under several stress conditions. However, the interplay between mitochondria and autophagy upon cell death signalling remains unclear. The T-cell receptor pathway signals the so-called activation-induced cell death (AICD) essential for immune tolerance regulation. Here, we show that this apoptotic pathway requires the inhibition of macroautophagy. Protein kinase-A activation downstream of T-cell receptor signalling inhibits macroautophagy upon AICD induction...
August 15, 2016: EMBO Journal
Bo-In Kwon, Tae Woo Kim, Kihyuk Shin, Yun Hee Kim, Chae Min Yuk, Jae-Min Yuk, Dong-Min Shin, Eun-Kyeong Jo, Chul-Ho Lee, Seung-Hyo Lee
BACKGROUND: Chronic granulomatous disease (CGD) patients, whom inherit abnormal function of NADPH oxidase 2 (Nox2), suffer from hyper inflammatory responses in lung as well as bacterial and fungal infection. There have been studies to reveal the function of Nox2 in hyper-inflammatory diseases, especially in asthma, but the exact role of Nox2 in asthma is still unclear and controversial. Therefore, we attempted to clarify the exact role of Nox2 in asthma, using various experimental asthma models...
June 2, 2016: Allergy
Hannah Langlands, Peter G Blain, Paul A Jowsey
Fe65 undergoes a phosphatase-sensitive gel mobility shift after DNA damage, consistent with protein phosphorylation. A recent study identified Ser228 as a specific site of phosphorylation, targeted by the ATM and ATR protein kinases, with phosphorylation inhibiting the Fe65-dependent transcriptional activity of the amyloid precursor protein (APP). The direct binding of Fe65 to APP not only regulates target gene expression, but also contributes to secretase-mediated processing of APP, producing cytoactive proteolytic fragments including the APP intracellular domain (AICD) and cytotoxic amyloid β (Aβ) peptides...
2016: PloS One
Anja Schwiebs, Olga Friesen, Elisabeth Katzy, Nerea Ferreirós, Josef M Pfeilschifter, Heinfried H Radeke
Sphingosine 1-phosphate (S1P) is an immune modulatory lipid mediator and has been implicated in numerous pathophysiological processes. S1P is produced by sphingosine kinase 1 (Sphk1) and Sphk2. Dendritic cells (DCs) are central for the direction of immune responses and crucially involved in autoimmunity and cancerogenesis. In this study we examined the function and survival of bone marrow-derived DCs under long-term inflammatory stimulation. We observed that differentiated cells undergo activation-induced cell death (AICD) upon LPS stimulation with an increased metabolic activity shortly after stimulation, followed by a rapid activation of caspase 3 and subsequent augmented apoptosis...
2016: Frontiers in Pharmacology
Jiali Yu, Weibang Lu, Shaopeng Pei, Ke Gong, Liyun Wang, Linghui Meng, Yudong Huang, Joseph P Smith, Karl S Booksh, Qingwen Li, Joon-Hyung Byun, Youngseok Oh, Yushan Yan, Tsu-Wei Chou
The emergence of stretchable electronic devices has attracted intensive attention. However, most of the existing stretchable electronic devices can generally be stretched only in one specific direction and show limited specific capacitance and energy density. Here, we report a stretchable isotropic buckled carbon nanotube (CNT) film, which is used as electrodes for supercapacitors with low sheet resistance, high omnidirectional stretchability, and electro-mechanical stability under repeated stretching. After acid treatment of the CNT film followed by electrochemical deposition of polyaniline (PANI), the resulting isotropic buckled acid treated CNT@PANI electrode exhibits high specific capacitance of 1147...
May 24, 2016: ACS Nano
Natalia N Nalivaeva, Anthony J Turner
The amyloid precursor protein (APP) and acetylcholinesterase (AChE) are multi-faceted proteins with a wide range of vital functions, both crucially linked with the pathogenesis of Alzheimer's disease (AD). APP is the precursor of the Aβ peptide, the pathological agent in AD, while AChE is linked to its pathogenesis either by increasing cholinergic deficit or exacerbating Aβ fibril formation and toxicity. As such, both proteins are the main targets in AD therapeutics with AChE inhibitors being currently the only clinically available AD drugs...
April 7, 2016: Chemico-biological Interactions
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