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https://www.readbyqxmd.com/read/28209913/rapid-imaging-of-tumor-cell-death-in-vivo-using-the-c2a-domain-of-synaptotagmin-i
#1
André A Neves, Bangwen Xie, Sarah Fawcett, Israt S Alam, Timothy H Witney, Maaike M de Backer, Julia Summers, William Hughes, Sarah McGuire, Dmitry Soloviev, Jodie Miller, William J Howat, De-En Hu, Tiago B Rodrigues, David Y Lewis, Kevin M Brindle
Cell death is an important target for imaging the early response of tumors to treatment. We describe here validation of a phosphatidylserine-binding agent for detecting tumor cell death in vivo based on the C2A domain of Synaptotagmin-I. Methods: The capability of near infrared fluorophore-labeled and 99mTechnetium- and (111)Indium-labeled derivatives of C2Am for imaging tumor cell death, using planar near infrared fluorescence (NIRF) imaging and single photon computed tomography (SPECT) respectively, was evaluated in implanted and genetically engineered mouse models of lymphoma and in a human colorectal xenograft...
February 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28206771/magnetic-particle-imaging-a-novel-in-vivo-imaging-platform-for-cancer-detection
#2
Elaine Y Yu, Mindy Bishop, Bo Zheng, R Matthew Ferguson, Amit P Khandhar, Scott J Kemp, Kannan M Krishnan, Patrick W Goodwill, Steven M Conolly
Cancer remains one of the leading causes of death worldwide. Biomedical imaging plays a crucial role in all phases of cancer management. Physicians often need to choose the ideal diagnostic imaging modality for each clinical presentation based on complex trade-offs between spatial resolution, sensitivity, contrast, access, cost, and safety. Magnetic particle imaging (MPI) is an emerging tracer imaging modality that detects superparamagnetic iron oxide (SPIO) nanoparticle tracer with high image contrast (zero tissue background signal), high sensitivity (200 nM Fe) with linear quantitation and zero signal depth attenuation...
February 16, 2017: Nano Letters
https://www.readbyqxmd.com/read/28202759/relationship-between-measures-of-hiv-reactivation-and-the-decline-of-latent-reservoir-under-latency-reversing-agents
#3
Janka Petravic, Thomas A Rasmussen, Sharon R Lewin, Stephen J Kent, Miles P Davenport
Antiretroviral-free HIV remission requires substantial reduction of the number of latently infected cells and enhanced immune control of viremia. Latency-reversing agents (LRA) aim to eliminate latently infected cells by increasing the rate of reactivation of HIV transcription, which exposes these cells to killing by the immune system. As LRA are explored in clinical trials, it becomes increasingly important to assess the effect of increased HIV reactivation rate on the decline of latently infected cells, and estimate LRA efficacy in increasing virus reactivation...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28194400/eating-the-dead-to-keep-atherosclerosis-at-bay
#4
REVIEW
Megan L Brophy, Yunzhou Dong, Hao Wu, H N Ashiqur Rahman, Kai Song, Hong Chen
Atherosclerosis is the primary cause of coronary heart disease (CHD), ischemic stroke, and peripheral arterial disease. Despite effective lipid-lowering therapies and prevention programs, atherosclerosis is still the leading cause of mortality in the United States. Moreover, the prevalence of CHD in developing countries worldwide is rapidly increasing at a rate expected to overtake those of cancer and diabetes. Prominent risk factors include the hardening of arteries and high levels of cholesterol, which lead to the initiation and progression of atherosclerosis...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28194040/abnormal-degradation-of-the-neuronal-stress-protective-transcription-factor-hsf1-in-huntington-s-disease
#5
Rocio Gomez-Pastor, Eileen T Burchfiel, Daniel W Neef, Alex M Jaeger, Elisa Cabiscol, Spencer U McKinstry, Argenia Doss, Alejandro Aballay, Donald C Lo, Sergey S Akimov, Christopher A Ross, Cagla Eroglu, Dennis J Thiele
Huntington's Disease (HD) is a neurodegenerative disease caused by poly-glutamine expansion in the Htt protein, resulting in Htt misfolding and cell death. Expression of the cellular protein folding and pro-survival machinery by heat shock transcription factor 1 (HSF1) ameliorates biochemical and neurobiological defects caused by protein misfolding. We report that HSF1 is degraded in cells and mice expressing mutant Htt, in medium spiny neurons derived from human HD iPSCs and in brain samples from patients with HD...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28193887/tmem175-deficiency-impairs-lysosomal-and-mitochondrial-function-and-increases-%C3%AE-synuclein-aggregation
#6
Sarah Jinn, Robert E Drolet, Paige E Cramer, Andus Hon-Kit Wong, Dawn M Toolan, Cheryl A Gretzula, Bhavya Voleti, Galya Vassileva, Jyoti Disa, Marija Tadin-Strapps, David J Stone
Parkinson disease (PD) is a neurodegenerative disorder pathologically characterized by nigrostriatal dopamine neuron loss and the postmortem presence of Lewy bodies, depositions of insoluble α-synuclein, and other proteins that likely contribute to cellular toxicity and death during the disease. Genetic and biochemical studies have implicated impaired lysosomal and mitochondrial function in the pathogenesis of PD. Transmembrane protein 175 (TMEM175), the lysosomal K(+) channel, is centered under a major genome-wide association studies peak for PD, making it a potential candidate risk factor for the disease...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193668/towards-selective-mycobacterial-clpp1p2-inhibitors-with-reduced-activity-against-the-human-proteasome
#7
Wilfried Moreira, Sridhar Santhanakrishnan, Grace J Y Ngan, Choon Bing Low, Kanda Sangthongpitag, Anders Poulsen, Brian W Dymock, Thomas Dick
Mycobacterium tuberculosis (TB) is responsible for the greatest number of deaths worldwide due to a bacterial agent. We recently identified bortezomib (1) as a promising anti-TB compound. We showed that 1 inhibits the mycobacterial caseinolytic protease ClpP1P2 and exhibits bactericidal activity and established 1 and ClpP1P2 as an attractive lead/target couple. However, 1 is a human proteasome inhibitor currently approved for cancer therapy, and as such exhibits significant toxicity. Selective inhibition of the bacterial protease over the human proteasome is desirable in order to maintain antibacterial activity while reducing toxicity...
February 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28182273/association-of-time-varying-clearance-of-nivolumab-with-disease-dynamics-and-its-implications-on-exposure-response-analysis
#8
Chao Liu, Jingyu Yu, Hongshan Li, Jiang Liu, Yuan Xu, Pengfei Song, Qi Liu, Hong Zhao, James Xu, Virginia E Maher, Brian P Booth, Geoffrey Kim, Atiqur Rahman, Yaning Wang
Nivolumab is a human monoclonal antibody that blocks the interaction between PD-1 programmed death-1 (PD-1) and its ligands, PD-L1 and PD-L2. Nivolumab demonstrated efficacy in clinical trials for various types of cancer. A time-varying clearance was identified for nivolumab. We show that the change of clearance over time is associated with the post-treatment effects: clearance decreases when disease status improves. This interaction between post-treatment effects and drug exposure may lead to a biased steep estimate of exposure-response (E-R) relationship for efficacy...
February 9, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28176482/high-density-lipoprotein-associated-paraoxonase-1-activity-for-prediction-of-adverse-outcomes-in-outpatients-with-chronic-heart-failure
#9
Muhammad Hammadah, Andreas P Kalogeropoulos, Vasiliki V Georgiopoulou, Malory Weber, Yuping Wu, Stanley L Hazen, Javed Butler, W H Wilson Tang
AIMS: Decreased arylesterase (ArylE) activity of paraoxonase-1, a HDL-associated protein with anti-inflammatory and antioxidant properties, has been associated with increased risk of cardiac events in patients with ischaemic heart failure (HF). We aim to investigate the prognostic significance of changes in serum ArylE activity over time. METHODS AND RESULTS: We examined the association between baseline and follow-up serum ArylE activity and HF outcomes (death, cardiac transplantation, or ventricular assist device implantation) in 299 patients with HF enrolled in a prospective cohort study from January 2008 to July 2009, with 145 patients having available follow-up levels at 1 year...
February 7, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28176216/pcsk9-targets-important-for-lipid-metabolism
#10
Rainer Schulz, Klaus-Dieter Schlüter
Ischemic heart disease is the main cause of death worldwide and it is accelerated by increased low-density lipoprotein (LDL) cholesterol (LDL-C) and/or lipoprotein (a) (Lp(a)) concentrations. Proprotein convertase subtilisin/kexin type 9 (PCSK9) alters both LDL-C and in part Lp(a) concentrations through its ability to induce degradation of the LDL receptor (LDLR). PCSK9, however, has additional targets which are potentially involved in lipid metabolism regulation such as the very low density lipoprotein receptor (VLDL), CD36 (cluster of differentiation 36) and the epithelial cholesterol transporter (NPC1L1) and it affects expression of apolipoprotein B48...
February 7, 2017: Clinical Research in Cardiology Supplements
https://www.readbyqxmd.com/read/28166975/impact-of-a-killed-tritrichomonas-foetus-vaccine-on-clearance-of-the-organism-and-subsequent-fertility-of-heifers-following-experimental-inoculation
#11
Misty A Edmondson, Kellye S Joiner, Jennifer A Spencer, Kay P Riddell, Soren P Rodning, Julie A Gard, M Daniel Givens
Tritrichomonas foetus is a sexually transmitted reproductive pathogen of cattle that causes transient infertility, early embryonic death, metritis, pyometra, and sporadic abortions. The objective of this research was to assess the impact on reproductive health of vaccinating naïve heifers with a killed T. foetus vaccine (TrichGuard) before experimental exposure followed by breeding. A total of 40 beef heifers were randomly assigned into two treatment groups. Heifers where then vaccinated with two doses of TrichGuard or sham vaccinated with 0...
March 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28166165/automated-variable-aortic-control-vs-complete-aortic-occlusion-in-a-swine-model-of-hemorrhage
#12
Timothy K Williams, Lucas P Neff, M Austin Johnson, Rachel M Russo, Sarah-Ashley Ferencz, Anders J Davidson, Nathan F Clement, J Kevin Grayson, Todd E Rasmussen
BACKGROUND: Future endovascular hemorrhage control devices will require features that mitigate the adverse effects of vessel occlusion. Permissive regional hypoperfusion (PRH) with variable aortic control (VAC) is a novel strategy to minimize hemorrhage and reduce the ischemic burden of complete aortic occlusion (AO). The objective of this study was to compare PRH with VAC to AO in a lethal model of hemorrhage. METHODS: Twenty-five swine underwent cannulation of the supraceliac aorta, with diversion of aortic flow through an automated extracorporeal circuit...
February 4, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28165668/plant-life-needs-cell-death-but-does-plant-cell-death-need-cys-proteases
#13
REVIEW
Daniela J Sueldo, Renier A L van der Hoorn
Caspases are key regulators of apoptosis in animals. This correlation has driven plant researchers for decades to look for caspases regulating Programmed Cell Death (PCD) in plants. These studies revealed caspase-like activities, caspase-related proteases and cysteine (Cys) proteases regulating PCD in plants, but identified no caspases and no conserved, apoptosis-like death pathway. Here, we critically review the evidence for Cys proteases implicated in PCD in plants. We discuss the role of papain-like Cys proteases, vacuolar processing enzymes and metacaspases in PCD during the development of tracheary elements, seed coat, suspensor and tapetum and during the hypersensitive response...
February 6, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28157210/modulation-of-macrophage-antitumor-potential-by-apoptotic-lymphoma-cells
#14
Jorine J L P Voss, Catriona A Ford, Sofia Petrova, Lynsey Melville, Margaret Paterson, John D Pound, Pam Holland, Bruno Giotti, Tom C Freeman, Christopher D Gregory
In aggressive non-Hodgkin's lymphoma (NHL), constitutive apoptosis of a proportion of the tumor cell population can promote net tumor growth. This is associated with the accumulation of tumor-associated macrophages (TAMs) that clear apoptotic cells and exhibit pro-oncogenic transcriptional activation profiles characteristic of reparatory, anti-inflammatory and angiogenic programs. Here we consider further the activation status of these TAMs. We compare their transcriptomic profile with that of a range of other macrophage types from various tissues noting especially their expression of classically activated (IFN-γ and LPS) gene clusters - typically antitumor - in addition to their previously described protumor phenotype...
February 3, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28151933/specific-anti-glycan-antibodies-are-sustained-during-and-after-parasite-clearance-in-schistosoma-japonicum-infected-rhesus-macaques
#15
Y Y Michelle Yang, Xiao Hong Li, Katarzyna Brzezicka, Niels-Christian Reichardt, R Alan Wilson, Angela van Diepen, Cornelis H Hokke
BACKGROUND: Human immunity to Schistosoma infection requires many years of exposure, and multiple infections and treatments to develop. Unlike humans, rhesus macaques clear an established schistosome infection naturally at the same time acquiring immunity towards re-infection. In macaques, schistosome egg production decreases after 8 weeks post-infection and by week 22, physiological impairment of the worm caused by unclarified antibody-mediated processes is observed. Since strong antibody responses have been observed against schistosome glycan antigens in human and animal infections, we here investigate if anti-glycan antibodies are associated with immunity against schistosome infections in macaques...
February 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28149880/aldehyde-dehydrogenases-in-cancer-stem-cells-potential-as-therapeutic-targets
#16
COMMENT
David W Clark, Komaraiah Palle
Resistance to current chemotherapeutic or radiation-based cancer treatment strategies is a serious concern. Cancer stem cells (CSCs) are typically able to evade treatment and establish a recurrent tumor or metastasis, and it is these that lead to the majority of cancer deaths. Therefore, a major current goal is to develop treatment strategies that eliminate the resistant CSCs as well as the bulk tumor cells in order to achieve complete disease clearance. Aldehyde dehydrogenases (ALDHs) are important for maintenance and differentiation of stem cells as well as normal development...
December 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28145529/intracellular-accumulation-of-gold-nanoparticles-leads-to-inhibition-of-macropinocytosis-to-reduce-the-endoplasmic-reticulum-stress
#17
Nuray Gunduz, Hakan Ceylan, Mustafa O Guler, Ayse B Tekinay
Understanding the toxicity of nanomaterials remains largely limited to acute cellular response, i.e., short-term in vitro cell-death based assays, and analyses of tissue- and organ-level accumulation and clearance patterns in animal models, which have produced very little information about how these materials (from the toxicity point of view) interact with the complex intracellular machinery. In particular, understanding the mechanism of toxicity caused by the gradual accumulation of nanomaterials due to prolonged exposure times is essential yet still continue to be a largely unexplored territory...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28138137/programmed-cell-death-as-a-defence-against-infection
#18
REVIEW
Ine Jorgensen, Manira Rayamajhi, Edward A Miao
Eukaryotic cells can die from physical trauma, which results in necrosis. Alternatively, they can die through programmed cell death upon the stimulation of specific signalling pathways. In this Review, we discuss the role of different cell death pathways in innate immune defence against bacterial and viral infection: apoptosis, necroptosis, pyroptosis and NETosis. We describe the interactions that interweave different programmed cell death pathways, which create complex signalling networks that cross-guard each other in the evolutionary 'arms race' with pathogens...
January 31, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28134664/the-walking-dead-macrophage-inflammation-and-death-in-atherosclerosis
#19
Mary M Kavurma, Katey J Rayner, Denuja Karunakaran
PURPOSE OF REVIEW: To highlight recent studies that describe novel inflammatory and signaling mechanisms that regulate macrophage death in atherosclerosis. RECENT FINDINGS: Macrophages contribute to all stages of atherosclerosis. The traditional dogma states that in homeostatic conditions, macrophages undergo apoptosis and are efficiently phagocytosed to be cleared by a process called efferocytosis. In advanced atherosclerosis, however, defective efferocytosis results in secondary necrosis of these uncleared apoptotic cells, which ultimately contributes to the formation of the characteristic necrotic core and the vulnerable plaque...
January 27, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28134239/a-rab5-endosomal-pathway-mediates-parkin-dependent-mitochondrial-clearance
#20
Babette C Hammerling, Rita H Najor, Melissa Q Cortez, Sarah E Shires, Leonardo J Leon, Eileen R Gonzalez, Daniela Boassa, Sébastien Phan, Andrea Thor, Rebecca E Jimenez, Hong Li, Richard N Kitsis, Gerald W Dorn Ii, Junichi Sadoshima, Mark H Ellisman, Åsa B Gustafsson
Damaged mitochondria pose a lethal threat to cells that necessitates their prompt removal. The currently recognized mechanism for disposal of mitochondria is autophagy, where damaged organelles are marked for disposal via ubiquitylation by Parkin. Here we report a novel pathway for mitochondrial elimination, in which these organelles undergo Parkin-dependent sequestration into Rab5-positive early endosomes via the ESCRT machinery. Following maturation, these endosomes deliver mitochondria to lysosomes for degradation...
January 30, 2017: Nature Communications
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