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https://www.readbyqxmd.com/read/29352272/nuclear-p53-mediated-repression-of-autophagy-involves-pink1-transcriptional-down-regulation
#1
Thomas Goiran, Eric Duplan, Lila Rouland, Wejdane El Manaa, Inger Lauritzen, Julie Dunys, Han You, Frédéric Checler, Cristine Alves da Costa
p53 is a transcription factor that is implicated in the control of both apoptotic and autophagic cell death. This tumor suppressor elicits both pro-autophagic and anti-autophagic phenotypes depending of its intracellular localization. The ability of p53 to repress autophagy has been exclusively associated to its cytoplasmic localization. Here, we show that transcriptional activity of p53 also contributes to autophagy down-regulation. Thus, nuclear p53 controls PINK1, a key protein involved in the control of mitophagy, by repressing its promoter activity, protein and mRNA levels, ex-vivo and in vivo...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352268/cylindromatosis-mediates-neuronal-cell-death-in-vitro-and-in-vivo
#2
Goutham K Ganjam, Nicole Angela Terpolilli, Sebastian Diemert, Ina Eisenbach, Lena Hoffmann, Christina Reuther, Christiane Herden, Joachim Roth, Nikolaus Plesnila, Carsten Culmsee
The tumor-suppressor cylindromatosis (CYLD) is a deubiquitinating enzyme and key regulator of cell proliferation and inflammation. A genome-wide siRNA screen linked CYLD to receptor interacting protein-1 (RIP1) kinase-mediated necroptosis; however, the exact mechanisms of CYLD-mediated cell death remain unknown. Therefore, we investigated the precise role of CYLD in models of neuronal cell death in vitro and evaluated whether CYLD deletion affects brain injury in vivo. In vitro, downregulation of CYLD increased RIP1 ubiquitination, prevented RIP1/RIP3 complex formation, and protected neuronal cells from oxidative death...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29351897/transitions-between-circulatory-states-after-out-of-hospital-cardiac-arrest-protocol-for-an-observational-prospective-cohort-study
#3
Halvor Langeland, Daniel Bergum, Magnus Løberg, Knut Bjørnstad, Jan Kristian Damås, Tom Eirik Mollnes, Nils-Kristian Skjærvold, Pål Klepstad
BACKGROUND: The post cardiac arrest syndrome (PCAS) is responsible for the majority of in-hospital deaths following cardiac arrest (CA). The major elements of PCAS are anoxic brain injury and circulatory failure. OBJECTIVE: This study aimed to investigate the clinical characteristics of circulatory failure and inflammatory responses after out-of-hospital cardiac arrest (OHCA) and to identify patterns of circulatory and inflammatory responses, which may predict circulatory deterioration in PCAS...
January 19, 2018: JMIR Research Protocols
https://www.readbyqxmd.com/read/29351312/prognostic-relevance-of-elevated-pulmonary-arterial-pressure-assessed-non-invasively-analysis-in-a-large-patient-cohort-with-invasive-measurements-in-near-temporal-proximity
#4
Sebastian Greiner, Andreas Jud, Matthias Aurich, Christoph Geisenberger, Lorenz Uhlmann, Thomas Hilbel, Meinhard Kieser, Hugo A Katus, Derliz Mereles
BACKGROUND: The clinical relevance of non-invasively derived pulmonary arterial pressure (PAP) by Doppler echocardiography (DE) has been questioned in the past. However, transthoracic echocardiography is used as a cornerstone examination for patients with dyspnea and suspected pulmonary hypertension (PH). This study aimed to evaluate the prognostic value of non-invasive assessed PAP in a large population of patients with known or suspected cardiopulmonary disease. METHODS: The analyses are based on data of patients of a tertiary cardiology center that received right heart catheterization (RHC) as well as non-invasively assessed PAP by DE within five days, and includes serological and clinical parameters in a retrospective follow-up for up to eight years...
2018: PloS One
https://www.readbyqxmd.com/read/29351212/changes-in-the-expression-of-aqp4-and-aqp9-in-the-hippocampus-following-eclampsia-like-seizure
#5
Xinjia Han, Qian Huang, Lei Liu, Xiaoyan Sha, Bihui Hu, Huishu Liu
Eclampsia is a hypertensive disorder of pregnancy that is defined by the new onset of grand mal seizures on the basis of pre-eclampsia. Until now, the mechanisms underlying eclampsia were poorly understood. Brain edema is considered a leading cause of eclamptic seizures; aquaporins (AQP4 and AQP9), the glial water channel proteins mainly expressed in the nervous system, play an important role in brain edema. We studied AQP4 and AQP9 expression in the hippocampus of pre-eclamptic and eclamptic rats in order to explore the molecular mechanisms involved in brain edema...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29350905/ampulexins-a-new-family-of-peptides-in-venom-of-the-emerald-jewel-wasp-ampulex-compressa
#6
Eugene Moore, Ryan Arvidson, Christopher Banks, Jean Urenda, Elizabeth Duong, Haroun Mohammad, Michael E Adams
The parasitoid wasp Ampulex compressa injects venom directly into the brain and subesophageal ganglion of the cockroach Periplaneta americana, inducing a seven to ten day lethargy termed hypokinesia. Hypokinesia presents as a significant reduction in both escape response and spontaneous walking. We examined aminergic and peptidergic components of milked venom with HPLC and MALDI-TOF mass spectrometry. HPLC coupled with electrochemical detection confirmed presence of dopamine in milked venom, while mass spectrometry revealed that the venom gland and venom sac have distinct peptide profiles, with milked venom predominantly composed of venom sac peptides...
January 19, 2018: Biochemistry
https://www.readbyqxmd.com/read/29350596/enhancement-of-antitumor-activity-by-using-5-ala-mediated-sonodynamic-therapy-to-induce-apoptosis-in-malignant-gliomas-significance-of-high-intensity-focused-ultrasound-on-5-ala-sdt-in-a-mouse-glioma-model
#7
Satoshi Suehiro, Takanori Ohnishi, Daisuke Yamashita, Shohei Kohno, Akihiro Inoue, Masahiro Nishikawa, Shiro Ohue, Junya Tanaka, Takeharu Kunieda
OBJECTIVE High invasiveness of malignant gliomas frequently causes early local recurrence of the tumor, resulting in extremely poor outcome. To control such recurrence, novel therapies targeted toward infiltrating glioma cells around the tumor border are required. Here, the authors investigated the antitumor activity of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas to explore the possibility for clinical use of 5-ALA-mediated SDT (5-ALA-SDT). METHODS In vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells...
January 19, 2018: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29350470/specific-expression-of-pd-l1-in-rela-fusion-supratentorial-ependymoma-implications-for-pd-1-targeted-therapy
#8
Davis A Witt, Andrew M Donson, Vladimir Amani, Daniel C Moreira, Bridget Sanford, Lindsey M Hoffman, Michael H Handler, Jean M Mulcahy Levy, Kenneth L Jones, Anandani Nellan, Nicholas K Foreman, Andrea M Griesinger
BACKGROUND: A desperate need for novel therapies in pediatric ependymoma (EPN) exists, as chemotherapy remains ineffective and radiotherapy often fails. EPN have significant infiltration of immune cells, which correlates with outcome. Immune checkpoint inhibitors provide an avenue for new treatments. This study characterizes tumor-infiltrating immune cells in EPN and aims at predicting candidates for clinical trials using checkpoint inhibitors targeting PD-L1/PD-1 (programmed death ligand 1/programmed death 1)...
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29350382/risk-factors-for-adverse-outcomes-of-acute-coronary-syndrome-patients-single-center-experience-in-long-term-follow-up-of-treated-patients
#9
Marcin Grabowski, Krzysztof J Filipiak, Grzegorz Opolski, Renata Główczyńska, Monika Gawałko, Paweł Balsam, Andrzej Cacko, Zenon Huczek, Grzegorz Karpiński, Robert Kowalik, Franciszek Majstrak, Janusz Kochman
BACKGROUND: For patients experiencing an acute coronary syndrome (ACS), a crucial time to assess their prognosis and future management is at discharge from hospital. AIM: To identify patients' risk factors of mortality during post-discharge period following an ACS hospitalization. METHODS: We studied 672 consecutive ACS patients hospitalized and discharged alive between 2002 and 2004. The analysis was done in respect of the type of ACS, i...
January 19, 2018: Kardiologia Polska
https://www.readbyqxmd.com/read/29350172/comparison-of-dialysate-and-plasma-ntprobnp-in-prediction-of-clinical-outcomes-of%C3%A2-diabetic-and-nondiabetic-peritoneal-dialysis-patients%C3%A2
#10
Suleyman Koz, Idris Sahin, Mansur Kayatas, Sema Tulay Koz
BACKGROUND: Plasma level of N-terminal pro-brain natriuretic peptide (P-NTproBNP) is a useful marker in prediction of mortality in peritoneal dialysis (PD) patients. However, the predictive value of spent dialysate counterpart (D-NTproBNP) of plasma NTproBNP on mortality and dropout is not known. MATERIALS AND METHODS: Simultaneous P-NTproBNP and D-NTproBNP assays were performed after an overnight dwell in 44 scheduled ambulatory PD patients. Patients were followed for ~ 47 months...
January 19, 2018: Clinical Nephrology
https://www.readbyqxmd.com/read/29350082/quantitative-dti-metrics-in-a-canine-model-of-krabbe-disease-comparisons-versus-age-matched-controls-across-multiple-ages
#11
Jonathan Y Li, Dana M Middleton, Steven Chen, Leonard White, Carley R Corado, Charles Vite, Allison Bradbury, James M Provenzale
Purpose The purpose of this study was to compare quantitative diffusion tensor imaging metrics in dogs affected with a model of Krabbe disease to age-matched normal controls. We hypothesized that fractional anisotropy would be decreased and radial diffusivity would be increased in the Krabbe dogs. Methods We used a highly reproducible region-of-interest interrogation technique to measure fractional anisotropy and radial diffusivity in three different white matter regions within the internal capsule and centrum semiovale in four Krabbe affected brains and three age-matched normal control brains...
January 1, 2018: Neuroradiology Journal
https://www.readbyqxmd.com/read/29349723/species-diversity-and-tissue-specific-dispersal-of-necrophagous-diptera-on-human-bodies
#12
Victoria Bernhardt, Miklós Bálint, Marcel A Verhoff, Jens Amendt
In forensic entomology, many studies analyze fly activity and succession on dead bodies by using pig cadavers and a variety of small baited traps. Data on real human bodies are very rare. To address this shortcoming, we analyzed the fly fauna of 51 human bodies in Germany. Sex, age, place of discovery, and presumed time of death were noted. Larvae were sampled during autopsy according to body region or tissue. For every infested region, the total number of fly larvae were estimated and classified into categories of 1-10, 11-50, and 50+...
January 18, 2018: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/29349577/combination-therapy-with-sulfasalazine-and-valproic-acid-promotes-human-glioblastoma-cell-death-through-imbalance-of-the-intracellular-oxidative-response
#13
Carlos Gustavo Garcia, Suzana Assad Kahn, Luiz Henrique Medeiros Geraldo, Igor Romano, Ivan Domith, Deborah Christinne Lima E Silva, Fernando Dos Santos Assunção, Marcos José Ferreira, Camila Cabral Portugal, Jorge Marcondes de Souza, Luciana Ferreira Romão, Annibal Duarte Pereira Netto, Flávia Regina Souza Lima, Marcelo Cossenza
Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor and still lacks effective therapeutic strategies. It has already been shown that old drugs like sulfasalazine (SAS) and valproic acid (VPA) present antitumoral activities in glioma cell lines. SAS has also been associated with a decrease of intracellular glutathione (GSH) levels through a potent inhibition of xc- glutamate/cystine exchanger leading to an antioxidant deprotection. In the same way, VPA was recently identified as a histone deacetylase (HDAT) inhibitor capable of activating tumor suppression genes...
January 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29349556/neuropathology-correlates-of-cognitive-assessments
#14
Francesca M Brett, Hugh Kearney
BACKGROUND: Alzheimer's disease and other dementias are the fourth largest contributors to neurological disability and the second largest contributor to deaths from neurological disease. Described in the 1980s as 'the silent epidemic' these disorders principally, though not exclusively, affect persons 80 years or older, and in developed countries, this 'old old' population continues to grow. Definitive diagnosis of the underlying cause of the neurodegenerative disease relies on neuropathological evaluation...
January 18, 2018: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/29349290/a-novel-neuroprotective-mechanism-for-lithium-that-prevents-association-of-the-p75ntr-sortilin-receptor-complex-and-attenuates-prongf-induced-neuronal-death-in-vitro-and-in-vivo
#15
Shayri G Greenwood, Laura Montroull, Marta Volosin, Helen E Scharfman, Kenneth K Teng, Matthew Light, Risa Torkin, Fredrick Maxfield, Barbara L Hempstead, Wilma J Friedman
Neurotrophins play critical roles in the survival, maintenance and death of neurons. In particular, proneurotrophins have been shown to mediate cell death following brain injury induced by status epilepticus (SE) in rats. Previous studies have shown that pilocarpine-induced seizures lead to increased levels of proNGF, which binds to the p75NTR-sortilin receptor complex to elicit apoptosis. A screen to identify compounds that block proNGF binding and uptake into cells expressing p75 and sortilin identified lithium citrate as a potential inhibitor of proNGF and p75NTR-mediated cell death...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29348907/microsatellite-stability-and-mismatch-repair-proficiency-in-nasopharyngeal-carcinoma-may-not-predict-programmed-death-1-blockade-resistance
#16
Xiyi Liao, Liang Zhao, Sangang Wu, Hua Zheng, Haojun Chen, Huan Zhang, ZiJing Wang, Qin Lin
The US FDA granted accelerated approval to pembrolizumab for microsatellite instability-high and mismatch repair deficient cancers. The response of programmed death-1 blockade in mismatch repair proficiency (pMMR) colorectal cancer is very poor, however, whether such treatment is effective in pMMR nasopharyngeal carcinoma (NPC) remains unknown. We report a case of a 51-year-old man with NPC. PET-CT scan revealed a space-occupying lesion in the left lung, and the pathologic result confirmed the occupying lesion originated from NPC...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29346563/lc3-immunostaining-in-the-inferior-olivary-nuclei-of-cats-with-niemann-pick-disease-type-c1-is-associated-with-patterned-purkinje-cell-loss
#17
Brittney L Gurda, Jessica H Bagel, Samantha J Fisher, Mark L Schultz, Andrew P Lieberman, Peter Hand, Charles H Vite, Gary P Swain
The feline model of Niemann-Pick disease, type C1 (NPC1) recapitulates the clinical, neuropathological, and biochemical abnormalities present in children with NPC1. The hallmarks of disease are the lysosomal storage of unesterified cholesterol and multiple sphingolipids in neurons, and the spatial and temporal distribution of Purkinje cell death. In feline NPC1 brain, microtubule-associated protein 1 light chain 3 (LC3) accumulations, indicating autophagosomes, were found within axons and presynaptic terminals...
January 13, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29346537/cerebral-mitochondrial-dysfunction-associated-with-deep-hypothermic-circulatory-arrest-in-neonatal-swine
#18
Constantine D Mavroudis, Michael Karlsson, Tiffany Ko, Marco Hefti, Javier I Gentile, Ryan W Morgan, Ross Plyler, Kobina G Mensah-Brown, Timothy W Boorady, Richard W Melchior, Tami M Rosenthal, Brandon C Shade, Kellie L Schiavo, Susan C Nicolson, Thomas L Spray, Robert M Sutton, Robert A Berg, Daniel J Licht, J William Gaynor, Todd J Kilbaugh
OBJECTIVES: Controversy remains regarding the use of deep hypothermic circulatory arrest (DHCA) in neonatal cardiac surgery. Alterations in cerebral mitochondrial bioenergetics are thought to contribute to ischaemia-reperfusion injury in DHCA. The purpose of this study was to compare cerebral mitochondrial bioenergetics for DHCA with deep hypothermic continuous perfusion using a neonatal swine model. METHODS: Twenty-four piglets (mean weight 3.8 kg) were placed on cardiopulmonary bypass (CPB): 10 underwent 40-min DHCA, following cooling to 18°C, 10 underwent 40 min DHCA and 10 remained at deep hypothermia for 40 min; animals were subsequently rewarmed to normothermia...
January 15, 2018: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/29346405/oxytocin-alters-cell-fate-selection-of-rat-neural-progenitor-cells-in-vitro
#19
Arvind Palanisamy, Ramaswamy Kannappan, Zhiqiang Xu, Audrey Martino, Matthew B Friese, Justin D Boyd, Gregory Crosby, Deborah J Culley
Synthetic oxytocin (sOT) is widely used during labor, yet little is known about its effects on fetal brain development despite evidence that it reaches the fetal circulation. Here, we tested the hypothesis that sOT would affect early neurodevelopment by investigating its effects on neural progenitor cells (NPC) from embryonic day 14 rat pups. NPCs expressed the oxytocin receptor (OXTR), which was downregulated by 45% upon prolonged treatment with sOT. Next, we examined the effects of sOT on NPC death, apoptosis, proliferation, and differentiation using antibodies to NeuN (neurons), Olig2 (oligodendrocytes), and GFAP (astrocytes)...
2018: PloS One
https://www.readbyqxmd.com/read/29346028/biophysics-model-of-heavy-ion-degradation-of-neuron-morphology-in-mouse-hippocampal-granular-cell-layer-neurons
#20
Murat Alp, Francis A Cucinotta
Exposure to heavy-ion radiation during cancer treatment or space travel may cause cognitive detriments that have been associated with changes in neuron morphology and plasticity. Observations in mice of reduced neuronal dendritic complexity have revealed a dependence on radiation quality and absorbed dose, suggesting that microscopic energy deposition plays an important role. In this work we used morphological data for mouse dentate granular cell layer (GCL) neurons and a stochastic model of particle track structure and microscopic energy deposition (ED) to develop a predictive model of high-charge and energy (HZE) particle-induced morphological changes to the complex structures of dendritic arbors...
January 18, 2018: Radiation Research
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