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https://www.readbyqxmd.com/read/27902311/the-ubiquitin-ligase-e6ap-mediates-nonproteolytic-polyubiquitylation-of-%C3%AE-catenin-independent-of-the-e6-oncoprotein
#1
Yael Kuslansky, Sophia Sominsky, Anna Jackman, Cristina Gamell, Brendon J Monahan, Ygal Haupt, Rina Rosin-Arbesfeld, Levana Sherman
Recently we showed that the ubiquitin ligase E6AP stabilizes β-catenin and activates its transcriptional activity. These activities were enhanced by the human papillomavirus (HPV) E6 protein. In the present study we explored the function of E6AP that increases β-catenin stabilization and transcriptional activation. Here we report that E6AP interacts with β-catenin and mediates its nonproteolytic ubiquitylation, as evidenced in transiently transfected cell-based, and in vitro reconstitution ubiquitylation assays...
October 7, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27893381/a-compressed-sensing-based-decomposition-of-electrodermal-activity-signals
#2
Swayambhoo Jain, Urvashi Oswal, Kevin Xu, Brian Eriksson, Jarvis Haupt
The measurement and analysis of Electrodermal Activity (EDA) offers applications in diverse areas ranging from market research, to seizure detection, to human stress analysis. Unfortunately, the analysis of EDA signals is made difficult by the superposition of numerous components which can obscure the signal information related to a user's response to a stimulus. We show how simple pre-processing followed by a novel compressed sensing based decomposition can mitigate the effects of the undesired noise components and help reveal the underlying physiological signal...
November 23, 2016: IEEE Transactions on Bio-medical Engineering
https://www.readbyqxmd.com/read/27881154/targeted-next-generation-sequencing-identifies-novel-notch3-gene-mutations-in-cadasil-diagnostics-patients
#3
Neven Maksemous, Robert A Smith, Larisa M Haupt, Lyn R Griffiths
BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic, hereditary, small vessel disease of the brain causing stroke and vascular dementia in adults. CADASIL has previously been shown to be caused by varying mutations in the NOTCH3 gene. The disorder is often misdiagnosed due to its significant clinical heterogeneic manifestation with familial hemiplegic migraine and several ataxia disorders as well as the location of the currently identified causative mutations...
November 24, 2016: Human Genomics
https://www.readbyqxmd.com/read/27857289/use-of-photoacoustic-excitation-and-laser-vibrometry-to-remotely-detect-trace-explosives
#4
C M Wynn, R W Haupt, J H Doherty, R R Kunz, W Bai, G Diebold
In this paper, we examine a laser-based approach to remotely initiate, measure, and differentiate acoustic and vibrational emissions from trace quantities of explosive materials against their environment. Using a pulsed ultraviolet laser (266 nm), we induce a significant (>100  Pa) photoacoustic response from small quantities of military-grade explosives. The photoacoustic signal, with frequencies predominantly between 100 and 500 kHz, is detected remotely via a wideband laser Doppler vibrometer. This two-laser system can be used to rapidly detect and discriminate explosives from ordinary background materials, which have significantly weaker photoacoustic response...
November 10, 2016: Applied Optics
https://www.readbyqxmd.com/read/27852900/gradients-of-phosphatidylserine-contribute-to-plasma-membrane-charge-localization-and-cell-polarity-in-fission-yeast
#5
Armin Haupt, Nicolas Minc
Surface charges at the inner leaflet of the plasma membrane may contribute to regulate the surface recruitment of key signaling factors. Phosphatidylserine (PS) is an abundant charged lipid, which may regulate charge distribution in different cell types. In here, we characterize the subcellular distribution and function of PS in the rod-shaped, polarized fission yeast. We find that PS preferably accumulates at cell tips and defines a gradient of negative charges along the cell surface. This polarization depends on actin-mediated endocytosis and contributes to the subcellular partitioning of charged polarity-regulating Rho-GTPases like Rho1 or Cdc42 in a protein charge-dependent manner...
November 16, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27851074/1438-early-determination-of-outcomes-for-sirs-vs-qsofa-in-ed-sepsis-patients
#6
Dave Milzman, Matthew Paik, Kirsten Shuster, Rand Floyd, Aidan Neustadtl, Rob Haggerty, Shawn Haupt, Doug Johnson
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27807957/-the-contribution-of-the-italian-association-of-paediatric-haematology-and-oncology-aieop
#7
Roberto Rondelli, Momcilo Jankovic, Annarosa Soresina, Maria Grazia Valsecchi, Marisa De Rosa, Marina Cuttini, Riccardo Haupt, Maurizio Aricò, Gianni Bisogno, Franco Locatelli, Corrado Magnani, Franco Merletti, Marco Zecca, Andrea Pession
Since 1972, children affected by cancer took advantage from multi-centric diagnostic and therapeutic protocols produced by the Italian Association of paediatric haematology and oncology (AIEOP). At the beginning, these protocols were used in few well-trained centres, later in almost all Italian haemato-oncological centres. The need of a careful monitoring of his own activity induced AIEOP to achieve, in 1989, an Italian hospital- based registry (database Mod.1.01) of malignant tumours diagnosed and treated in the participating centres, with the aim to quantify the number of cases diagnosed and treated in the different centres, the agreement (or not) to official diagnostic- therapeutic protocols, and the extraregional migration...
September 2016: Epidemiologia e Prevenzione
https://www.readbyqxmd.com/read/27795959/large-gliadin-peptides-detected-in-the-pancreas-of-nod-and-healthy-mice-following-oral-administration
#8
Susanne W Bruun, Knud Josefsen, Julia T Tanassi, Aleš Marek, Martin H F Pedersen, Ulrik Sidenius, Martin Haupt-Jorgensen, Julie C Antvorskov, Jesper Larsen, Niels H Heegaard, Karsten Buschard
Gluten promotes type 1 diabetes in nonobese diabetic (NOD) mice and likely also in humans. In NOD mice and in non-diabetes-prone mice, it induces inflammation in the pancreatic lymph nodes, suggesting that gluten can initiate inflammation locally. Further, gliadin fragments stimulate insulin secretion from beta cells directly. We hypothesized that gluten fragments may cross the intestinal barrier to be distributed to organs other than the gut. If present in pancreas, gliadin could interact directly with the immune system and the beta cells to initiate diabetes development...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27744369/paradoxical-effects-of-saa-on-lipoprotein-oxidation-suggest-a-new-antioxidant-function-for-saa
#9
Shobini Jayaraman, Christian Haupt, Olga Gursky
Oxidative stress and inflammation, which involve a dramatic increase in serum amyloid A (SAA) levels, are critical in the development of atherosclerosis. Most SAA circulates on plasma HDL particles, altering their cardioprotective properties. SAA-enriched HDL has diminished anti-oxidant effects on LDL, which may contribute to atherogenesis. We determined combined effects of SAA enrichment and oxidation on biochemical changes in HDL. Normal human HDLs were incubated with SAA, oxidized by various factors (Cu(2+), myeloperoxidase, H2O2, OCl(-)), and analyzed for lipid and protein modifications and biophysical remodeling...
December 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27723228/basal-insulin-peglispro-overview-of-a-novel-long-acting-insulin-with-reduced-peripheral-effect-resulting-in-a-hepato-preferential-action
#10
S J Jacober, M J Prince, J M Beals, M L Hartman, Y Qu, H Linnebjerg, P Garhyan, A Haupt
Basal insulin peglispro (BIL) is a novel basal insulin with a flat, prolonged activity profile. BIL has been demonstrated in a dog model, in healthy men and in patients with type 1 diabetes (T1D) to have significant hepato-preferential action resulting from reduced peripheral activity. In the IMAGINE-Phase 3 clinical trial program, more than 6000 patients were included, of whom ~3900 received BIL. Of the 7 pivotal IMAGINE trials, 3 studies were double-blinded and 3 were in T1D patients. BIL consistently demonstrated a greater HbA1c reduction, less glycaemic variability and a clinically relevant reduction in the rates of nocturnal hypoglycaemia across comparator [glargine and isophane insulin (NPH)] studies...
October 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27723227/different-effects-of-basal-insulin-peglispro-and-insulin-glargine-on-liver-enzymes-and-liver-fat-content-in-patients-with-type-1-and-type-2-diabetes
#11
K Cusi, A J Sanyal, S Zhang, B J Hoogwerf, A M Chang, S J Jacober, J M Bue-Valleskey, A N Higdon, E J Bastyr, A Haupt, M L Hartman
AIMS: To compare effects of basal insulin peglispro (BIL), a hepatopreferential insulin, to insulin glargine (glargine) on aminotransferases and liver fat content (LFC) in patients with type 1 and type 2 diabetes (T1D, T2D). MATERIALS AND METHODS: Data from two Phase 2 and five Phase 3 randomized trials comparing BIL and glargine in 1709 T1D and 3662 T2D patients were integrated for analysis of liver laboratory tests. LFC, measured by magnetic resonance imaging (MRI) at baseline, 26 and 52 weeks, was analyzed in 182 T1D patients, 176 insulin-naïve T2D patients and 163 T2D patients previously treated with basal insulin...
October 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27702740/neuro-cognitive-mechanisms-of-simultanagnosia-in-patients-with-posterior-cortical-atrophy
#12
Julia Neitzel, Marion Ortner, Marleen Haupt, Petra Redel, Timo Grimmer, Igor Yakushev, Alexander Drzezga, Peter Bublak, Christoph Preul, Christian Sorg, Kathrin Finke
Posterior cortical atrophy is dominated by progressive degradation of parieto-occipital grey and white matter, and represents in most cases a variant of Alzheimer's disease. Patients with posterior cortical atrophy are characterized by increasing higher visual and visuo-spatial impairments. In particular, a key symptom of posterior cortical atrophy is simultanagnosia i.e. the inability to perceive multiple visual objects at the same time. Two neuro-cognitive mechanisms have been suggested to underlie simultanagnosia, either reduced visual short-term memory capacity or decreased visual processing speed possibly resulting from white matter impairments over and above damage to cortical brain areas...
December 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27675986/effectiveness-of-stereotactic-body-radiation-therapy-in-treatment-of-sarcoma-metastasis-to-the-lung-experience-at-a-tertiary-referral-center
#13
A Lindsay, E Haupt, C Chan, A Spiguel, M T Scarborough, C P Gibbs, R A Zlotecki
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27671727/ensuring-the-quality-of-stem-cell-derived-in-vitro-models-for-toxicity-testing
#14
Glyn N Stacey, Sandra Coecke, Anna-Bal Price, Lyn Healy, Paul Jennings, Anja Wilmes, Christian Pinset, Magnus Ingelman-Sundberg, Jochem Louisse, Simone Haupt, Darren Kidd, Andrea Robitski, Heinz-Georg Jahnke, Gilles Lemaitre, Glenn Myatt
Quality control of cell cultures used in new in vitro toxicology assays is crucial to the provision of reliable, reproducible and accurate toxicity data on new drugs or constituents of new consumer products. This chapter explores the key scientific and ethical criteria that must be addressed at the earliest stages of developing toxicology assays based on human pluripotent stem cell (hPSC) lines. It also identifies key considerations for such assays to be acceptable for regulatory, laboratory safety and commercial purposes...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27665183/fret-energy-transfer-via-pdots-improves-the-efficiency-of-photodynamic-therapy-and-leads-to-rapid-cell-death
#15
Sara Haupt, Itay Lazar, Hana Weitman, Yaron Shav-Tal, Benjamin Ehrenberg
Photodynamic therapy (PDT) is well established as a clinical treatment modality for various diseases, including cancer and especially for the treatment of superficial tumors. However, one of the disadvantages of the photoactivatable molecules is their low absorbance in the optical window for photosensitizer excitation. The use of nanoparticles in photodynamic therapy can address this deficiency and improve treatment efficiency. Pdots are nano-sized particles, composed of conjugated chromophoric polymers. By mixing them with PEGylated phospholipids they can become soluble and stable colloids...
September 14, 2016: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/27661454/improved-decision-making-for-prioritizing-tumor-targeting-antibodies-in-human-xenografts-utility-of-fluorescence-imaging-to-verify-tumor-target-expression-antibody-binding-and-optimization-of-dosage-and-application-schedule
#16
Michael Dobosz, Ute Haupt, Werner Scheuer
Preclinical efficacy studies of antibodies targeting a tumor-associated antigen are only justified when the expression of the relevant antigen has been demonstrated. Conventionally, antigen expression level is examined by immunohistochemistry of formalin-fixed paraffin-embedded tumor tissue section. This method represents the diagnostic "gold standard" for tumor target evaluation, but is affected by a number of factors, such as epitope masking and insufficient antigen retrieval. As a consequence, variances and discrepancies in histological staining results can occur, which may influence decision-making and therapeutic outcome...
September 23, 2016: MAbs
https://www.readbyqxmd.com/read/27643694/late-cardiac-events-after-childhood-cancer-methodological-aspects-of-the-pan-european-study-pancaresurfup
#17
Elizabeth A M Feijen, Anna Font-Gonzalez, Elvira C van Dalen, Helena J H van der Pal, Raoul C Reulen, David L Winter, Claudia E Kuehni, Riccardo Haupt, Daniela Alessi, Julianne Byrne, Edit Bardi, Zsuzsanna Jakab, Desiree Grabow, Stanislaw Garwicz, Momcilo Jankovic, Gill A Levitt, Roderick Skinner, Lorna Zadravec Zaletel, Lars Hjorth, Wim J E Tissing, Florent de Vathaire, Mike M Hawkins, Leontien C M Kremer
BACKGROUND AND AIM: Childhood cancer survivors are at high risk of long-term adverse effects of cancer and its treatment, including cardiac events. The pan-European PanCareSurFup study determined the incidence and risk factors for cardiac events among childhood cancer survivors. The aim of this article is to describe the methodology of the cardiac cohort and nested case-control study within PanCareSurFup. METHODS: Eight data providers in Europe participating in PanCareSurFup identified and validated symptomatic cardiac events in their cohorts of childhood cancer survivors...
2016: PloS One
https://www.readbyqxmd.com/read/27642610/gluten-free-diet-only-during-pregnancy-efficiently-prevents-diabetes-in-nod-mouse-offspring
#18
Julie C Antvorskov, Knud Josefsen, Martin Haupt-Jorgensen, Petra Fundova, David P Funda, Karsten Buschard
Studies have documented that the pathogenesis of autoimmune diabetes is influenced by the intake of gluten. Aims. To investigate the importance of gluten exposure during pregnancy and the subsequent development of autoimmune diabetes in offspring. Methods. Nonobese diabetic mice were divided into 7 groups to receive combinations of gluten-free and standard diet before, during, or after pregnancy. Diabetes incidence in offspring was followed in each group (n = 16-27) for 310 days. Insulitis score and intestinal expression of T-cell transcription factors (RT-QPCR) were evaluated in animals from the different diet groups...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27641331/restoration-of-tumor-suppression-in-prostate-cancer-by-targeting-the-e3-ligase-e6ap
#19
P J Paul, D Raghu, A-L Chan, T Gulati, L Lambeth, E Takano, M J Herold, J Hagekyriakou, R L Vessella, C Fedele, M Shackleton, E D Williams, S Fox, S Williams, S Haupt, C Gamell, Y Haupt
Restoration of tumor suppression is an attractive onco-therapeutic approach. It is particularly relevant when a tumor suppressor is excessively degraded by an overactive oncogenic E3 ligase. We previously discovered that the E6-associated protein (E6AP; as classified in the human papilloma virus context) is an E3 ligase that has an important role in the cellular stress response, and it directly targets the tumor-suppressor promyelocytic leukemia protein (PML) for proteasomal degradation. In this study, we have examined the role of the E6AP-PML axis in prostate cancer (PC)...
December 1, 2016: Oncogene
https://www.readbyqxmd.com/read/27633439/outcome-comorbidity-hospitalization-and-30-day-mortality-after-closure-of-acute-perforations-and-postoperative-anastomotic-leaks-by-the-over-the-scope-clip-otsc-in-an-unselected-cohort-of-patients
#20
M Raithel, H Albrecht, W Scheppach, M Farnbacher, W Haupt, A F Hagel, V Schellerer, F Vitali, M F Neurath, H T Schneider
BACKGROUND: Acute gastrointestinal (GI) wall defects contain a high risk of morbidity and mortality and may be closed endoscopically by a full-thickness over-the-scope clip (OTSC). METHODS: Unselected consecutive patients presenting with acute non-surgical perforations or postoperative anastomotic leaks or perforations underwent attempted OTSC placement as primary closure method after interdisciplinary consensus in three tertiary referral centres. Their clinical data and intervention characteristics were evaluated in an intention to treat analysis during a 24-month period to assess closure rates, 30-day mortality, hospitalization and comorbidity...
September 15, 2016: Surgical Endoscopy
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