tbuckley/cabot-search huggingface dataset:
Identification of novel Angiostatin binding partners using a protein array (27K) based high-throughput protein-protein-interaction screen
Authors: Stefan Muschal, Tong Lee, Bernd Korn, Judah Folkman, Peter Huber, Kashi Javaherian, Amir Abdollahi
Journal: Cancer Research (2008)

378  Angiostatin is a key endogenous angiogenesis inhibitor. Since its discovery in 1994, a number of studies have reported potent anti-tumor and antiangiogenic activities of this agent. However, the molecular mechanism of action, including definite receptors or binding partners and the consecutive intracellular signalling patterns are not completely understood.  The aim of this study was to identify potential receptor and cellular binding partners of angiostatin. First, the Fc-fragment of immunoglobulin was linked to human angiostatin by recombinant expression of fused hFc-angiostatin. We used the Fc fragment as a tag to tract and detect potential membrane, cytosolic, nuclear and mitochondrial binding partners of angiostatin.  A comprehensive protein array platform, containing ~ 27,648 unique protein fragments, was generated using cDNA expression clones in an E. coli expression vector. Proteins were verified for proper expression and printed in duplicates onto two PVDF membranes. This represents one of the largest protein sets interrogated in array-based protein-protein interaction studies to date. Differential binding of human Fc-angiostatin vs. human Fc fragment with spotted proteins on the array were detected using HRP-conjugated anti-Fc antibody.  This technical platform enabled us to identify a series of novel angiostatin binding partners. Noteworthy, a substantial portion of angiostatin binding partners were located to the mitochondrial compartment and are functionally involved in the cellular metabolism and oxidative processes e.g. peroxiredoxins, glutathione S-transferase, NADH dehydrogenase or mitochondrial import receptor subunit (TOM20 homolog). In support to the quality of our array based approach, we also found several previously described angiostatin interacting proteins such as annexin A2.  Angiostatin binding to a selected subset of identified proteins was further confirmed by immuno-precipitation analysis. The affinity and binding kinetics of angiostatin to the identified proteins are evaluated using label-free surface plasmon resonance based technology (Biacore). The in-vivo importance of the identified protein-protein interactions in angiostatin signalling is confirmed by cellular co-localization and functional gain (c-DNA transfection) and loss of function (RNAi) studies.  Here, we describe a novel high-throughput screening strategy to detect potential protein-protein interactions. Using this method, we identified a series of potential targets of angiostatin. Functional validation of these proteins might not only enhance our understanding of angiostatin’s mechanism of action but also elucidate promising targets for the antiangiogenic cancer therapy.
Abstract 18316: Nocturia, Nocturnal Blood Pressure Burden and Cardiac Load: Significant Predictors of Heart Failure Incidence in the Japanese at High-Risk of Cardiovascular Disease
Authors: Michiaki Nagai, Satoshi Niijima, Satoshi Hoshide, Masahisa Shimpo, Kazuomi Kario
Journal: Circulation (2017)

Introduction: Several studies reported significant relationships between hypertension, cardiac load and nocturia. However, the impact of nocturia, nocturnal blood pressure (BP) burden and cardiac load on congestive heart failure (CHF) incidence has not been established in the prospective studies. Hypothesis: We hypothesized that nocturia, nocturnal BP and B-type natriuretic peptide (BNP) might be associated with congestive heart failure (CHF) incidence mediated by urinary albumin (UA) in the Japanese at high-risk of cardiovascular disease. Methods: Among 4310 patients with one or more cardiovascular risks recruited for the Japan Morning Surge-Home Blood Pressure Study, the measurements of home BP during nighttime as well as BNP were performed in the 2785 patients (63.5 years old, male 48.9%). A self-administered questionnaire included items on nocturia was used. Results: According to the number of nocturia, patients were divided into the three groups (no void: n= 1571; one to two void: n=989; ≥ 3 voids pe...
Brexit will damage health
Authors: Fiona Godlee, Donna Kinnair, Chaand Nagpaul
Journal: BMJ (2018)

Within the next few weeks, the UK House of Commons is expected to vote on the withdrawal agreement to exit the EU.The prime minister has said that the choice for MPs will be between the "Chequers deal" 1 if and in what guise it still exists, and, by default if this is not approved, a "no deal" Brexit.We are concerned that either outcome has the potential to cause serious and lasting damage to the nation's health. 2You may think there is nothing you can do to influence these events.This editorial, jointly from the BMA, the Royal College of Nursing, and The BMJ, seeks to persuade you otherwise.Concern about the damaging effects of a no deal Brexit has intensified as the consequences have become clearer and the date of departure approaches.It is now widely accepted that the UK's economy will be badly hit, with inevitable cuts to funding for health and social care.But a no deal Brexit also poses serious immediate and long term threats to the supply of medicines and devices, to staffing for health and social care, to research funding and collaboration, and to public health.
HDAC stimulates gene expression through BRD4 availability in response to IFN and in interferonopathies
Authors: Isabelle J. Marié, Hao-Ming Chang, David E. Levy
Journal: The Journal of Experimental Medicine (2018)

In contrast to the common role of histone deacetylases (HDACs) for gene repression, HDAC activity provides a required positive function for IFN-stimulated gene (ISG) expression. Here, we show that HDAC1/2 as components of the Sin3A complex are required for ISG transcriptional elongation but not for recruitment of RNA polymerase or transcriptional initiation. Transcriptional arrest by HDAC inhibition coincides with failure to recruit the epigenetic reader Brd4 and elongation factor P-TEFb due to sequestration of Brd4 on hyperacetylated chromatin. Brd4 availability is regulated by an equilibrium cycle between opposed acetyltransferase and deacetylase activities that maintains a steady-state pool of free Brd4 available for recruitment to inducible promoters. An ISG expression signature is a hallmark of interferonopathies and other autoimmune diseases. Combined inhibition of HDAC1/2 and Brd4 resolved the aberrant ISG expression detected in cells derived from patients with two inherited interferonopathies, ISG15 and USP18 deficiencies, defining a novel therapeutic approach to ISG-associated autoimmune diseases.
Author Correction: Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA
Authors: Mohammad Ariful Islam, Yingjie Xu, Wei Tao, Jessalyn M. Ubellacker, Michael Lim, Daniel Aum, Gha Young Lee, Kun Zhou, Harshal Zope, Mikyung Yu, Wuji Cao, James Trevor Oswald, Meshkat Dinarvand, Morteza Mahmoudi, Robert Langer, Philip W. Kantoff, Omid C. Farokhzad, Bruce R. Zetter, Jinjun Shi
Journal: Nature Biomedical Engineering (2018)
Antimicrobial prescribing in long-term care facilities: a nationwide point-prevalence study, Slovenia, 2016
Authors: Dora Stepan, Lea Ušaj, Marija Petek Šter, Marjetka Smolinger Galun, Hermina Smole, Bojana Beović
Journal: Eurosurveillance (2018)

Residents in long-term care are at high risk of infections because of their old age and many related health problems that lead to frequent antibiotic prescribing. The aim of the study was to assess antibiotic use in Slovenian long-term care facilities (LTCFs). The point-prevalence study was conducted between April and June 2016. Online questionnaires were sent to all Slovenian LTCFs. Eighty (68.4%) of the 117 LTCFs contacted, caring for 13,032 residents (70.6% of all Slovenian LTCF residents), responded to the survey. On the day of the study, the mean antibiotic prevalence per LTCF was 2.4% (95% confidence interval: 1.94-2.66). Most (70.2%) of the residents taking antibiotics were female. Most residents were being treated for respiratory tract (42.7%) or urinary tract (33.3%) infections. Co-amoxiclav and fluoroquinolones were the most frequently prescribed antibiotics (41.0% and 22.3% respectively). Microbiological tests were performed for 5.2% of residents receiving antibiotics. Forty nine (19.8%) residents receiving antibiotics were colonised with multidrug-resistant bacteria (MDR). Antibiotic use in Slovenian LTCFs is not very high, but most prescribed antibiotics are broad-spectrum. Together with low use of microbiological testing and high prevalence of colonisation with MDR bacteria the situation is worrisome and warrants the introduction of antimicrobial stewardship interventions.
Abstract LB-334: Signals from the microenvironment induce a malignant program accompanied by de novo epigenetic remodeling
Authors: Nancy Dumont, Yongping G. Crawford, Paul A. Reynolds, Matthew B. Wilson, Mahvash Sigaroudinia, Mona L. Gauthier, Colleen A. Fordyce, Thea D. Tlsty
Journal: Cancer Research (2008)

Abstract Introduction: The active acquisition of epigenetic changes is a poorly understood but important process in development, differentiation, and disease. Our work has recently demonstrated that repression of the p16/pRb pathway in human epithelial cells, a condition common to stem cells and many tumor cells, induces dynamic epigenetic remodeling resulting in the targeted methylation of selected CpG islands. We hypothesized that cells in this epigenetically-plastic state can be programmed by the microenvironment to acquire epigenetic changes that promote tumorigenesis. Methods: Normal human mammary epithelial cells (HMEC) and HMEC with repressed p16 were first transduced with constitutively active Ha-rasV12. In order to mimic the secretory aspects of the extracellular environment, the cells were subsequently cultured in a serum-rich environment. Results: When p16-repressed cells were challenged with oncogenic stress, they failed to undergo the classic proliferative arrest as documented in normal cells. When further stressed by being cultured in a serum-rich environment, they spontaneously immortalized and exhibited phenotypic changes indicative of epithelial to mesenchymal transition (EMT). The EMT was accompanied by de novo methylation of the E-cadherin promoter and increased motility. Conclusions: These data demonstrate that signals from the microenvironment can induce phenotypic and gene expression changes that result in de novo epigenetic alterations important in tumor progression.
Preventive role of beta blockers and renin-angiotensin inhibitors in anthracycline-induced cardiotoxicity among adult cancer patients: A meta-analysis
Authors: D.B.L. Sacdalan, M.D. Tiongson, K.A. Mondragon, L. Abrahan, J. Añonuevo, G. Fernando, F.E. Punzalan
Journal: Annals of Oncology (2018)
Abstract 18712: Fimasartan, an Angiotensin II Receptor Antagonist, Improves Heart Failure and Survival in Zebrafish Model
Authors: Hae-Young Lee, Hailian Quan, Byung-Hee Oh, Seung Hyeok Seok
Journal: Circulation (2017)

We developed zebrafish heart failure (HF) model and investigated the protecting role of an angiotensin II receptor antagonist, fimasartan (FMS, 200 μM). HF was induced by short term (12 hr) treatment of a known cardiotoxic drug, terfenadine (Ter, 20μM) in zebrafish larvae at 72 hour post-fertilization. Markedly dilated ventricles, swelling of the chambers and reduced systolic function, all of which were the typical features of human HF, were observed in transgenic cmlc:GFP zebrafish, which express green fluorescent protein (GFP) in the cardiomyocytes. However, FMS pretreatment preserved systolic function with the fractional shortening (vehicle 37.3±2.1 vs Ter 8.4±0.7 vs Ter with FMS 21.7±2.1, p<0.01HH). To demonstrate that Ter-induced cardiac arrhythmia, we used a cardiovascular automatic analysis system (MicroZebraLabTM, Viewpoint) to determine time interval of heart beat and mean erythrocyte cell velocity (nl/second). A significant increase in heart beat irregularity (p<0.01, vehicle 0.1±0.1 vs. Ter 0.5...
Does alanyl-glutamine supplementation offer potential to improve peritoneal dialysate biocompatibility?
Authors: Martin Wilkie, Simon Davies
Journal: Kidney International (2018)

Peritoneal dialysis technique survival remains challenging due to peritonitis and long-term alterations to peritoneal membrane function and integrity. Up to now, the development of less bio-incompatible dialysis solutions have not had a major impact on these aspects of the therapy. A novel approach, supplementing dialysis solutions with a cytoprotective additive, alanyl-glutamine, has shown benefits to surrogate biomarkers of cell function in a randomized controlled study.
Dilated Cardiomyopathy Due to BLC2-Associated Athanogene 3 (BAG3) Mutations
Authors: Fernando Domínguez, Sofía Cuenca, Zofia Bilińska, Rocío Toro, Eric Villard, Roberto Barriales-Villa, Juan Pablo Ochoa, Folkert Asselbergs, Arjan Sammani, Maria Franaszczyk, Mohammed Akhtar, Maria José Coronado-Albi, Diego Rangel-Sousa, Jose F. Rodriguez-Palomares, Juan Jiménez-Jáimez, José Manuel Garcia-Pinilla, Tomás Ripoll-Vera, Maria Victoria Mogollón-Jiménez, Ana Fontalba-Romero, Dolores Garcia-Medina, Julian Palomino-Doza, David de Gonzalo-Calvo, Marcos Cicerchia, Joel Salazar-Mendiguchia, Clara Salas, Sabine Pankuweit, Thomas Morris Hey, Jens Mogensen, Paul J. Barton, Philippe Charron, Perry Elliott, Pablo Garcia-Pavia, Hans Eiskjær, Roberto Barriales, Xusto Fernández Fernández, Marcos Cicerchia, Lorenzo Monserrat, Juan Pablo Ochoa, Joel Salazar-Mendiguchia, Maria Victoria Mogollón, Tomás Ripoll, Philippe Charron, Pascale Richard, Eric Villard, Julian Palomino Doza, Ana Fontalba, Luis Alonso-Pulpón, Marta Cobo-Marcos, Fernando Domínguez, Pablo Garcia-Pavia, Manuel Gómez-Bueno, Esther González-López, Aitor Hernández-Hernández, Francisco José Hernández-Pérez, Ángela López-Sainz, Alejandra Restrepo-Córdoba, Javier Segovia-Cubero, Rocio Toro, David de Gonzalo-Calvo, Félix Rosa Longobardo, Javier Limeres, Jose F. Rodriguez-Palomares, Jose Manuel Garcia-Pinilla, Miguel A. López-Garrido, Juan Jiménez-Jaimez, Dolores Garcia-Medina, Diego Rangel Sousa, Maria Luisa Peña, Jens Mogensen, Thomas Morris-Hey, Paul J. Barton, Stuart A. Cook, William Midwinter, Angharad M. Roberts, James S. Ware, Roddy Walsh, Mohammed Akhtar, Perry M. Elliott, Luis Rocha-Lopes, Konstantinos Savvatis, Petros Syrris, Ewa Michalak, Rafal Ploski, Malgorzata Sobieszczanska-Malek, Zofia Bilińska, Sabine Pankuweit, Folkert Asselbergs, Annette Baas, Dennis Dooijes, Arjan Sammani
Journal: Journal of the American College of Cardiology (2018)
Successful Field Test of a Combined Health Access Strategy and Novel Device to Screen for Sickle Cell Disease (SCD) in Rural Sub-Saharan Africa
Authors: Catherine Mupela Chunda-Liyoka, Ashok A Kumar, Pauline M Sambo, Felicity Lubinda, Tyler Humpton, Pauline Okuku, Chimuka Miyanda, Justine Mulindwa, Judy Im I, Kerry Maguire, George M Whitesides, Thomas P. Stossel
Journal: Blood (2018)
Abstract 324: Assessment in Therapeutic Hypothermia Protocol: A Quality Assessment Initiative and Analysis of Hemodynamic and Laboratory Parameters
Authors: Ediz Tasan, Alison Bailey, Charles Campbell
Journal: Circulation (2014)

Background: Therapeutic hypothermia (TH) is often considered for comatose patients with return of spontaneous circulation after cardiac arrest (CA). While patients undergoing out-of-hospital ventricular fibrillation cardiac arrest are thought to benefit most from TH, the individualized benefit of initiating TH is unknown. Using a combination of clinical and laboratory parameters at presentation, we sought a model to predict survival and discharge to home. Methods: We performed a retrospective study of patients undergoing TH after CA at the University of Kentucky Hospital from 4/1/11 to 12/31/13. Records confirmed by chart review. The primary outcomes were discharge disposition and death. We conducted logistic regression analyses to identify predictors of home discharge and survival. Results: The series included 80 patients (mean±SD age was 55.2±14.9, and 61% were male). The overall mortality rate was 67.9% with survivor home discharge disposition of 21.2%. The Apache II Score (estimated odds ratio [OR] 1.167) was a significant predictor of death; moreover, though not itself a significant predictor of death, troponin improved the ability of Apache II to predict death. The Apache II Score (OR 0.882) and Mean Arterial Pressure (OR 1.049) were significant predictors of home discharge. Figures 1 and 2 display estimated probabilities of survival and home discharge based on two-predictor logistic regression models. Conclusions: In patients undergoing TH, a favorable prognosis is anticipated given certain values for hemodynamic and laboratory parameters. Thus, the patient’s clinical presentation may provide additional guidance when considering initiation of TH after CA.
Role of P2X3 receptors in scratching behavior in mouse models
Authors: Miho Shiratori-Hayashi, Ayumi Hasegawa, Honami Toyonaga, Tsugunobu Andoh, Takeshi Nakahara, Makiko Kido-Nakahara, Masutaka Furue, Yasushi Kuraishi, Kazuhide Inoue, Xinzhong Dong, Makoto Tsuda
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 19812: Endothelial Dysfunction is Associated With Cardiovascular Events in Male Patients After ST-Segment Elevation Myocardial Infarction
Authors: Ryosuke Satou, Yasushi Matsuzawa, Eiichi Akiyama, Chika Kawashima, Hiroyuki Suzuki, Masaaki Konishi, Nobuhiko Maejima, Noriaki Iwahashi, Kiyoshi Hibi, Masami Kosuge, Toshiaki Ebina, Kazuo Kimura, Kouichi Tamura
Journal: Circulation (2017)

Introduction: Endothelial dysfunction plays a pivotal role in the progression of atherosclerosis and subsequent cardiovascular events. Advanced endothelial dysfunction in patients with stable coron...
Genomics of Klebsiella pneumoniae ST16 producing NDM-1, CTX-M-15, and OXA-232
Authors: P. Espinal, E. Nucleo, M. Caltagirone, V. Mattioni Marchetti, M.R. Fernandes, V. Biscaro, R. Rigoli, A. Carattoli, R. Migliavacca, L. Villa
Journal: Clinical Microbiology and Infection (2018)
Twenty Year Trends and Sex Differences in Young Adults Hospitalized With Acute Myocardial Infarction
Authors: Sameer Arora, George A. Stouffer, Anna M. Kucharska-Newton, Arman Qamar, Muthiah Vaduganathan, Ambarish Pandey, Deborah Porterfield, Ron Blankstein, Wayne D. Rosamond, Deepak L. Bhatt, Melissa C. Caughey
Journal: Circulation (2019)

Sex differences are known to exist in the management of older patients presenting with acute myocardial infarction (AMI). Few studies have examined the incidence and risk factors of AMI among young patients, or whether clinical management differs by sex.
Whole-Brain Neuronal Activity Displays Crackling Noise Dynamics
Authors: Adrián Ponce-Alvarez, Adrien Jouary, Martin Privat, Gustavo Deco, Germán Sumbre
Journal: Neuron (2018)

Previous studies suggest that the brain operates at a critical point in which phases of order and disorder coexist, producing emergent patterned dynamics at all scales and optimizing several brain functions. Here, we combined light-sheet microscopy with GCaMP zebrafish larvae to study whole-brain dynamics in vivo at near single-cell resolution. We show that spontaneous activity propagates in the brain's three-dimensional space, generating scale-invariant neuronal avalanches with time courses and recurrence times that exhibit statistical self-similarity at different magnitude, temporal, and frequency scales. This suggests that the nervous system operates close to a non-equilibrium phase transition, where a large repertoire of spatial, temporal, and interactive modes can be supported. Finally, we show that gap junctions contribute to the maintenance of criticality and that, during interactions with the environment (sensory inputs and self-generated behaviors), the system is transiently displaced to a more ordered regime, conceivably to limit the potential sensory representations and motor outcomes.
Abstract 10851: Effect of Glycemic State on Postprandial Hyperlipidemia and Hyperinsulinemia in Patients With Coronary Artery Disease
Authors: Akihiro Nakamura, Yuto Monma, Shoko Kajitani, Yosuke Terui, Kazuki Noda, Sota Nakajima, Hideaki Endo, Tohru Takahashi, Eiji Nozaki
Journal: Circulation (2015)

Background: Both postprandial hyperlipidemia and hyperinsulinemia have been thought to play an important role in the development of atherosclerosis, and to be a potent risk factor for cardiovascular event. Methods: To examine effects of glycemic state on postprandial hyperlipidemia and hyperinsulinemia in patients with coronary artery disease (CAD), a total of 146 consecutive male patients with angiographically confirmed CAD were loaded with a high-fat and high-glucose test meal. CAD patients were divided into three groups as “non-diabetic”, “prediabetic”, and “diabetic” CAD groups. 28 male normoglycemic patients without CAD matched on age were served as control subjects. Results: The serum triglyceride (TG) and remnant-like particle cholesterol (RLP-C) levels at the 6th hour in diabetic CAD group showed significantly higher than non-diabetic CAD group, and the area under the curves (AUCs) of these levels in diabetic CAD group were significantly greater than non-diabetic CAD group (TG, P = 0.0287; RLP-C, P = 0.0386). There were no significant differences in the AUCs of TG or RLP-C between prediabetic and non-diabetic CAD group. The AUCs of plasma insulin levels or insulin resistance index (IRI): (AUCs of insulin) x (AUCs of glucose) as the insulin resistance marker were greater in diabetic CAD group than non-diabetic CAD group (insulin, P = 0.0311; IRI, P = 0.0235). The AUCs of serum TG or RLP-C levels showed a correlation with the AUCs of plasma insulin (AUC-TG, r = 0.4381, P &lt;0.0001; AUC-RLC-P, r = 0.3953, P &lt;0.0001), and they correlated well with the insulin resistance index (AUC-TG, r = 0.7194, P &lt;0.0001; AUC-RLC-P, r = 0.6621, P &lt;0.0001). Conclusions: We found that the insulin resistance showed a close relationship with postprandial hyperlipidemia in CAD patients. Diabetic, but not prediabetic state, may be a risk for postprandial impaired lipid metabolism.
Competing Risks for a Diagnosis of Invasive Breast Cancer—Reply
Authors: Adam R. Brentnall, Diana S. M. Buist, Jack Cuzick
Journal: JAMA Oncology (2018)

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