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Manuel A Schmidt, Tobias Engelhorn, Arnd Dörfler, Georg Michelson
MR Diffusion Tensor Imaging (DTI) enables visualisation of the visual system in glaucoma; it has been shown that the atrophy of the optic radiation is more pronounced in glaucoma than in age-matched controls. The atrophy of the optic radiation thereby correlates with OCT and visual field measures. Diffusion tensor imaging permits quantification of the axonal integrity of the optic radiation by calculation of fractional anisotropy (FA) and radial diffusivity (RD). Both within and also outside the visual system, there are substantial changes in FA and RD, changes suggesting a complex neurodegenerative disease...
February 2019: Klinische Monatsblätter Für Augenheilkunde
Sarah E Burkhart, Roxanna J Llinas, Bonnie Bartel
Peroxisomes rely on peroxins (PEX proteins) for biogenesis, importing membrane and matrix proteins, and fission. PEX16, which is implicated in peroxisomal membrane protein targeting and forming nascent peroxisomes from the endoplasmic reticulum (ER), is unusual among peroxins because it is inserted co-translationally into the ER and localizes to both ER and peroxisomal membranes. PEX16 mutations in humans, yeast, and plants confer some common peroxisomal defects; however, apparent functional differences have impeded the development of a unified model for PEX16 action...
February 14, 2019: Journal of Integrative Plant Biology
Bushra Hayat, Biswajit Padhy, Pranjya Paramita Mohanty, Debasmita Pankaj Alone
Pseudoexfoliation (PEX), an ocular disorder involving deposition of proteinaceous fibrils on the surface of anterior eye tissues, is a major contributing factor to worldwide glaucoma. Excessive production and accumulation of fibrillar materials in PEX could be an indication of proteostasis imbalance. This study aims at investigating the differential expression of various genes involved in unfolded protein response and ubiquitin proteasome pathway in pseudoexfoliation (PEX) patients compared to non-PEX controls using lens capsule tissue as the study material...
February 7, 2019: Experimental Eye Research
Pierce G Young, Michael J Passalacqua, Kevin Chappell, Roxanna J Llinas, Bonnie Bartel
Macroautophagy is a process through which eukaryotic cells degrade large substrates including organelles, protein aggregates, and invading pathogens. Over 40 autophagy-related (ATG) genes have been identified through forward-genetic screens in yeast. Although homology-based analyses have identified conserved ATG genes in plants, only a few atg mutants have emerged from forward-genetic screens in Arabidopsis thaliana. We developed a screen that consistently recovers Arabidopsis atg mutations by exploiting mutants with defective LON2/At5g47040, a protease implicated in peroxisomal quality control...
February 8, 2019: Autophagy
Ranjani Somayaji, Michael D Parkins, Anand Shah, Stacey L Martiniano, Michael M Tunney, Jennifer S Kahle, Valerie J Waters, J Stuart Elborn, Scott C Bell, Patrick A Flume, Donald R VanDevanter
BACKGROUND: Antimicrobial susceptibility testing (AST) is a cornerstone of infection management. Cystic fibrosis (CF) treatment guidelines recommend AST to select antimicrobial treatments for CF airway infection but its utility in this setting has never been objectively demonstrated. METHODS: We conducted a systematic review of primary published articles designed to address two PICO (patient, intervention, comparator, outcome) questions: 1) "For individuals with CF, is clinical response to antimicrobial treatment of bacterial airways infection predictable from AST results available at treatment initiation?" and 2) "For individuals with CF, is clinical response to antimicrobial treatment of bacterial airways infection affected by the method used to guide antimicrobial selection?" Relationships between AST results and clinical response (changes in pulmonary function, weight, signs and symptoms of respiratory tract infection, and time to next event) were assessed for each article and results were compared across articles when possible...
January 29, 2019: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
Adela Arapović, Sandra Prgomet, Marijan Saraga, Tanja Kovačević, Zoltán Prohászka, Ranka Despot, Eugenija Marušić, Josipa Radić
BACKGROUND Thrombotic thrombocytopenic purpura (TTP) in children is a rare life-threatening syndrome, characterized by microangiopathic hemolytic anemia, thrombocytopenia with renal dysfunction, neurologic symptoms, and fever. TTP is usually caused by deficient activity of von Willebrand factor cleaving protease (ADAMTS13), due to either gene mutations or acquired via anti-ADAMTS13 autoantibodies. It can be triggered by bone marrow or solid organ transplantation, cardiothoracic-, abdominal-, and orthopedic surgeries, infections including very rarely Helicobacter pylori infection...
January 31, 2019: American Journal of Case Reports
Monika Hermanová, Petr Orság, Jana Balintová, Michal Hocek, Miroslav Fojta
We present a novel dual redox labeling approach enabling a facile relative evaluation of protein-DNA interactions based on immunoprecipitation at magnetic beads (MBIP) with subsequent electrochemical detection. DNA probes labeled with two different electroactive markers, benzofurazane and nitrobenzene, which yield reduction peaks at distinct potentials, were synthesized using primer extension (PEX) reaction. We show that using the labeled DNA probes, specific and non-specific binding of the p53 protein can be distinguished in a simple competition binding experiment, as a strong preference of the p53 protein was observed towards DNA probes bearing a specific p53 binding site (p53CON), which is in agreement with known binding properties of the p53 protein...
March 7, 2019: Analytica Chimica Acta
Tresa J Stradomska
Peroxisomes are multifunctional microorganelles that play a key role in numerous biochemical processes adapting dynamically to the current physiological requirements of the cell. The disturbance of the peroxisome structure due to mutations in different PEX and non-PEX genes coding functional peroxisomal proteins is the pathogenic basis of the peroxisomal disorders. The β-oxidation process of very long-chain fatty acids (VLCFA) is a unique metabolic pathway located exclusively in the peroxisome. This determines that VLCFA is the main biomarker for the diagnosis of peroxisomal diseases...
December 29, 2018: Postepy Biochemii
Elizabeth Juarez-Colunga, Margaret Rosenfeld, Edith T Zemanick, Brandie Wagner
BACKGROUND: Pulmonary exacerbations (PEx) are important contributors to morbidity and mortality in cystic fibrosis (CF). Understanding risk factors for PEx is critical to improve treatment; pulmonary exacerbations also serve as an important outcome in CF clinical trials. Current risk estimates generally only evaluate time to the first PEx. Methods accounting for multiple exacerbations during the observation period could provide more power to detect significant risk factors. METHODS: The Early Pseudomonas Infection Control (EPIC) Observational Study enrolled participants between 2004 and 2006 who were ≤ 12 years of age and negative for Pseudomonas aeruginosa...
January 11, 2019: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
S Arcudi, B Ferrari, S Pontiggia, A Tufano, A Artoni, I Mancini, F Peyvandi
BACKGROUND: Severe ADAMTS13 deficiency has been recognized as the main risk factor for recurrence of thrombotic thrombocytopenic purpura (TTP). Several conditions including surgery may influence the levels of ultra large Von Willebrand factor and ADAMTS13, acting as a trigger for an acute TTP event. OBJECTIVES: To report our experience for management of six patients affected with acquired TTP who underwent elective surgery after a prophylactic treatment to restore ADAMTS13 activity levels...
January 10, 2019: Journal of Thrombosis and Haemostasis: JTH
Patrick A Flume, Ellison D Suthoff, Mark Kosinski, Gautham Marigowda, Alexandra L Quittner
BACKGROUND: We explored the time-dependent impact of pulmonary exacerbations (PEx) on health-related quality of life (HRQoL) using Cystic Fibrosis Questionnaire-Revised (CFQ-R) data from 2 large cystic fibrosis (CF) trials. METHODS: This exploratory post-hoc analysis evaluated the impact of PEx on CFQ-R domains of functioning in 80 patients with CF (homozygous for F508del-CFTR), aged ≥14 years randomized to placebo in the TRAFFIC and TRANSPORT trials who experienced 1 PEx...
December 23, 2018: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
Tansu Gonen, Savas Guzel, Kadircan H Keskinbora
PURPOSE: To investigate the YKL-40, as a marker of inflammation, in aqueous humor and serum of cataract patients with and without pseudoexfoliation syndrome (PEX). METHODS: Aqueous humor and serum samples were obtained from 44 patients who underwent phacoemulsification surgery. All patients were divided into two groups: PEX (n = 24) and control (n = 20). YKL-40 levels were measured with enzyme-linked immunosorbent assay (ELISA). The differences between the groups were assessed by using Chi-square and independent sample t-tests...
December 18, 2018: Eye
A C van Marle, J Joubert, S M Meiring
OBJECTIVE: Thrombotic thrombocytopenic purpura (TTP) results from a deficiency in the Von Willebrand factor (VWF) cleaving protease, ADAMTS13. Treatment involves plasma exchange (PEX) therapy with either fresh frozen plasma (FFP), cryosupernatant (CSP) or solvent/detergent-treated plasma (SDP), available in South Africa as Bioplasma FDP. The aim of the study was to generate in vitro data on these products, and to explore possible differences between the products that may offer treatment advantages...
December 5, 2018: Transfusion and Apheresis Science
Seyhan Dikci, Emrah Öztürk, Penpe Gül Fırat, Turgut Yılmaz, Mehmet Çağatay Taşkapan, Saim Yoloğlu
OBJECTIVE: To investigate whether serum vitamin D levels have an effect on pseudoexfolation (PEX) glaucoma/syndrome development and on the control of glaucoma in these cases. METHOD: A total of 31 cases with PEX glaucoma, 34 cases with the PEX syndrome and 43 control subjects of similar age and sex were included in the study. Vitamin D levels were compared between the groups and also between the cases where glaucoma surgery was performed or not. RESULTS: PEX glaucoma group consisted of 17 males and 14 females, PEX syndrome group of 27 males and 7 females, and the control group of 27 males and 16 females...
November 27, 2018: Endocrine, Metabolic & Immune Disorders Drug Targets
Vishal C Kalel, Pascal Mäser, Michael Sattler, Ralf Erdmann, Grzegorz M Popowicz
Glycosomes evolved as specialized system for glycolysis in trypanosomatids. These organelle rely on protein import to maintain function. A machinery of peroxin (PEX) proteins is responsible for recognition and transport of glycosomal proteins to the organelle. Disruption of PEX-based import system was expected to be a strategy against trypanosomatids. Recently, a proof of this hypothesis has been presented. Here, we review current information about trypanosomatids' glycosomal transport components as targets for new trypanocidal therapies...
November 24, 2018: Current Opinion in Microbiology
Kak-Ming Ling, Luke W Garratt, Timo Lassmann, Stephen M Stick, Anthony Kicic
Chronic lung disease remains the primary cause of mortality in cystic fibrosis (CF). Growing evidence suggests respiratory viral infections are often more severe in CF compared to healthy peers and contributes to pulmonary exacerbations (PEx) and deterioration of lung function. Rhinovirus is the most prevalent respiratory virus detected, particularly during exacerbations in children with CF <5 years old. However, even though rhinoviral infections are likely to be one of the factors initiating the onset of CF lung disease, there is no effective targeted treatment...
2018: Frontiers in Pharmacology
Fritz H Hengerer, Gerd U Auffarth, Christoffer Riffel, Ina Conrad-Hengerer
INTRODUCTION: The aim of this study was to assess 36-month outcomes after cataract surgery and implantation of two second-generation trabecular micro-bypass stents (iStent inject, Glaukos Corporation, San Clemente, CA, USA) into eyes with predominantly primary open-angle glaucoma (POAG) or pseudoexfoliative glaucoma (PEX). METHODS: This prospective, non-randomized, consecutive cohort study included eyes with POAG (n = 60), PEX (n = 15), appositional narrow-angle (n = 4), pigmentary (n = 1), or neovascular (secondary) (n = 1) glaucoma and cataract requiring surgery...
December 2018: Ophthalmology and Therapy
Ling Qian, Shulin Yu, Zhen Chen, Zhiqiang Meng, Shenglin Huang, Peng Wang
Pancreatic cancer is one of the most aggressive human malignancies and is associated with a dismal prognosis, which can be contributed to its atypical symptoms, metastatic propensity, and significant chemoresistance. Emerging evidence shows that pancreatic cancer cell-derived exosomes (PEXs) play critical roles in tumorigenesis and tumor development, as they are involved in drug resistance, immune evasion and metabolic reprograming, and distant metastasis of pancreatic cancer. Their numerous differentially expressed and functional contents make PEXs promising screening tools and therapeutic targets, which require further exploration...
November 9, 2018: Biochimica et biophysica acta. Reviews on cancer
Patrick Zadravec, Barbara M Braunger, Benjamin Melzer, Markus Kroeber, Michael R Bösl, Herbert Jägle, Ursula Schlötzer-Schrehardt, Ernst R Tamm
Sequence variants in LOXL1 coding for the secreted enzyme lysyl oxidase homolog 1 (LOXL1) associate with pseudoexfoliation (PEX) syndrome, a condition that is characterized by the deposition of extracellular fibrillar PEX material in the anterior eye and other parts of the body. Since the specific role of LOXL1 in the pathogenesis of PEX is unclear, and an increase in its expression was reported for early stages of PEX syndrome, we generated and studied transgenic mice with ocular overexpression of its mouse ortholog Loxl1...
November 3, 2018: Experimental Eye Research
Francesca Di Cara, Richard A Rachubinski, Andrew J Simmonds
Peroxisomes are ubiquitous membrane-enclosed organelles involved in lipid processing and reactive oxygen detoxification. Mutations in human peroxisome biogenesis genes ( Peroxin , PEX or Pex ) cause developmental disabilities and often early death. Pex5 and Pex7 are receptors that recognize different peroxisomal targeting signals called PTS1 and PTS2, respectively, and traffic proteins to the peroxisomal matrix. We characterized mutants of Drosophila melanogaster Pex5 and Pex7 and found that adult animals are affected in lipid processing...
November 2, 2018: Genetics
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