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https://www.readbyqxmd.com/read/28867616/the-mammalian-proteasome-activator-pa28-forms-an-asymmetric-%C3%AE-4%C3%AE-3-complex
#1
Eva M Huber, Michael Groll
The heptameric proteasome activator (PA) 28αβ is known to modulate class I antigen processing by docking onto 20S proteasome core particles (CPs). The exact stoichiometry and arrangement of its α and β subunits, however, is still controversial. Here we analyzed murine PA28 complexes regarding structure and assembly. Strikingly, PA28α, PA28β, and PA28αβ preparations form heptamers, but solely PA28α and PA28αβ associate with CPs. Co-expression of α and β yields one unique PA28αβ species with an unchangeable subunit composition...
August 22, 2017: Structure
https://www.readbyqxmd.com/read/28845686/mental-disorder-symptoms-among-public-safety-personnel-in-canada
#2
R Nicholas Carleton, Tracie O Afifi, Sarah Turner, Tamara Taillieu, Sophie Duranceau, Daniel M LeBouthillier, Jitender Sareen, Rose Ricciardelli, Renee S MacPhee, Dianne Groll, Kadie Hozempa, Alain Brunet, John R Weekes, Curt T Griffiths, Kelly J Abrams, Nicholas A Jones, Shadi Beshai, Heidi A Cramm, Keith S Dobson, Simon Hatcher, Terence M Keane, Sherry H Stewart, Gordon J G Asmundson
BACKGROUND: Canadian public safety personnel (PSP; e.g., correctional workers, dispatchers, firefighters, paramedics, police officers) are exposed to potentially traumatic events as a function of their work. Such exposures contribute to the risk of developing clinically significant symptoms related to mental disorders. The current study was designed to provide estimates of mental disorder symptom frequencies and severities for Canadian PSP. METHODS: An online survey was made available in English or French from September 2016 to January 2017...
January 1, 2017: Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie
https://www.readbyqxmd.com/read/28653854/a-thermogelling-supramolecular-hydrogel-with-sponge-like-morphology-as-a-cytocompatible-bioink
#3
Thomas Lorson, Sebastian Jaksch, Michael M Lübtow, Tomasz Jüngst, Jürgen Groll, Tessa Lühmann, Robert Luxenhofer
Biocompatible polymers that form thermoreversible supramolecular hydrogels have gained great interest in biomaterials research and tissue engineering. When favorable rheological properties are achieved at the same time, they are particularly promising candidates as material that allow for the printing of cells, so-called bioinks. We synthesized a novel thermogelling block copolymer and investigated the rheological properties of its aqueous solution by viscosimetry and rheology. The polymers undergo thermogelation between room temperature and body temperature, form transparent hydrogels of surprisingly high strength (G' > 1000 Pa) and show rapid and complete shear recovery after stress...
June 27, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28525266/gliotoxin-biosynthesis-structure-mechanism-and-metal-promiscuity-of-carboxypeptidase-glij
#4
Antoine Marion, Michael Groll, Daniel H Scharf, Kirstin Scherlach, Manuel Glaser, Holger Sievers, Michael Schuster, Christian Hertweck, Axel A Brakhage, Iris Antes, Eva M Huber
The formation of glutathione (GSH) conjugates, best known from the detoxification of xenobiotics, is a widespread strategy to incorporate sulfur into biomolecules. The biosynthesis of gliotoxin, a virulence factor of the human pathogenic fungus Aspergillus fumigatus, involves attachment of two GSH molecules and their sequential decomposition to yield two reactive thiol groups. The degradation of the GSH moieties requires the activity of the Cys-Gly carboxypeptidase GliJ, for which we describe the X-ray structure here...
July 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28520856/control-of-multidrug-resistant-pseudomonas-aeruginosa-in-allogeneic-hematopoietic-stem-cell-transplant-recipients-by-a-novel-bundle-including-remodeling-of-sanitary-and-water-supply-systems
#5
Annelene Kossow, Stefanie Kampmeier, Stefanie Willems, Wolfgang E Berdel, Andreas H Groll, Birgit Burckhardt, Rossig Claudia, Christoph Groth, Evgeny A Idelevich, Frank Kipp, Alexander Mellmann, Matthias Stelljes
Background: Infections by multidrug-resistant Pseudomonas aeruginosa (MDRPa) are an important cause of morbidity and mortality in patients after allogeneic hematopoietic stem cell transplantation (HSCT). Humid environments can serve as a reservoir and source of infection by this pathogen. To minimize the risk of infection from these reservoirs, we performed extensive remodeling of sanitation and water installations as the focus of our hygiene bundle. Methods: During the reconstruction of our transplantation unit (April 2011-April 2014) we implemented several technical modifications to reduce environmental contamination by and subsequent spreading of MDRPa, including a newly designed shower drain, disinfecting siphons underneath the sinks, and rimless toilets...
September 15, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28516169/hybrid-pixel-waveform-hpwf-enabled-cdte-detectors-for-small-animal-gamma-ray-imaging-applications
#6
A Groll, K Kim, H Bhatia, J C Zhang, J H Wang, Z M Shen, L Cai, J Dutta, Q Li, L J Meng
This paper presents the design and preliminary evaluation of small-pixel CdTe gamma ray detectors equipped with a hybrid pixel-waveform (HPWF) readout system for gamma ray imaging applications with additional discussion on CZT due to its similarity. The HPWF readout system utilizes a pixelated anode readout circuitry which is designed to only provide the pixel address. This readout circuitry works in coincidence with a high-speed digitizer to sample the cathode waveform which provides the energy, timing, and depth-of-interaction (DOI) information...
January 2017: IEEE transactions on radiation and plasma medical sciences
https://www.readbyqxmd.com/read/28496433/interplay-between-mutations-and-efflux-in-drug-resistant-clinical-isolates-of-mycobacterium-tuberculosis
#7
Diana Machado, Tatiane S Coelho, João Perdigão, Catarina Pereira, Isabel Couto, Isabel Portugal, Raquel De Abreu Maschmann, Daniela F Ramos, Andrea von Groll, Maria L R Rossetti, Pedro A Silva, Miguel Viveiros
Numerous studies show efflux as a universal bacterial mechanism contributing to antibiotic resistance and also that the activity of the antibiotics subject to efflux can be enhanced by the combined use of efflux inhibitors. Nevertheless, the contribution of efflux to the overall drug resistance levels of clinical isolates of Mycobacterium tuberculosis is poorly understood and still is ignored by many. Here, we evaluated the contribution of drug efflux plus target-gene mutations to the drug resistance levels in clinical isolates of M...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28459614/guideline-for-the-management-of-fever-and-neutropenia-in-children-with-cancer-and-hematopoietic-stem-cell-transplantation-recipients-2017-update
#8
REVIEW
Thomas Lehrnbecher, Paula Robinson, Brian Fisher, Sarah Alexander, Roland A Ammann, Melissa Beauchemin, Fabianne Carlesse, Andreas H Groll, Gabrielle M Haeusler, Maria Santolaya, William J Steinbach, Elio Castagnola, Bonnie L Davis, L Lee Dupuis, Aditya H Gaur, Wim J E Tissing, Theo Zaoutis, Robert Phillips, Lillian Sung
Purpose To update a clinical practice guideline (CPG) for the empirical management of fever and neutropenia (FN) in children with cancer and hematopoietic stem-cell transplantation recipients. Methods The International Pediatric Fever and Neutropenia Guideline Panel is a multidisciplinary and multinational group of experts in pediatric oncology and infectious diseases that includes a patient advocate. For questions of risk stratification and evaluation, we updated systematic reviews of observational studies...
June 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28443987/seroprevalence-of-bactericidal-antibodies-against-serogroup-b-and-c-meningococci-in-a-university-hospital
#9
C A C Gioia, A P S Lemos, M C O Gorla, R Mendoza-Sassi, B S Figueredo, T Ballester, A Von Groll, B Wedig, N V Ethur, L Bragança, P E A Silva, L G Milagres
Meningococcus serogroup B (MenB), clonal complex 32 (cc 32), was the Brazilian epidemic strain of meningococcal disease (MD) in the 1990's. Currently, meningococcus serogroup C (MenC), cc 103, is responsible for most of the cases of the disease in Brazil. The aim of this study was to investigate the seroprevalence of bactericidal antibody (SBA) against representative epidemic strains of MenC, (N753/00 strain, C:23:P1.22,14-6, cc103) and MenB, (Cu385/83 strain, B:4,7:P1.15,19, cc32) in students and employees of a university hospital in the State of Rio Grande do Sul (RS, Brazil)...
April 20, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28349614/progressive-histoplasmosis-with-hemophagocytic-lymphohistiocytosis-and-epithelioid-cell-granulomatosis-a-case-report-and-review-of-the-literature
#10
Arik Bernard Schulze, Britta Heptner, Torsten Kessler, Birgit Baumgarten, Viorelia Stoica, Michael Mohr, Rainer Wiewrodt, Viktoria Susanne Warneke, Wolfgang Hartmann, Jörg Wüllenweber, Christoph Schülke, Michael Schäfers, Dunja Wilmes, Karsten Becker, Lars Henning Schmidt, Andreas H Groll, Wolfgang E Berdel
Histoplasmosis in central Europe is a rare fungal disease with diverse clinical presentations. Apart from acute pulmonary histoplasmosis and involvement of the central nervous system, the most serious clinical presentation is progressive disseminated histoplasmosis which is generally associated with severe immunodeficiency and, in particular, advanced human immunodeficiency virus infection. Here, we report on an immunocompetent female residing in a non-endemic area, presenting with progressive disseminated histoplasmosis after a remote travel history to Thailand and Costa Rica...
March 27, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28242173/the-presence-of-cardiovascular-disease-does-not-modify-the-weak-impact-obesity-has-on-health-related-quality-of-life-in-patients-with-hip-osteoarthritis-in-the-khoala-cohort
#11
Laurie Renaudin, Francis Guillemin, Jacques Pouchot, Anne-Christine Rat
OBJECTIVE: In people with hip osteoarthritis (OA), the impact of obesity on health-related quality of life (HRQoL) remains unknown. Also whether cardiovascular conditions can modify the obesity-HRQoL relation has not been explored. We aimed to (1) study the cross-sectional relationship between body mass index (BMI) and HRQoL in symptomatic hip OA patients and determine whether cardiovascular comorbidity modifies this relationship and (2) examine the impact of BMI on the course of HRQoL over time...
February 24, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/27939757/the-ccaat-binding-complex-cbc-in-aspergillus-species
#12
REVIEW
Peter Hortschansky, Hubertus Haas, Eva M Huber, Michael Groll, Axel A Brakhage
The CCAAT binding complex (CBC), consisting of a heterotrimeric core structure, is highly conserved in eukaryotes and constitutes an important general transcriptional regulator. Scope of the review. In this review we discuss the scientific history and the current state of knowledge of the multiple gene regulatory functions, protein motifs and structure of the CBC in fungi with a special focus on Aspergillus species. Major conclusions and general significance. Initially identified as a transcriptional activator of respiration in Saccharomyces cerevisiae, in other fungal species the CBC was found to be involved in highly diverse pathways, but a general rationale for its involvement was missing...
May 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27884636/an-in-vitro-and-in-vivo-study-of-peptide-functionalized-nanoparticles-for-brain-targeting-the-importance-of-selective-blood-brain-barrier-uptake
#13
Gerard H Bode, Gregory Coué, Christian Freese, Karin E Pickl, Maria Sanchez-Purrà, Berta Albaiges, Salvador Borrós, Ewoud C van Winden, Leto-Aikaterini Tziveleka, Zili Sideratou, Johan F J Engbersen, Smriti Singh, Krystyna Albrecht, Jürgen Groll, Martin Möller, Andy J G Pötgens, Christoph Schmitz, Eleonore Fröhlich, Christian Grandfils, Frank M Sinner, C James Kirkpatrick, Harry W M Steinbusch, Hans-Georg Frank, Ronald E Unger, Pilar Martinez-Martinez
Targeted delivery of drugs across endothelial barriers remains a formidable challenge, especially in the case of the brain, where the blood-brain barrier severely limits entry of drugs into the central nervous system. Nanoparticle-mediated transport of peptide/protein-based drugs across endothelial barriers shows great potential as a therapeutic strategy in a wide variety of diseases. Functionalizing nanoparticles with peptides allows for more efficient targeting to specific organs. We have evaluated the hemocompatibilty, cytotoxicity, endothelial uptake, efficacy of delivery and safety of liposome, hyperbranched polyester, poly(glycidol) and acrylamide-based nanoparticles functionalized with peptides targeting brain endothelial receptors, in vitro and in vivo...
April 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27789522/a-humanized-yeast-proteasome-identifies-unique-binding-modes-of-inhibitors-for-the-immunosubunit-%C3%AE-5i
#14
Eva M Huber, Wolfgang Heinemeyer, Gerjan de Bruin, Herman S Overkleeft, Michael Groll
Inhibition of the immunoproteasome subunit β5i alleviates autoimmune diseases in preclinical studies and represents a promising new anti-inflammatory therapy. However, the lack of structural data on the human immunoproteasome still hampers drug design. Here, we systematically determined the potency of seven α' β' epoxyketone inhibitors with varying N-caps and P3-stereochemistry for mouse/human β5c/β5i and found pronounced differences in their subunit and species selectivity. Using X-ray crystallography, the compounds were analyzed for their modes of binding to chimeric yeast proteasomes that incorporate key parts of human β5c, human β5i or mouse β5i and the neighboring β6 subunit...
December 1, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27697762/population-pharmacokinetics-of-liposomal-amphotericin-b-in-immunocompromised-children
#15
Jodi M Lestner, Andreas H Groll, Ghaith Aljayyoussi, Nita L Seibel, Aziza Shad, Corina Gonzalez, Lauren V Wood, Paul F Jarosinski, Thomas J Walsh, William W Hope
Liposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited pharmacokinetic (PK) data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults. Our objective was to describe the pharmacokinetics of LAmB in children aged 1 to 17 years with suspected or documented IFD. Thirty-five children were treated with LAmB at doses of 2.5 to 10 mg kg(-1) daily. Samples were taken at baseline and at 0...
December 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27554995/the-use-of-a-cartilage-decellularized-matrix-scaffold-for-the-repair-of-osteochondral-defects-the-importance-of-long-term-studies-in-a-large-animal-model
#16
R A Vindas Bolaños, S M Cokelaere, J M Estrada McDermott, K E M Benders, U Gbureck, S G M Plomp, H Weinans, J Groll, P R van Weeren, J Malda
OBJECTIVE: To investigate the effect of decellularized cartilage-derived matrix (CDM) scaffolds, by itself and as a composite scaffold with a calcium phosphate (CaP) base, for the repair of osteochondral defects. It was hypothesized that the chondral defects would heal with fibrocartilaginous tissue and that the composite scaffold would result in better bone formation. METHODS: After an 8-week pilot experiment in a single horse, scaffolds were implanted in eight healthy horses in osteochondral defects on the medial trochlear ridge of the femur...
March 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/27438186/structure-based-design-of-%C3%AE-5c-selective-inhibitors-of-human-constitutive-proteasomes
#17
Bo-Tao Xin, Gerjan de Bruin, Eva M Huber, Andrej Besse, Bogdan I Florea, Dmitri V Filippov, Gijsbert A van der Marel, Alexei F Kisselev, Mario van der Stelt, Christoph Driessen, Michael Groll, Herman S Overkleeft
This work reports the development of highly potent and selective inhibitors of the β5c catalytic activity of human constitutive proteasomes. The work describes the design principles, large hydrophobic P3 residue and small hydrophobic P1 residue, that led to the synthesis of a panel of peptide epoxyketones; their evaluation and the selection of the most promising compounds for further analyses. Structure-activity relationships detail how in a logical order the β1c/i, β2c/i, and β5i activities became resistant to inhibition as compounds were diversified stepwise...
August 11, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27144156/canadian-physicians-attitudes-towards-accessing-mental-health-resources
#18
Tariq M Hassan, M Selim Asmer, Nadeem Mazhar, Tariq Munshi, Tanya Tran, Dianne L Groll
Despite their rigorous training, studies have shown that physicians experience higher rates of mental illness, substance abuse, and suicide compared to the general population. An online questionnaire was sent to a random sample of physicians across Canada to assess physicians' knowledge of the incidence of mental illness among physicians and their attitudes towards disclosure and treatment in a hypothetical situation where one developed a mental illness. We received 139 responses reflecting mostly primary care physicians and nonsurgical specialists...
2016: Psychiatry Journal
https://www.readbyqxmd.com/read/26964885/a-unified-mechanism-for-proteolysis-and-autocatalytic-activation-in-the-20s-proteasome
#19
Eva M Huber, Wolfgang Heinemeyer, Xia Li, Cassandra S Arendt, Mark Hochstrasser, Michael Groll
Biogenesis of the 20S proteasome is tightly regulated. The N-terminal propeptides protecting the active-site threonines are autocatalytically released only on completion of assembly. However, the trigger for the self-activation and the reason for the strict conservation of threonine as the active site nucleophile remain enigmatic. Here we use mutagenesis, X-ray crystallography and biochemical assays to suggest that Lys33 initiates nucleophilic attack of the propeptide by deprotonating the Thr1 hydroxyl group and that both residues together with Asp17 are part of a catalytic triad...
2016: Nature Communications
https://www.readbyqxmd.com/read/26838860/real-time-measurement-of-protein-adsorption-on-electrophoretically-deposited-hydroxyapatite-coatings-and-magnetron-sputtered-metallic-films-using-the-surface-acoustic-wave-technique
#20
M Meininger, T Schmitz, T Wagner, A Ewald, U Gbureck, J Groll, C Moseke
Surface acoustic wave (SAW) biosensors are highly sensitive for mass binding and are therefore used to detect protein-protein and protein-antibody interactions. Whilst the standard surface of the chips is a thin gold film, measurements on implant- or bone-like surfaces could significantly enhance the range of possible applications for this technique. The aim of this study was to establish methods to coat biosensor chips with Ti, TiN, and silver-doped TiN using physical vapor deposition as well as with hydroxyapatite by electrophoresis...
April 1, 2016: Materials Science & Engineering. C, Materials for Biological Applications
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