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https://www.readbyqxmd.com/read/27889468/mitochondrial-cristae-remodelling-is-associated-with-disrupted-opa1-oligomerisation-in-the-huntington-s-disease-r6-2-fragment-model
#1
Tanja Hering, Kerstin Kojer, Nathalie Birth, Jaqueline Hallitsch, Jan-Willem Taanman, Michael Orth
There is evidence of an imbalance of mitochondrial fission and fusion in patients with Huntington's disease (HD) and HD animal models. Fission and fusion are important for mitochondrial homeostasis including mitochondrial DNA (mtDNA) maintenance and may be relevant for the selective striatal mtDNA depletion that we observed in the R6/2 fragment HD mouse model. We aimed to investigate the fission/fusion balance and the integrity of the mitochondrial membrane system in cortex and striatum of end-stage R6/2 mice and wild-type animals...
November 23, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27884336/predictive-value-of-clinical-scoring-and-simplified-gait-analysis-for-acetabulum-fractures
#2
Benedikt J Braun, Julian Wrona, Nils T Veith, Mika Rollman, Marcel Orth, Steven C Herath, Jörg H Holstein, Tim Pohlemann
BACKGROUND: Fractures of the acetabulum show a high, long-term complication rate. The aim of the present study was to determine the predictive value of clinical scoring and standardized, simplified gait analysis on the outcome after these fractures. METHODS: Forty-one patients with acetabular fractures treated between 2008 and 2013 and available, standardized video recorded aftercare were identified from a prospective database. A visual gait score was used to determine the patients walking abilities 6-m postoperatively...
December 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27868347/identification-of-extreme-motor-phenotypes-in-huntington-s-disease
#3
Ulrike Braisch, Birgit Hay, Rainer Muche, Dietrich Rothenbacher, G Bernhard Landwehrmeyer, Jeffrey D Long, Michael Orth
The manifestation of motor signs in Huntington's disease (HD) has a well-known inverse relationship with HTT CAG repeat length, but the prediction is far from perfect. The probability of finding disease modifiers is enhanced in individuals with extreme HD phenotypes. We aimed to identify extreme HD motor phenotypes conditional on CAG and age, such as patients with very early or very late onset of motor manifestation. Retrospective data were available from 1,218 healthy controls and 9,743 HD participants with CAG repeats ≥40, and a total of about 30,000 visits...
November 21, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/27867017/genomic-amplification-of-fanconi-anemia-complementation-group-a-fanca-in-head-and-neck-squamous-cell-carcinoma-hnscc-cellular-mechanisms-of-radioresistance-and-clinical-relevance
#4
Julia Hess, Kristian Unger, Michael Orth, Ulrike Schötz, Lars Schüttrumpf, Verena Zangen, Igor Gimenez-Aznar, Agata Michna, Ludmila Schneider, Ramona Stamp, Martin Selmansberger, Herbert Braselmann, Ludwig Hieber, Guido A Drexler, Sebastian Kuger, Diana Klein, Verena Jendrossek, Anna A Friedl, Claus Belka, Horst Zitzelsberger, Kirsten Lauber
Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance...
November 17, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27852003/the-neuropsychology-of-first-impressions-evidence-from-huntington-s-disease
#5
Reiner Sprengelmeyer, Andrew W Young, Eva-Maria Baldas, Iris Ratheiser, Clare A M Sutherland, Hans-Peter Müller, Georg Grön, Sigurd D Süssmuth, G Bernhard Landwehrmeyer, Michael Orth
Impairments of emotion recognition have been widely documented in Huntington's disease (HD), but little is known concerning how these relate to other aspects of social cognition, including first impressions of traits such as trustworthiness and dominance. Here, we introduce a novel and sensitive method to investigate the ability to evaluate trustworthiness and dominance from facial appearance, with control tasks measuring ability to perceive differences between comparable stimuli. We used this new method together with standard tests of face perception to investigate social cognition in HD...
October 21, 2016: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
https://www.readbyqxmd.com/read/27800150/immunoglobulin-detection-in-wild-birds-effectiveness-of-three-secondary-anti-avian-igy-antibodies-in-direct-elisas-in-41-avian-species
#6
Carol A Fassbinder-Orth, Travis E Wilcoxen, Tiffany Tran, Raoul K Boughton, Jeanne M Fair, Erik K Hofmeister, Jennifer L Grindstaff, Jen C Owen
Immunological reagents for wild, non-model species are limited or often non-existent for many species.In this study, we compare the reactivity of a new anti-passerine IgY secondary antibody with existing secondary antibodies developed for use with birds. Samples from 41 species from the following six avian orders were analysed: Anseriformes (1 family, 1 species), Columbiformes (1 family, 2 species), Galliformes (1 family, 1 species), Passeriformes (16 families, 34 species), Piciformes (1 family, 2 species) and Suliformes (1 family, 1 species)...
October 2016: Methods in Ecology and Evolution
https://www.readbyqxmd.com/read/27797677/diagnostic-performance-of-us-for-differentiating-perforated-from-nonperforated-pediatric-appendicitis-a-prospective-cohort-study
#7
Jennifer L Carpenter, Robert C Orth, Wei Zhang, Monica E Lopez, Kate L Mangona, R Paul Guillerman
Purpose To prospectively evaluate the diagnostic performance of ultrasonography (US) for differentiating perforated from nonperforated pediatric appendicitis and to investigate the association between specific US findings and perforation. Materials and Methods This HIPAA-compliant study had institutional review board approval, and the need for informed consent was waived. All abdominal US studies performed for suspected pediatric appendicitis at one institution from July 1, 2013, to July 9, 2014, were examined prospectively...
October 31, 2016: Radiology
https://www.readbyqxmd.com/read/27789340/macroscopic-cartilage-repair-scoring-of-defect-fill-integration-and-total-points-correlate-with-corresponding-items-in-histological-scoring-systems-a-study-in-adult-sheep
#8
Lars Goebel, Patrick Orth, Magali Cucchiarini, Dietrich Pape, Henning Madry
OBJECTIVE: To correlate osteochondral repair assessed by validated macroscopic scoring systems with established semiquantitative histological analyses in an ovine model and to test the hypothesis that important macroscopic individual categories correlate with their corresponding histological counterparts. METHODS: In the weight-bearing portion of medial femoral condyles (n = 38) of 19 female adult Merino sheep (age 2 to 4 years; weight 70 ± 20 kg) full-thickness chondral defects were created (size 4 x 8 mm; ICRS grade 3C) and treated with Pridie drilling...
October 24, 2016: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/27743426/14-3-3-proteins-regulate-k2p-5-1-surface-expression-on-t-lymphocytes
#9
Juncal Fernández-Orth, Petra Ehling, Tobias Ruck, Susann Pankratz, Majella-Sophie Hofmann, Peter Landgraf, Daniela C Dieterich, Karl-Heinz Smalla, Thilo Kähne, Guiscard Seebohm, Thomas Budde, Heinz Wiendl, Stefan Bittner, Sven G Meuth
K2P 5.1 channels (also called TASK-2 or KCNK5) have already been shown to be relevant in the pathophysiology of autoimmune disease since they are known to be upregulated on peripheral and central T lymphocytes of multiple sclerosis (MS) patients. Moreover, overexpression of K2P 5.1 channels in vitro provokes enhanced T-cell effector functions. However, the molecular mechanisms regulating intracellular K2P 5.1 channel trafficking are unknown so far. Thus, the aim of the study is to elucidate the trafficking of K2P 5...
October 15, 2016: Traffic
https://www.readbyqxmd.com/read/27732858/breast-cancer-derived-lung-metastases-show-increased-pyruvate-carboxylase-dependent-anaplerosis
#10
Stefan Christen, Doriane Lorendeau, Roberta Schmieder, Dorien Broekaert, Kristine Metzger, Koen Veys, Ilaria Elia, Joerg Martin Buescher, Martin Franz Orth, Shawn Michael Davidson, Thomas Georg Philipp Grünewald, Katrien De Bock, Sarah-Maria Fendt
Cellular proliferation depends on refilling the tricarboxylic acid (TCA) cycle to support biomass production (anaplerosis). The two major anaplerotic pathways in cells are pyruvate conversion to oxaloacetate via pyruvate carboxylase (PC) and glutamine conversion to α-ketoglutarate. Cancers often show an organ-specific reliance on either pathway. However, it remains unknown whether they adapt their mode of anaplerosis when metastasizing to a distant organ. We measured PC-dependent anaplerosis in breast-cancer-derived lung metastases compared to their primary cancers using in vivo (13)C tracer analysis...
October 11, 2016: Cell Reports
https://www.readbyqxmd.com/read/27699957/the-vulnerability-of-study-participants-in-the-context-of-transnational-biomedical-research-from-conceptual-considerations-to-practical-implications
#11
Helen Grete Orth, Silke Schicktanz
Outsourcing clinical trials sponsored by pharmaceutical companies from industrialized countries to low- (middle)-income countries - summarized as transnational biomedical research (TBR) - has lead to many concerns about ethical standards. Whether study participants are particularly vulnerable is one of those concerns. However, the concept of vulnerability is still vague and varies in its definition. Despite the fact that important international ethical guidelines such as the Declaration of Helsinki by the World Medical Association or the Ethical Guidelines for Biomedical Research Involving Human Subjects by the Council of International Organizations of Medical Sciences refer to vulnerability as ethical principle, each of their approaches are different...
October 4, 2016: Developing World Bioethics
https://www.readbyqxmd.com/read/27649498/high-throughput-random-mutagenesis-and-single-molecule-real-time-sequencing-of-the-muscle-nicotinic-acetylcholine-receptor
#12
Paul J Groot-Kormelink, Sandrine Ferrand, Nicholas Kelley, Anke Bill, Felix Freuler, Pierre-Eloi Imbert, Anthony Marelli, Nicole Gerwin, Lucia G Sivilotti, Loren Miraglia, Anthony P Orth, Edward J Oakeley, Ulrich Schopfer, Sandra Siehler
High throughput random mutagenesis is a powerful tool to identify which residues are important for the function of a protein, and gain insight into its structure-function relation. The human muscle nicotinic acetylcholine receptor was used to test whether this technique previously used for monomeric receptors can be applied to a pentameric ligand-gated ion channel. A mutant library for the α1 subunit of the channel was generated by error-prone PCR, and full length sequences of all 2816 mutants were retrieved using single molecule real time sequencing...
2016: PloS One
https://www.readbyqxmd.com/read/27624438/basic-science-of-osteoarthritis
#13
Magali Cucchiarini, Laura de Girolamo, Giuseppe Filardo, J Miguel Oliveira, Patrick Orth, Dietrich Pape, Pascal Reboul
Osteoarthritis (OA) is a prevalent, disabling disorder of the joints that affects a large population worldwide and for which there is no definitive cure. This review provides critical insights into the basic knowledge on OA that may lead to innovative end efficient new therapeutic regimens. While degradation of the articular cartilage is the hallmark of OA, with altered interactions between chondrocytes and compounds of the extracellular matrix, the subchondral bone has been also described as a key component of the disease, involving specific pathomechanisms controlling its initiation and progression...
December 2016: Journal of Experimental Orthopaedics
https://www.readbyqxmd.com/read/27624327/comparison-of-rapid-hybridization-based-pathogen-identification-and-resistance-evaluation-in-sepsis-using-the-verigene%C3%A2-device-paired-with-good-old-culture
#14
Michael Berktold, Wolfgang Mutschlechner, Dorothea Orth-Höller
Rapid microbial diagnostics is important for septicemic patients. The current gold standard is blood culture with consecutive pathogen identification and antimicrobial susceptibility testing. However, these culture-based methods need at least 48 h.The aim of this study was to compare Verigene(®) (Nanosphere, Northbrook, IL, USA), a rapid hybridization-based method, with conventional culture-based methods for detection of pathogens and resistance markers from positive blood cultures of septic patients.In 85 of 100 tested blood culture samples (85 %), pathogen identification as well as resistance profile were identical in Verigene and conventional culture...
September 13, 2016: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/27596562/a-novel-algorithm-for-a-precise-analysis-of-subchondral-bone-alterations
#15
Liang Gao, Patrick Orth, Lars K H Goebel, Magali Cucchiarini, Henning Madry
Subchondral bone alterations are emerging as considerable clinical problems associated with articular cartilage repair. Their analysis exposes a pattern of variable changes, including intra-lesional osteophytes, residual microfracture holes, peri-hole bone resorption, and subchondral bone cysts. A precise distinction between them is becoming increasingly important. Here, we present a tailored algorithm based on continuous data to analyse subchondral bone changes using micro-CT images, allowing for a clear definition of each entity...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27595634/the-importance-of-methyl-positioning-and-tautomeric-equilibria-for-imidazole-nucleophilicity
#16
Renan B Campos, Leociley R A Menezes, Andersson Barison, Dean J Tantillo, Elisa S Orth
Imidazole (IMZ) rings catalyze many biological dephosphorylation processes. The methyl positioning effect on IMZs reactivity has long intrigued scientists and its full understanding comprises a promising tool for designing highly efficient IMZ-based catalysts. We evaluated all monosubstituted methylimidazoles (xMEI) in the reaction with diethyl 2,4-dinitrophenyl phosphate by kinetics studies, NMR analysis and DFT calculations. All xMEI showed remarkable rate enhancements, up to 1.9×10(5) fold, compared with spontaneous hydrolysis...
October 17, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27588391/regulation-of-matrix-metalloproteinases-mmps-expression-and-secretion-in-mda-mb-231-breast-cancer-cells-by-lim-and-sh3-protein-1-lasp1
#17
Marcel Endres, Susanne Kneitz, Martin F Orth, Ruwan K Perera, Alma Zernecke, Elke Butt
The process of tumor invasion requires degradation of extracellular matrix by proteolytic enzymes. Cancer cells form protrusive invadopodia, which produce and release matrix metalloproteinases (MMPs) to degrade the basement membrane thereby enabling metastasis. We investigated the effect of LASP1, a newly identified protein in invadopodia, on expression, secretion and activation of MMPs in invasive breast tumor cell lines.By analyzing microarray data of in-house generated control and LASP1-depleted MDA-MB-231 breast cancer cells, we observed downregulation of MMP1, -3 and -9 upon LASP1 depletion...
August 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27574332/genetic-modification-of-human-peripheral-blood-aspirates-using-recombinant-adeno-associated-viral-vectors-for-articular-cartilage-repair-with-a-focus-on-chondrogenic-transforming-growth-factor-%C3%AE-gene-delivery
#18
Janina Frisch, Patrick Orth, Jagadeesh Kumar Venkatesan, Ana Rey-Rico, Gertrud Schmitt, Dieter Kohn, Henning Madry, Magali Cucchiarini
: : Transplantation of genetically modified peripheral blood aspirates that carry chondrogenically competent progenitor cells may offer new, convenient tools to treat articular cartilage lesions compared with the more complex and invasive application of bone marrow concentrates or of bone marrow-derived mesenchymal stem cells. Here, we show that recombinant adeno-associated viral (rAAV) vectors are powerful gene vehicles capable of successfully targeting primary human peripheral blood aspirates in a stable and safe manner, allowing for an efficient and long-term transgene expression in such samples (up to 63 days with use of a lacZ reporter gene and for at least 21 days with application of the pleiotropic, chondrogenic factor transforming growth factor-β [TGF-β])...
August 29, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27559058/marine-phytophthora-species-can-hamper-conservation-and-restoration-of-vegetated-coastal-ecosystems
#19
Laura L Govers, Willem A Man In 't Veld, Johan P Meffert, Tjeerd J Bouma, Patricia C J van Rijswick, Jannes H T Heusinkveld, Robert J Orth, Marieke M van Katwijk, Tjisse van der Heide
Phytophthora species are potent pathogens that can devastate terrestrial plants, causing billions of dollars of damage yearly to agricultural crops and harming fragile ecosystems worldwide. Yet, virtually nothing is known about the distribution and pathogenicity of their marine relatives. This is surprising, as marine plants form vital habitats in coastal zones worldwide (i.e. mangrove forests, salt marshes, seagrass beds), and disease may be an important bottleneck for the conservation and restoration of these rapidly declining ecosystems...
August 31, 2016: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/27477323/natural-variation-in-sensory-motor-white-matter-organization-influences-manifestations-of-huntington-s-disease
#20
Michael Orth, Sarah Gregory, Rachael I Scahill, Isabella Sm Mayer, Lora Minkova, Stefan Klöppel, Kiran K Seunarine, Lara Boyd, Beth Borowsky, Ralf Reilmann, G Bernhard Landwehrmeyer, Blair R Leavitt, Raymund Ac Roos, Alexandra Durr, Geraint Rees, John C Rothwell, Douglas Langbehn, Sarah J Tabrizi
While the HTT CAG-repeat expansion mutation causing Huntington's disease (HD) is highly correlated with the rate of pathogenesis leading to disease onset, considerable variance in age-at-onset remains unexplained. Therefore, other factors must influence the pathogenic process. We asked whether these factors were related to natural biological variation in the sensory-motor system. In 243 participants (96 premanifest and 35 manifest HD; 112 controls), sensory-motor structural MRI, tractography, resting-state fMRI, electrophysiology (including SEP amplitudes), motor score ratings, and grip force as sensory-motor performance were measured...
December 2016: Human Brain Mapping
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