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https://www.readbyqxmd.com/read/29775601/cells-stiffen-for-cytokines
#1
Richard Newton, Daniel J Müller
In this issue of Cell Chemical Biology, Knoops et al. (2018) use a novel approach in immunology: combining confocal microscopy and atomic force microscopy to unravel the specific interaction of oxidized peroxiredoxin-5 with Toll-like receptor 4 that leads to the release of interleukin-1β and the stiffening of mammalian cells.
May 17, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29774302/ocular-histopathology-and-immunohistochemical-analysis-in-the-oldest-known-individual-with-autosomal-dominant-vitreoretinochoroidopathy
#2
Morton F Goldberg, Scott McLeod, Mark Tso, Kirk Packo, Malia Edwards, Imran A Bhutto, Rajkumar Baldeosingh, Charles Eberhart, Bernhard H F Weber, Gerard A Lutty
Purpose: To assess the immunohistochemical and histopathological changes in a subject with Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC). Design: Case study. Participant: Ninety two year-old Caucasian male with ADVIRC. Methods: The subject was documented clinically for 54 Years. The retina/choroid complex of the right eye was evaluated with cryosections stained with hematoxylin and eosin or periodic acid schiff reagent...
April 2018: Ophthalmology Retina
https://www.readbyqxmd.com/read/29773864/igg-single-chain-trail-fusion-proteins-for-tumour-therapy
#3
Martin Siegemund, Felix Schneider, Meike Hutt, Oliver Seifert, Ines Müller, Dagmar Kulms, Klaus Pfizenmaier, Roland E Kontermann
Single-chain formats of TNF-related apoptosis inducing ligand (scTRAIL) can serve as effector components of tumour-associated antigen-targeted as well as non-targeted fusion proteins, being characterized by high tumour cell-specific induction of apoptosis through death receptor activation. We studied the suitability of immunoglobulin G as a scaffold for oligovalent and bispecific TRAIL fusion proteins. Thus, we developed novel targeted hexa- and dodecavalent IgG-scTRAIL molecules by fusing scTRAIL to the C-terminus of either light (LC-scTRAIL) or heavy immunoglobulin chain (HC-scTRAIL), or to both ends (LC/HC-scTRAIL) of the anti-EGFR IgG antibody hu225...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773673/lysosomal-proteome-and-secretome-analysis-identifies-missorted-enzymes-and-their-non-degraded-substrates-in-mucolipidosis-iii-mouse-cells
#4
Giorgia Di Lorenzo, Renata Voltolini Velho, Dominic Winter, Melanie Thelen, Shiva Ahmadi, Michaela Schweizer, Raffaella De Pace, Kerstin Cornils, Timur Alexander Yorgan, Saskia Grüb, Irm Hermans-Borgmeyer, Thorsten Schinke, Sven Müller-Loennies, Thomas Braulke, Sandra Pohl
Targeting of soluble lysosomal enzymes requires mannose 6-phosphate (M6P) signals whose formation is initiated by the hexameric N-acetylglucosamine (GlcNAc)-1-phosphotransferase complex (α2β2γ2). Upon proteolytic cleavage by site-1 protease, the α/β-subunit precursor is catalytically activated but the functions of γ-subunits (Gnptg) in M6P modification of lysosomal enzymes are unknown. To investigate this, we analyzed the Gnptg expression in mouse tissues, primary cultured cells, and in Gnptg reporter mice in vivo, and found high amounts in the brain, eye, kidney, femur, vertebra and fibroblasts...
May 17, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29768203/unconventional-secretion-mediates-the-trans-cellular-spreading-of-tau
#5
Taxiarchis Katsinelos, Marcel Zeitler, Eleni Dimou, Andromachi Karakatsani, Hans-Michael Müller, Eliana Nachman, Julia P Steringer, Carmen Ruiz de Almodovar, Walter Nickel, Thomas R Jahn
The progressive deposition of misfolded hyperphosphorylated tau is a pathological hallmark of tauopathies, including Alzheimer's disease. However, the underlying molecular mechanisms governing the intercellular spreading of tau species remain elusive. Here, we show that full-length soluble tau is unconventionally secreted by direct translocation across the plasma membrane. Increased secretion is favored by tau hyperphosphorylation, which provokes microtubule detachment and increases the availability of free protein inside cells...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29768202/sensory-neuropathy-causing-mutations-in-atl3-cause-aberrant-er-membrane-tethering
#6
Michiel Krols, Sammy Detry, Bob Asselbergh, Leonardo Almeida-Souza, Anna Kremer, Saskia Lippens, Riet De Rycke, Vicky De Winter, Franz-Josef Müller, Ingo Kurth, Harvey T McMahon, Savvas N Savvides, Vincent Timmerman, Sophie Janssens
The endoplasmic reticulum (ER) is a complex network of sheets and tubules that is continuously remodeled. The relevance of this membrane dynamics is underscored by the fact that mutations in atlastins (ATLs), the ER fusion proteins in mammals, cause neurodegeneration. How defects in this process disrupt neuronal homeostasis is unclear. Using electron microscopy (EM) volume reconstruction of transfected cells, neurons, and patient fibroblasts, we show that hereditary sensory and autonomic neuropathy (HSAN)-causing ATL3 mutants promote aberrant ER tethering hallmarked by bundles of laterally attached ER tubules...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29767277/microglial-density-determines-the-appearance-of-pathological-neovascular-tufts-in-oxygen-induced-retinopathy
#7
Wenqin Xu, Zhicha Hu, Yang Lv, Guorui Dou, Zifeng Zhang, Haiyan Wang, Yusheng Wang
The oxygen-induced retinopathy (OIR) animal model established in C57 mice and SD rats has been widely used in retinal neovascular disease studies, while Balb/c mice have not been used because Balb/c OIR mice lack neovascular tufts. One study found a substantial difference in the density of retinal microglia between C57 and Balb/c mice; however, no direct evidence could clarify whether the density of retinal microglia in Balb/c mice led to this difference. In our study, intraperitoneal injection of minocycline was used to inhibit the activation of microglia and intravitreal injection of clodronate liposomes was used to decrease the density of microglia in Balb/c OIR model mice...
May 16, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29766021/transduction-patterns-of-adeno-associated-viral-vectors-in-a-laser-induced-choroidal-neovascularization-mouse-model
#8
Si Hyung Lee, Ye Seul Kim, Seung Kwan Nah, Hee Jong Kim, Ha Yan Park, Jin Young Yang, Keerang Park, Tae Kwann Park
Adeno-associated virus (AAV) vector is a promising platform technology for ocular gene therapy. Recently clinical successes to treat choroidal neovascularization (CNV) in wet type age-related macular degeneration have been reported. However, because pathologic conditions of the retina may alter the tropism of viral vectors, it is necessary to evaluate the transduction efficiency of different serotypes of AAV vectors in the retinas with CNVs. Here, we show the patterns and efficacy of transduction of AAV2, -5, and -8 vectors in a laser-induced CNV mouse model...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29765449/effects-of-single-and-combined-low-frequency-electromagnetic-fields-and-simulated-microgravity-on-gene-expression-of-human-mesenchymal-stem-cells-during-chondrogenesis
#9
Susanne Mayer-Wagner, Florian Hammerschmid, Helmut Blum, Stefan Krebs, Julia I Redeker, Boris M Holzapfel, Volkmar Jansson, Peter E Müller
Introduction: Low frequency electromagnetic fields (LF-EMF) and simulated microgravity (SMG) have been observed to affect chondrogenesis. A controlled bioreactor system was developed to apply LF-EMF and SMG singly or combined during chondrogenic differentiation of human mesenchymal stem cells (hMSCs) in 3D culture. Material and methods: An external motor gear SMG bioreactor was combined with magnetic Helmholtz coils for EMF (5 mT; 15 Hz). Pellets of hMSCs (±TGF-β3) were cultured (P5) under SMG, LF-EMF, LF-EMF/SMG and control (1 g) conditions for 3 weeks...
April 2018: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/29765300/detection-of-dna-double-strand-breaks-by-%C3%AE-h2ax-does-not-result-in-53bp1-recruitment-in-mouse-retinal-tissues
#10
Brigitte Müller, N M Ellinwood, Birgit Lorenz, Knut Stieger
Gene editing is an attractive potential treatment of inherited retinopathies. However, it often relies on endogenous DNA repair. Retinal DNA repair is incompletely characterized in humans and animal models. We investigated recruitment of the double stranded break (DSB) repair complex of γH2AX and 53bp1 in both developing and mature mouse neuroretinas. We evaluated the immunofluorescent retinal expression of these proteins during development (P07-P30) in normal and retinal degeneration models, as well as in potassium bromate induced DSB repair in normal adult (3 months) retinal explants...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29763601/the-p-s85c-mutation-in-matr3-impairs-stress-granule-formation-in-matrin-3-myopathy
#11
Alexander Mensch, Beate Meinhardt, Nadine Bley, Stefan Hüttelmaier, Ilka Schneider, Gisela Stoltenburg-Didinger, Torsten Kraya, Tobias Müller, Stephan Zierz
Matrin-3-related distal myopathy is characterized mainly by progressive distal weakness of the lower extremities. The mutation p.S85C in matrin-3 (MATR3) has been identified as disease-causing alteration, whereas the specific molecular mechanisms leading to the muscle disease have not been elucidated. In the present study, muscle biopsy samples from six patients and fibroblasts from four patients harboring p.S85C mutation in MATR3 were analyzed. No specific changes in matrin-3 localization or expression were observed...
May 12, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29763583/m%C3%A3-ller-glial-cells-contribute-to-dim-light-vision-in-the-spectacled-caiman-caiman-crocodilus-fuscus-analysis-of-retinal-light-transmission
#12
Silke Agte, Alexey Savvinov, Anett Karl, Astrid Zayas-Santiago, Elke Ulbricht, Vladimir I Makarov, Andreas Reichenbach, Andreas Bringmann, Serguei N Skatchkov
In this study, we show the capability of Müller glial cells to transport light through the inverted retina of reptiles, specifically the retina of the spectacled caimans. Thus, confirming that Müller cells of lower vertebrates also improve retinal light transmission. Confocal imaging of freshly isolated retinal wholemounts, that preserved the refractive index landscape of the tissue, indicated that the retina of the spectacled caiman is adapted for vision under dim light conditions. For light transmission experiments, we used a setup with two axially aligned objectives imaging the retina from both sides to project the light onto the inner (vitreal) surface and to detect the transmitted light behind the retina at the receptor layer...
May 12, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29762718/cell-penetrating-thiazole-peptides-inhibit-c-myc-expression-via-site-specific-targeting-of-c-myc-g-quadruplex
#13
Debasish Dutta, Manish Debnath, Diana Müller, Rakesh Paul, Tania Das, Irene Bessi, Harald Schwalbe, Jyotirmayee Dash
The structural differences among different G-quadruplexes provide an opportunity for site-specific targeting of a particular G-quadruplex structure. However, majority of G-quadruplex ligands described thus far show little selectivity among different G-quadruplexes. In this work, we delineate the design and synthesis of a crescent-shaped thiazole peptide that preferentially stabilizes c-MYC quadruplex over other promoter G-quadruplexes and inhibits c-MYC oncogene expression. Biophysical analysis such as Förster resonance energy transfer (FRET) melting and fluorescence spectroscopy show that the thiazole peptide TH3 can selectively interact with the c-MYC G-quadruplex over other investigated G-quadruplexes and duplex DNA...
May 14, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29761228/patterns-of-care-analysis-for-head-neck-cancer-of-unknown-primary-site-a-survey-inside-the-german-society-of-radiation-oncology-degro
#14
Jens Müller von der Grün, Dimitra Bon, Claus Rödel, Panagiotis Balermpas
BACKGROUND: Due to the absence of randomized trials, the optimal management for squamous cell cancer of unknown primary in the head and neck region (SCCHN CUP) remains controversial. Current strategies are based on retrospective studies, clinical experience, and institutional policies. METHODS: An anonymous questionnaire with a total of 24 questions was created and distributed by the use of an online version (Google Forms®, Google, Mountain View, CA, USA) as well as a printout version as equivalent option...
May 14, 2018: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/29760101/design-of-an-allosterically-modulated-doxycycline-and-doxorubicin-drug-binding-protein
#15
Karin Schmidt, Bernd R Gardill, Alina Kern, Peter Kirchweger, Michael Börsch, Yves A Muller
The allosteric interplay between distant functional sites present in a single protein provides for one of the most important regulatory mechanisms in biological systems. While the design of ligand-binding sites into proteins remains challenging, this holds even truer for the coupling of a newly engineered binding site to an allosteric mechanism that regulates the ligand affinity. Here it is shown how computational design algorithms enabled the introduction of doxycycline- and doxorubicin-binding sites into the serine proteinase inhibitor (serpin) family member α1-antichymotrypsin...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29759373/random-motion-of-chromatin-is-influenced-by-lamin-a-interconnections
#16
Fereydoon Taheri, Buse Isbilir, Gabriele Müller, Jan W Krieger, Giuseppe Chirico, Jörg Langowski, Katalin Tóth
Using fluorescence correlation spectroscopy in single-plane illumination microscopy, we investigated the dynamics of chromatin in interphase mouse adult fibroblast cell nuclei under the influence of the intermediate filament protein lamin A. We find that 1) lamin A-eGFP and histone H2A-mRFP show significant comobility, indicating that their motions are clearly interconnected in the nucleus, and 2) that the random motion of histones H2A within the chromatin network is subdiffusive, i.e., the effective diffusion coefficient decreases for slow timescales...
May 11, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29756633/immunotherapy-in-head-and-neck-cancer-scientific-rationale-current-treatment-options-and-future-directions
#17
Uta Rothschild, Laurent Muller, Axel Lechner, Hans A Schlösser, Dirk Beutner, Heinz Läubli, Alfred Zippelius, Sacha I Rothschild
Head and neck squamous cell carcinoma (HNSCC) is a frequent tumour arising from multiple anatomical subsites in the head and neck region. The treatment for early-stage disease is generally single modality, either surgery or radiotherapy. The treatment for locally advanced tumours is multimodal. For recurrent/metastatic HNSCC palliative chemotherapy is standard of care. The prognosis is limited and novel treatment approaches are urgently needed. HNSCC evades immune responses through multiple resistance mechanisms...
May 14, 2018: Swiss Medical Weekly
https://www.readbyqxmd.com/read/29755320/mechanically-gated-ion-channels-in-mammalian-hair-cells
#18
REVIEW
Xufeng Qiu, Ulrich Müller
Hair cells in the inner ear convert mechanical stimuli provided by sound waves and head movements into electrical signal. Several mechanically evoked ionic currents with different properties have been recorded in hair cells. The search for the proteins that form the underlying ion channels is still in progress. The mechanoelectrical transduction (MET) channel near the tips of stereociliary in hair cells, which is responsible for sensory transduction, has been studied most extensively. Several components of the sensory mechanotransduction machinery in stereocilia have been identified, including the multi-transmembrane proteins tetraspan membrane protein in hair cell stereocilia (TMHS)/LHFPL5, transmembrane inner ear (TMIE) and transmembrane channel-like proteins 1 and 2 (TMC1/2)...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29754509/-new-and-traditional-directions-in-the-biology-and-management-of-childhood-acute-lymphoblastic-leukemia
#19
Bálint Egyed, Gábor Kovács, Nóra Kutszegi, Andrea Rzepiel, Judit Csányiné Sági, Dániel János Erdélyi, Judit Müller, Ágnes Félné Semsei
Owing to clinical trials and improvement over the past few decades, the majority of children with acute lymphoblastic leukemia (ALL) survive by first-line chemotherapy and combat with the problems of returning to community. However, many patients may have severe acute or late therapeutic side effects, and the survival rate in some groups (e.g., patients with MLL rearrangements, hypodiploidy, IKZF1 mutation or early precursor T cell phenotype) is far behind the average. Innovative strategies in medical attendance provide better clinical outcomes for them: complete gene diagnostics, molecularly targeted anticancer treatment, immuno-oncology and immune cell therapy...
May 2018: Orvosi Hetilap
https://www.readbyqxmd.com/read/29753729/controlled-microenvironments-to-evaluate-chemotactic-properties-of-cultured-m%C3%A3-ller-glia
#20
Juan Pena, Nihan Dulger, Tanya Singh, Jing Zhou, Robert Majeska, Stephen Redenti, Maribel Vazquez
Emerging therapies have begun to evaluate the abilities of Müller glial cells (MGCs) to protect and/or regenerate neurons following retina injury. The migration of donor cells is central to many reparative strategies, where cells must achieve appropriate positioning to facilitate localized repair. Although chemical cues have been implicated in the MGC migratory responses of numerous retinopathies, MGC-based therapies have yet to explore the extent to which external biochemical stimuli can direct MGC behavior...
May 10, 2018: Experimental Eye Research
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