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Cyrill Wehling, Oliver Amon, Martin Bommer, Bernd Hoppe, Karim Kentouche, Gesa Schalk, Rolf Weimer, Michael Wiesener, Bernd Hohenstein, Burkhard Tönshoff, Rainer Büscher, Henry Fehrenbach, Ömer-Necmi Gök, Michael Kirschfink
Various complement-mediated renal disorders are currently treated with the complement inhibitor eculizumab. By blocking the cleavage of C5 this monoclonal antibody prevents cell damage caused by complement-mediated inflammation. We included 23 patients with atypical hemolytic uremic syndrome (aHUS, n=12), C3 glomerulopathies (C3G, n=9) and acute antibody-mediated renal graft rejection (AMR, n=2), treated with eculizumab in 12 hospitals in Germany. We explored the course of complement activation biomarkers and the benefit of therapeutic drug monitoring of eculizumab...
October 26, 2016: Clinical and Experimental Immunology
Takamichi Kanbayashi, Takaharu Yamauchi, Yosuke Miyaji, Masahiro Sonoo
INTRODUCTION: Recent studies have shown that stimulation occurs at the anode of stimulating electrodes instead of anodal block. This phenomenon may become a pitfall in F-wave examinations. METHODS: Subjects were 10 healthy volunteers. Their ulnar nerve was stimulated at the wrist with the cathode placed distally. Antidromic impulses were evaluated using the mixed nerve action potential (MNAP) at the elbow. RESULTS: Anodal stimulation occurred for both sensory and motor fibers at 22 mm proximal to the anode on average, which may theoretically shorten the F-wave latency by about 0...
October 26, 2016: Muscle & Nerve
Mary K McGahon, José A Fernández, Durga P Dash, Jon McKee, David A Simpson, Alex V Zholos, J Graham McGeown, Tim M Curtis
Purpose: Activation of the transient receptor potential channels, TRPC6, TRPM4, and TRPP1 (PKD2), has been shown to contribute to the myogenic constriction of cerebral arteries. In the present study we sought to determine the potential role of various mechanosensitive TRP channels to myogenic signaling in arterioles of the rat retina. Methods: Rat retinal arterioles were isolated for RT-PCR, Fura-2 Ca2+ microfluorimetry, patch-clamp electrophysiology, and pressure myography studies...
October 1, 2016: Investigative Ophthalmology & Visual Science
David A Bushinsky, Patrick Rossignol, David M Spiegel, Wade W Benton, Jinwei Yuan, Geoffrey A Block, Christopher S Wilcox, Rajiv Agarwal
BACKGROUND: Persistent hyperkalemia (serum potassium (K) ≥5.5 mEq/l) is a common condition in hemodialysis (HD) patients, is associated with increased mortality, and treatment options are limited. The effect of patiromer, a gastrointestinal K binder, on serum K was examined in HD patients. METHODS: Six hyperkalemic HD patients (5 anuric) were admitted to clinical research units for 15 days (1 pretreatment week and 1 patiromer treatment week) and they received a controlled diet with identical meals on corresponding days of pretreatment and treatment weeks...
October 27, 2016: American Journal of Nephrology
Shyam Nyati, Areeb Chator, Katerina Schinske, Brandon S Gregg, Brian Dale Ross, Alnawaz Rehemtulla
The sterile alpha motif and leucine zipper containing kinase ZAK (AZK, MLT, MLK7), is a MAPK-kinase kinase (MKKK). Like most MAPKKKs which are known to activate the c-Jun. amino-terminal kinase (JNK) pathway, ZAK has been shown to participate in the transduction of Transforming growth factor-β (TGF-β)-mediated non-canonical signaling. A role for ZAK in SMAD-dependent, canonical TGF-β signaling has not been previously appreciated. Using a combination of functional genomics and biochemical techniques, we demonstrate that ZAK regulates canonical TGFβRI/II signaling in lung and breast cancer cell lines and may serve as a key node in the regulation of TGFBR kinase activity...
October 23, 2016: Translational Oncology
Dror Alishekevitz, Svetlana Gingis-Velitski, Orit Kaidar-Person, Lilach Gutter-Kapon, Sandra D Scherer, Ziv Raviv, Emmanuelle Merquiol, Yael Ben-Nun, Valeria Miller, Chen Rachman-Tzemah, Michael Timaner, Yelena Mumblat, Neta Ilan, David Loven, Dov Hershkovitz, Ronit Satchi-Fainaro, Galia Blum, Jonathan P Sleeman, Israel Vlodavsky, Yuval Shaked
While chemotherapy strongly restricts or reverses tumor growth, the response of host tissue to therapy can counteract its anti-tumor activity by promoting tumor re-growth and/or metastases, thus limiting therapeutic efficacy. Here, we show that vascular endothelial growth factor receptor 3 (VEGFR3)-expressing macrophages infiltrating chemotherapy-treated tumors play a significant role in metastasis. They do so in part by inducing lymphangiogenesis as a result of cathepsin release, leading to VEGF-C upregulation by heparanase...
October 25, 2016: Cell Reports
Sangyun Lee, Heather B Mayes, Jessica M J Swanson, Gregory A Voth
The ClC family of transmembrane proteins functions throughout nature to control the transport of Cl- ions across biological membranes. ClC-ec1 from Escherichia coli is an antiporter, coupling the transport of Cl- and H+ ions in opposite directions and driven by the concentration gradients of the ions. Despite keen interest in this protein, the molecular mechanism of the Cl-/H+ coupling has not been fully elucidated. Here, we have used multiscale simulation to help identify the essential mechanism of the Cl-/H+ coupling...
October 26, 2016: Journal of the American Chemical Society
Rene Daer, Josh P Cutts, David A Brafman, Karmella A Haynes
In order to efficiently edit eukaryotic genomes, it is critical to test the impact of chromatin dynamics on CRISPR/Cas9 function and develop strategies to adapt the system to eukaryotic contexts. So far, research has extensively characterized the relationship between the CRISPR endonuclease Cas9 and the composition of the RNA-DNA duplex that mediates the system's precision. Evidence suggests that chromatin modifications and DNA packaging can block eukaryotic genome editing by custom-built DNA endonucleases like Cas9; however, the underlying mechanism of Cas9 inhibition is unclear...
October 26, 2016: ACS Synthetic Biology
Uri Landes, Alon Barsheshet, Ariel Finkelstein, Victor Guetta, Abid Assali, Amir Halkin, Hanna Vaknin-Assa, Amit Segev, Tamir Bental, Jeremy Ben-Shoshan, Israel M Barbash, Ran Kornowski
BACKGROUND: About a decade past the first transcatheter aortic valve implantation (TAVI), data are limited regarding temporal trends accompanying its evolution from novel technology to mainstream therapy. We evaluated these trends in a large multicenter TAVI registry. HYPOTHESIS: TAVI is changing and improving with time. METHODS: Patients who underwent TAVI between January 2008 and December 2014 at 3 high-volume Israeli centers were divided into 5 time quintiles according to procedure date...
October 26, 2016: Clinical Cardiology
Eliška Matoušová, Petr Koukal, Bedřich Formánek, Martin Kotora
A synthesis of the unsaturated side chain of callyspongiolide has been accomplished from two chiral building blocks prepared by catalytic asymmetric procedures applied on simple starting materials. The synthesis of the chiral benzylic alcohol was based on an enantioselective aldol reaction of a substituted benzaldehyde catalyzed by a chiral amine, whereas the chiral homoallyl alcohol was prepared by the enantioselective crotylboration of iodomethacryl aldehyde catalyzed by a chiral phosphoric acid. Both fragments were joined together by using standard Sonogashira coupling conditions...
October 26, 2016: Organic Letters
Leonardo Miziara Barboza Ferreira, Suzy Sayuri Sassamoto Kurokawa, Jovan Duran Alonso, Douglas Lopes Cassimiro, Ana Luiza Ribeiro de Souza, Mariana Fonseca, Victor Hugo Vitorino Sarmento, Luis Octavio Regasini, Clóvis Augusto Ribeiro
Supra-amphiphiles are a new class of building blocks that are fabricated by means of non-covalent forces. In this work, we studied the formation of supra-amphiphiles by combining hydrophilic meglumine (MEG) with hydrophobic maleated castor oils (MACO). Spectroscopic analysis demonstrated that ionic interactions are the main driving force in the fabrication of these materials. Subsequently, supra-amphiphile/water systems were examined for their structure and water behavior by polarized optical microscopy (POM), small angle x-ray scattering (SAXS), and differential scanning calorimetry (DSC)...
October 26, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
Xingjuan Zhao, Xiaoli Yu, Yong-Ill Lee, Hong-Guo Liu
Composite thin films with well-defined and parallel nanowires were fabricated from the binary blends of a diblock copolymer polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) and several homo-polystyrenes (h-PSs) at the air/liquid interface through a facile technique, which involves solution self-assembly, interface adsorption, and further self-organization processes. It was confirmed that the nanowires that appeared at the air/water interface came from the cylindrical micelles formed in solution. Interestingly, the diameters of the nanowires are uniform and can be tuned precisely from 45 to 247 nm by incorporating the h-PS molecules into the micellar core...
October 26, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
Cannada Andrew Lewis, Justus Aaron Calvin, Edward F Valeev
We describe the Clustered Low Rank (CLR) framework for block-sparse and block-low-rank tensor representation and computation. The CLR framework exploits the tensor structure revealed by basis clustering; computational savings arise from low-rank compression of tensor blocks and performing block arithmetic in the low-rank form whenever beneficial. The precision is rigorously controlled by 2 parameters, avoiding ad-hoc heuristics, such as domains: one controls the CLR block rank truncation and the other controls screening of small contributions in arithmetic operations on CLR tensors to propagate sparsity through expressions...
October 26, 2016: Journal of Chemical Theory and Computation
Feng Zhou, Ke-Hua Gu, Zhen-Yu Zhang, Meng-Yao Zhang, Sheng Zhou, Zhihao Shen, Xing-He Fan
By making use of the host-guest interactions between the host molecule tris-o-phenylenedioxycyclotriphosphazene (TPP) and the rod-coil block copolymer (BCP) poly(ethylene oxide)-block-poly(octyl 4'-octyloxy-2-vinylbiphenyl-4-carboxylate) (PEO-b-PVBP), the supramolecular rod-rod block copolymer P(EO@TPP)-b-PVBP was constructed. It consists of a crystalline segment P(EO@TPP) with a hexagonal crystalline structure and a columnar nematic liquid-crystalline segment (PVBP). As the PVBP segments arrange themselves as columnar nematic phases, the crystalline structure of the inclusion complex P(EO@TPP), which has a smaller diameter, is destroyed...
October 26, 2016: Angewandte Chemie
Lisa Sandersjöö, Andreas Jonsson, John Löfblom
Proteases are involved in fundamental biological processes and are important tools in both biotechnological and biomedical research. An important property of proteases is to discriminate among potential substrates. Here, we present a new method for substrate profiling of proteases. The substrates are displayed between two anti-idiotypic affinity domains on the Gram-positive bacterium Staphylococcus carnosus. The first domain functions as a reporter tag and has affinity for a labeled reporter protein, whereas the second domain blocks the reporter tag from interacting with the reporter protein...
October 26, 2016: Biotechnology Journal
I B Beloglazova, E S Zubkova, Z I Tsokolaeva, Yu S Stafeev, K V Dergilev, E I Ratner, M V Shestakova, O Yu Sukhareva, E V Parfenova, M Yu Men'shikov
We studied the effect of urokinase, its recombinant forms, and domain fragments on migration and proliferation of adipose tissue mesenchymal stromal cells (MSCs) and MMP secretion by these cells. Urokinase, but not its recombinant forms, slightly induced directed migration of MSCs. Spontaneous migration of MSCs increased under the action of urokinase or its isolated kringle domain. Migration induced by platelet-derived growth factor was inhibited by proteolytically inactive form of urokinase, the kringle domain, and blocking antibody to urokinase receptor...
October 26, 2016: Bulletin of Experimental Biology and Medicine
Tobias Cohen, Toni M Schwarz, Frederic Vigant, Thomas J Gardner, Rosmel E Hernandez, Benhur Lee, Domenico Tortorella
Human cytomegalovirus is a ubiquitous β-herpesvirus that infects many different cell types through an initial binding to cell surface receptors followed by a fusion event at the cell membrane or endocytic vesicle. A recent high-throughput screen to identify compounds that block a step prior to viral gene expression identified podofilox as a potent and nontoxic inhibitor. Time-of-addition studies in combination with quantitative-PCR analysis demonstrated that podofilox limits an early step of virus entry at the cell surface...
October 24, 2016: Viruses
Charanya Sampathkumar, Yuan-Ju Wu, Mayur Vadhvani, Thorsten Trimbuch, Britta Eickholt, Christian Rosenmund
Mutations in the MECP2 gene cause the neurodevelopmental disorder Rett syndrome (RTT). Previous studies have shown that altered MeCP2 levels result in aberrant neurite outgrowth and glutamatergic synapse formation. However, causal molecular mechanisms are not well understood since MeCP2 is known to regulate transcription of a wide range of target genes. Here, we describe a key role for a constitutive BDNF feed forward signaling pathway in regulating synaptic response, general growth and differentiation of glutamatergic neurons...
October 26, 2016: ELife
Karina K Kedzior, Eileen Wehmann, Mathew Martin-Iverson
BACKGROUND: Cannabis use is associated with an attention-dependent deficit in prepulse inhibition of the startle reflex (PPI). The aim of the current study was to investigate startle habituation in cannabis users and healthy controls during two attentional tasks. METHODS: Auditory startle reflex was recorded from orbicularis oculi muscle while participants (12 controls and 16 regular cannabis users) were either attending to or ignoring 100 dB startling pulses. Startle habituation was measured as the absolute reduction in startle magnitude on block 2 (last nine trials) vs...
October 26, 2016: BMC Psychology
Ronan F O'Toole, Shakti D Shukla, Eugene H Walters
Expression of the platelet-activating factor receptor is upregulated in the respiratory epithelium of smokers and chronic obstructive pulmonary disease patients. We have recently determined that increased expression of PAFr correlates with higher levels of adhesion to human bronchial epithelial cells by non-typable Haemophilus influenzae and Streptococcus pneumoniae which are major bacterial pathogens in acute exacerbations of COPD. In addition, we found that a PAFr antagonist decreased the adhesion of both respiratory bacterial pathogens to non-cigarette exposure control levels...
October 26, 2016: Journal of Translational Medicine
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