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https://www.readbyqxmd.com/read/28735026/regulated-viral-bdnf-delivery-in-combination-with-schwann-cells-promotes-axonal-regeneration-through-capillary-alginate-hydrogels-after-spinal-cord-injury
#1
Shengwen Liu, Beatrice Sandner, Thomas Schackel, LaShae Nicholson, Abdelwahed Chtarto, Liliane Tenenbaum, Radhika Puttagunta, Rainer Müller, Norbert Weidner, Armin Blesch
Grafting of cell-seeded alginate capillary hydrogels into a spinal cord lesion site provides an axonal bridge while physically directing regenerating axonal growth in a linear pattern. However, without an additional growth stimulus, bridging axons fail to extend into the distal host spinal cord. Here we examined whether a combinatory strategy would support regeneration of descending axons across a cervical (C5) lateral hemisection lesion in the rat spinal cord. Following spinal cord transections, Schwann cell (SC)-seeded alginate hydrogels were grafted to the lesion site and AAV5 expressing brain-derived neurotrophic factor (BDNF) under control of a tetracycline-regulated promoter was injected caudally...
July 19, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28734709/worldwide-fracture-prediction
#2
Ghada El-Hajj Fuleihan, Marlene Chakhtoura, Jane A Cauley, Nariman Chamoun
The substantial increase in the burden of non-communicable diseases in general and osteoporosis in particular, necessitates the establishment of efficient and targeted diagnosis and treatment strategies. This chapter reviews and compares different tools for osteoporosis screening and diagnosis; it also provides an overview of different treatment guidelines adopted by countries worldwide. While access to dual-energy X-ray absorptiometry to measure bone mineral density (BMD) is limited in most areas in the world, the introduction of risk calculators that combine risk factors, with or without BMD, have resulted in a paradigm shift in osteoporosis screening and management...
July 19, 2017: Journal of Clinical Densitometry
https://www.readbyqxmd.com/read/28731690/the-metal-drives-the-chemistry-dual-functions-of-acireductone-dioxygenase
#3
Aditi R Deshpande, Thomas C Pochapsky, Dagmar Ringe
Acireductone dioxygenase (ARD) from the methionine salvage pathway (MSP) is a unique enzyme that exhibits dual chemistry determined solely by the identity of the divalent transition-metal ion (Fe(2+) or Ni(2+)) in the active site. The Fe(2+)-containing isozyme catalyzes the on-pathway reaction using substrates 1,2-dihydroxy-3-keto-5-methylthiopent-1-ene (acireductone) and dioxygen to generate formate and the ketoacid precursor of methionine, 2-keto-4-methylthiobutyrate, whereas the Ni(2+)-containing isozyme catalyzes an off-pathway shunt with the same substrates, generating methylthiopropionate, carbon monoxide, and formate...
July 21, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28728609/multiple-myeloma-can-be-accurately-diagnosed-in-acute-kidney-injury-patients-using-a-rapid-serum-free-light-chain-test
#4
Jennifer L J Heaney, John P Campbell, Punit Yadav, Ann E Griffin, Meena Shemar, Jennifer H Pinney, Mark T Drayson
BACKGROUND: Acute kidney injury (AKI) is common in patients with multiple myeloma (MM). Whether serum free light chain (sFLC) measurements can distinguish between myeloma and other causes of AKI requires confirmation to guide early treatment. A rapid and portable sFLC test (Seralite®) is newly available and could reduce delays in obtaining sFLC results and accelerate diagnosis in patients with unexplained AKI. This study evaluated the accuracy of Seralite® to identify MM as the cause of AKI...
July 20, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28726522/steerable-induction-of-the-thymosin-%C3%A3-4-mrtf-a-pathway-via-aav-based-overexpression-induces-therapeutic-neovascularization
#5
Tilman Ziegler, Markus Kraus, Wira Husada, Florian Gesenhues, Qui Jiang, Olaf Pinkenburg, Teresa Trenkwalder, Karl-Ludwig Laugwitz, Ferdinand le Noble, Christian Weber, Christian Kupatt, Rabea Hinkel
Viral vectors have been frequently used in a variety of preclinical animal models to deliver genetic constructs into tissues. Among the vectors used, adeno-associated viral vectors (AAVs) may be targeted to specific tissues, depending on the serotype used. Moreover, they show robust expression for prolonged periods of time and have a low immunogenic potential. Furthermore, AAVs, unlike other vector systems, only display a low rate of genomic integration. However, to ensure efficient transgene production, expression is typically driven by constitutively active promoters, such as the CMV promotor...
July 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28724435/ww-domain-binding-protein-2-an-adaptor-protein-closely-linked-to-the-development-of-breast-cancer
#6
REVIEW
Shuai Chen, Han Wang, Yu-Fan Huang, Ming-Li Li, Jiang-Hong Cheng, Peng Hu, Chuan-Hui Lu, Ya Zhang, Na Liu, Chi-Meng Tzeng, Zhi-Ming Zhang
The WW domain is composed of 38 to 40 semi-conserved amino acids shared with structural, regulatory, and signaling proteins. WW domain-binding protein 2 (WBP2), as a binding partner of WW domain protein, interacts with several WW-domain-containing proteins, such as Yes kinase-associated protein (Yap), paired box gene 8 (Pax8), WW-domain-containing transcription regulator protein 1 (TAZ), and WW-domain-containing oxidoreductase (WWOX) through its PPxY motifs within C-terminal region, and further triggers the downstream signaling pathway in vitro and in vivo...
July 19, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28719061/tailored-engineering-of-an-unusual-c4h9nh3-2-ch3nh3-2pb3br10-two-dimensional-multilayered-perovskite-ferroelectric-for-high-performance-photodetectors
#7
Junhua Luo, Lina Li, Zhihua Sun, Peng Wang, Weida Hu, Sasa Wang, Chengmin Ji, Maochun Hong
Two-dimensional (2D) layered hybrid perovskites have shown great potentials in optoelectronics. However, although great efforts have been made, 2D hybrid perovskite ferroelectrics remain rare. Here, we constructed the first ferroelectric with 2D multilayered perovskite framework, (C4H9NH3)2(CH3NH3)2Pb3Br10 (1), by tailored alloying mixed-organic-cations into the prototype of CH3NH3PbBr3. For the first time, concrete ferroelectricity was created by molecular reorientation and synergic ordering of organic cations, which is unprecedented for the known 2D hybrid perovskites...
July 18, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28719024/the-immunoproteasome-an-old-player-with-a-novel-and-emerging-role-in-alloimmunity
#8
S K Eskandari, M A J Seelen, G Lin, J R Azzi
Modern treatment strategies for the maintenance of allograft acceptance frequently target ubiquitously-expressed pathways, leading to significant side-effects and poor long-term allograft outcomes. Constitutive proteasome inhibitors, which have recently been introduced for the treatment of antibody-mediated rejection, target the ubiquitously-expressed proteasome. To limit off-target effects and serious mechanism-based toxicity, however, these inhibitors are administered intermittently and suboptimally. Immunoproteasomes, which are an inducible subset of proteasomes enriched in immune cells, replace constitutive proteasomes after cell exposure to proinflammatory cytokines such as interferon-γ...
July 18, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28717180/a-three-mirnas-signature-predicts-survival-in-cervical-cancer-using-bioinformatics-analysis
#9
Bin Liang, Yunhui Li, Tianjiao Wang
Growing evidences showed that a large number of miRNAs were abnormally expressed in cervical cancer tissues and played irreplaceable roles in tumorigenesis, progression and metastasis. The aim of the present study was to identify the differential miRNAs expression between cervical cancer and normal cervical tissues by analyzing the high-throughput miRNA data downloaded from TCGA database. Additionally, we evaluated the prognostic values of the differentially expressed miRNAs and constructed a three-miRNA signature that could effectively predict patient survival...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715957/the-transduction-cascade-in-retinal-on-bipolar-cells-signal-processing-and-disease
#10
Kirill A Martemyanov, Alapakkam P Sampath
Our robust visual experience is based on the reliable transfer of information from our photoreceptor cells, the rods and cones, to higher brain centers. At the very first synapse of the visual system, information is split into two separate pathways, ON and OFF, which encode increments and decrements in light intensity, respectively. The importance of this segregation is borne out in the fact that receptive fields in higher visual centers maintain a separation between ON and OFF regions. In the past decade, the molecular mechanisms underlying the generation of ON signals have been identified, which is unique in its use of a G-protein signaling cascade...
July 17, 2017: Annual Review of Vision Science
https://www.readbyqxmd.com/read/28715764/ddt-related-compounds-as-non-extractable-residues-in-submarine-sediments-of-the-palos-verdes-shelf-california-usa
#11
S Kucher, J Schwarzbauer
The Palos Verdes Shelf (PVS) and the continental slope off the Palos Verdes Peninsula are highly contaminated by degradation products of the pesticide DDT (1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene). Sediment samples from two box cores were analyzed to obtain further information about the fate of DDT and its degradation products within the environment. After solvent extraction, an alkaline hydrolysis procedure was applied. A comprehensive screening for 26 DDT compounds revealed that DDT and its degradates contaminate not only the extractable fraction but also the fraction released by alkaline hydrolysis...
July 10, 2017: Chemosphere
https://www.readbyqxmd.com/read/28715649/excellent-response-to-anti-pd-1-therapy-in-a-patient-with-hepatocellular-carcinoma-case-report-and-review-of-literature
#12
Hirva Mamdani, Howard Wu, Bert H O'Neil, Amikar Sehdev
Hepatocellular carcinoma (HCC) is an aggressive cancer associated with high mortality worldwide. HCC develops in the setting of underlying cirrhosis due to chronic liver disease. Surgery is usually considered the treatment of choice for early disease; however, most patients have locally advanced or metastatic HCC at diagnosis in which case treatments are limited. Immune checkpoint blockade of programmed death receptor-1 (PD-1) pathway offers a potential treatment strategy based on the encouraging results of the phase I/II trial of nivolumab (Checkmate 040 trial)...
May 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28713682/predictive-biomarkers-of-immunotherapy-for-non-small-cell-lung-cancer-results-from-an-experts-panel-meeting-of-the-italian-association-of-thoracic-oncology
#13
REVIEW
Cesare Gridelli, Andrea Ardizzoni, Massimo Barberis, Federico Cappuzzo, Francesca Casaluce, Romano Danesi, Giancarlo Troncone, Filippo De Marinis
Unleashing the potential of immune system to fight cancer has become one of the main promising treatment modalities for advanced non-small cell lung cancer (NSCLC). The knowledge of numerous factors that come into play in the cancer-immunity cycle provide a wide range of potential therapeutic targets, including monoclonal antibodies that inhibits the programmed death-1 (PD-1) checkpoint pathway. Over the last two years, nivolumab, pembrolizumab and atezolizumab received approval for treatment of pretreated advanced NSCLC, and more recently, immunotherapy with pembrolizumab is the new standard of care as first-line in patients with high levels of programmed death-ligand 1 (PD-L1) expression...
June 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28711737/subthalamic-deep-brain-stimulation-sweet-spots-and-hyperdirect-cortical-connectivity-in-parkinson-s-disease
#14
Harith Akram, Stamatios N Sotiropoulos, Saad Jbabdi, Dejan Georgiev, Philipp Mahlknecht, Jonathan Hyam, Thomas Foltynie, Patricia Limousin, Enrico De Vita, Marjan Jahanshahi, Marwan Hariz, John Ashburner, Tim Behrens, Ludvic Zrinzo
OBJECTIVES: Firstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy. METHODS: High angular resolution diffusion imaging in twenty patients with advanced Parkinson's disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation...
July 12, 2017: NeuroImage
https://www.readbyqxmd.com/read/28711146/drug-repositioning-strategies-for-the-identification-of-novel-therapies-for-rheumatic-autoimmune-inflammatory-diseases
#15
REVIEW
Amrie C Grammer, Peter E Lipsky
Rheumatic Autoimmune Inflammatory Diseases such as Sjögren's and lupus lack modern treatments. Less than 5% of drugs approved by the FDA from 2014 to mid-2016 had a RAID indication. Many RAID standard-of-care drugs were repurposed based on serendipitous observations, similarity-of-disease categorization, and/or off-target effects. Recently, drug repurposing has become more intentional, relying on an evolving awareness of molecular underpinnings, as well as a better understanding of drug-target interactions by computational modeling...
August 2017: Rheumatic Diseases Clinics of North America
https://www.readbyqxmd.com/read/28710275/a-ph-dependent-switch-promotes-%C3%AE-synuclein-fibril-formation-via-glutamate-residues
#16
Gina M Moriarty, Michael P Olson, Tamr B Atieh, Maria K Janowska, Sagar D Khare, Jean Baum
Alpha-synuclein (αS) is the primary protein associated with Parkinson's disease, and undergoes aggregation from its intrinsically disordered monomeric form to a cross-β fibrillar form. The closely related homolog beta-synuclein (βS) is essentially fibril resistant under cytoplasmic physiological conditions. Toxic gain of function by βS has been linked to dysfunction, but the aggregation behavior of βS under altered pH is not well understood. In this work, we compare fibril formation of αS and βS at pH 7...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28709498/targeting-fyn-kinase-in-alzheimer-s-disease
#17
REVIEW
Haakon B Nygaard
The past decade has brought tremendous progress in unraveling the pathophysiology of Alzheimer's disease (AD). While increasingly sophisticated immunotherapy targeting soluble and aggregated brain amyloid-beta (Aβ) continues to dominate clinical research in AD, a deeper understanding of Aβ physiology has led to the recognition of distinct neuronal signaling pathways linking Aβ to synaptotoxicity and neurodegeneration and to new targets for therapeutic intervention. Identifying specific signaling pathways involving Aβ has allowed for the development of more precise therapeutic interventions targeting the most relevant molecular mechanisms leading to AD...
June 13, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28709319/golf-course-and-funnel-energy-landscapes-protein-folding-concepts-in-martensites
#18
N Shankaraiah
We use protein folding energy landscape concepts such as golf course and funnel to study re-equilibration in athermal martensites under systematic temperature quench Monte Carlo simulations. On quenching below a transition temperature, the seeded high-symmetry parent-phase austenite that converts to the low-symmetry product-phase martensite, through autocatalytic twinning or elastic photocopying, has both rapid conversions and incubation delays in the temperature-time-transformation phase diagram. We find the rapid (incubation delays) conversions at low (high) temperatures arises from the presence of large (small) size of golf-course edge that has the funnel inside for negative energy states...
June 2017: Physical Review. E
https://www.readbyqxmd.com/read/28709293/fluorescence-correlation-spectroscopy-experiments-to-quantify-free-diffusion-coefficients-in-reaction-diffusion-systems-the-case-of-ca-2-and-its-dyes
#19
Lorena Sigaut, Cecilia Villarruel, María Laura Ponce, Silvina Ponce Dawson
Many cell signaling pathways involve the diffusion of messengers that bind and unbind to and from intracellular components. Quantifying their net transport rate under different conditions then requires having separate estimates of their free diffusion coefficient and binding or unbinding rates. In this paper, we show how performing sets of fluorescence correlation spectroscopy (FCS) experiments under different conditions, it is possible to quantify free diffusion coefficients and on and off rates of reaction-diffusion systems...
June 2017: Physical Review. E
https://www.readbyqxmd.com/read/28706179/nilotinib-induced-recurrent-gastric-polyps-case-report-and-review-of-literature
#20
Nancy Kassem, Omar M Ismail, Halima Elomri, Mohamad A Yassin
BACKGROUND Tyrosine kinase inhibitors (TKIs) are currently an important targeted drug class in the treatment of chronic myeloid leukemia (CML). Imatinib was the first approved TKI for CML in 2001. Nilotinib is a second-generation TKI, approved in 2007; it inhibits BCR-ABL, PDGFR, and c-KIT, and is 30 times more potent than imatinib. Tyrosine kinase enzymes are expressed in multiple tissues and are involved in several signaling pathways; they have been shown to have several off-target side effects. CASE REPORT We report a case of an elderly male with CML and no history of gastrointestinal diseases, treated with nilotinib, and developed recurrent gastric polyps after three years of treatment...
July 14, 2017: American Journal of Case Reports
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