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https://www.readbyqxmd.com/read/29454290/ligand-based-computer-aided-drug-design-reveals-new-tropomycin-receptor-kinase-a-trka-inhibitors
#1
Rand Shahin, Iman Mansi, Lubna Swellmeen, Tahani Alwidyan, Nabil Al-Hashimi, Yaser Al-Qarar'h, Omar Shaheen
Targeting tropomycin kinase A (TrkA) by small molecule inhibitors is considered as a promising strategy for treating several human cancers. To achieve this goal, a ligand based QSAR model was applied using the Discovery studio 4.5 (DS 4.5). Hence, a total list of 161 TrkA inhibitors was investigated. The TrkA inhibitors were extensively explored to detect their optimal physicochemical properties and pharmacophoric binding modes, which were converted into numeric descriptors and allowed to compete within the context of the Genetic Function Algorithm (GFA) approximations to find the subset of terms that correlates best with the activity...
January 13, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29453841/beyond-cost-benefit-analysis-in-the-governance-of-synthetic-biology
#2
Wendell Wallach, Marc Saner, Gary Marchant
For many innovations, oversight fits nicely within existing governance mechanisms; nevertheless, others pose unique public health, environmental, and ethical challenges. Synthetic artemisinin, for example, has many precursors in laboratory-developed drugs that emulate natural forms of the same drug. The policy challenges posed by synthetic artemisinin do not differ significantly in kind from other laboratory-formulated drugs. Synthetic biofuels and gene drives, however, fit less clearly into existing governance structures...
January 2018: Hastings Center Report
https://www.readbyqxmd.com/read/29453822/full-genome-sequencing-of-porcine-circovirus-3-field-strains-from-denmark-italy-and-spain-demonstrates-a-high-within-europe-genetic-heterogeneity
#3
G Franzo, M Legnardi, C K Hjulsager, F Klaumann, L E Larsen, J Segales, M Drigo
Porcine circovirus 3 (PCV3) is a new species of the Circovirus genus, which has recently been associated with different clinical syndromes. Its presence has been reported in different countries of North and South America, Asia and recently also Europe (Poland). However, different from the other continents, no European PCV3 sequence is currently available in public databases. There is a strong need of epidemiological data and full-genome sequences from Europe because of its relevance in the understanding of PCV3 molecular epidemiology and control...
February 16, 2018: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/29453689/sustained-sensorimotor-control-as-intermittent-decisions-about-prediction-errors-computational-framework-and-application-to-ground-vehicle-steering
#4
Gustav Markkula, Erwin Boer, Richard Romano, Natasha Merat
A conceptual and computational framework is proposed for modelling of human sensorimotor control and is exemplified for the sensorimotor task of steering a car. The framework emphasises control intermittency and extends on existing models by suggesting that the nervous system implements intermittent control using a combination of (1) motor primitives, (2) prediction of sensory outcomes of motor actions, and (3) evidence accumulation of prediction errors. It is shown that approximate but useful sensory predictions in the intermittent control context can be constructed without detailed forward models, as a superposition of simple prediction primitives, resembling neurobiologically observed corollary discharges...
February 16, 2018: Biological Cybernetics
https://www.readbyqxmd.com/read/29453517/probable-diagnosis-of-a-patient-with-niemann-pick-disease-type-c-managing-pitfalls-of-exome-sequencing
#5
William A Zeiger, Nasheed I Jamal, Maren T Scheuner, Patricia Pittman, Kimiyo M Raymond, Massimo Morra, Shri K Mishra
Here, we present a case of a 31-year-old man with progressive cognitive decline, ataxia, and dystonia. Extensive laboratory, radiographic, and targeted genetic studies over the course of several years failed to yield a diagnosis. Initial whole exome sequencing through a commercial laboratory identified several variants of uncertain significance; however, follow-up clinical examination and testing ruled each of these out. Eventually, repeat whole exome sequencing identified a known pathogenic intronic variant in the NPC1 gene (NM_000271...
February 17, 2018: JIMD Reports
https://www.readbyqxmd.com/read/29453392/a-novel-flatworm-specific-gene-implicated-in-reproduction-in-macrostomum-lignano
#6
Magda Grudniewska, Stijn Mouton, Margriet Grelling, Anouk H G Wolters, Jeroen Kuipers, Ben N G Giepmans, Eugene Berezikov
Free-living flatworms, such as the planarian Schmidtea mediterranea, are extensively used as model organisms to study stem cells and regeneration. The majority of flatworm studies so far focused on broadly conserved genes. However, investigating what makes these animals different is equally informative for understanding its biology and might have biomedical value. We re-analyzed the neoblast and germline transcriptional signatures of the flatworm M. lignano using an improved transcriptome assembly and show that germline-enriched genes have a high fraction of flatworm-specific genes...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453263/enzyme-activities-of-two-recombinant-heme-including-peroxidases-tv-dyp1-and-tv-vp2-identified-from-the-secretome-of-trametes-versicolor
#7
Sawsan Amara, Thomas Perrot, David Navarro, Aurélie Deroy, Amine Benkhelfallah, Amani Chalak, Marianne Daou, Didier Chevret, Craig B Faulds, Jean Guy Berrin, Mélanie Morel-Rouhier, Eric Gelhaye, Eric Record
Trametes versicolor is a wood inhabiting Agaricomycete known for its ability to cause strong white rot decay on hardwood and for its high tolerance toward phenolic compounds. The goal of the present work was to give insights on the molecular biology and biochemistry of heme-including class-II and dye-decolorizing peroxidases secreted from this fungus. Proteomic analysis of the secretome of T. versicolor BRFM1218 grown on oak wood revealed a set of 200 secreted proteins among which were a dye-decolorizing peroxidase Tv DyP1 and a versatile peroxidase Tv VP2...
February 16, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29453171/finger-strength-individuation-and-their-interaction-relationship-to-hand-function-and-corticospinal-tract-injury-after-stroke
#8
Eric T Wolbrecht, Justin B Rowe, Vicky Chan, Morgan L Ingemanson, Steven C Cramer, David J Reinkensmeyer
OBJECTIVE: The goal of this study was to determine the relative contributions of finger weakness and reduced finger individuation to reduced hand function after stroke, and their association with corticospinal tract (CST) injury. METHODS: We measured individuated and synergistic maximum voluntary contractions (MVCs) of the index and middle fingers, in both flexion and extension, of 26 individuals with a chronic stroke using a robotic exoskeleton. We quantified finger strength and individuation, and defined a novel metric that combines them - "multifinger capacity"...
February 3, 2018: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/29452987/cell-therapy-for-peripheral-artery-disease
#9
REVIEW
Nikolaos G Frangogiannis
Patients with severe peripheral artery disease (PAD) who are not candidates for revascularization have poor prognosis. Cell therapy using peripheral blood-derived or bone marrow-derived mononuclear cells, mesenchymal stem cells, or marker-specific subsets of bone marrow cells with angiogenic properties may hold promise for no-option PAD patients. Injected cells may exert beneficial actions by enhancing local angiogenesis (either through maturation of endothelial progenitors, or through secretion of angiogenic mediators), or by transducing cytoprotective signals that preserve tissue structure...
February 13, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29452778/reproductive-history-and-physical-functioning-in-midlife-the-bogalusa-heart-study
#10
Emily W Harville, Wei Chen, Jack Guralnik, Lydia A Bazzano
OBJECTIVE: To examine the relationship between reproductive history, pregnancy complications, and later physical function. STUDY DESIGN: The Bogalusa Heart Study is a long-running study of cardiovascular health in a semirural community. 761 women were interviewed about their pregnancy history and complications, and underwent tests of physical function. Logistic models for dichotomous outcomes and linear models for continuous outcomes were used, adjusted for covariates...
March 2018: Maturitas
https://www.readbyqxmd.com/read/29452340/congenital-abnormalities-of-the-male-reproductive-system-and-risk-of-autism-spectrum-disorders
#11
Ran S Rotem, Gabriel Chodick, Michael Davidovitch, Russ Hauser, Brent A Coull, Marc G Weisskopf
Androgens have an extensive influence on brain development in regions of the brain that are relevant for autism spectrum disorder (ASD), yet their etiological involvement remains unclear. Hypospadias (abnormal positioning of the urethral opening) and cryptorchidism (undescended testes) are 2 relatively common male birth defects that are strongly associated with prenatal androgen deficiencies. Having either disorder is a proxy indicator of atypical gestational androgen exposure, yet the association between these disorders and autism has not been extensively studied...
February 14, 2018: American Journal of Epidemiology
https://www.readbyqxmd.com/read/29452156/establishment-of-a-prkag2-cardiac-syndrome-disease-model-and-mechanism-study-using-human-induced-pluripotent-stem-cells
#12
Yongkun Zhan, Xiaolei Sun, Bin Li, Huanhuan Cai, Chen Xu, Qianqian Liang, Chao Lu, Ruizhe Qian, Sifeng Chen, Lianhua Yin, Wei Sheng, Guoying Huang, Aijun Sun, Junbo Ge, Ning Sun
PRKAG2 cardiac syndrome is a distinct form of human cardiomyopathy characterized by cardiac hypertrophy, ventricular pre-excitation and progressive cardiac conduction disorder. However, it remains unclear how mutations in the PRKAG2 gene give rise to such a complicated disease. To investigate the underlying molecular mechanisms, we generated disease-specific hiPSC-derived cardiomyocytes from two brothers both carrying a heterozygous missense mutation c.905G>A (R302Q) in the PRKAG2 gene and further corrected the R302Q mutation with CRISPR-Cas9 mediated genome editing...
February 13, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29451880/apolipoprotein-e-genotype-does-not-moderate-the-associations-of-depressive-symptoms-neuroticism-and-allostatic-load-with-cognitive-ability-and-cognitive-aging-in-the-lothian-birth-cohort-1936
#13
Zander Crook, Tom Booth, Simon R Cox, Janie Corley, Dominika Dykiert, Paul Redmond, Alison Pattie, Adele M Taylor, Sarah E Harris, John M Starr, Ian J Deary
OBJECTIVES: In this replication-and-extension study, we tested whether depressive symptoms, neuroticism, and allostatic load (multisystem physiological dysregulation) were related to lower baseline cognitive ability and greater subsequent cognitive decline in older adults, and whether these relationships were moderated by the E4 allele of the apolipoprotein E (APOE) gene. We also tested whether allostatic load mediated the relationships between neuroticism and cognitive outcomes. METHODS: We used data from the Lothian Birth Cohort 1936 (n at Waves 1-3: 1,028 [M age = 69...
2018: PloS One
https://www.readbyqxmd.com/read/29451436/novel-posterior-artificial-atlanto-odontoid-joint-for-atlantoaxial-instability-a-biomechanical-study
#14
Kai Shen, Zhongliang Deng, Junsong Yang, Chao Liu, Ranxi Zhang
OBJECTIVE Atlantoaxial instability is usually corrected by anterior and/or posterior C1-2 fusion. However, fusion can lead to considerable loss of movement at the C1-2 level, which can adversely impact a patient's quality of life. In this study, the authors investigated the stability and function of a novel posterior artificial atlanto-odontoid joint (NPAAJ) by using cadaveric cervical spines. METHODS The Oc-C7 regions from 10 cadaveric spines were used for anteroposterior (AP) translation and range of motion (ROM) tests while intact and after destabilization, NPAAJ implantation, and double-rod fixation...
February 16, 2018: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/29451287/computational-identification-of-the-binding-mechanism-of-a-triple-reuptake-inhibitor-amitifadine-for-the-treatment-of-major-depressive-disorder
#15
Weiwei Xue, Panpan Wang, Gao Tu, Fengyuan Yang, Guoxun Zheng, Xiaofeng Li, Xiaoxu Li, Yuzong Chen, Xiaojun Yao, Feng Zhu
Amitifadine, the only drug ever clinically tested in Phase 3 for treating depression, is a triple reuptake inhibitor (TRI) that simultaneously interacts with human monoamine transporters (MATs) including hSERT, hNET and hDAT. This novel multi-target strategy improves drug efficacy and reduces the toxic side effects of drugs. However, the binding modes accounting for amitifadine's polypharmacological mode of action are still elusive, and extensive exploration of the amitifadine-target interactions between amitifadine and MATs is urgently needed...
February 16, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29451214/optimization-of-micropatterned-poly-lactic-co-glycolic-acid-films-for-enhancing-dorsal-root-ganglion-cell-orientation-and-extension
#16
Ching-Wen Li, Brett Davis, Jill Shea, Himanshu Sant, Bruce Kent Gale, Jayant Agarwal
Nerve conduits have been a viable alternative to the 'gold standard' autograft for treating small peripheral nerve gap injuries. However, they often produce inadequate functional recovery outcomes and are ineffective in large gap injuries. Ridge/groove surface micropatterning has been shown to promote neural cell orientation and guide growth. However, optimization of the ratio of ridge/groove parameters to promote orientation and extension for dorsal root ganglion (DRG) cells on poly(lactic-co-glycolic acid) (PLGA) films has not been previously conducted...
January 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29450567/coronal-tibial-anteromedial-tunnel-location-has-minimal-effect-on-knee-biomechanics
#17
Shigehiro Asai, Donghwi Kim, Yuichi Hoshino, Chan-Woong Moon, Akira Maeyama, Monica Linde, Patrick Smolinski, Freddie H Fu
PURPOSE: Studies have found anatomic variation in the coronal position of the insertion site of anteromedial (AM) bundle of the anterior cruciate ligament (ACL) on the tibia, which can lead to questions about tunnel placement during ACL reconstruction. The purpose of this study was to determine how mediolateral placement of the tibial AM graft tunnel in double-bundle ACL reconstructions affects knee biomechanics. METHODS: Two different types of double-bundle ACL reconstructions were performed...
February 15, 2018: Knee Surgery, Sports Traumatology, Arthroscopy: Official Journal of the ESSKA
https://www.readbyqxmd.com/read/29450249/towards-an-understanding-of-self-directed-language-as-a-mechanism-of-behavior-change-a-novel-strategy-for-eliciting-client-language-under-laboratory-conditions
#18
Benjamin O Ladd, Tracey A Garcia, Kristen G Anderson
Introduction: Change talk (CT) and sustain talk (ST) are thought to reflect underlying motivation and be important mechanisms of behavior change (MOBCs). However, greater specificity and experimental rigor is needed to establish CT and ST as MOBCs. Testing the effects of self-directed language under laboratory conditions is one promising avenue. The current study presents a replication and extension of research examining the feasibility for using simulation tasks to elicit self-directed language...
June 2018: Addictive Behaviors Reports
https://www.readbyqxmd.com/read/29449679/tert-promoter-mutation-in-adult-granulosa-cell-tumor-of-the-ovary
#19
Jessica A Pilsworth, Dawn R Cochrane, Zhouchunyang Xia, Geraldine Aubert, Anniina E M Färkkilä, Hugo M Horlings, Satoshi Yanagida, Winnie Yang, Jamie L P Lim, Yi Kan Wang, Ali Bashashati, Jacqueline Keul, Adele Wong, Kevin Norris, Sara Y Brucker, Florin-Andrei Taran, Bernhard Krämer, Annette Staebler, Esther Oliva, Sohrab P Shah, Stefan Kommoss, Friedrich Kommoss, C Blake Gilks, Duncan M Baird, David G Huntsman
The telomerase reverse transcriptase (TERT) gene is highly expressed in stem cells and silenced upon differentiation. Cancer cells can attain immortality by activating TERT to maintain telomere length and telomerase activity, which is a crucial step of tumorigenesis. Two somatic mutations in the TERT promoter (C228T; C250T) have been identified as gain-of-function mutations that promote transcriptional activation of TERT in multiple cancers, such as melanoma and glioblastoma. A recent study investigating TERT promoter mutations in ovarian carcinomas found C228T and C250T mutations in 15...
February 15, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29449281/mri-features-of-aquaporin-4-antibody-positive-longitudinally-extensive-transverse-myelitis-insights-into-the-diagnosis-of-neuromyelitis-optica-spectrum-disorders
#20
C G Chee, K S Park, J W Lee, H W Ahn, E Lee, Y Kang, H S Kang
BACKGROUND AND PURPOSE: Longitudinally extensive transverse myelitis is a well-documented spinal manifestation of neuromyelitis optica spectrum disorders, however, other forms of nontumorous myelopathy can also manifest as longitudinally extensive transverse myelitis. Our aim was to evaluate the MR imaging features of aquaporin-4 antibody-positive longitudinally extensive transverse myelitis, which is strongly associated with neuromyelitis optica spectrum disorders. MATERIALS AND METHODS: We evaluated cervicomedullary junction involvement, cord expansion ratios, bright spotty lesions, the number of involved segments, skipped lesions, enhancement patterns, and axial distribution patterns using spinal MR imaging of 41 patients with longitudinally extensive transverse myelitis who underwent aquaporin-4 antibody testing...
February 15, 2018: AJNR. American Journal of Neuroradiology
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