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https://www.readbyqxmd.com/read/29458203/precision-pharmacology-for-alzheimer-s-disease
#1
REVIEW
Harald Hampel, Andrea Vergallo, Lisi Flores Aguilar, Norbert Benda, Karl Broich, A Claudio Cuello, Jeffrey Cummings, Bruno Dubois, Howard J Federoff, Massimo Fiandaca, Remy Genthon, Marion Haberkamp, Eric Karran, Mark Mapstone, George Perry, Lon S Schneider, Lindsay A Welikovitch, Janet Woodcock, Filippo Baldacci, Simone Lista
The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses...
February 16, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29458004/real-time-analysis-of-cleavage-and-religation-activity-of-human-topoisomerase-1-based-on-ternary-fluorescence-resonance-energy-transfer-dna-substrate
#2
Zhenxing Wang, Hui Ouyang, Cinzia Tesauro, Alessio Ottaviani, Yong He, Paola Fiorani, Hui Xie, Alessandro Desideri, Zhifeng Fu
Human topoisomerase 1B is a ubiquitous and essential enzyme involved in relaxing the topological state of supercoiled DNA to allow the progression of fundamental DNA metabolism. Its enzymatic catalytic cycle consists of cleavage and religation reaction. A ternary fluorescence resonance energy transfer biosensor based on a suicide DNA substrate conjugated with three fluorophores has been developed to monitor both cleavage and religation Topoisomerase I catalytic function. The presence of fluorophores does not alter the specificity of the enzyme catalysis on the DNA substrate...
February 16, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29457783/cellular-senescence-in-brain-aging-and-neurodegenerative-diseases-evidence-and-perspectives
#3
Darren J Baker, Ronald C Petersen
Along with a general decline in overall health, most chronic degenerative human diseases are inherently associated with increasing age. Age-associated cognitive impairments and neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases, are potentially debilitating conditions that lack viable options for treatment, resulting in a tremendous economic and societal cost. Most high-profile clinical trials for neurodegenerative diseases have led to inefficacious results, suggesting that novel approaches to treating these pathologies are needed...
February 19, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29457758/appraising-cervical-mucus-a-new-approach-to-evaluating-contraceptives
#4
Leo Han, Emily Padua, Alison Edelman, Jeffrey T Jensen
PURPOSE: Timing of sample collection represents a major source of variability in studies evaluating the effects of administered agents on cervical mucus in naturally-cycling women. We sought to create and validate an artificial model of the cervical mucus cycle using exogenous E2 and P4 replacement in ovarian suppressed women. MATERIALS AND METHODS: We conducted a prospective experiment (clinicaltrials.gov, NCT02969590) examining cervical mucus changes in six women during natural and artificial menstrual cycles [leuprolide acetate, estradiol transdermal patch (0...
February 19, 2018: European Journal of Contraception & Reproductive Health Care
https://www.readbyqxmd.com/read/29457722/spatially-and-temporally-resolved-detection-of-arsenic-in-a-capillary-dbd-by-hydride-generation-high-resolved-optical-emission-spectrometry
#5
Sebastian Burhenn, Jan Kratzer, Milan Svoboda, Felix David Klute, Antje Michels, Damir Veza, Joachim Franzke
A new method for arsenic detection by optical emission spectrometry (OES) is presented. Arsine (AsH3) is generated from liquid solutions by means of hydride generation (HG) and introduced into a capillary dielectric barrier discharge (DBD) where it is atomized and excited. A great challenge in OES is the reduction of the recorded background signal because it negatively affects the limit of detection (LOD). In conventional DBD-OES methods the signal intensity of the line of interest, in this case arsenic, is integrated over a long timescale...
February 19, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29457707/peripheral-neurostimulation-breaks-the-shuffling-steps-patterns-in-parkinsonian-gait-a-double-blind-randomized-longitudinal-study-with-automated-mechanical-peripheral-stimulation
#6
Manuela Galli, Caterina Vicidomini, Ana F Rozin Kleiner, Laura Vacca, Veronica Cimolin, Claudia Condoluci, Fabrizio Stocchi, Maria F DE Pandis
BACKGROUND: The shuffling steps pattern is a typical feature of gait in patients affected by Parkinson's Disease (PD), which progressively reduces their quality of life, being related to the risk of falls in this population. Recently, Automated Mechanical Peripheral Stimulation (AMPS) was presented as an integrative rehabilitative treatment based on peripheral stimulation able to improve the gait spatiotemporal parameters in PD patients. AIM: To evaluate the effects of AMPS on shuffling steps pattern by analyzing the kinematic and spatio-temporal gait parameters...
February 19, 2018: European Journal of Physical and Rehabilitation Medicine
https://www.readbyqxmd.com/read/29457354/nitrogen-enriched-carbon-cnt-composites-based-on-schiff-base-networks-ultrahigh-n-content-and-enhanced-lithium-storage-properties
#7
Zhichang Xiao, Qi Song, Ruiying Guo, Debin Kong, Shanke Zhou, Xiaoxiong Huang, Rashid Iqbal, Linjie Zhi
To improve the electrochemical performance of carbonaceous anodes for lithium ion batteries (LIBs), the incorporation of both well-defined heteroatom species and the controllable 3D porous networks are urgently required. In this work, a novel N-enriched carbon/carbon nanotube composite (NEC/CNT) through a chemically induced precursor-controlled pyrolysis approach is developed. Instead of conventional N-containing sources or precursors, Schiff-base network (SNW-1) enables the desirable combination of a 3D polymer with intrinsic microporosity and ultrahigh N-content, which can significantly promote the fast transport of both Li+ and electron...
February 19, 2018: Small
https://www.readbyqxmd.com/read/29457297/the-impact-of-bacteriophages-on-phyllosphere-bacterial-abundance-and-composition
#8
Norma M Morella, Annika L Gomez, Grant Wang, Michelle S Leung, Britt Koskella
Interactions between bacteria and bacteriophage viruses (phages) are known to influence pathogen growth and virulence, microbial diversity, and even biogeochemical cycling. Lytic phages in particular infect and lyse their host cells, and can therefore have significant effects on cell densities as well as competitive dynamics within microbial communities. Despite the known impacts of lytic phages on the ecology and evolution of bacteria in free-living communities, little is known about the role of lytic phages in host-associated microbiomes...
February 19, 2018: Molecular Ecology
https://www.readbyqxmd.com/read/29457204/prevention-and-management-of-childhood-obesity
#9
Aashima Dabas, Anju Seth
Childhood obesity has been recognized as a global pandemic. Preventive strategies have proven to be the most effective public health intervention in curbing this pandemic. A multi-component approach involving dietary modification and advocacy for a healthy lifestyle comprising of regular physical activity, minimizing screen time and behavioral interventions have been found beneficial in preventing obesity. A life-cycle approach has been recommended where preventive interventions go as far back as affecting maternal, fetal and early childhood nutrition and lifestyle...
February 19, 2018: Indian Journal of Pediatrics
https://www.readbyqxmd.com/read/29455888/identification-of-process-transfer-function-parameters-in-event-based-pi-control-loops
#10
J Sánchez, M Guinaldo, A Visioli, S Dormido
This paper presents a method to estimate the parameters of first and second order systems with time delays with different accuracy levels for autotuning of event-based PI control loops. In particular, the event-based sampling condition applied in this work is based on the sampling strategy known as symmetric-send-on-delta (SSOD). The method is based on forcing the system to enter into a limit cycle and on using the information achieved from the oscillation to estimate the transfer function parameters. By manipulating the PI controller, the system can reach different limit cycles as a consequence of the intersections of the Nyquist map of the process with the describing function reciprocal of the event-based sampler...
February 15, 2018: ISA Transactions
https://www.readbyqxmd.com/read/29455660/the-relevance-of-tyrosine-kinase-inhibitors-for-global-metabolic-pathways-in-cancer
#11
REVIEW
Michaela Poliaková, Daniel M Aebersold, Yitzhak Zimmer, Michaela Medová
Tumor metabolism is a thrilling discipline that focuses on mechanisms used by cancer cells to earn crucial building blocks and energy to preserve growth and overcome resistance to various treatment modalities. At the same time, therapies directed specifically against aberrant signalling pathways driven by protein tyrosine kinases (TKs) involved in proliferation, metastasis and growth count for several years to promising anti-cancer approaches. In this respect, small molecule inhibitors are the most widely used clinically relevant means for targeted therapy, with a rising number of approvals for TKs inhibitors...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455527/mechanical-division-of-cell-sized-liposomes
#12
Siddharth Deshpande, Willem Kasper Spoelstra, Marleen van Doorn, Jacob Kerssemakers, Cees Dekker
Liposomes, self-assembled vesicles with a lipid-bilayer boundary similar to cell membranes, are extensively used in both fundamental and applied sciences. Manipulation of their physical properties, such as growth and division, may significantly expand their use as model systems in cellular and synthetic biology. Several approaches have been explored to controllably divide liposomes, such as shape transformation through temperature cycling, incorporation of additional lipids, and the encapsulation of protein division machinery...
February 18, 2018: ACS Nano
https://www.readbyqxmd.com/read/29455101/does-pedicle-screw-fixation-of-the-subaxial-cervical-spine-provide-adequate-stabilization-in-a-multilevel-vertebral-body-fracture-model-an-in-vitro-biomechanical-study
#13
John Duff, Mir M Hussain, Noelle Klocke, Jonathan A Harris, Soumya S Yandamuri, Lukas Bobinski, Roy T Daniel, Brandon S Bucklen
BACKGROUND: Cervical vertebral body fractures generally are treated through an anterior-posterior approach. Cervical pedicle screws offer an alternative to circumferential fixation. This biomechanical study quantifies whether cervical pedicle screws alone can restore the stability of a three-column vertebral body fracture, making standard 360° reconstruction unnecessary. METHODS: Range of motion (2.0 Nm) in flexion-extension, lateral bending, and axial rotation was tested on 10 cadaveric specimens (five/group) at C2-T1 with a spine kinematics simulator...
February 14, 2018: Clinical Biomechanics
https://www.readbyqxmd.com/read/29453691/effect-of-phosphorylation-and-single-nucleotide-polymorphisms-on-caspase-substrates-processing
#14
Sonu Kumar, Piotr Cieplak
Posttranslational modifications that involve either reversible covalent modification of proteins or irreversible proteolysis are central to the regulation of key cellular mechanisms, including apoptosis, cell-cycle regulation and signal transduction. There is mounting evidence suggesting cross-talk between proteases and kinases. For instance: caspases, a class of proteases involved in programmed cell death-apoptosis, cleave a large set of various types of proteins. Simultaneously, kinases restrict caspase activity by phosphorylating their protein substrates in the vicinity of cleavage site...
February 16, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29453268/high-microbial-diversity-promotes-soil-ecosystem-functioning
#15
Pierre-Alain Maron, Amadou Sarr, Aurore Kaisermann, Jean Lévêque, Olivier Mathieu, Julien Guigue, Battle Karimi, Laetitia Bernard, Samuel Dequiedt, Sébastien Terrat, Abad Chabbi, Lionel Ranjard
In soil, the link between microbial diversity and carbon transformations is challenged by the concept of functional redundancy. Here, we hypothesized that functional redundancy may decrease with increasing carbon source recalcitrance, and that coupling of diversity with C-cycling may change accordingly. We manipulated microbial diversity to examine how diversity decrease affects the decomposition of easily degradable ( i.e. allochthonous plant residues) vs. recalcitrant ( i.e. autochthonous organic matter) C-sources...
February 16, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29452776/women-specific-risk-factors-for-heart-failure-a-genetic-approach
#16
REVIEW
Jet van der Kemp, Yvonne T van der Schouw, Folkert W Asselbergs, N Charlotte Onland-Moret
Heart failure is a complex disease, which is presented differently by men and women. Several studies have shown that reproductive factors, such as age at natural menopause, parity and polycystic ovarian syndrome (PCOS), may play a role in the development of heart failure. Shared genetics may provide clues to underlying mechanisms; however, this has never been examined. Therefore, the aim of the current study was to explore whether any reproductive factor is potentially related to heart failure in women, based on genetic similarities...
March 2018: Maturitas
https://www.readbyqxmd.com/read/29452575/a-machine-learning-approach-to-detect-changes-in-gait-parameters-following-a-fatiguing-occupational-task
#17
Amir Baghdadi, Fadel M Megahed, Ehsan T Esfahani, Lora A Cavuoto
The purpose of this study is to provide a method for classifying non-fatigued versus fatigued states following manual material handling. A method of template matching pattern recognition for feature extraction (1$ Recognizer) along with the support vector machine (SVM) model for classification were applied on the kinematics of gait cycles segmented by our stepwise search-based segmentation algorithm. A single inertial measurement unit (IMU) on the ankle was used, providing a minimally intrusive and inexpensive tool for monitoring...
February 16, 2018: Ergonomics
https://www.readbyqxmd.com/read/29452422/asynchronous-and-pathological-windows-of-implantation-two-causes-of-recurrent-implantation-failure
#18
P Sebastian-Leon, N Garrido, J Remohí, A Pellicer, P Diaz-Gimeno
STUDY QUESTION: Is endometrial recurrent implantation failure (RIF) only a matter of an asynchronous (displaced) window of implantation (WOI), or could it also be a pathological (disrupted) WOI? SUMMARY ANSWER: Our predictive results demonstrate that both displaced and disrupted WOIs exist and can present independently or together in the same RIF patient. WHAT IS KNOWN ALREADY: Since 2002, many gene expression signatures associated with endometrial receptivity and RIF have been described...
February 14, 2018: Human Reproduction
https://www.readbyqxmd.com/read/29452241/raw-material-variability-of-an-active-pharmaceutical-ingredient-and-its-relevance-for-processability-in-secondary-continuous-pharmaceutical-manufacturing
#19
F Stauffer, V Vanhoorne, G Pilcer, P-F Chavez, S Rome, M A Schubert, L Aerts, T De Beer
Active Pharmaceutical Ingredients (API) raw material variability is not always thoroughly considered during pharmaceutical process development, mainly due to low quantities of drug substance available. However, synthesis, crystallization routes and production sites evolve during product development and product life cycle leading to changes in physical material attributes which can potentially affect their processability. Recent literature highlights the need for a global approach to understand the link between material synthesis, material variability, process and product quality...
February 13, 2018: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/29451908/cas9-mediated-excision-of-proximal-dnasei-h3k4me3-signatures-confers-robust-silencing-of-microrna-and-long-non-coding-rna-genes
#20
Harshavardhan Janga, Marina Aznaourova, Fabian Boldt, Katrin Damm, Arnold Grünweller, Leon N Schulte
CRISPR/Cas9-based approaches have greatly facilitated targeted genomic deletions. Contrary to coding genes however, which can be functionally knocked out by frame-shift mutagenesis, non-coding RNA (ncRNA) gene knockouts have remained challenging. Here we present a universal ncRNA knockout approach guided by epigenetic hallmarks, which enables robust gene silencing even in provisionally annotated gene loci. We build on previous work reporting the presence of overlapping histone H3 lysine 4 tri-methylation (H3K4me3) and DNaseI hypersensitivity sites around the transcriptional start sites of most genes...
2018: PloS One
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