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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/29458174/networks-that-link-cytoskeletal-regulators-and-diaphragm-proteins-underpin-filtration-function-in-drosophila-nephrocytes
#2
Simi Muraleedharan, Aksah Sam, Helen Skaer, Maneesha S Inamdar
Insect nephrocytes provide a valuable model for kidney disease, as they are structurally and functionally homologous to mammalian kidney podocytes. They possess an exceptional macromolecular assembly, the nephrocyte diaphragm (ND), which serves as a filtration barrier and helps maintain tissue homeostasis by filtering out wastes and toxic products. However, the elements that maintain nephrocyte architecture and the ND are not understood. We show that Drosophila nephrocytes have a unique cytoplasmic cluster of F-actin, which is maintained by the microtubule cytoskeleton and Rho-GTPases...
February 16, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29458171/toxicology-studies-of-furosine-in-vitro-in-vivo-and-exploration-of-the-related-mechanism
#3
Hui-Ying Li, Lei Xing, Jia-Qi Wang, Nan Zheng
AIM: Furosine is one of the Maillard reaction products (MRPs) and is found in a variety of heat-processed food. Yet its toxicity is still unclear. The present study was designed to assess furosine toxicity in cell models and in CD-1 mice, respectively. METHODS: In vitro, the effects of furosine on the cell viability, cell cycle and apoptosis (Hek293, HepG2, SK-N-SH and Caco2) were detected and evaluated, sensitive cell lines and proper dosage of furosine for further animal experiment were determined, and the mechanisms of toxicity were explored...
February 16, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29458165/a-microbial-identification-framework-for-risk-assessment
#4
Stéphane Bernatchez, Valar Anoop, Zeina Saikali, Marie Breton
Micro-organisms are increasingly used in a variety of products for commercial uses, including cleaning products. Such microbial-based cleaning products (MBCP) are represented as a more environmentally-friendly alternative to chemically based cleaning products. The identity of the micro-organisms formulated into these products is often considered confidential business information and is not revealed or it is only partly revealed (i.e., identification to the genus, not to the species). That paucity of information complicates the evaluation of the risk associated with their use...
February 16, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29458147/sessein-and-isosessein-with-anti-inflammatory-antibacterial-and-antioxidant-activity-isolated-from-salvia-sessei-benth
#5
Abraham Gómez-Rivera, Manasés González-Cortazar, Maribel Herrera-Ruíz, Alejandro Zamilpa, Verónica Rodríguez-López
ETHNOPHARMACOLOGICAL RELEVANCE: Salvia sessei Benth, popularly known as "pipilolxochitl" or "sabanito", is a plant utilized in Mexico in traditional medicine for the treatment of erysipela. To date, only one report, to our knowledge, has been found in which a royleanone-type diterpene of the aerial parts of the species was isolated but, again to our knowledge, studies have not been conducted on the pharmacological activity of extracts and compounds isolated from this plant...
February 16, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29458139/molecular-and-tissue-alterations-of-collagens-in-fibrosis
#6
REVIEW
Sylvie Ricard-Blum, Georges Baffet, Nathalie Théret
The collagen network is altered in fibrotic diseases associated with extracellular matrix (ECM) biosynthesis and remodeling. This mini-review focuses on the quantitative and qualitative modifications of collagens occurring at the molecular and tissue levels in fibrosis. They result from changes in collagen expression, biosynthesis, enzymatic cross-linking and degradation by several protease families. These molecular modifications, which are mostly regulated by TGF-β, are associated with altered collagen organization at the tissue level, leading to a fibrotic signature that can be analyzed by Second Harmonic Generation (SHG) microscopy...
February 16, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29458126/structural-and-mechanistic-analysis-of-the-choline-sulfatase-from-sinorhizobium-melliloti-a-class-i-sulfatase-specific-for-an-alkyl-sulfate-ester
#7
Bert van Loo, Markus Schober, Eugene Valkov, Magdalena Heberlein, Erich Bornberg-Bauer, Kurt Faber, Marko Hyvönen, Florian Hollfelder
Hydrolysis of organic sulfate esters proceeds by two distinct mechanisms, water attacking at either sulfur (S-O bond cleavage) or carbon (C-O bond cleavage). In primary and secondary alkyl sulfates attack at carbon is favored, whereas in aromatic sulfates and sulfated sugars attack at sulfur is preferred. This mechanistic distinction is mirrored in the classification of enzymes that catalyze sulfate ester hydrolysis: arylsulfatases catalyze S-O cleavage in sulfate sugars and arylsulfates and alkyl sulfatases break the C-O bond of alkyl sulfates...
February 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29458112/compatible-osmolytes-modulate-mitochondrial-function-in-a-marine-osmoconformer-crassostrea-gigas-thunberg-1793
#8
Eugene P Sokolov, Inna M Sokolova
Salinity is an important environmental factor affecting physiology of marine organisms. Osmoconformers such as marine mollusks maintain metabolic function despite changes of the osmolarity and composition of the cytosol during salinity shifts. Currently, metabolic responses to the salinity-induced changes of the intracellular milieu are not well understood. We studied the effects of osmolarity (450 vs. 900 mOsm) and compatible osmolytes (70-590 mM of taurine or betaine) on isolated gill mitochondria of a marine osmoconformer, the Pacific oyster Crassostrea gigas...
February 16, 2018: Mitochondrion
https://www.readbyqxmd.com/read/29458109/modulation-of-cyp1a1-metabolism-from-adverse-health-effects-to-chemoprevention-and-therapeutic-options
#9
Melina Mescher, Thomas Haarmann-Stemmann
The human cytochrome P450 (CYP) 1A1 gene encodes a monooxygenase that metabolizes multiple exogenous and endogenous substrates. CYP1A1 has become infamous for its oxidative metabolism of benzo[a]pyrene and related polycyclic aromatic hydrocarbons, converting these chemicals into very potent human carcinogens. CYP1A1 expression is mainly controlled by the aryl hydrocarbon receptor (AHR), a transcription factor whose activation is induced by binding of persistent organic pollutants, including polycyclic aromatic hydrocarbons and dioxins...
February 16, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29458106/combi-metal-organic-framework-combi-mof-of-%C3%AE-amylase-and-glucoamylase-for-one-pot-starch-hydrolysis
#10
Manish Salgaonkar, Shamraja S Nadar, Virendra K Rathod
The multi-enzyme biocatalyst allows to run in vitro multi-step cascade reactions in a single pot. An efficient combi-metal organic frameworks (combi-MOF) of α-amylase and glucoamylase for one pot starch hydrolysis was constructed by mixing zinc acetate and 2‑methylimmidazole with enzyme mixture in one pot under biocompatible conditions. The prepared combi-MOF was characterized and analyzed by powder X-ray diffraction (PXRD), Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM)...
February 16, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29458085/the-effect-of-surface-charge-and-ph-on-the-physiological-behaviour-of-cobalt-copper-manganese-antimony-zinc-and-titanium-oxide-nanoparticles-in-vitro
#11
Tiina Titma
The precise knowledge on various interactions of metal nanoparticles (NP) in a living organism is scarce. It is expected that metals can bind to nucleic acids, peptides and proteins (e.g. enzymes), and modify the functioning of vital cellular compartments after entering the organism. The predictive factors for quantitative nanostructure-activity relationship (QNAR) analysis could enhance efficient and harmless usage of nanoparticles (NPs) in the industry as well in the medicine. The studies value the composition of the NP corona determined by time, temperature and source of protein which has been found to implicate the physiological behaviour of NPs...
February 16, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29458071/b-cells-in-operational-tolerance
#12
REVIEW
M Chesneau, R Danger, J-P Soulillou, S Brouard
Transplantation is currently the therapy of choice for endstage organ failure even though it requires long-term immunossuppresive therapy, with its numerous side effects, for acceptance of the transplanted organ. In rare cases however, patients develop operational tolerance, that is, graft survival without immunosuppression. Studies conducted on these patients reveal genetic, phenotypic, and functional signatures. They provide a better understanding of the immunological mechanisms involved in operational tolerance and define biomarkers that could be used to adapt immunosuppressive treatment to the individual, safely reduce immunosuppression doses, and ideally and safely guide immunosuppression withdrawal...
February 16, 2018: Human Immunology
https://www.readbyqxmd.com/read/29458057/roles-of-the-insulin-signaling-pathway-in-insect-development-and-organ-growth
#13
Xianyu Lin, Guy Smagghe
Organismal development is a complex process as it requires coordination of many aspects to grow into fit individuals, such as the control of body size and organ growth. Therefore, the mechanisms of precise control of growth are essential for ensuring the growth of organisms at a correct body size and proper organ proportions during development. The control of the growth rate and the duration of growth (or the cessation of growth) are required in size control. The insulin signaling pathway and the elements involved are essential in the control of growth...
February 16, 2018: Peptides
https://www.readbyqxmd.com/read/29458011/inflammatory-cytokines-induce-podoplanin-expression-at-the-tumor-invasive-front
#14
Akiko Kunita, Vanessa Baeriswyl, Claudia Meda, Erik Cabuy, Kimiko Takeshita, Enrico Giraudo, Andreas Wicki, Masashi Fukayama, Gerhard Christofori
Tumor invasion is a critical first step in the organismic dissemination of cancer cells and the formation of metastasis in distant organs, the most important prognostic factor and the actual cause of death in most of the cancer patients. We report here that the cell surface protein podoplanin (PDPN), a potent inducer of cancer cell invasion, is conspicuously expressed by the invasive front of squamous cell carcinomas (SCC) of the cervix in patients and in the transgenic HPV/E2 mouse model of cervical cancer...
February 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29457987/the-rap2c-gtpase-facilitates-b-cell-receptor-induced-reorientation-of-the-microtubule-organizing-center
#15
Jia C Wang, Jeff Y-J Lee, May Dang-Lawson, Caitlin Pritchard, Michael R Gold
When B lymphocytes encounter antigen-bearing surfaces, B-cell receptor (BCR) signaling initiates remodeling of the F-actin network and reorientation of the microtubule-organizing center (MTOC) towards the antigen contact site. We have previously shown that the Rap1 GTPase, an evolutionarily conserved regulator of cell polarity, is essential for these processes and that Rap1-regulated actin remodeling is required for MTOC polarization. The role of Rap2 proteins in establishing cell polarity is not well understood...
February 19, 2018: Small GTPases
https://www.readbyqxmd.com/read/29457972/a-stable-metal-organic-framework-featuring-local-buffer-environment-for-carbon-dioxide-fixation
#16
Hongming He, Qi Sun, Wenyang Gao, Jason A Perman, Fuxing Sun, Guangshan Zhu, Briana Aguila, Katherine Forrest, Brian Space, Shengqian Ma
A majority of metal-organic frameworks (MOFs) fail to preserve their physical and chemical properties after exposure to acidic, neutral, or alkaline aqueous solutions, therefore limiting their practical applications in many areas. The strategy demonstrated herein is the design and synthesis of an organic ligand that behaves as a buffer to drastically boost the aqueous stability of a porous MOF (JUC-1000), which maintains its structural integrity at low and high pH values. The local buffer environment resulting from the weak acid-base pairs of the custom-designed organic ligand also greatly facilitates the performance of JUC-1000 in the chemical fixation of carbon dioxide under ambient conditions, outperforming a series of benchmark catalysts...
February 19, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29457971/visible-light-photocatalysis-does-it-make-a-difference-in-organic-synthesis
#17
Leyre Marzo, Santhosh K Pagire, Oliver Reiser, Burkhard König
Visible light photocatalysis has evolved over the last decade into a widely used method in organic synthesis. For many important transformations, such as cross-coupling reactions, alpha-amino functionalizations, cycloadditions, ATRA reactions, or fluorinations, photocatalytic variants have been reported. In this review, we try to compare classical and photocatalytic procedures for selected classes of reactions and highlight their advantages and limitations. In many cases, the photocatalytic reactions proceed at milder reaction conditions, typically at room temperature, and stoichiometric reagents are replaced by simple oxidants or reductants, like air oxygen or amines...
February 19, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29457963/3-t-mr-imaging-of-proximal-femur-microarchitecture-in-subjects-with-and-without-fragility-fracture-and-nonosteoporotic-proximal-femur-bone-mineral-density
#18
Gregory Chang, Chamith S Rajapakse, Cheng Chen, Arakua Welbeck, Kenneth Egol, Ravinder R Regatte, Punam K Saha, Stephen Honig
Purpose To determine if 3-T magnetic resonance (MR) imaging of proximal femur microarchitecture can allow discrimination of subjects with and without fragility fracture who do not have osteoporotic proximal femur bone mineral density (BMD). Materials and Methods Sixty postmenopausal women (30 with and 30 without fragility fracture) who had BMD T scores of greater than -2.5 in the hip were recruited. All subjects underwent dual-energy x-ray absorptiometry to assess BMD and 3-T MR imaging of the same hip to assess bone microarchitecture...
February 19, 2018: Radiology
https://www.readbyqxmd.com/read/29457959/biosynthesis-and-applications-of-prenylquinones
#19
Makoto Kawamukai
Prenylquinones are isoprenoid compounds with a characteristic quinone structure and isoprenyl tail that are ubiquitous in almost all living organisms. There are four major prenylquinone classes: ubiquinone (UQ), menaquinone (MK), plastoquinone (PQ), and rhodoquinone (RQ). The quinone structure and isoprenyl tail length differ among organisms. UQ, PQ, and RQ contain benzoquinone, while MK contains naphthoquinone. UQ, MK, and RQ are involved in oxidative phosphorylation, while PQ functions in photosynthetic electron transfer...
February 19, 2018: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29457926/the-contribution-of-theory-to-the-design-delivery-and-evaluation-of-interprofessional-curricula-beme-guide-no-49
#20
Sarah Hean, Christopher Green, Elizabeth Anderson, Debra Morris, Carol John, Richard Pitt, Cath O'Halloran
BACKGROUND: Interprofessional curricula have often lacked explicit reference to theory despite calls for a more theoretically informed field that illuminates curricular assumptions and justifies curricular practices. AIM: To review the contributions of theory to the design, delivery, and evaluation of interprofessional curricula. METHODS: Four databases were searched (1988-2015). Studies demonstrating explicit and a high-quality contribution of theory to the design, delivery or evaluation of interprofessional curricula were included...
February 19, 2018: Medical Teacher
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