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https://www.readbyqxmd.com/read/28717925/complex-biomembrane-mimetics-on-the-sub-nanometer-scale
#1
REVIEW
Frederick A Heberle, Georg Pabst
Biomimetic lipid vesicles are indispensable tools for gaining insight into the biophysics of cell physiology on the molecular level. The level of complexity of these model systems has steadily increased, and now spans from domain-forming lipid mixtures to asymmetric lipid bilayers. Here, we review recent progress in the development and application of elastic neutron and X-ray scattering techniques for studying these systems in situ and under physiologically relevant conditions on the nanometer to sub-nanometer length scales...
July 17, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28717010/phosphorylation-of-the-kainate-receptor-kar-auxiliary-subunit-neto2-at-serine-409-regulates-synaptic-targeting-of-the-kar-subunit-gluk1
#2
Richa Madan Lomash, Nengyin Sheng, Yan Li, Roger A Nicoll, Katherine W Roche
Synaptic strength at excitatory synapses is determined by the presence of glutamate receptors (i.e. AMPA, NMDA and kainate receptors) at the synapse. Synaptic strength is modulated by multiple factors including assembly of different receptor subunits, interaction with auxiliary subunits and post translational modifications of either the receptors or their auxiliary subunits. Using mass spectrometry, we find that the intracellular region of neuropilin and tolloid-like proteins (Neto)1 and Neto2, the auxiliary subunits of KARs are phosphorylated by multiple kinases in vitro...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28716527/identification-of-a-synergistic-combination-of-smac-mimetic-and-bortezomib-to-trigger-cell-death-in-b-cell-non-hodgkin-lymphoma-cells
#3
Irfan Ahmed Bhatti, Behnaz Ahangarian Abhari, Simone Fulda
Recently, copy number gains and increased expression levels of cIAP1 and cIAP2 have been reported in B-cell non-Hodgkin lymphomas (NHL). Therefore, we investigated the therapeutic potential of the Smac mimetic BV6 that antagonizes cIAP1/2 and XIAP. Here, we discover that subtoxic concentrations of BV6 prime B-cell NHL cells to proteasome inhibitor Bortezomib-induced cell death. Synergistic induction of cell death by BV6 and Bortezomib is confirmed by calculation of combination index in different cell lines, emphasizing the broader relevance of this combination...
July 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28715858/biomimetic-nitrogen-doped-titania-nanoparticles-as-a-colorimetric-platform-for-hydrogen-peroxide-detection
#4
Muhammad Nasir, Sajid Rauf, Nawshad Muhammad, Mian Hasnain Nawaz, Aqif Anwar Chaudhry, Muhammad Hamza Malik, Shakir Ahmad Shahid, Akhtar Hayat
Nanoparticles proved a viable alternative to the already used sensing and diagnostics methods due to their low cost, good stability, easy availability and easy synthesis. In the present approach, nitrogen doped titania nanoparticles are prepared through freeze drying method, and subsequently stabilized through ionic liquid. These nanoparticles were characterized through various techniques such as X-ray diffraction (XRD), Fourier transformation infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), BET pore size and surface area analyzer, X-ray photoelectron spectroscopy (XPS) and UV-Visible diffuse reflectance spectroscopy (UV-Vis...
July 6, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28715207/antifreeze-protein-mimetic-metallohelices-with-potent-ice-recrystallization-inhibition-activity
#5
Daniel Mitchell, Guy J Clarkson, David J Fox, Rebecca A Vipond, Peter Scott, Matthew I Gibson
Antifreeze proteins are produced by extremophile species to control ice formation and growth, and have potential applications in many fields. There are few examples of synthetic materials which can reproduce their potent ice recrystallization inhibition property. We report that self-assembled enantiomerically-pure, amphipathic metallohelicies inhibited ice growth at just 20 μM. Structure-property relationships and calculations support the hypothesis that amphipathicity is the key motif for activity. This opens up a new field of metallo-organic antifreeze protein mimetics and provides insight into the origins of ice-growth inhibition...
July 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28714852/the-small-molecule-mimetic-agonist-trimebutine-of-adhesion-molecule-l1-contributes-to-functional-recovery-after-spinal-cord-injury-in-mice
#6
Junping Xu, Chengliang Hu, Qiong Jiang, Hongchao Pan, Huifan Shen, Melitta Schachner
Curing spinal cord injury (SCI) in mammals is a daunting task because of the lack of permissive mechanisms and strong inhibitory responses at and around the lesion. The neural cell adhesion molecule L1CAM (L1) has been shown to favor axonal regrowth and enhance neuronal survival and synaptic plasticity, and thus constitutes a viable target to promote regeneration after SCI. Since delivery of full-length L1 or its extracellular domain could encounter difficulties in translation to therapy in humans, we have identified several small organic compounds that bind to L1 and stimulate neuronal survival, neuronal migration, and neurite outgrowth in an L1-dependent manner...
July 14, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28714408/biomaterials-and-supercritical-fluid-technologies-which-perspectives-to-fabricate-artificial-extracellular-matrix
#7
Della Porta Giovanna, E Reverchon, N Maffulli
The foundation of tissue engineering for either therapeutic or diagnostic applications is the ability to exploit living cells. Tissue engineering utilizes living cells as engineering materials implanted, seeded or bio-plotted into an artificial structure capable of supporting three-dimensional tissue formation. These structures, typically called scaffolds, are critical, both ex vivo and in vivo, to influence their own microenvironments. Scaffolds can serve the following purposes: allow cell attachment and migration, deliver and retain cells and biochemical factors, enable diffusion of vital cell nutrients or expressed products, exert certain mechanical and biological influences to modify the behaviour of the cell phase...
July 13, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28713162/abt-263-induces-g1-g0-phase-arrest-apoptosis-and-autophagy-in-human-esophageal-cancer-cells-in-vitro
#8
Qing-Huan Lin, Fu-Chang Que, Chun-Ping Gu, De-Sheng Zhong, Dan Zhou, Yi Kong, Le Yu, Shu-Wen Liu
Both the anti- and pro-apoptotic members of the Bcl-2 family are regulated by a conserved Bcl-2 homology (BH3) domain. ABT-263 (Navitoclax), a novel BH3 mimetic and orally bioavailable Bcl-2 family inhibitor with high affinity for Bcl-xL, Bcl-2 and Bcl-w has entered clinical trials for cancer treatment. But the anticancer mechanisms of ABT-263 have not been fully elucidated. In this study we investigated the effects of ABT-263 on human esophageal cancer cells in vitro and to explore its anticancer mechanisms...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28712765/losartan-reverses-cox-2-dependent-vascular-dysfunction-in-offspring-of-hyperglycaemic-rats
#9
Diego Barbosa de Queiroz, Fernanda Elizabethe Ramos-Alves, Juliana Santos-Rocha, Gloria Pinto Duarte, Fabiano Elias Xavier
AIMS: This study examined whether chronic treatment with losartan, an angiotensin II type 1 receptor (AT1R) antagonist, might reverse COX-2-mediated vascular dysfunction in mesenteric resistance arteries (MRA) from offspring of hyperglycaemic rats. MATERIALS AND METHODS: Male 12-month-old offspring of hyperglycaemic (O-DR) and normoglycaemic (O-CR) rats were treated with losartan (15mg·kg·day(-1)) during 2months. Third order MRA of untreated and losartan-treated O-DR and O-CR were mounted in wire myograph for isometric tension measurements...
July 13, 2017: Life Sciences
https://www.readbyqxmd.com/read/28712306/targeting-intrinsic-apoptosis-and-other-forms-of-cell-death-by-bh3-mimetics-in-glioblastoma
#10
Georg Karpel-Massler, Chiaki Tsuge Ishida, Yiru Zhang, Marc-Eric Halatsch, M-Andrew Westhoff, Markus D Siegelin
Novel approaches to treat malignant brain tumors are necessary since these neoplasms still display an unfavorable prognosis. Areas covered: In this review, the authors summarize and analyze recent preclinical data that suggest that targeting intrinsic apoptosis may be a suitable strategy for the treatment of malignant gliomas. They focus on the anti-apoptotic Bcl-2 family members of proteins and the recent drug developments in that field with a special focus on BH3-mimetics. With the discovery of BH3-mimetics that interfere with anti-apoptotic Bcl-2 family members in the low nanomolar range significant excitement has been generated towards these class of inhibitors, such as ABT-737, ABT-263 and the most recent successor, ABT-199 which is most advanced with respect to clinical application...
July 17, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28711498/promotion-of-hair-growth-by-newly-synthesized-ceramide-mimetic-compound
#11
Bu-Mahn Park, Soon-Sun Bak, Kyung-Oh Shin, Minhee Kim, Daehwan Kim, Sang-Hun Jung, Sekyoo Jeong, Young Kwan Sung, Hyunjong Kim
Based on the crucial roles of ceramides in skin barrier function, use of ceramides or their structural mimetic compounds, pseudoceramides, as cosmetic ingredients are getting more popular. While currently used pseudoceramides are intended to substitute the structural roles of ceramides in stratum corneum, development of bioactive pseudoceramides has been repeatedly reported. In this study, based on the potential involvement of sphingolipids in hair cycle regulation, we investigated the effects of newly synthesized pseudoceramide, bis-oleamido isopropyl alcohol (BOI), on hair growth using cultured human hair follicles and animal models...
July 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28710552/the-african-froghopper-ptyelus-flavescens-suborder-cicadomorpha-contains-two-novel-and-one-known-peptides-of-the-adipokinetic-hormone%C3%A2-akh-family-structure-function-and-comparison-with-aphid-akh-suborder-sternorrhyncha
#12
Gerd Gäde, Petr Šimek, Heather G Marco
The rationale of "green pesticides" in food security is to use information about endogenous hormones of pest insects to make peptide mimetics that will act against the pest insects to alter their behaviour or physiology, while taking care not to harm beneficial insects or other organisms in the food chain. Such "green" insecticides are designed thus, on the basis of neuropeptide ligand-receptor interaction and it is of paramount interest to have finally a mimetic at hand that is harmful only to pest insects...
July 14, 2017: Amino Acids
https://www.readbyqxmd.com/read/28710492/nek1-kinase-domain-structure-and-its-dynamic-protein-interactome-after-exposure-to-cisplatin
#13
Talita D Melo-Hanchuk, Priscila Ferreira Slepicka, Gabriela Vaz Meirelles, Fernanda Luisa Basei, Diogo Ventura Lovato, Daniela Campos Granato, Bianca Alves Pauletti, Romenia Ramos Domingues, Adriana Franco Paes Leme, Alessandra Luiza Pelegrini, Guido Lenz, Stefan Knapp, Jonathan M Elkins, Jörg Kobarg
NEK family kinases are serine/threonine kinases that have been functionally implicated in the regulation of the disjunction of the centrosome, the assembly of the mitotic spindle, the function of the primary cilium and the DNA damage response. NEK1 shows pleiotropic functions and has been found to be mutated in cancer cells, ciliopathies such as the polycystic kidney disease, as well as in the genetic diseases short-rib thoracic dysplasia, Mohr-syndrome and amyotrophic lateral sclerosis. NEK1 is essential for the ionizing radiation DNA damage response and priming of the ATR kinase and of Rad54 through phosphorylation...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710476/inflammatory-pain-control-by-blocking-oxidized-phospholipid-mediated-trp-channel-activation
#14
Beatrice Oehler, Katrin Kistner, Corinna Martin, Jürgen Schiller, Rafaela Mayer, Milad Mohammadi, Reine-Solange Sauer, Milos R Filipovic, Francisco R Nieto, Jan Kloka, Diana Pflücke, Kerstin Hill, Michael Schaefer, Marzia Malcangio, Peter W Reeh, Alexander Brack, Robert Blum, Heike L Rittner
Phospholipids occurring in cell membranes and lipoproteins are converted into oxidized phospholipids (OxPL) by oxidative stress promoting atherosclerotic plaque formation. Here, OxPL were characterized as novel targets in acute and chronic inflammatory pain. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) and its derivatives were identified in inflamed tissue by mass spectrometry and binding assays. They elicited calcium influx, hyperalgesia and induced pro-nociceptive peptide release...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710347/effects-of-lipoic-acid-on-high-fat-diet-induced-alteration-of-synaptic-plasticity-and-brain-glucose-metabolism-a-pet-ct-and-13-c-nmr-study
#15
Zhigang Liu, Ishan Patil, Harsh Sancheti, Fei Yin, Enrique Cadenas
High-fat diet (HFD)-induced obesity is accompanied by insulin resistance and compromised brain synaptic plasticity through the impairment of insulin-sensitive pathways regulating neuronal survival, learning, and memory. Lipoic acid is known to modulate the redox status of the cell and has insulin mimetic effects. This study was aimed at determining the effects of dietary administration of lipoic acid on a HFD-induced obesity model in terms of (a) insulin signaling, (b) brain glucose uptake and neuronal- and astrocytic metabolism, and (c) synaptic plasticity...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709828/augmenting-the-efficacy-of-anti-cocaine-catalytic-antibodies-through-chimeric-hapten-design-and-combinatorial-vaccination
#16
Cody J Wenthur, Xiaoqing Cai, Beverly A Ellis, Kim D Janda
Given the need for further improvements in anti-cocaine vaccination strategies, a chimeric hapten (GNET) was developed that combines chemically-stable structural features from steady-state haptens with the hydrolytic functionality present in transition-state mimetic haptens. Additionally, as a further investigation into the generation of an improved bifunctional antibody pool, sequential vaccination with steady-state and transition-state mimetic haptens was undertaken. While GNET induced the formation of catalytically-active antibodies, it did not improve overall behavioral efficacy...
July 5, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28709001/ciliary-hedgehog-signaling-restricts-injury-induced-adipogenesis
#17
Daniel Kopinke, Elle C Roberson, Jeremy F Reiter
Injured skeletal muscle regenerates, but with age or in muscular dystrophies, muscle is replaced by fat. Upon injury, muscle-resident fibro/adipogenic progenitors (FAPs) proliferated and gave rise to adipocytes. These FAPs dynamically produced primary cilia, structures that transduce intercellular cues such as Hedgehog (Hh) signals. Genetically removing cilia from FAPs inhibited intramuscular adipogenesis, both after injury and in a mouse model of Duchenne muscular dystrophy. Blocking FAP ciliation also enhanced myofiber regeneration after injury and reduced myofiber size decline in the muscular dystrophy model...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28708281/cooperation-of-hif-and-ncam-mediated-mechanisms-in-cell-viability-of-hippocampal-cultures-after-oxygen-glucose-deprivation
#18
Lushnikova Iryna, Nikandrova Yelyzaveta, Skibo Galyna
Neurodegenerative diseases of different genesis are the result of cellular damages including those caused by oxygen and glucose deficit. Neuronal survival or death in brain pathologies depends on a variety of interrelated molecular mechanisms. A key role in modulation of neuron viability belongs to HIF (hypoxia-inducible factor) and NCAM (neural cell adhesion molecules) signaling pathways. In this work we used organotypic and dissociated hippocampal cultures to analyze cell viability and HIF-1α immunopositive (HIF-1α(+) ) signal after 30 minutes oxygen-glucose deprivation (OGD) followed by 24 h of reoxygenation in the presence of FGL (synthetic NCAM-derived mimetic peptide)...
July 14, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28707890/immersion-depths-of-lipid-carbons-in-bicelles-measured-by-paramagnetic-relaxation-enhancement
#19
Jobst Liebau, Lena Mäler
Myriads of biological processes occur in or at cellular lipid membranes. Knowledge about the localization of proteins, lipids, and other molecules within biological membranes is thus crucial for the understanding of such processes. Here, we present a method to determine the immersion depths of lipid carbon atoms in membranes by paramagnetic relaxation enhancement (PRE) caused by the presence of doxylated lipids. As membrane mimetics, we employ small isotropic bicelles made of synthetic lipids and of natural Escherichia coli phospholipid extract...
July 14, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28706950/effects-of-cobalt-chloride-a-hypoxia-mimetic-agent-on-autophagy-and-atrophy-in-skeletal-c2c12-myotubes
#20
Rui Chen, Ting Jiang, Yanling She, Jiehua Xu, Cheng Li, Shanyao Zhou, Huijuan Shen, Huacai Shi, Shuang Liu
BACKGROUND: Hypoxia-induced autophagy and muscle wasting occur in several environmental and pathological conditions. However, the molecular mechanisms underlying the effects of the hypoxia-mimetic agent CoCl2 on autophagy and muscle atrophy are still unclear. METHODS: C2C12 myotubes were exposed to increasing concentrations of CoCl2 for 24 hours. Quantitative RT-PCR, Western blotting, and transmission electron microscopy were performed to confirm autophagy occurs...
2017: BioMed Research International
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