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https://www.readbyqxmd.com/read/27910741/topotecan-liposomes-a-visit-from-a-molecular-to-a-therapeutic-platform
#1
Shivani Saraf, Ankit Jain, Pooja Hurkat, Sanjay Kumar Jain
Topotecan (TPT), a potent anticancer camptothecin analog, is well described for the treatment of ovarian cancer, but has also anticancer activity against small-cell and non-small-cell lung cancer, breast cancer, and acute leukemia. Various nanocarriers, including liposomes, have been exploited for targeted delivery of TPT. However, there are a number of challenges with TPT delivery using TPT liposomes (TLs), such as low encapsulation efficiency, physiological pH labile E ring (hydrolysis), accelerated blood clearance, multidrug resistance, and cancer metastases...
2016: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/27904881/sfr1-a-tetrahymena-thermophila-sfi1-repeat-protein-modulates-the-production-of-cortical-row-basal-bodies
#2
Westley Heydeck, Alexander J Stemm-Wolf, Janin Knop, Christina C Poh, Mark Winey
Basal bodies are essential microtubule-based structures that template, anchor, and orient cilia at the cell surface. Cilia act primarily in the generation of directional fluid flow and sensory reception, both of which are utilized for a broad spectrum of cellular processes. Although basal bodies contribute to vital cell functions, the molecular contributors of their assembly and maintenance are poorly understood. Previous studies of the ciliate Tetrahymena thermophila revealed important roles for two centrin family members in basal body assembly, separation of new basal bodies, and stability...
November 2016: MSphere
https://www.readbyqxmd.com/read/27903740/protective-t-cell-responses-featured-by-concordant-recognition-of-middle-east-respiratory-syndrome-coronavirus-derived-cd8-t-cell-epitopes-and-host-mhc
#3
William J Liu, Jiaming Lan, Kefang Liu, Yao Deng, Yanfeng Yao, Shaolian Wu, Hong Chen, Lingling Bao, Haifeng Zhang, Min Zhao, Qihui Wang, Lingxia Han, Yan Chai, Jianxun Qi, Jincun Zhao, Songdong Meng, Chuan Qin, George F Gao, Wenjie Tan
The coordinated recognition of virus-derived T cell epitopes and MHC molecules by T cells plays a pivotal role in cellular immunity-mediated virus clearance. It has been demonstrated that the conformation of MHC class I (MHC I) molecules can be adjusted by the presented peptide, which impacts T cell activation. However, it is still largely unknown whether the conformational shift of MHC I influences the protective effect of virus-specific T cells. In this study, utilizing the Middle East respiratory syndrome coronavirus-infected mouse model, we observed that through the unusual secondary anchor Ile5, a CD8(+) T cell epitope drove the conformational fit of Trp(73) on the α1 helix of murine MHC I H-2K(d) In vitro renaturation and circular dichroism assays indicated that this shift of the structure did not influence the peptide/MHC I binding affinity...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27902705/neuronal-ndrg4-is-essential-for-nodes-of-ranvier-organization-in-zebrafish
#4
Laura Fontenas, Flavia De Santis, Vincenzo Di Donato, Cindy Degerny, Béatrice Chambraud, Filippo Del Bene, Marcel Tawk
Axon ensheathment by specialized glial cells is an important process for fast propagation of action potentials. The rapid electrical conduction along myelinated axons is mainly due to its saltatory nature characterized by the accumulation of ion channels at the nodes of Ranvier. However, how these ion channels are transported and anchored along axons is not fully understood. We have identified N-myc downstream-regulated gene 4, ndrg4, as a novel factor that regulates sodium channel clustering in zebrafish. Analysis of chimeric larvae indicates that ndrg4 functions autonomously within neurons for sodium channel clustering at the nodes...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27900841/the-role-of-the-prod1-membrane-anchor-in-newt-limb-regeneration
#5
Kaoru Nomura, Yasushi Tanimoto, Fumio Hayashi, Erisa Harada, Xiao-Yuan Shan, Masafumi Shionyu, Atsushi Hijikata, Tsuyoshi Shirai, Kenichi Morigaki, Keiko Shimamoto
Prod1 is a protein that regulates limb regeneration in salamanders by determining the direction of limb growth. Prod1 is attached to the membrane by a glycosylphosphatidylinositol (GPI) anchor, but the role of membrane anchoring in the limb regeneration process is poorly understood. In this study, we investigated the functional role of the anchoring of Prod1 to the membrane by using its synthetic mimics in combination with solid-state NMR spectroscopy and fluorescent microscopy techniques. Anchoring did not affect the three-dimensional structure of Prod1 but did induce aggregation by aligning the molecules and drastically reducing the molecular motion on the two-dimensional membrane surface...
November 30, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27899590/different%C3%A2-enhancer-classes-in-drosophila-bind-distinct-architectural-proteins-and-mediate-unique-chromatin-interactions-and-3d-architecture
#6
Caelin Cubeñas-Potts, M Jordan Rowley, Xiaowen Lyu, Ge Li, Elissa P Lei, Victor G Corces
Eukaryotic gene expression is regulated by enhancer-promoter interactions but the molecular mechanisms that govern specificity have remained elusive. Genome-wide studies utilizing STARR-seq identified two enhancer classes in Drosophila that interact with different core promoters: housekeeping enhancers (hkCP) and developmental enhancers (dCP). We hypothesized that the two enhancer classes are occupied by distinct architectural proteins, affecting their enhancer-promoter contacts. By evaluating ChIP-seq occupancy of architectural proteins, typical enhancer-associated proteins, and histone modifications, we determine that both enhancer classes are enriched for RNA Polymerase II, CBP, and architectural proteins but there are also distinctions...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27897422/a-million-turnover-molecular-anode-for-catalytic-water-oxidation
#7
Jordi Creus, Roc Matheu, Itziar Peñafiel, Dooshaye Moonshiram, Pascal Blondeau, Jordi Benet-Buchholz, Jordi García-Antón, Xavier Sala, Cyril Godard, Antoni Llobet
Molecular ruthenium-based water oxidation catalyst precursors of general formula [Ru(tda)(L(i) )2 ] (tda(2-) is [2,2':6',2''-terpyridine]-6,6''-dicarboxylato; L(1) =4-(pyren-1-yl)-N-(pyridin-4-ylmethyl)butanamide, 1 b; L(2) =4-(pyren-1-yl)pyridine), 1 c), have been prepared and thoroughly characterized. Both complexes contain a pyrene group allowing ready and efficiently anchoring via π interactions on multi-walled carbon nanotubes (MWCNT). These hybrid solid state materials are exceptionally stable molecular water-oxidation anodes capable of carrying out more than a million turnover numbers (TNs) at pH 7 with an Eapp =1...
December 5, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27892522/sars-cov-fusion-peptides-induce-membrane-surface-ordering-and-curvature
#8
Luis G M Basso, Eduardo F Vicente, Edson Crusca, Eduardo M Cilli, Antonio J Costa-Filho
Viral membrane fusion is an orchestrated process triggered by membrane-anchored viral fusion glycoproteins. The S2 subunit of the spike glycoprotein from severe acute respiratory syndrome (SARS) coronavirus (CoV) contains internal domains called fusion peptides (FP) that play essential roles in virus entry. Although membrane fusion has been broadly studied, there are still major gaps in the molecular details of lipid rearrangements in the bilayer during fusion peptide-membrane interactions. Here we employed differential scanning calorimetry (DSC) and electron spin resonance (ESR) to gather information on the membrane fusion mechanism promoted by two putative SARS FPs...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27890830/time-course-of-glial-changes-in-the-hyperhomocysteinemia-model-of-vascular-cognitive-impairment-and-dementia-vcid
#9
Tiffany L Sudduth, Erica M Weekman, Brittani R Price, Jennifer L Gooch, Abigail Woolums, Christopher M Norris, Donna M Wilcock
Vascular cognitive impairment and dementia (VCID) is the second leading cause of dementia behind Alzheimer's disease (AD) and is a frequent co-morbidity with AD. Despite its prevalence, little is known about the molecular mechanisms underlying the cognitive dysfunction resulting from cerebrovascular disease. Astrocytic end-feet almost completely surround intraparenchymal blood vessels in the brain and express a variety of channels and markers indicative of their specialized functions in the maintenance of ionic and osmotic homeostasis and gliovascular signaling...
November 25, 2016: Neuroscience
https://www.readbyqxmd.com/read/27888218/diverting-cert-mediated-ceramide-transport-to-mitochondria-triggers-bax-dependent-apoptosis
#10
Amrita Jain, Oliver Beutel, Katharina Ebell, Sergey Korneev, Joost C M Holthuis
A deregulation of ceramide biosynthesis in the ER is frequently linked to induction of mitochondrial apoptosis. While in vitro studies suggest that ceramides may initiate cell death by acting directly on mitochondria, their actual contribution to the apoptotic response in living cells is unclear. In here, we analyzed the consequences of targeting the biosynthetic flow of ceramides to mitochondria using a ceramide transfer protein equipped with an outer mitochondrial membrane anchor, mitoCERT. Cells expressing mitoCERT import ceramides into mitochondria and undergo Bax-dependent apoptosis...
November 25, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27887567/fluorescence-chromosome-banding-and-fish-mapping-in-perennial-ryegrass-lolium-perenne-l
#11
Helal A Ansari, Nicholas W Ellison, Shalome A Bassett, Syed W Hussain, Gregory T Bryan, Warren M Williams
BACKGROUND: The unambiguous identification of individual chromosomes is a key part of the genomic characterization of any species. In this respect, the development and application of chromosome banding techniques has revolutionised mammalian and especially, human genomics. However, partly because of the traditional use of chromosome squash preparations, consistent fluorescence banding has rarely been achieved in plants. Here, successful fluorescence chromosome banding has been achieved for the first time in perennial ryegrass (Lolium perenne), a forage and turf grass with a large genome and a symmetrical karyotype with chromosomes that are difficult to distinguish...
November 25, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27886315/cellular-membrane-anchored-fluorescent-probe-with-aggregation-induced-emission-characteristics-for-selective-detection-of-cu-2-ions
#12
Danni Liu, Shenglu Ji, Heran Li, Liang Hong, Deling Kong, Xin Qi, Dan Ding
The exploration of advanced fluorescent probes that can detect divalent copper (Cu(2+)) in aqueous environments and even in live organisms is particularly valuable for understanding the occurrence and development of Cu(2+)-related diseases. In this work, we report the design and synthesis of an aggregation-induced emission luminogen (AIEgen)-based probe (TPE-Py-EEGTIGYG) by integrating an AIEgen, TPE-Py, with a peptide, EEGTIGYG, which can selectively detect Cu(2+) in both aqueous solution and live cells. Peptide EEGTIGYG has dual functionality in the probe design, namely improving water solubility and providing specific cell membrane-binding ability...
November 25, 2016: Faraday Discussions
https://www.readbyqxmd.com/read/27886308/impact-of-the-molecular-structure-and-adsorption-mode-of-d-%C3%AF-a-dye-sensitizers-with-a-pyridyl-group-in-dye-sensitized-solar-cells-on-the-adsorption-equilibrium-constant-for-dye-adsorption-on-tio2-surface
#13
Yousuke Ooyama, Naoya Yamaguchi, Joji Ohshita, Yutaka Harima
D-π-A dyes NI-4 bearing a pyridyl group, YNI-1 bearing two pyridyl groups and YNI-2 bearing two thienylpyridyl groups as the anchoring group on the TiO2 surface have been developed as dye sensitizers for dye-sensitized solar cells (DSSCs), where NI-4 and YNI-2 can adsorb onto the TiO2 electrode through the formation of the coordinate bond between the pyridyl group of the dye and the Lewis acid site (exposed Ti(n+) cations) on the TiO2 surface, but YNI-1 is predominantly adsorbed on the TiO2 electrode through the formation of the hydrogen bond between the pyridyl group of the dye and the Brønsted acid sites (surface-bound hydroxyl groups, Ti-OH) on the TiO2 surface...
November 25, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27884160/the-d-domain-of-lrrc4-anchors-erk1-2-in-the-cytoplasm-and-competitively-inhibits-mek-erk-activation-in-glioma-cells
#14
Zeyou Wang, Qin Guo, Rong Wang, Gang Xu, Peiyao Li, Yingnan Sun, Xiaoling She, Qiang Liu, Qiong Chen, Zhibin Yu, Changhong Liu, Jing Xiong, Guiyuan Li, Minghua Wu
BACKGROUND: As a well-characterized key player in various signal transduction networks, extracellular-signal-regulated kinase (ERK1/2) has been widely implicated in the development of many malignancies. We previously found that Leucine-rich repeat containing 4 (LRRC4) was a tumor suppressor and a negative regulator of the ERK/MAPK pathway in glioma tumorigenesis. However, the precise molecular role of LRRC4 in ERK signal transmission is unclear. METHODS: The interaction between LRRC4 and ERK1/2 was assessed by co-immunoprecipitation and GST pull-down assays in vivo and in vitro...
November 25, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27874122/surface-induced-symmetry-reduction-in-molecular-switching-asymmetric-cis-trans-switching-of-ch3s-au-sch3-on-au-111
#15
Jianzhi Gao, Lin Tang, Scott Holmes, Fangsen Li, Richard E Palmer, Quanmin Guo
The cis-trans isomerization of CH3S-Au-SCH3 driven by the tip of the scanning tunneling microscope is investigated at 77 K. CH3S-Au-SCH3 anchored on the Au(111) surface with the S-Au-S axis parallel to the substrate functions as a molecular switch due to the flipping of the CH3 groups. The bonding between CH3S-Au-SCH3 and Au(111) leads to asymmetric isomerization where one of the two methyl groups flips much more effectively than the other, despite the symmetry of CH3S-Au-SCH3. Our findings suggest the possibility of constructing similar molecular switches that can be operated at room temperature and a potential route for fine-tuning of molecular switches in future nanoscale electro-mechanical devices...
December 1, 2016: Nanoscale
https://www.readbyqxmd.com/read/27873198/fabrication-of-bio-function-preserved-saccharide-microarray-chips-with-cyanuric-chloride-as-a-rotatable-linker
#16
Yi Chen, Chanjuan Liu, Xiao Wang
Microarray-based saccharide chips possess an inherent property of high throughput but remain hard to use in practice due mainly to their fabrication problems, which have led to many strategies proposed but nearly none can immobilize small saccharides without losing their bio-affinity. Herein introduced is an easy strategy able to directly immobilize all intact saccharides on solid surface with excellent preservation of their molecular recognition ability. The core idea is to anchor a saccharide molecule on a universally rotatable molecular frame to free its spatial adjustment during molecular recognition process...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27872309/phosphate-binding-pocket-in-dicer-2-paz-domain-for-high-fidelity-sirna-production
#17
Suresh K Kandasamy, Ryuya Fukunaga
The enzyme Dicer produces small silencing RNAs such as micro-RNAs (miRNAs) and small interfering RNAs (siRNAs). In Drosophila, Dicer-1 produces ∼22-24-nt miRNAs from pre-miRNAs, whereas Dicer-2 makes 21-nt siRNAs from long double-stranded RNAs (dsRNAs). How Dicer-2 precisely makes 21-nt siRNAs with a remarkably high fidelity is unknown. Here we report that recognition of the 5'-monophosphate of a long dsRNA substrate by a phosphate-binding pocket in the Dicer-2 PAZ (Piwi, Argonaute, and Zwille/Pinhead) domain is crucial for the length fidelity, but not the efficiency, in 21-nt siRNA production...
November 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27872205/molecular-architecture-of-the-yeast-elongator-complex-reveals-an-unexpected-asymmetric-subunit-arrangement
#18
Dheva T Setiaputra, Derrick Th Cheng, Shan Lu, Jesse M Hansen, Udit Dalwadi, Cindy Hy Lam, Jeffrey L To, Meng-Qiu Dong, Calvin K Yip
Elongator is a ~850 kDa protein complex involved in multiple processes from transcription to tRNA modification. Conserved from yeast to humans, Elongator is assembled from two copies of six unique subunits (Elp1 to Elp6). Despite the wealth of structural data on the individual subunits, the overall architecture and subunit organization of the full Elongator and the molecular mechanisms of how it exerts its multiple activities remain unclear. Using single-particle electron microscopy (EM), we revealed that yeast Elongator adopts a bilobal architecture and an unexpected asymmetric subunit arrangement resulting from the hexameric Elp456 subassembly anchored to one of the two Elp123 lobes that form the structural scaffold...
November 21, 2016: EMBO Reports
https://www.readbyqxmd.com/read/27871938/the-role-of-gpi-anchored-axonal-glycoproteins-in-neural-development-and-neurological-disorders
#19
REVIEW
Gianfranco Gennarini, Antonella Bizzoca, Sabrina Picocci, Daniela Puzzo, Patrizia Corsi, Andrew J W Furley
This review article focuses on the Contactin (CNTN) subset of the Immunoglobulin supergene family (IgC2/FNIII molecules), whose components share structural properties (the association of Immunoglobulin type C2 with Fibronectin type III domains), as well as a general role in cell contact formation and axonal growth control. IgC2/FNIII molecules include 6 highly related components (CNTN 1-6), associated with the cell membrane via a Glycosyl Phosphatidyl Inositol (GPI)-containing lipid tail. Contactin 1 and Contactin 2 share ~50 (49...
November 18, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27871385/surface-charge-modification-increases-firefly-luciferase-rigidity-without-alteration-in-bioluminescence-spectra
#20
Mojtaba Mortazavi, Saman Hosseinkhani
Protein engineering can provide useful approaches for loop anchoring and mutation of surface-exposed loop residues to Arg for the design of thermostable proteins. In this context and due to the high proportion of surface loops, some of the solvent-exposed residues in the Lampyris turkestanicus luciferase were mutated to Arg. Using the red-emitter mutant luciferase (E354R/Arg356), the single (-Q35R, -I182R, -I232R and -L300R), double (-Q35R/I232R) and triple (-Q35R/I232R/I182R) mutant luciferases were introduced...
January 2017: Enzyme and Microbial Technology
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