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https://www.readbyqxmd.com/read/28549531/targeting-the-akt-gsk-3-bcl-2-axis-in-acute-myeloid-leukemia
#1
REVIEW
Maria Rosaria Ricciardi, Simone Mirabilii, Roberto Licchetta, Monica Piedimonte, Agostino Tafuri
Over the last few decades, there has been significant progress in the understanding of the pathogenetic mechanisms of the Acute Myeloid Leukemia (AML). However, despite important advances in elucidating molecular mechanisms, the treatment of AML has not improved significantly, remaining anchored at the standard chemotherapy regimen "3 + 7", with the prognosis of patients remaining severe, especially for the elderly and for those not eligible for transplant procedures. The biological and clinical heterogeneity of AML represents the major obstacle that hinders the improvement of prognosis and the identification of new effective therapeutic approaches...
May 19, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28548292/hypertriglyceridemic-acute-pancreatitis-in-an-emergency-department-the-typical-clinical-features-and-genetic-variants
#2
Wan Jun Chen, Xiao Fan Sun, Rui Xue Zhang, Min Jie Xu, Tong Hai Dou, Xiao Bin Zhang, Min Zhong, Wei Qiang Yang, Li Liu, Xiao Ye Lu, Chang Qing Zhu
OBJECTIVE: To investigate the clinical characteristics of hypertriglyceridemic acute pancreatitis (HTGAP), and the molecular foundation contributing to the hypertriglyceridemia in this group of patients. METHODS: Clinical data from 329 patients with AP were collected and analyzed. All the patients were divided into 1) HTGAP group (n = 40), with fasting serum triglyceride ≥ 500 mg/dL; and 2) NHTGAP group (n = 289). Next, the targeted next-generation sequencing was applied in 11 HTGAP patients to detect the genetic mutation associated with hypertriglyceridemia that included apolipoprotein A-5 (APOA5), apolipoprotein C-3 (APOC3), apolipoprotein E (APOE), BLK proto-oncogene, lipoprotein lipase (LPL), apolipoprotein C-2 (APOC2), glycosylphosphatidylinositol anchored high density lipoprotein binding protein-1(GPIHBP1), and lipase maturation factor-1(LMF1)...
May 26, 2017: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28547816/three-component-aminoalkylations-yielding-dihydronaphthoxazine-based-sirtuin-inhibitors-scaffold-modification-and-exploration-of-space-for-polar-side-chains
#3
Steffen Vojacek, Katja Beese, Zayan Alhalabi, Sören Swyter, Anja Bodtke, Carola Schulzke, Manfred Jung, Wolfgang Sippl, Andreas Link
Nonpolar derivatives of heterocyclic aromatic screening hits like the non-selective sirtuin inhibitor splitomicin tend to be poorly soluble in biological fluids. Unlike sp(3) -rich natural products, flat aromatic compounds are prone to stacking and often difficult to optimize into leads with activity in cellular systems. The aim of this work was to identify anchor points for the introduction of sp(3) -rich fragments with polar functional groups into the newly discovered active (IC50  = 5 μM) but nonpolar scaffold 1,2-dihydro-3H-naphth[1,2-e][1,3]oxazine-3-thione by a molecular modeling approach...
May 26, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28546385/using-rna-seq-for-genomic-scaffold-placement-correcting-assemblies-and-genetic-map-creation-in-a-common-brassica-rapa-mapping-population
#4
R J Cody Markelz, Michael F Covington, Marcus T Brock, Upendra K Devisetty, Daniel J Kliebenstein, Cynthia Weinig, Julin N Maloof
Brassica rapa is a model species for agronomic, ecological, evolutionary and translational studies. Here we describe high-density SNP discovery and genetic map construction for a Brassica rapa recombinant inbred line (RIL) population derived from field collected RNA-seq data. This high-density genotype data enables the detection and correction of putative genome mis-assemblies and accurate assignment of scaffold sequences to their likely genomic locations. These assembly improvements represent 7.1-8.0% of the annotated Brassica rapa genome...
May 25, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28538101/chemical-endgroup-modified-diblock-copolymers-elucidate-anchor-and-chain-mechanism-of-membrane-stabilization
#5
Evelyne M Houang, Karen J Haman, Mihee Kim, Wenjia Zhang, Dawn A Lowe, Yuk Yin Sham, Timothy P Lodge, Benjamin J Hackel, Frank S Bates, Joseph M Metzger
Block copolymers can be synthesized in an array of architectures and compositions to yield diverse chemical properties. The triblock copolymer Poloxamer 188 (P188), the family archetype, consisting of a hydrophobic polypropylene oxide core flanked by hydrophilic polyethylene oxide chains, can stabilize cellular membranes during stress. However, little is known regarding the molecular basis of membrane interaction by copolymers in living organisms. By leveraging diblock architectural design, discrete end-group chemistry modifications can be tested...
May 24, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28537379/molecular-rhodium-complexes-supported-on-the-metal-oxide-like-nodes-of-metal-organic-frameworks-and-on-zeolite-hy-catalysts-for-ethylene-hydrogenation-and-dimerization
#6
Varinia Bernales, Dong Yang, Jun Yu, Gamze Gümüşlü, Christopher J Cramer, Bruce C Gates, Laura Gagliardi
Metal-organic frameworks (MOFs) with nodes consisting of zirconium oxide clusters (Zr6) offer new opportunities as supports for catalysts with well-defined, essentially molecular, structures. We used the precursor Rh(C2H4)2(acac) (acac is acetylacetonate) to anchor Rh(I) complexes to the nodes of the MOF UiO-67 and, for comparison, to the zeolite dealuminated HY (DAY). These were characterized experimentally by measurement of catalytic activities and selectivities for ethylene hydrogenation and dimerization in a once-through flow reactor at 298 K and 1 bar...
May 24, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28536590/miniature-inverted-repeat-transposable-element-insertions-provide-a-source-of-intron-length-polymorphism-markers-in-the-carrot-daucus-carota-l
#7
Katarzyna Stelmach, Alicja Macko-Podgórni, Gabriela Machaj, Dariusz Grzebelus
The prevalence of non-autonomous class II transposable elements (TEs) in plant genomes may serve as a tool for relatively rapid and low-cost development of gene-associated molecular markers. Miniature inverted-repeat transposable element (MITE) copies inserted within introns can be exploited as potential intron length polymorphism (ILP) markers. ILPs can be detected by PCR with primers anchored in exon sequences flanking the target introns. Here, we designed primers for 209 DcSto (Daucus carota Stowaway-like) MITE insertion sites within introns along the carrot genome and validated them as candidate ILP markers in order to develop a set of markers for genotyping the carrot...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28533751/docetaxel-loaded-nanoparticles-assembled-from-%C3%AE-cyclodextrin-calixarene-giant-surfactants-physicochemical-properties-and-cytotoxic-effect-in-prostate-cancer-and-glioblastoma-cells
#8
Laura Gallego-Yerga, Inmaculada Posadas, Cristina de la Torre, Jesús Ruiz-Almansa, Francesco Sansone, Carmen Ortiz Mellet, Alessandro Casnati, José M García Fernández, Valentín Ceña
Giant amphiphiles encompassing a hydrophilic β-cyclodextrin (βCD) component and a hydrophobic calix[4]arene (CA4) module undergo self-assembly in aqueous media to afford core-shell nanospheres or nanocapsules, depending on the nanoprecipitation protocol, with high docetaxel (DTX) loading capacity. The blank and loaded nanoparticles have been fully characterized by dynamic light scattering (DLS), ζ-potential measurements and cryo-transmission electron microscopy (cryo-TEM). The data are compatible with the distribution of the drug between the nanoparticle core and the shell, where it is probably anchored by inclusion of the DTX aromatic moieties in βCD cavities...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28531887/expression-and-characterization-of-membrane-type-4-matrix-metalloproteinase-mt4-mmp-and-its-different-forms-in-melanoma
#9
Bettina Hieronimus, Julian Pfohl, Christian Busch, Lutz Graeve
BACKGROUND/AIMS: Membrane-type matrix metalloproteinases (MT-MMPs) are expressed on the cell surface and hydrolyze extracellular matrix components and signaling molecules by which they influence cancer cell migration and metastasis. Two of the six known MT-MMPs are anchored to the plasma membrane via a GPI anchor, one of which is MT4-MMP. Only little is known about MT4-MMP expression, synthesis, regulation and degradation. METHODS: We analyzed several human cancer cell lines as well as tissue homogenates using Western blotting and quantitative PCR for the expression of MT4-MMP...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28528970/the-many-faces-of-compartmentalized-pka-signalosomes
#10
REVIEW
Omar Torres-Quesada, Johanna E Mayrhofer, Eduard Stefan
Cellular signal transmission requires the dynamic formation of spatiotemporally controlled molecular interactions. At the cell surface information is received by receptor complexes and relayed through intracellular signaling platforms which organize the actions of functionally interacting signaling enzymes and substrates. The list of hormone or neurotransmitter pathways that utilize the ubiquitous cAMP-sensing protein kinase A (PKA) system is expansive. This requires that the specificity, duration, and intensity of PKA responses are spatially and temporally restricted...
May 18, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28526096/pvgama-reticulocyte-binding-activity-predicting-conserved-functional-regions-by-natural-selection-analysis
#11
Luis A Baquero, Darwin A Moreno-Pérez, Diego Garzón-Ospina, Johanna Forero-Rodríguez, Heidy D Ortiz-Suárez, Manuel A Patarroyo
BACKGROUND: Adhesin proteins are used by Plasmodium parasites to bind and invade target cells. Hence, characterising molecules that participate in reticulocyte interaction is key to understanding the molecular basis of Plasmodium vivax invasion. This study focused on predicting functionally restricted regions of the P. vivax GPI-anchored micronemal antigen (PvGAMA) and characterising their reticulocyte binding activity. RESULTS: The pvgama gene was initially found in P...
May 19, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28523073/improved-axenic-hydroponic-whole-plant-propagation-for-rapid-production-of-roots-as-transformation-target-tissue
#12
Kyle Benzle, Katrina Cornish
BACKGROUND: Plant roots are used as an efficient target tissue for plant transformation assays. In root propagable species transformed roots are able to regenerate into whole plants without the addition of exogenous hormones, thus avoiding somaclonal variation associated with many plant transformation protocols. Plants grown in soil or soilless solid medium have roots that tend to be extremely delicate and are difficult to sterilize in advance of plant transformation experiments. Axenic tissue culture plants grown on semi-solid media are slow to produce large amounts of biomass compared to plants grown in solution-based media...
2017: Plant Methods
https://www.readbyqxmd.com/read/28515150/receptor-for-advanced-glycation-end-products-is-targeted-by-fbxo10-for-ubiquitination-and-degradation
#13
John Evankovich, Travis Lear, Alison Mckelvey, Sarah Dunn, James Londino, Yuan Liu, Bill B Chen, Rama K Mallampalli
The receptor for advanced glycation end products (RAGE) is a highly expressed cell membrane receptor serving to anchor lung epithelia to matrix components, and it also amplifies inflammatory signaling during acute lung injury. However, mechanisms that regulate its protein concentrations in cells remain largely unknown. Here we show that RAGE exhibits an extended life span in lung epithelia (t½ 6 h), is monoubiquitinated at K374, and is degraded in lysosomes. The RAGE ligand ODN2006, a synthetic oligodeoxynucleotide resembling pathogenic hypomethylated CpG DNA, promotes rapid lysosomal RAGE degradation through activation of protein kinase C zeta (PKCζ), which phosphorylates RAGE...
May 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28512785/clinical-immunological-molecular-analyses-and-outcomes-of-iranian-patients-with-lrba-deficiency-a-longitudinal-study
#14
Gholamreza Azizi, Hassan Abolhassani, Seyed Alireza Mahdaviani, Zahra Chavoshzadeh, Peyman Eshghi, Reza Yazdani, Fatemeh Kiaee, Mohammadreza Shaghaghi, Javad Mohammadi, Nima Rezaei, Lennart Hammarström, Asghar Aghamohammadi
BACKGROUND: LPS-responsive beige-like anchor protein (LRBA) deficiency is a combined immunodeficiency caused by mutation in LRBA gene. The patients have a variety of clinical symptoms including hypogammaglobulinemia, recurrent infections, autoimmunity and enteropathy. METHODS: A total of 17 LRBA-deficient patients were enrolled in this longitudinal study. For all patients, demographic information, clinical records, laboratory and molecular data were collected. RESULTS: Hypogammaglobulinemia were reported in 14 (82...
May 17, 2017: Pediatric Allergy and Immunology
https://www.readbyqxmd.com/read/28510460/effects-of-membrane-defects-and-polymer-hydrophobicity-on-networking-kinetics-of-vesicles
#15
Yan Xia, Hyun-Sook Jang, Zhiqiang Shen, Geoffrey D Bothun, Ying Li, Mu-Ping Nieh
The kinetics of clustering unilamellar vesicles induced by inverse Pluronics, poly(propylene oxide)m-poly(ethylene oxide)n-poly(propylene oxide)m, POm-EOn-POm, were investigated via experiments and molecular dynamic simulations. Two important factors for controlling the networking kinetics are the membrane defects presumably located at the interfacial region between two lipid domains induced by acyl chain mismatch, and the polymer hydrophobicity. As expected, the clustering rate increases significantly with increasing bilayer defects on the membrane where the insertion of PPO is likely to take place because of the reduced energy barrier for the insertion of PO...
May 16, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28510056/the-two-sides-of-a-lipid-protein-story
#16
REVIEW
Luis G Mansor Basso, Luis F Santos Mendes, Antonio J Costa-Filho
Protein-membrane interactions play essential roles in a variety of cell functions such as signaling, membrane trafficking, and transport. Membrane-recruited cytosolic proteins that interact transiently and interfacially with lipid bilayers perform several of those functions. Experimental techniques capable of probing changes on the structural dynamics of this weak association are surprisingly limited. Among such techniques, electron spin resonance (ESR) has the enormous advantage of providing valuable local information from both membrane and protein perspectives by using intrinsic paramagnetic probes in metalloproteins or by attaching nitroxide spin labels to proteins and lipids...
June 2016: Biophysical Reviews
https://www.readbyqxmd.com/read/28507663/molecular-engineering-and-sequential-cosensitization-for-preventing-the-trade-off-effect-with-photovoltaic-enhancement
#17
Weiwei Zhang, Yongzhen Wu, Xin Li, Erpeng Li, Xiongrong Song, Huiyun Jiang, Chao Shen, Hao Zhang, He Tian, Wei-Hong Zhu
In dye-sensitized solar cells (DSSCs), it is essential to use rational molecular design to obtain promising photosensitizers with well-matched energy levels and narrow optical band gaps. However, the "trade-off" effect between the photocurrent and photovoltage is still a challenge. Here we report four benzoxidazole based D-A-π-A metal-free organic dyes (WS-66, WS-67, WS-68 and WS-69) with different combinations of π-spacer units and anchoring-acceptor groups. Either extending the π-spacer or enhancing the electron acceptor can efficiently modulate the molecular energy levels, leading to a red-shift in the absorption spectra...
March 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28507137/arabidopsis-glycosylphosphatidylinositol-anchored-protein-llg1-associates-with-and-modulates-fls2-to-regulate-innate-immunity
#18
Qiujing Shen, Gildas Bourdais, Huairong Pan, Silke Robatzek, Dingzhong Tang
Plants detect and respond to pathogen invasion with membrane-localized pattern recognition receptors (PRRs), which recognize pathogen-associated molecular patterns (PAMPs) and activate downstream immune responses. Here we report that Arabidopsis thaliana LORELEI-LIKE GPI-ANCHORED PROTEIN 1 (LLG1), a coreceptor of the receptor-like kinase FERONIA, regulates PRR signaling. In a forward genetic screen for suppressors of enhanced disease resistance 1 (edr1), we identified the point mutation llg1-3, which suppresses edr1 disease resistance but does not affect plant growth and development...
May 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28507000/the-cell-wall-localized-atypical-%C3%AE-1-3-glucanase-zerzaust-controls-tissue-morphogenesis-in-arabidopsis-thaliana
#19
Prasad Vaddepalli, Lynette Fulton, Jennifer Wieland, Katrin Wassmer, Milena Schaeffer, Stefanie Ranf, Kay Schneitz
Orchestration of cellular behavior in plant organogenesis requires integration of intercellular communication and cell wall dynamics. The underlying signaling mechanisms are poorly understood. Tissue morphogenesis in Arabidopsis depends on the receptor-like kinase STRUBBELIG. Mutations in ZERZAUST were previously shown to result in a strubbelig-like mutant phenotype. Here we report on the molecular identification and functional characterization of ZERZAUST We show that ZERZAUST encodes a putative GPI-anchored β-1,3 glucanase suggested to degrade the cell wall polymer callose...
May 15, 2017: Development
https://www.readbyqxmd.com/read/28502782/time-resolved-x-ray-solution-scattering-reveals-the-structural-photoactivation-of-a-light-oxygen-voltage-photoreceptor
#20
Oskar Berntsson, Ralph P Diensthuber, Matthijs R Panman, Alexander Björling, Ashley J Hughes, Léocadie Henry, Stephan Niebling, Gemma Newby, Marianne Liebi, Andreas Menzel, Robert Henning, Irina Kosheleva, Andreas Möglich, Sebastian Westenhoff
Light-oxygen-voltage (LOV) receptors are sensory proteins controlling a wide range of organismal adaptations in multiple kingdoms of life. Because of their modular nature, LOV domains are also attractive for use as optogenetic actuators. A flavin chromophore absorbs blue light, forms a bond with a proximal cysteine residue, and induces changes in the surroundings. There is a gap of knowledge on how this initial signal is relayed further through the sensor to the effector module. To characterize these conformational changes, we apply time-resolved X-ray scattering to the homodimeric LOV domain from Bacillus subtilis YtvA...
May 8, 2017: Structure
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