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https://www.readbyqxmd.com/read/28526063/targeting-the-cxcr4-pathway-using-a-novel-anti-cxcr4-igg1-antibody-pf-06747143-in-chronic-lymphocytic-leukemia
#1
Manoj K Kashyap, Carlos I Amaya-Chanaga, Deepak Kumar, Brett Simmons, Nanni Huser, Yin Gu, Max Hallin, Kevin Lindquist, Rolla Yafawi, Michael Y Choi, Ale-Ali Amine, Laura Z Rassenti, Cathy Zhang, Shu-Hui Liu, Tod Smeal, Valeria R Fantin, Thomas J Kipps, Flavia Pernasetti, Januario E Castro
BACKGROUND: The CXCR4-CXCL12 axis plays an important role in the chronic lymphocytic leukemia (CLL)-microenvironment interaction. Overexpression of CXCR4 has been reported in different hematological malignancies including CLL. Binding of the pro-survival chemokine CXCL12 with its cognate receptor CXCR4 induces cell migration. CXCL12/CXCR4 signaling axis promotes cell survival and proliferation and may contribute to the tropism of leukemia cells towards lymphoid tissues and bone marrow...
May 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28521704/dopamine-d2-receptors-dimers-how-can-we-pharmacologically-target-them
#2
Marco Carlia, Shivakumar Kolachalam, Stefano Aringhieri, Mario Rossib, Luca Giovannini, Roberto Maggio, Marco Scarselli
Dopamine D2 and D3 receptors are important pharmacological targets in Schizophrenia and Parkinson's disease. Intriguingly, many studies have shown that they form homo- and heterodimers, and they can be targeted in specific tissues with new drugs. In this direction, many efforts have been made to develop new molecules that are able to interact with these receptor dimeric complexes. Among various strategies for targeting dopamine receptors dimers, two distinct classes of compounds, such as bivalent and bitopic ligands, have gained particular attention and their use in pharmacology looks promising...
May 18, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28521477/t-cell-immunity-induced-by-a-bivalent-salmonella-based-ceacam6-and-4-1bbl-vaccines-in-a-rat-colorectal-cancer-model
#3
Chunhui Jin, Xiaoqing Duan, Yingying Liu, Jianhong Zhu, Ke Zhang, Yuanting Zhang, Tingting Xia, Yajun Fei, Jianxin Ye
The present study investigated the anti-tumor mechanisms of recombinant non-specific cross-reacting antigen (CEACAM6) and 4-1BB ligand (4-1BBL) Salmonella-based vaccines, and the effect that these vaccinations have on memory T cells and T helper (Th) cell polarization. Colon tumors were induced in rats via 1,2-dimethylhydrazine (DMH) injections. Rats were then treated with injections of attenuated Salmonella typhimurium carrying pIRES-CEACAM6, pIRES-4-1BBL or pIRES-CEACAM6-4-1BBL. In total, 4 vaccine injections, one every other week, were administered during the 8 weeks subsequent to the DMH injection...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28516164/engineered-ligand-based-vegfr-antagonists-with-increased-receptor-binding-affinity-more-effectively-inhibit-angiogenesis
#4
Shiven Kapur, Adam P Silverman, Anne Z Ye, Niv Papo, Darren Jindal, Mark S Blumenkranz, Jennifer R Cochran
Pathologic angiogenesis is mediated by the coordinated action of the vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling axis, along with crosstalk contributed by other receptors, notably αvβ3 integrin. We build on earlier work demonstrating that point mutations can be introduced into the homodimeric VEGF ligand to convert it into an antagonist through disruption of binding to one copy of VEGFR2. This inhibitor has limited potency, however, due to loss of avidity effects from bivalent VEGFR2 binding...
March 2017: Bioengineering & Translational Medicine
https://www.readbyqxmd.com/read/28513551/the-regulatory-capacity-of-bivalent-genes-a-theoretical-approach
#5
Torsten Thalheim, Maria Herberg, Markus Loeffler, Joerg Galle
Bivalent genes are frequently associated with developmental and lineage specification processes. Resolving their bivalency enables fast changes in their expression, which potentially can trigger cell fate decisions. Here, we provide a theoretical model of bivalency that allows for predictions on the occurrence, stability and regulatory capacity of this prominent modification state. We suggest that bivalency enables balanced gene expression heterogeneity that constitutes a prerequisite of robust lineage priming in somatic stem cells...
May 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28510303/cucurbit-8-uril-and-14-3-3-based-binary-bivalent-supramolecular-protein-assembly-platform-and-co-crystal-structure
#6
Pim de Vink, Jeroen Briels, Thomas Schrader, Lech Milroy, Luc Brunsveld, Christian Ottmann
Interactions between proteins frequently employ recognition sequences that engage in multivalent binding events. Dimeric 14-3-3 adapter proteins represent a prominent example, typically binding partner proteins in a phosphorylation-dependent mono- or bivalent manner. Here we describe the development of a cucurbit[8]uril (Q8)-based supramolecular system, which in conjunction with the 14-3-3 protein dimer acts as a binary and bivalent protein assembly platform. We fused the phenylalanine-glycine-glycine (FGG) tripeptide motif to the N-terminus of the 14-3-3-binding epitope of the estrogen receptor α (ERα), for selective binding to Q8...
May 16, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28506937/bivalirudin-infusion-to-reduce-ventricular-infarction-the-open-label-randomised-bivalirudin-infusion-for-ventricular-infarction-limitation-bival-study
#7
Robert Jan van Geuns, Georgios Sideris, Niels Van Royen, Rami El Mahmoud, Roberto Diletti, Claire Bal Dit Sollier, Jerome Garot, Nina W Van Der Hoeven, Bernardo Cortese, Li Ding, Ilknur Lechthaler, Efthymios N Deliargyris, Prodromos Anthopoulos, Ludovic Drouet
AIMS: The aim of the study was to investigate whether bivalirudin versus unfractionated heparin (UFH) reduces infarct size (IS) for primary percutaneous coronary intervention (PPCI) in large acute myocardial infarction (AMI). METHODS AND RESULTS: This multicentre open-label trial randomised 78 patients undergoing PPCI for large AMI to bivalirudin or UFH. The primary endpoint was IS, assessed by cardiac magnetic resonance (CMR) five days after PPCI. Secondary endpoints included index of microcirculatory resistance (IMR), CMR-assessed microvascular obstruction (MVO) and ejection fraction, and biomarkers for thrombin activity and cell injury...
May 16, 2017: EuroIntervention
https://www.readbyqxmd.com/read/28505203/cytological-and-morphological-analysis-of-hybrids-between-brassicoraphanus-and-brassica-napus-for-introgression-of-clubroot-resistant-trait-into-brassica-napus-l
#8
Zongxiang Zhan, Chinedu Charles Nwafor, Zhaoke Hou, Jianfang Gong, Bin Zhu, Yingfen Jiang, Yongming Zhou, Jiangsheng Wu, Zhongyun Piao, Yue Tong, Chao Liu, Chunyu Zhang
Interspecific hybridization is a powerful tool for improvement of crop species, it has the potential to broaden the genetic base and create new plant forms for breeding programs. Synthetic allopolyploid is a widely-used model for the study of genetic recombination and fixed heterosis in Brassica. In Brassica napus breeding, identification and introgression of new sources of clubroot resistance trait from wild or related species into it by hybridization is a long-term crop management strategy for clubroot disease...
2017: PloS One
https://www.readbyqxmd.com/read/28502659/apc-c-cdh1-enables-removal-of-shugoshin-2-from-the-arms-of-bivalent-chromosomes-by-moderating-cyclin-dependent-kinase-activity
#9
Ahmed Rattani, Randy Ballesteros Mejia, Katherine Roberts, Maurici B Roig, Jonathan Godwin, Michael Hopkins, Manuel Eguren, Luis Sanchez-Pulido, Elwy Okaz, Sugako Ogushi, Magda Wolna, Jean Metson, Alberto M Pendás, Marcos Malumbres, Béla Novák, Mary Herbert, Kim Nasmyth
In mammalian females, germ cells remain arrested as primordial follicles. Resumption of meiosis is heralded by germinal vesicle breakdown, condensation of chromosomes, and their eventual alignment on metaphase plates. At the first meiotic division, anaphase-promoting complex/cyclosome associated with Cdc20 (APC/C(Cdc20)) activates separase and thereby destroys cohesion along chromosome arms. Because cohesion around centromeres is protected by shugoshin-2, sister chromatids remain attached through centromeric/pericentromeric cohesin...
May 10, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28501334/exchangeable-sodium-percentage-decrease-in-saline-sodic-soil-after-basic-oxygen-furnace-slag-application-in-a-lysimeter-trial
#10
Chiara Pistocchi, Giorgio Ragaglini, Valentina Colla, Teresa Annunziata Branca, Cristiano Tozzini, Lea Romaniello
The Basic Oxygen Furnace Slag results from the conversion of hot metal into steel. Some properties of this slag, such as the high pH or calcium and magnesium content, makes it suitable for agricultural use as a soil amendment. Slag application to agricultural soils is allowed in some European countries, but to date there is no common regulation in the European Union. In Italy soils in coastal areas are often affected by excess sodium, which has several detrimental effects on the soil structure and crop production...
May 10, 2017: Journal of Environmental Management
https://www.readbyqxmd.com/read/28499554/effectiveness-of-hpv-vaccines-against-genital-warts-in-women-from-valencia-spain
#11
Esther Navarro-Illana, Mónica López-Lacort, Pedro Navarro-Illana, Juan José Vilata, Javier Diez-Domingo
OBJECTIVES: To assess the effectiveness of the HPV vaccines in preventing genital warts in young women. DESIGN: Population-based study using health databases. SETTING: Valencian Community (Spain). PARTICIPANTS: All girls and women aged 14-19years who were registered in the Valencian Community between January 2009 and December 2014 (n=279,787). MAIN OUTCOME MEASURES: Incident cases of genital warts were defined as the first activation of diagnosis code ICD-9-CM 078...
June 5, 2017: Vaccine
https://www.readbyqxmd.com/read/28495590/concurrent-activation-of-%C3%AE-2-adrenergic-receptor-and-blockage-of-gpr55-disrupts-pro-oncogenic-signaling-in-glioma-cells
#12
Artur Wnorowski, Justyna Such, Rajib K Paul, Robert P Wersto, Fred E Indig, Krzysztof Jozwiak, Michel Bernier, Irving W Wainer
Activation of β2-adrenergic receptor (β2AR) and deorphanized GPR55 has been shown to modulate cancer growth in diverse tumor types in vitro and in xenograft models in vivo. (R,R')-4'-methoxy-1-naphthylfenoterol [(R,R')-MNF] is a bivalent compound that agonizes β2AR but inhibits GPR55-mediated pro-oncogenic responses. Here, we investigated the molecular mechanisms underlying the anti-tumorigenic effects of concurrent β2AR activation and GPR55 blockade in C6 glioma cells using (R,R')-MNF as a marker ligand...
May 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28494440/nuclear-architecture-of-mouse-spermatocytes-chromosome-topology-heterochromatin-and-nucleolus
#13
Soledad Berrios
The nuclear organization of spermatocytes in meiotic prophase I is primarily determined by the synaptic organization of the bivalents that are bound by their telomeres to the nuclear envelope and described as arc-shaped trajectories through the 3D nuclear space. However, over this basic meiotic organization, a spermatocyte nuclear architecture arises that is based on higher-ordered patterns of spatial associations among chromosomal domains from different bivalents that are conditioned by the individual characteristics of chromosomes and the opportunity for interactions between their domains...
May 12, 2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28494361/ferrocene-functionalized-graphitic-carbon-nitride-as-an-enhanced-heterogeneous-catalyst-of-fenton-reaction-for-degradation-of-rhodamine-b-under-visible-light-irradiation
#14
Kun-Yi Andrew Lin, Jyun-Ting Lin
To enhance degradation of Rhodamine B (RhB), a toxic xanthene dye, an iron-doped graphitic carbon nitride (CN) is prepared by establishing a covalent bond (-CN-) bridging ferrocene (Fc) and CN via a Schiff base reaction. The π-conjugation between the aromatic Fc and CN can be much enhanced by the covalent bond, thereby facilitating the bulk-to-surface charge transfer and separation as well as reversible photo-redox reactions during photocatalytic reactions. Thus, the resulting Fc-CN exhibits a much higher catalytic activity than CN to activate hydrogen peroxide (HP) for RhB degradation, because the photocatalytically generated electrons from CN can activate HP and effectively maintain the bivalence state of Fe in Fc, which also induces the activation of HP...
May 3, 2017: Chemosphere
https://www.readbyqxmd.com/read/28493891/antibody-to-hsv-gd-peptide-induced-by-vaccination-does-not-protect-against-hsv-2-infection-in-hsv-2-seronegative-women
#15
Peter B Gilbert, Jean-Louis Excler, Georgia D Tomaras, Lindsay N Carpp, Barton F Haynes, Hua-Xin Liao, David C Montefiori, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayaphan, Jaranit Kaewkungwal, Gustavo H Kijak, Sodsai Tovanabutra, Donald P Francis, Carter Lee, Faruk Sinangil, Phillip W Berman, Nakorn Premsri, Prayura Kunasol, Robert J O'Connell, Nelson L Michael, Merlin L Robb, Rhoda Morrow, Lawrence Corey, Jerome H Kim
BACKGROUND: In the HIV-1 vaccine trial RV144, ALVAC-HIV prime with an AIDSVAX® B/E boost reduced HIV-1 acquisition by 31% at 42 months post first vaccination. The bivalent AIDSVAX® B/E vaccine contains two gp120 envelope glycoproteins, one from the subtype B HIV-1 MN isolate and one from the subtype CRF01_AE A244 isolate. Each envelope glycoprotein harbors a highly conserved 27-amino acid HSV-1 glycoprotein D (gD) tag sequence that shares 93% sequence identity with the HSV-2 gD sequence...
2017: PloS One
https://www.readbyqxmd.com/read/28493337/cas6-processes-tight-and-relaxed-repeat-rna-via-multiple-mechanisms-a-hypothesis
#16
REVIEW
Jana Sefcikova, Mitchell Roth, Ge Yu, Hong Li
RNA molecules are flexible yet foldable. Proteins must cope with this structural duality when forming biologically active complexes with RNA. Recent studies of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs)-mediated RNA immunity illustrate some remarkable mechanisms with which proteins interact with RNA. Currently known structures of CRISPR-Cas6 endoribonucleases bound with RNA suggest a conserved protein recognition mechanism mediated by RNA stem-loops. However, a survey of CRISPR RNA reveals that many repeats either lack a productive stem-loop (Relaxed) or possess stable but inhibitory structures (Tight), which raises the question of how the enzyme processes structurally diverse RNA...
May 11, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28488882/development-of-bioanalytical-assays-for-variegin-a-peptide-based-bivalent-direct-thrombin-inhibitor
#17
Norrapat Shih, Leonardo Pinto de Carvalho, Yie Hou Lee, Mauricio Macario Rocha, Adriano Henrique Pereira Barbosa, José Marconi A de Sousa, Antonio Carlos de C Carvalho, R Manjunatha Kini, Mark Y Chan
AIM: Variegin is an anticoagulant peptide that will be tested in porcine models of percutaneous coronary intervention. We developed three bioanalytical assays for variegin quantitation and utilized these methods to evaluate pharmacokinetics of variegin in pigs. Results & methodology: The LC-MS/MS, thrombin amidolytic and modified thrombin time assays had a quantitation range of 21.6-5541.7, 10.8-5541.7 and 5.4-5541.7 nM in human plasma, respectively. The elimination half-lives obtained using the LC-MS/MS, modified thrombin time and thrombin amidolytic assays were 52...
May 10, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28485408/genetic-and-pharmacological-antagonism-of-nk1-receptor-prevents-opiate-abuse-potential
#18
A J Sandweiss, M I McIntosh, A Moutal, R Davidson-Knapp, J Hu, A K Giri, T Yamamoto, V J Hruby, R Khanna, T M Largent-Milnes, T W Vanderah
Development of an efficacious, non-addicting analgesic has been challenging. Discovery of novel mechanisms underlying addiction may present a solution. Here we target the neurokinin system, which is involved in both pain and addiction. Morphine exerts its rewarding actions, at least in part, by inhibiting GABAergic input onto substance P (SP) neurons in the ventral tegmental area (VTA), subsequently increasing SP release onto dopaminergic neurons. Genome editing of the neurokinin 1 receptor (NK1R) in the VTA renders morphine non-rewarding...
May 9, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28484685/vi-capsular-polysaccharide-produced-by-recombinant-salmonella-enterica-serovar-paratyphi-a-confers-immunoprotection-against-infection-by-salmonella-enterica-serovar-typhi
#19
Kun Xiong, Chunyue Zhu, Zhijin Chen, Chunping Zheng, Yong Tan, Xiancai Rao, Yanguang Cong
Enteric fever is predominantly caused by Salmonella enterica serovar Typhi and Salmonella enterica serovar Paratyphi A, and accounts for an annual global incidence of 26.9 millions. In recent years, the rate of S. Paratyphi A infection has progressively increased. Currently licensed vaccines for typhoid fever, live Ty21a vaccine, Vi subunit vaccine, and Vi-conjugate vaccine, confer inadequate cross immunoprotection against enteric fever caused by S. Paratyphi A. Therefore, development of bivalent vaccines against enteric fever is urgently required...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28483453/bivalent-o-glycoside-mimetics-with-s-disulfide-se-substitutions-and-aromatic-core-synthesis-molecular-modeling-and-inhibitory-activity-on-biomedically-relevant-lectins-in-assays-of-increasing-physiological-relevance
#20
Herbert Kaltner, Tamás Szabó, Krisztina Fehér, Sabine André, Sára Balla, Joachim C Manning, László Szilágyi, Hans-Joachim Gabius
The emerging significance of recognition of cellular glycans by lectins for diverse aspects of pathophysiology is a strong incentive for considering development of bioactive and non-hydrolyzable glycoside derivatives, for example by introducing S/Se atoms and the disulfide group instead of oxygen into the glycosidic linkage. We report the synthesis of 12 bivalent thio-, disulfido- and selenoglycosides attached to benzene/naphthalene cores. They present galactose, for blocking a plant toxin, or lactose, the canonical ligand of adhesion/growth-regulatory galectins...
April 9, 2017: Bioorganic & Medicinal Chemistry
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