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https://www.readbyqxmd.com/read/29141211/lateral-preoptic-control-of-the-lateral-habenula-through-convergent-glutamate-and-gaba-transmission
#1
David J Barker, Jorge Miranda-Barrientos, Shiliang Zhang, David H Root, Hui-Ling Wang, Bing Liu, Erin S Calipari, Marisela Morales
The lateral habenula (LHb) is a brain structure that participates in cognitive and emotional processing and has been implicated in several mental disorders. Although one of the largest inputs to the LHb originates in the lateral preoptic area (LPO), little is known about how the LPO participates in the regulation of LHb function. Here, we provide evidence that the LPO exerts bivalent control over the LHb through the convergent transmission of LPO glutamate and γ-aminobutyric acid (GABA) onto single LHb neurons...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29140444/safety-and-immunogenicity-of-different-formulations-of-norovirus-vaccine-candidate-in-healthy-adults-a-randomized-controlled-double-blind-clinical-trial
#2
G Leroux-Roels, J P Cramer, P M Mendelman, J Sherwood, R Clemens, A Aerssens, I De Coster, A Borkowski, F Baehner, P Van Damme
Background: We investigated safety and immunogenicity of 1-2 doses of different bivalent virus-like particle (VLP) norovirus vaccine candidate (NoV) formulations in healthy 18-64-year-olds. Methods: On Days 1 and 28 participants (n=420) randomized to 14 equal groups received intramuscular control vaccine (hepatitis A) or one of 11 NoV formulations contained varying dosages of GI.1 and GII.4c genotype VLP antigens with Al(OH)3, and 0μg, 15μg or 50μg MPL. Immunogenicity was assessed on Days 1, 28, 56, 208 and 393...
November 13, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29140439/bivalent-vaccine-effectiveness-against-type-specific-hpv-positivity-evidence-for-cross-protection-against-oncogenic-types-among-dutch-sti-clinic-visitors
#3
Petra J Woestenberg, Audrey J King, Birgit H B van Benthem, Robine Donken, Suzan Leussink, Fiona R M van der Klis, Hester E de Melker, Marianne A B van der Sande, Christian J P A Hoebe, Johannes A Bogaards
Background: Observational post-marketing studies are important to assess vaccine effectiveness (VE). We estimated VE from the bivalent human papillomavirus (HPV) vaccine against HPV positivity of vaccine and non-vaccine types in a high-risk population. Methods: We included all vaccine-eligible women from the PASSYON study, a biennial cross-sectional survey in Dutch sexually transmitted infection clinics. Vaginal swabs were analyzed using a PCR-based assay (SPF10-LiPA25) able to detect the 12 high-risk HPV (hrHPV) types 16/18/31/33/35/39/45/51/52/56/58/59...
November 11, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29140158/endosomal-trafficking-regulates-receptor-mediated-transcytosis-of-antibodies-across-the-blood-brain-barrier
#4
Arsalan S Haqqani, Christie E Delaney, Eric Brunette, Ewa Baumann, Graham K Farrington, William Sisk, John Eldredge, Wen Ding, Tammy-Lynn Tremblay, Danica B Stanimirovic
Current methods for examining antibody trafficking are either non-quantitative such as immunocytochemistry or require antibody labeling with tracers. We have developed a multiplexed quantitative method for antibody 'tracking' in endosomal compartments of brain endothelial cells. Rat brain endothelial cells were co-incubated with blood-brain barrier (BBB)-crossing FC5, monovalent FC5Fc or bivalent FC5Fc fusion antibodies and control antibodies. Endosomes were separated using sucrose-density gradient ultracentrifugation and analyzed using multiplexed mass spectrometry to simultaneously quantify endosomal markers, receptor-mediated transcytosis (RMT) receptors and the co-incubated antibodies in each fraction...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29139297/direct-exosome-quantification-via-bivalent-cholesterol-labeled-dna-anchor-for-signal-amplification
#5
Fang He, Hui Liu, Xinggang Guo, Bin-Cheng Yin, Bang-Ce Ye
Exosomes, as an important subpopulation of extracellular vesicles (EVs), play an important role in intercellular communications in various important pathophysiological processes, especially cancer-related. However, reliable and convenient quantitative methods for their determination are still technically challenging. In this study, we developed an efficient and direct method by combining immunoaffinity and lipid membrane surface modification into a single platform for specific isolation and accurate quantification of exosomes...
November 15, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29138400/accessibility-of-the-histone-h3-tail-in-the-nucleosome-for-binding-of-paired-readers
#6
Jovylyn Gatchalian, Xiaodong Wang, Jinzen Ikebe, Khan L Cox, Adam H Tencer, Yi Zhang, Nathaniel L Burge, Luo Di, Matthew D Gibson, Catherine A Musselman, Michael G Poirier, Hidetoshi Kono, Jeffrey J Hayes, Tatiana G Kutateladze
Combinatorial polyvalent contacts of histone-binding domains or readers commonly mediate localization and activities of chromatin-associated proteins. A pair of readers, the PHD fingers of the protein CHD4, has been shown to bivalently recognize histone H3 tails. Here we describe a mechanism by which these linked but independent readers bind to the intact nucleosome core particle (NCP). Comprehensive NMR, chemical reactivity, molecular dynamics, and fluorescence analyses point to the critical roles of intra-nucleosomal histone-DNA interactions that reduce the accessibility of H3 tails in NCP, the nucleosomal DNA, and the linker between readers in modulating nucleosome- and/or histone-binding activities of the readers...
November 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29137925/polycomb-repression-complex-2-is-required-for-the-maintenance-of-retinal-progenitor-cells-and-balanced-retinal-differentiation
#7
Naoko Fujimura, Andrea Kuzelova, Anja Ebert, Hynek Strnad, Jitka Lachova, Ondrej Machon, Meinrad Busslinger, Zbynek Kozmik
Polycomb repressive complexes maintain transcriptional repression of genes encoding crucial developmental regulators through chromatin modification. Here we investigated the role of Polycomb repressive complex 2 (PRC2) in retinal development by inactivating its key components Eed and Ezh2. Conditional deletion of Ezh2 resulted in a partial loss of PRC2 function and accelerated differentiation of Müller glial cells. In contrast, inactivation of Eed led to the ablation of PRC2 function at early postnatal stage...
November 11, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29131585/antibody-templated-assembly-of-an-rna-mimic-of-green-fluorescent-protein
#8
Alessandro Bertucci, Alessandro Porchetta, Francesco Ricci
One of the most intriguing ways through which Nature achieves regulation of biological pathways encompasses the coordination of non-covalent interactions that bring biomolecules to be co-localized in a designated restricted space. This nano-confinement leads to a drastic increase in the effective local concentration of the species involved, which ultimately triggers reactions that would otherwise not occur at the low concentrations found in cells. Inspired by this mechanism, we have explored the possibility of using antibodies as bivalent biomolecular substrates for the templated assembly of a functional RNA structure...
November 13, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29129453/hepatitis-b-virus-core-particles-containing-multiple-epitopes-confer-protection-against-enterovirus-71-and-coxsackievirus-a16-infection-in-mice
#9
Chunling Huo, Jie Yang, Lei Lei, Lei Qiao, Jiantao Xin, Zishu Pan
Human enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two major causative agents of hand-foot-and-mouth disease (HFMD). To investigate novel combined vaccines to prevent EV71 and CA16 infection, we constructed chimeric virus-like particles (tHBc/SPA or tHBc/SP VLPs) displaying conserved epitopes of EV71 (aa 208-222 of VP1 and aa 248-263 of VP2) and CA16 (aa271-285 of VP1) using a truncated hepatitis B virus core carrier (tHBc). Immunization with the chimeric VLPs induced epitope- or virus-specific IgG and neutralization antibodies against EV71 and CA16 in the mice...
November 9, 2017: Vaccine
https://www.readbyqxmd.com/read/29120074/a-fret-sensor-to-monitor-bivalent-sumo-sim-interactions-in-sumo-chain-binding
#10
Lisa J Kost, Henning D Mootz
The small ubiquitin-like modifier (SUMO) can be assembled into polymeric chains as part of its diverse biochemical signal pattern when conjugated to substrate proteins. SUMO chain recognition is facilitated by receptor proteins containing at least two SUMO-interacting motifs (SIMs). Only little is known about the structure of SUMO chains, both in unliganded form and when complexed with multi-SIM protein partners. We have developed a FRET sensor based on a linear dimer of human SUMO-2 as a minimal SUMO chain analog...
November 9, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29118097/molecular-recognition-of-ternary-complexes-a-new-dimension-in-the-structure-guided-design-of-chemical-degraders
#11
REVIEW
Scott J Hughes, Alessio Ciulli
Molecular glues and bivalent inducers of protein degradation (also known as PROTACs) represent a fascinating new modality in pharmacotherapeutics: the potential to knockdown previously thought 'undruggable' targets at sub-stoichiometric concentrations in ways not possible using conventional inhibitors. Mounting evidence suggests these chemical agents, in concert with their target proteins, can be modelled as three-body binding equilibria that can exhibit significant cooperativity as a result of specific ligand-induced molecular recognition...
November 8, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/29115156/development-and-evaluation-of-novel-recombinant-adenovirus-based-vaccine-candidates-for-infectious-bronchitis-virus-and-mycoplasma-gallisepticum-in-chickens
#12
Dongchao Zhang, Yuqing Long, Meng Li, Jianfang Gong, Xiaohui Li, Jing Lin, Jiali Meng, Keke Gao, Ruili Zhao, Tianming Jin
Avian infectious bronchitis (IB) caused by the infectious bronchitis virus (IBV) and mycoplasmosis caused by Mycoplasma gallisepticum (MG) are two major respiratory diseases in chickens that have resulted in severe economic losses in the poultry industry. We constructed a recombinant adenovirus that simultaneously expresses the S1 spike glycoprotein of IBV and the TM-1 protein of MG (pBH-S1-TM-1-EGFP). For comparison, we constructed two recombinant adenoviruses (pBH-S1-EGFP and pBH-TM-1-EGFP) that express either the S1 spike glycoprotein or the TM-1 protein alone...
November 8, 2017: Avian Pathology: Journal of the W.V.P.A
https://www.readbyqxmd.com/read/29114361/meiotic-behaviour-and-its-implication-on-species-inter-relationship-in-the-genus-curcuma-linnaeus-1753-zingiberaceae
#13
Judith Mary Lamo, Satyawada Rama Rao
In this paper, detailed meiotic analysis was investigated in seven species of Curcuma (Linnaeus, 1753) which can contribute significantly to our understanding about species inter-relationship, speciation and evolution. The species were divided into two groups viz., Group I having 2n = 42 (C. comosa Roxburgh, 1810, C. haritha Mangaly & M.Sabu, 1993, C. mangga Valeton & Zijp, 1917, and C. motana Roxburgh, 1800) and Group II with 2n = 63 (C. caesia Roxburgh, 1810, C. longa Linnaeus, 1753 and C. sylvatica Valeton, 1918)...
2017: Comparative Cytogenetics
https://www.readbyqxmd.com/read/29114358/cytogenetic-analysis-of-five-ctenidae-species-araneae-detection-of-heterochromatin-and-18s-rdna-sites
#14
Matheus Pires Rincão, João Lucas Chavari, Antonio Domingos Brescovit, Ana Lúcia Dias
The present study aimed to cytogenetically analyse five Ctenidae species Ctenus ornatus (Keyserling, 1877), Ctenus medius (Keyserling, 1891), Phoneutria nigriventer (Keyserling, 1891), Viracucha andicola (Simon, 1906), and Enoploctenus cyclothorax (Philip Bertkau, 1880), from Brazil. All species presented a 2n♂ = 28 except for V. andicola, which showed 2n♂ = 29. Analysis of segregation and behavior of sex chromosomes during male meiosis showed a sex chromosome system of the type X1X20 in species with 28 chromosomes and X1X2X30 in V...
2017: Comparative Cytogenetics
https://www.readbyqxmd.com/read/29114353/a-chromosomal-analysis-of-nepa-cinerea-linnaeus-1758-and-ranatra-linearis-linnaeus-1758-heteroptera-nepidae
#15
Robert B Angus, Constance Jeangirard, Desislava Stoianova, Snejana Grozeva, Valentina G Kuznetsova
An account is given of the karyotypes and male meiosis of the Water Scorpion Nepa cinerea Linnaeus, 1758 and the Water Stick Insect Ranatra linearis (Linnaeus, 1758) (Heteroptera, Nepomorpha, Nepidae). A number of different approaches and techniques were tried: the employment of both male and female gonads and mid-guts as the sources of chromosomes, squash and air-drying methods for chromosome preparations, C-banding and fluorescence in situ hybridization (FISH) for chromosome study. We found that N. cinerea had a karyotype comprising 14 pairs of autosomes and a multiple sex chromosome system, which is X1X2X3X4Y (♂) / X1X1X2X2X3X3X4X4 (♀), whereas R...
2017: Comparative Cytogenetics
https://www.readbyqxmd.com/read/29111677/novel-bivalent-5-ht2a-receptor-antagonists-exhibit-high-affinity-and-potency-in-vitro-and-efficacy-in-vivo
#16
Claudia A Soto, Matthew J Shashack, Robert G Fox, Marcy J Bubar, Kenner C Rice, Cheryl S Watson, Kathryn A Cunningham, Scott R Gilbertson, Noelle C Anastasio
The 5-HT2AR plays an important role in various neuropsychiatric disorders including cocaine use disorder and schizophrenia. Homodimerization of this receptor has been suggested but tools that allow direct assessment of 5-HT2AR:5-HT2AR homodimer relevance in these disorders are necessary. We chemically modified the selective 5-HT2AR antagonist M100907 to synthesize a series of homobivalent ligands connected by ethylene glycol linkers of varying lengths that may be useful tools to probe 5-HT2AR:5-HT2AR homodimer function...
November 7, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29110680/fraction-of-high-grade-cervical-intraepithelial-lesions-attributable-to-genotypes-targeted-by-a-nonavalent-hpv-vaccine-in-galicia-spain
#17
S Perez, A Iñarrea, R Pérez-Tanoira, M Gil, E López-Díez, O Valenzuela, M Porto, L Alberte-Lista, M A Peteiro-Cancelo, A Treinta, R Carballo, M C Reboredo, M E Alvarez-Argüelles, M J Purriños
BACKGROUND: Human papillomavirus (HPV) bivalent and quadrivalent vaccines have been widely implemented in worldwide organized immunization programs. A nonavalent HPV vaccine is now available in several countries. The objective was to describe the fraction of squamous non-invasive high-grade cervical intraepithelial lesions attributable to genotypes targeted by bi-quadrivalent vaccines and by nonavalent vaccine according to age and diagnosis in women living in the city of Vigo (Galicia, Spain)...
November 6, 2017: Virology Journal
https://www.readbyqxmd.com/read/29107594/genes-associated-with-pancreas-development-and-function-maintain-open-chromatin-in-ipscs-generated-from-human-pancreatic-beta-cells
#18
Matthias Thurner, Liraz Shenhav, Agata Wesolowska-Andersen, Amanda J Bennett, Amy Barrett, Anna L Gloyn, Mark I McCarthy, Nicola L Beer, Shimon Efrat
Current in vitro islet differentiation protocols suffer from heterogeneity and low efficiency. Induced pluripotent stem cells (iPSCs) derived from pancreatic beta cells (BiPSCs) preferentially differentiate toward endocrine pancreas-like cells versus those from fibroblasts (FiPSCs). We interrogated genome-wide open chromatin in BiPSCs and FiPSCs via ATAC-seq and identified ∼8.3k significant, differential open chromatin sites (DOCS) between the two iPSC subtypes (false discovery rate [FDR] < 0.05). DOCS where chromatin was more accessible in BiPSCs (Bi-DOCS) were significantly enriched for known regulators of endodermal development, including bivalent and weak enhancers, and FOXA2 binding sites (FDR < 0...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29105901/a-comparative-study-of-synthetic-and-semisynthetic-approaches-for-ligating-the-epidermal-growth-factor-to-a-bivalent-scaffold
#19
Anna Lena Gell, Nadja Groysbeck, Christian F W Becker, Anne C Conibear
A prominent target of monoclonal antibodies as targeted therapies for cancer is the epidermal growth factor receptor, which is overexpressed on the surface of various cancer cell types. Its natural binder, the epidermal growth factor (EGF), is a 53 amino acid polypeptide. Anticancer synthetic targeted immune system engagers (ISErs) comprising two 'binder' peptides, which are attached to a scaffold conveying immune stimulating 'effector' properties, via monodisperse polyethylene glycol chains. So far, preparation of ISErs has been limited to the use of small peptides (8-20 amino acids) as binding functionalities, and they have been entirely synthesized by solid phase peptide synthesis...
November 6, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/29102758/microfluidic-device-as-a-facile-in-vitro-tool-to-generate-and-investigate-lipid-gradients
#20
Brittany M Neumann, Devin Kenney, Qi Wen, Arne Gericke
This work describes a method that utilizes a microfluidic gradient generator to develop lateral lipid gradients in supported lipid bilayers (SLB). This methodology that we have developed provides freedom of choice with respect to the lipid composition as well as the shape of the lipid gradient. For instance, the steepness of the gradient, within certain limits of its functional behavior, can be chosen based upon the experimental objectives. In addition, the device has the ability to create a protein or bivalent cation gradient in the aqueous phase above the lipid bilayer and to elicit a gradient specific response in the SLB...
November 1, 2017: Chemistry and Physics of Lipids
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