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https://www.readbyqxmd.com/read/29342416/identification-of-novel-quinazolinedione-derivatives-as-ror%C3%AE-t-inverse-agonist
#1
Yoshiyuki Fukase, Ayumu Sato, Yoshihide Tomata, Atsuko Ochida, Mitsunori Kono, Kazuko Yonemori, Keiko Koga, Toshitake Okui, Masashi Yamasaki, Yasushi Fujitani, Hideyuki Nakagawa, Ryoukichi Koyama, Masaharu Nakayama, Robert Skene, Bi-Ching Sang, Isaac Hoffman, Junya Shirai, Satoshi Yamamoto
Novel small molecules were synthesized and evaluated as retinoic acid receptor-related orphan receptor-gamma t (RORγt) inverse agonists for the treatment of inflammatory and autoimmune diseases. A hit compound, 1, was discovered by high-throughput screening of our compound library. The structure-activity relationship (SAR) study of compound 1 showed that the introduction of a chlorine group at the 3-position of 4-cyanophenyl moiety increased the potency and a 3-methylpentane-1,5-diamide linker is favorable for the activity...
December 28, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29342409/development-and-characterization-of-an-allergoid-of-cat-dander-for-immunotherapy
#2
J P Sola, Y Pedreño, A Cerezo, M Peñalver-Mellado
BACKGROUND: Allergy to cats is a frequent cause of sensitization to indoor allergens and currently there are few alternatives to specific immunotherapy with cat native extracts. The objective is to develop and characterize a new allergoid to increase the tools available for use in clinical practice. METHODS: The allergoid cat dander extract (ACD) was developed from a native cat dander extract (NCD) by modification with glutaraldehyde, and the optimal process control was determined by SDS-PAGE, DOT BLOT and determination of free amine groups...
January 13, 2018: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/29342381/long-term-follow-up-of-monoclonal-gammopathy-of-undetermined-significance
#3
Robert A Kyle, Dirk R Larson, Terry M Therneau, Angela Dispenzieri, Shaji Kumar, James R Cerhan, S Vincent Rajkumar
Background Monoclonal gammopathy of undetermined significance (MGUS) occurs in approximately 3% of persons 50 years of age or older. Methods We studied 1384 patients who were residing in southeastern Minnesota and in whom MGUS was diagnosed at the Mayo Clinic in the period from 1960 through 1994; the median follow-up was 34.1 years (range, 0.0 to 43.6). The primary end point was progression to multiple myeloma or another plasma-cell or lymphoid disorder. Results During 14,130 person-years of follow-up, MGUS progressed in 147 patients (11%), a rate that was 6...
January 18, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29342354/a-highly-dynamic-loop-of-the-pseudomonas-aeruginosa-pa14-type-iv-pilin-is-essential-for-pilus-assembly
#4
Ylan Nguyen, Stephen Boulton, E Tyler McNicholl, Madoka Akimoto, Hanjeong Harvey, Francisca Aidoo, Giuseppe Melacini, Lori L Burrows
Type IVa pili (T4aP) are long, thin surface filaments involved in attachment, motility, biofilm formation, and DNA uptake. They are important virulence factors for many bacteria, including Pseudomonas aeruginosa, an opportunistic pathogen and common cause of hospital-acquired infections. Each helical filament contains thousands of monomers of the major pilin subunit, PilA. Each P. aeruginosa strain expresses one of five phylogenetically distinct major pilins, which vary in sequence and the nature of their associated accessory protein(s)...
January 17, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29342277/finding-nemo-hybrid-assembly-with-oxford-nanopore-and-illumina-reads-greatly-improves-the-clownfish-amphiprion-ocellaris-genome-assembly
#5
Mun Hua Tan, Christopher M Austin, Michael P Hammer, Yin Peng Lee, Laurence J Croft, Han Ming Gan
Background: Some of the most widely recognised coral-reef fishes are clownfish or anemonefishes, members of the family Pomacentridae (subfamily: Amphiprioninae). They are popular aquarium species due to their bright colours, adaptability to captivity and fascinating behavior. Their breeding biology (sequential hermaphrodites) and symbiotic mutualism with sea anemones have attracted much scientific interest. Moreover, there are some curious geographic-based phenotypes which warrant investigation...
January 12, 2018: GigaScience
https://www.readbyqxmd.com/read/29342245/structure-function-relationships-of-olfactory-and-taste-receptors
#6
Maik Behrens, Loïc Briand, Claire A de March, Hiroaki Matsunami, Atsuko Yamashita, Wolfgang Meyerhof, Simone Weyand
The field of chemical senses has made major progress in understanding the cellular mechanisms of olfaction and taste in the past two decades. However, the molecular understanding of odour and taste recognition is still lagging far behind and will require solving multiple structures of the relevant full-length receptors in complex with native ligands to achieve this goal. However, the development of multiple complimentary strategies for the structure determination of G protein-coupled receptors (GPCRs) makes this goal realistic...
January 12, 2018: Chemical Senses
https://www.readbyqxmd.com/read/29342242/meiotic-spindle-formation-in-mammalian-oocytes-implications-for-human-infertility
#7
Suk Namgoong, Nam-Hyung Kim
In the final stage of oogenesis, mammalian oocytes generate a meiotic spindle and undergo chromosome segregation to yield an egg that is ready for fertilization. Herein, we describe the recent advances in understanding the mechanisms controlling formation of the meiotic spindle in metaphase I (MI) and metaphase II (MII) in mammalian oocytes, and focus on the differences between mouse and human oocytes. Unlike mitotic cells, mammalian oocytes lack typical centrosomes that consist of two centrioles and the surrounding pericentriolar matrix proteins (PCM), which serve as microtubule-organizing centers (MTOCs) in most somatic cells...
January 12, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29342196/low-fitness-is-associated-with-abdominal-adiposity-and-low-grade-inflammation-independent-of-bmi
#8
Anne-Sophie Wedell-Neergaard, Louise Eriksen, Morten Grønbæk, Bente Klarlund Pedersen, Rikke Krogh-Madsen, Janne Tolstrup
OBJECTIVE: Up to 30% of obese individuals are metabolically healthy. Metabolically healthy obese (MHO) individuals are characterized by having low abdominal adiposity, low inflammation level and low risk of developing metabolic comorbidity. In this study, we hypothesize that cardiorespiratory fitness (fitness) is a determinant factor for the MHO individuals and aim to investigate the associations between fitness, abdominal adiposity and low-grade inflammation within different BMI categories...
2018: PloS One
https://www.readbyqxmd.com/read/29342181/optimization-of-mneongreen-for-homo-sapiens-increases-its-fluorescent-intensity-in-mammalian-cells
#9
Emiko Tanida-Miyake, Masato Koike, Yasuo Uchiyama, Isei Tanida
Green fluorescent protein (GFP) is tremendously useful for investigating many cellular and intracellular events. The monomeric GFP mNeonGreen is about 3- to 5-times brighter than GFP and monomeric enhanced GFP and shows high photostability. The maturation half-time of mNeonGreen is about 3-fold faster than that of monomeric enhanced GFP. However, the cDNA sequence encoding mNeonGreen contains some codons that are rarely used in Homo sapiens. For better expression of mNeonGreen in human cells, we synthesized a human-optimized cDNA encoding mNeonGreen and generated an expression plasmid for humanized mNeonGreen under the control of the cytomegalovirus promoter...
2018: PloS One
https://www.readbyqxmd.com/read/29342175/immunocontraceptive-target-repertoire-defined-by-systematic-identification-of-sperm-membrane-alloantigens-in-a-single-species
#10
Nathaly Cormier, John J McGlone, John Leszyk, Daniel M Hardy
Sperm competence in animal fertilization requires the collective activities of numerous sperm-specific proteins that are typically alloimmunogenic in females. Consequently, sperm membrane alloantigens are potential targets for contraceptives that act by blocking the proteins' functions in gamete interactions. Here we used a targeted proteomics approach to identify the major alloantigens in swine sperm membranes and lipid rafts, and thereby systematically defined the repertoire of these sperm-specific proteins in a single species...
2018: PloS One
https://www.readbyqxmd.com/read/29342168/reduction-in-musca-domestica-fecundity-by-dsrna-mediated-gene-knockdown
#11
Neil D Sanscrainte, Hanayo Arimoto, Christy M Waits, Lucy Y Li, Dana Johnson, Chris Geden, James J Becnel, Alden S Estep
House flies (Musca domestica) are worldwide agricultural pests with estimated control costs at $375 million annually in the U.S. Non-target effects and widespread resistance challenge the efficacy of traditional chemical control. Double stranded RNA (dsRNA) has been suggested as a biopesticide for M. domestica but a phenotypic response due to the induction of the RNAi pathway has not been demonstrated in adults. In this study female house flies were injected with dsRNA targeting actin-5C or ribosomal protein (RP) transcripts RPL26 and RPS6...
2018: PloS One
https://www.readbyqxmd.com/read/29342166/effects-of-vitamin-d-on-insulin-resistance-and-myosteatosis-in-diet-induced-obese-mice
#12
Elisa Benetti, Raffaella Mastrocola, Fausto Chiazza, Debora Nigro, Giuseppe D'Antona, Valentina Bordano, Roberto Fantozzi, Manuela Aragno, Massimo Collino, Marco Alessandro Minetto
Epidemiological studies pointed out to a strong association between vitamin D deficiency and type 2 diabetes prevalence. However, the role of vitamin D supplementation in the skeletal muscle, a tissue that play a crucial role in the maintenance of glucose homeostasis, has been scarcely investigated so far. On this basis, this study aimed to evaluate the effect of vitamin D supplementation in a murine model of diet-induced insulin resistance with particular attention to the effects evoked on the skeletal muscle...
2018: PloS One
https://www.readbyqxmd.com/read/29342162/comparison-of-diagnostic-methods-to-detect-histoplasma-capsulatum-in-serum-and-blood-samples-from-aids-patients
#13
Katia Cristina Dantas, Roseli Santos de Freitas, Marcos Vinicius da Silva, Paulo Ricardo Criado, Olinda do Carmo Luiz, Adriana Pardini Vicentini
BACKGROUND: Although early and rapid detection of histoplasmosis is essential to prevent morbidity and mortality, few diagnostic tools are available in resource-limited areas, especially where it is endemic and HIV/AIDS is also epidemic. Thus, we compared conventional and molecular methods to detect Histoplasma capsulatum in sera and blood from HIV/AIDS patients. METHODOLOGY: We collected a total of 40 samples from control volunteers and patients suspected of histoplasmosis, some of whom were also infected with other pathogens...
2018: PloS One
https://www.readbyqxmd.com/read/29342159/prediction-of-novel-target-genes-and-pathways-involved-in-bevacizumab-resistant-colorectal-cancer
#14
Precious Takondwa Makondi, Chia-Hwa Lee, Chien-Yu Huang, Chi-Ming Chu, Yu-Jia Chang, Po-Li Wei
Bevacizumab combined with cytotoxic chemotherapy is the backbone of metastatic colorectal cancer (mCRC) therapy; however, its treatment efficacy is hampered by therapeutic resistance. Therefore, understanding the mechanisms underlying bevacizumab resistance is crucial to increasing the therapeutic efficacy of bevacizumab. The Gene Expression Omnibus (GEO) database (dataset, GSE86525) was used to identify the key genes and pathways involved in bevacizumab-resistant mCRC. The GEO2R web tool was used to identify differentially expressed genes (DEGs)...
2018: PloS One
https://www.readbyqxmd.com/read/29342156/specialized-attachment-structure-of-the-fish-pathogenic-oomycete-saprolegnia-parasitica
#15
Svetlana Rezinciuc, Jose Vladimir Sandoval-Sierra, Yolanda Ruiz-León, Pieter van West, Javier Diéguez-Uribeondo
The secondary cysts of the fish pathogen oomycete Saprolegnia parasitica possess bundles of long hooked hairs that are characteristic to this economically important pathogenic species. Few studies have been carried out on elucidating their specific role in the S. parasitica life cycle and the role they may have in the infection process. We show here their function by employing several strategies that focus on descriptive, developmental and predictive approaches. The strength of attachment of the secondary cysts of this pathogen was compared to other closely related species where bundles of long hooked hairs are absent...
2018: PloS One
https://www.readbyqxmd.com/read/29342154/three-unrelated-and-unexpected-amino-acids-determine-the-susceptibility-of-the-interface-cysteine-to-a-sulfhydryl-reagent-in-the-triosephosphate-isomerases-of-two-trypanosomes
#16
Selma Díaz-Mazariegos, Nallely Cabrera, Ruy Perez-Montfort
Proteins with great sequence similarity usually have similar structure, function and other physicochemical properties. But in many cases, one or more of the physicochemical or functional characteristics differ, sometimes very considerably, among these homologous proteins. To better understand how critical amino acids determine quantitative properties of function in proteins, the responsible residues must be located and identified. This can be difficult to achieve, particularly in cases where multiple amino acids are involved...
2018: PloS One
https://www.readbyqxmd.com/read/29342139/structure-and-mutagenesis-reveal-essential-capsid-protein-interactions-for-kshv-replication
#17
Xinghong Dai, Danyang Gong, Hanyoung Lim, Jonathan Jih, Ting-Ting Wu, Ren Sun, Z Hong Zhou
Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma, a cancer that commonly affects patients with AIDS and which is endemic in sub-Saharan Africa. The KSHV capsid is highly pressurized by its double-stranded DNA genome, as are the capsids of the eight other human herpesviruses. Capsid assembly and genome packaging of herpesviruses are prone to interruption and can therefore be targeted for the structure-guided development of antiviral agents. However, herpesvirus capsids-comprising nearly 3,000 proteins and over 1,300 Å in diameter-present a formidable challenge to atomic structure determination and functional mapping of molecular interactions...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29342124/the-root-of-atractylodes-macrocephala-koidzumi-prevents-obesity-and-glucose-intolerance-and-increases-energy-metabolism-in-mice
#18
Mi Young Song, Soo-Kyoung Lim, Jing-Hua Wang, Hojun Kim
Targeting energy expenditure offers a strategy for treating obesity more effectively and safely. In previous studies, we found that the root of Atractylodes macrocephala Koidzumi (Atractylodis Rhizoma Alba, ARA) increased energy metabolism in C2C12 cells. Here, we investigated the effects of ARA on obesity and glucose intolerance by examining energy metabolism in skeletal muscle and brown fat in high-fat diet (HFD) induced obese mice. ARA decreased body weight gain, hepatic lipid levels and serum total cholesterol levels, but did not modify food intake...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29342086/copy-number-variation-in-sox6-contributes-to-chicken-muscle-development
#19
Shudai Lin, Xiran Lin, Zihao Zhang, Mingya Jiang, Yousheng Rao, Qinghua Nie, Xiquan Zhang
Copy number variations (CNVs), which cover many functional genes, are associated with complex diseases, phenotypic diversity and traits that are economically important to raising chickens. The sex-determining region Y-box 6 (Sox6) plays a key role in fast-twitch muscle fiber differentiation of zebrafish and mice, but it is still unknown whether SOX6 plays a role in chicken skeletal muscle development. We identified two copy number polymorphisms (CNPs) which were significantly related to different traits on the genome level in chickens by AccuCopy® and CNVplex® analyses...
January 17, 2018: Genes
https://www.readbyqxmd.com/read/29342075/enrichment-and-identification-of-the-most-abundant-zinc-binding-proteins-in-developing-barley-grains-by-zinc-imac-capture-and-nano-lc-ms-ms
#20
Giuseppe Dionisio, Mohammad Nasir Uddin, Eva Vincze
Background: Zinc accumulates in the embryo, aleurone, and subaleurone layers at different amounts in cereal grains. Our hypothesis is that zinc could be stored bound, not only to low MW metabolites/proteins, but also to high MW proteins as well. Methods: In order to identify the most abundant zinc binding proteins in different grain tissues, we microdissected barley grains into (1) seed coats; (2) aleurone/subaleurone; (3) embryo; and (4) endosperm. Initial screening for putative zinc binding proteins from the different tissue types was performed by fractionating proteins according to solubility (Osborne fractionation), and resolving those via Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE) followed by polyvinylidene fluoride (PVDF) membrane blotting and dithizone staining...
January 17, 2018: Proteomes
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