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https://www.readbyqxmd.com/read/28445864/tumor-antigen-glycosaminoglycan-modification-regulates-antibody-drug-conjugate-delivery-and-cytotoxicity
#1
Helena C Christianson, Julien A Menard, Vineesh Indira Chandran, Erika Bourseau-Guilmain, Dmitry Shevela, Jon Lidfeldt, Ann-Sofie Månsson, Silvia Pastorekova, Johannes Messinger, Mattias Belting
Aggressive cancers are characterized by hypoxia, which is a key driver of tumor development and treatment resistance. Proteins specifically expressed in the hypoxic tumor microenvironment thus represent interesting candidates for targeted drug delivery strategies. Carbonic anhydrase (CAIX) has been identified as an attractive treatment target as it is highly hypoxia specific and expressed at the cell-surface to promote cancer cell aggressiveness. Here, we find that cancer cell internalization of CAIX is negatively regulated by post-translational modification with chondroitin or heparan sulfate glycosaminoglycan chains...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445592/polo-like-kinase-1-is-a-proviral-host-factor-for-hepatitis-b-virus-replication
#2
Ahmed M Diab, Adrien Foca, Floriane Fusil, Thomas Lahlali, Pascal Jalaguier, Fouzia Amirache, Lia N'Guyen, Nathalie Isorce, François-Loïc Cosset, Fabien Zoulim, Ourania M Andrisani, David Durantel
Chronic Hepatitis B Virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC) and current treatments for CHB and HCC are perfectible. Herein, we identified cellular Serine/Threonine Polo-like-kinase 1 (PLK1) as a positive effector of HBV replication. The aim of this study was to demonstrate the proviral role of PLK1 in HBV biosynthesis and validate PLK1 inhibition a potential antiviral strategy. To this end, we employed physiologically relevant HBV infection models of Primary Human Hepatocytes (PHH) and differentiated HepaRG cells, in conjunction with pharmacologic PLK1 inhibitors, siRNA-mediated knockdown, and overexpression of constitutively active PLK1 (PLK1(CA) )...
April 26, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28445543/comparative-genomic-analysis-between-corynebacterium-pseudotuberculosis-strains-isolated-from-buffalo
#3
Marcus Vinicius Canário Viana, Henrique Figueiredo, Rommel Ramos, Luis Carlos Guimarães, Felipe Luiz Pereira, Fernanda Alves Dorella, Salah Abdel Karim Selim, Mohammad Salaheldean, Artur Silva, Alice R Wattam, Vasco Azevedo
Corynebacterium pseudotuberculosis is a Gram-positive, pleomorphic, facultative intracellular pathogen that causes Oedematous Skin Disease (OSD) in buffalo. To better understand the pathogenic mechanisms of OSD, we performed a comparative genomic analysis of 11 strains of C. pseudotuberculosis isolated from different buffalo found to be infected in Egypt during an outbreak that occurred in 2008. Sixteen previously described pathogenicity islands (PiCp) were present in all of the new buffalo strains, but one of them, PiCp12, had an insertion that contained both a corynephage and a diphtheria toxin gene, both of which may play a role in the adaptation of C...
2017: PloS One
https://www.readbyqxmd.com/read/28445526/biosynthesis-of-the-oxygenated-diterpene-nezukol-in-the-medicinal-plant-isodon-rubescens-is-catalyzed-by-a-pair-of-diterpene-synthases
#4
Kyle A Pelot, David M Hagelthorn, J Bennett Addison, Philipp Zerbe
Plants produce an immense diversity of natural products (i.e. secondary or specialized metabolites) that offer a rich source of known and potentially new pharmaceuticals and other desirable bioproducts. The Traditional Chinese Medicinal plant Isodon rubescens (Lamiaceae) contains an array of bioactive labdane-related diterpenoid natural products. Of these, the ent-kauranoid oridonin is the most prominent specialized metabolite that has been extensively studied for its potent antimicrobial and anticancer efficacy...
2017: PloS One
https://www.readbyqxmd.com/read/28445050/involvement-of-wrky-transcription-factors-in-aba-induced-cold-tolerance-of-banana-fruit
#5
Dong-Lan Luo, Liang-Jie Ba, Wei Shan, Jian-Fei Kuang, Wang-Jin Lu, Jian-Ye Chen
Phytohormone abscisic acid (ABA) and plant-specific WRKY transcription factors (TFs) have been implicated to play important roles in various stress responses. The involvement of WRKY TFs in ABA-mediated cold tolerance of economical fruits, such as banana fruit, however remains largely unknown. Here, we reported that ABA application could induce expressions of ABA biosynthesis-related genes MaNCED1 and MaNCED2, increase endogenous ABA contents and thereby enhance cold tolerance in banana fruit. Four banana fruit WRKY TFs, designated as MaWRKY31, MaWRKY33, MaWRKY60, and MaWRKY71, were identified and characterized...
April 26, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28444797/the-transcription-factor-myb115-contributes-to-the-regulation-of-proanthocyanidin-biosynthesis-and-enhances-fungal-resistance-in-poplar
#6
Lijun Wang, Lingyu Ran, Yisu Hou, Qiaoyan Tian, Chaofeng Li, Rui Liu, Di Fan, Keming Luo
Proanthocyanidins (PAs) are major defense phenolic compounds in the leaves of poplar (Populus spp.) in response to abiotic and biotic stresses. Transcriptional regulation of PA biosynthetic genes by the MYB-basic helix-loop-helix (bHLH)-WD40 complexes in poplar is not still fully understood. Here, an Arabidopsis TT2-like gene MYB115 was isolated from Populus tomentosa and characterized by various molecular, genetic and biochemical approaches. MYB115 restored PA productions in the seed coat of the Arabidopsis tt2 mutant...
April 26, 2017: New Phytologist
https://www.readbyqxmd.com/read/28444604/effect-of-%C3%AE-irradiation-on-fumonisin-producing-fusarium-associated-with-animal-and-poultry-feed-mixtures
#7
B V Deepthi, A P Gnanaprakash, M Y Sreenivasa
Contamination of animal and poultry feeds by Fusarium and the mycotoxin Fumonisin B1 is frequent in the feed supply chain. The present study evaluated the prevalence of fumonisin B1 producing Fusarium among irradiated and non-irradiated animal and poultry feed mixtures. Further, the efficiency of γ-rays (2.5, 5.0, 7.5, and 10.0 kGy) to minimize Fusarium growth and biosynthesis of fumonisin B1 in artificially inoculated feed was evaluated. A total of 108 feed samples were collected in which 45.37% of feed mixtures were contaminated with Fusarium species...
May 2017: 3 Biotech
https://www.readbyqxmd.com/read/28444444/bioinformatic-and-expression-analyses-on-carotenoid-dioxygenase-genes-in-fruit-development-and-abiotic-stress-responses-in-fragaria-vesca
#8
Yong Wang, Guanqun Ding, Tingting Gu, Jing Ding, Yi Li
Carotenoid dioxygenases, including 9-cis-epoxycarotenoid dioxygenases (NCEDs) and carotenoid cleavage dioxygenases (CCDs), can selectively cleave carotenoids into various apocarotenoid products that play important roles in fleshy fruit development and abiotic stress response. In this study, we identified 12 carotenoid dioxygenase genes in diploid strawberry Fragaria vesca, and explored their evolution with orthologous genes from nine other species. Phylogenetic analyses suggested that the NCED and CCDL groups moderately expanded during their evolution, whereas gene numbers of the CCD1, CCD4, CCD7, and CCD8 groups maintained conserved...
April 25, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28444368/simultaneous-targeting-of-multiple-gene-homeologues-to-alter-seed-oil-production-in-camelina-sativa
#9
J A Aznar-Moreno, T P Durrett
The ability to easily transform Camelina sativa with biosynthetic enzymes derived from other plants has made this oil seed crop an ideal platform for the production of unusual lipids valuable for different applications. However, in addition to expressing transgenic enzymes, the suppression of endogenous enzyme activity to reduce competition for common substrates or cofactors is also required to enhance the production of target compounds. As camelina possesses a relatively undifferentiated hexaploid genome, up to three gene homeologues can encode for any particular enzymatic activity, complicating efforts to alter endogenous biosynthetic pathways...
April 21, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28443932/nucleoside-linked-shunt-products-in-the-reaction-catalyzed-by-the-class-c-radical-s-adenosylmethionine-methyltransferase-nosn
#10
Wei Ding, Yujie Wu, Xinjian Ji, Haocheng Qianzhu, Fener Chen, Zixin Deng, Yi Yu, Qi Zhang
NosN is a class C radical S-adenosylmethionine (SAM) methyltransferase (RSMT) involved in the biosynthesis of nosiheptide, a clinically interesting thiopeptide antibiotic produced by Streptomyces actuosus. NosN employs an unprecedented catalytic mechanism, in which SAM is converted to 5'-methylthioadenosine (MTA) as a direct methyl donor. In this study, we report identification of several nucleoside-linked shunt products in the NosN-catalyzed reaction. Comparative analysis of NosN and the class A RSMT RlmN and further density functional theory (DFT) calculations reveal important mechanistic insights into the catalyses of the two types of enzymes, showing that the radical intermediates generated by similar pathways can have very diverse reactivities...
April 26, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28443658/dceo-biotechnology-tools-to-design-construct-evaluate-and-optimize-the-metabolic-pathway-for-biosynthesis-of-chemicals
#11
Xiulai Chen, Cong Gao, Liang Guo, Guipeng Hu, Qiuling Luo, Jia Liu, Jens Nielsen, Jian Chen, Liming Liu
Chemical synthesis is a well established route for producing many chemicals on a large scale, but some drawbacks still exist in this process, such as unstable intermediates, multistep reactions, complex process control, etc. Biobased production provides an attractive alternative to these challenges, but how to make cells into efficient factories is challenging. As a key enabling technology to develop efficient cell factories, design-construction-evaluation-optimization (DCEO) biotechnology, which incorporates the concepts and techniques of pathway design, pathway construction, pathway evaluation, and pathway optimization at the systems level, offers a conceptual and technological framework to exploit potential pathways, modify existing pathways and create new pathways for the optimal production of desired chemicals...
April 26, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28443130/modular-design-of-picroside-ii-biosynthesis-deciphered-through-ngs-transcriptomes-and-metabolic-intermediates-analysis-in-naturally-variant-chemotypes-of-a-medicinal-herb-picrorhiza-kurroa
#12
Varun Kumar, Ankush Bansal, Rajinder S Chauhan
Picroside-II (P-II), an iridoid glycoside, is used as an active ingredient of various commercial herbal formulations available for the treatment of liver ailments. Despite this, the knowledge of P-II biosynthesis remains scarce owing to its negligence in Picrorhiza kurroa shoots which sets constant barrier for function validation experiments. In this study, we utilized natural variation for P-II content in stolon tissues of different P. kurroa accessions and deciphered its metabolic route by integrating metabolomics of intermediates with differential NGS transcriptomes...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28443112/transcriptome-guided-mining-of-genes-involved-in-crocin-biosynthesis
#13
Aijia Ji, Jing Jia, Zhichao Xu, Ying Li, Wu Bi, Fengming Ren, Chunnian He, Jie Liu, Kaizhi Hu, Jingyuan Song
Gardenia jasminoides is used in traditional Chinese medicine and has drawn attention as a rich source of crocin, a compound with reported activity against various cancers, depression and cardiovascular disease. However, genetic information on the crocin biosynthetic pathway of G. jasminoides is scarce. In this study, we performed a transcriptome analysis of the leaves, green fruits, and red fruits of G. jasminoides to identify and predict the genes that encode key enzymes responsible for crocin production, compared with Crocus sativus...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28443016/genetics-of-aggression-in-alzheimer-s-disease-ad
#14
Walter J Lukiw, Evgeny I Rogaev
Alzheimer's disease (AD) is a terminal, age-related neurological syndrome exhibiting progressive cognitive and memory decline, however AD patients in addition exhibit ancillary neuropsychiatric symptoms (NPSs) and these include aggression. In this communication we provide recent evidence for the mis-regulation of a small family of genes expressed in the human hippocampus that appear to be significantly involved in expression patterns common to both AD and aggression. DNA array- and mRNA transcriptome-based gene expression analysis and candidate gene association and/or genome-wide association studies (CGAS, GWAS) of aggressive attributes in humans have revealed a surprisingly small subset of six brain genes that are also strongly associated with altered gene expression patterns in AD...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28442603/aspergillus-fumigatus-trehalose-regulatory-subunit-homolog-moonlights-to-mediate-cell-wall-homeostasis-through-modulation-of-chitin-synthase-activity
#15
Arsa Thammahong, Alayna K Caffrey-Card, Sourabh Dhingra, Joshua J Obar, Robert A Cramer
Trehalose biosynthesis is found in fungi but not humans. Proteins involved in trehalose biosynthesis are essential for fungal pathogen virulence in humans and plants through multiple mechanisms. Loss of canonical trehalose biosynthesis genes in the human pathogen Aspergillus fumigatus significantly alters cell wall structure and integrity, though the mechanistic link between these virulence-associated pathways remains enigmatic. Here we characterize genes, called tslA and tslB, which encode proteins that contain domains similar to those corresponding to trehalose-6-phosphate phosphatase but lack critical catalytic residues for phosphatase activity...
April 25, 2017: MBio
https://www.readbyqxmd.com/read/28442547/biosynthesis-of-proresolving-lipid-mediators-by-vascular-cells-and-tissues
#16
Anuran Chatterjee, Sevan Komshian, Brian E Sansbury, Bian Wu, Giorgio Mottola, Mian Chen, Matthew Spite, Michael S Conte
Recent evidence suggests that specialized proresolving lipid mediators (SPMs) generated from docosahexaenoic acid (DHA) can modulate the vascular injury response. However, cellular sources for these autacoids within the vessel wall remain unclear. Here, we investigated whether isolated vascular cells and tissues can produce SPMs and assessed expression and subcellular localization of the key SPM biosynthetic enzyme 5-lipoxygenase (LOX) in vascular cells. Intact human arteries incubated with DHA ex vivo produced 17-hydroxy DHA (17-HDHA) and D-series resolvins, as assessed by liquid chromatography-tandem mass spectrometry...
April 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28442472/functional-and-metabolomic-consequences-of-atp-dependent-potassium-channel-inactivation-in-human-islets
#17
Changhong Li, Amanda M Ackermann, Kara E Boodhansingh, Tricia R Bhatti, Chengyang Liu, Jonathan Schug, Nicolai Doliba, Bing Han, Karen E Cosgrove, Indraneel Banerjee, Franz M Matschinsky, Itzhak Nissim, Klaus H Kaestner, Ali Naji, N Scott Adzick, Mark J Dunne, Charles A Stanley, Diva D De León
Loss-of-function mutations of β-cell KATP channels cause the most severe form of congenital hyperinsulinism (KATPHI). KATPHI is characterized by fasting and protein-induced hypoglycemia that is unresponsive to medical therapy. For a better understanding of the pathophysiology of KATPHI, we examined cytosolic calcium, insulin secretion, oxygen consumption, and [U-(13)C]glucose metabolism in islets isolated from the pancreases of children with KATPHI who required pancreatectomy. Basal cytosolic calcium ([Ca(2+)] i ) and insulin secretion were higher in KATPHI islets compared to controls...
April 25, 2017: Diabetes
https://www.readbyqxmd.com/read/28442441/aspergillus-flavus-aswa-a-gene-homolog-of-aspergillus-nidulans-oefc-regulates-sclerotial-development-and-biosynthesis-of-sclerotium-associated-secondary-metabolites
#18
Perng-Kuang Chang, Leslie L Scharfenstein, Robert W Li, Natalia Arroyo-Manzanares, Sarah De Saeger, José Diana Di Mavungu
Aspergillus flavus aswA (AFLA_085170) is a gene encoding a Zn(II)2Cys6 DNA-binding domain and a transcriptional activation domain, DUF3468. Disruption of aswA yielded strains that made a truncated gene transcript and generated a fungus that produced a greatly increased number of sclerotia. These sclerotia were odd-shaped and non-pigmented (white) and different from oval and pigmented (dark brown to black) mature sclerotia. Transcriptomic analysis of the ΔaswA strain grown on potato dextrose agar plates and Wickerham agar plates showed that expression of clustering genes involved in the biosynthesis of three sclerotium-associated secondary metabolites was down-regulated...
April 22, 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28442426/identification-of-a-wza-like-gene-involved-in-capsule-biosynthesis-pathogenicity-and-biofilm-formation-in-riemerella-anatipestifer
#19
Haibo Yi, Biao Yuan, Jibin Liu, Dekang Zhu, Ying Wu, Mingshu Wang, Renyong Jia, Kunfeng Sun, Qiao Yang, Shun Chen, Mafeng Liu, Xiaoyue Chen, Anchun Cheng
Duck infectious serositis is the most serious bacterial disease of ducks. It is caused by Riemerella anatipestifer (RA) infection. The capsule plays an important role in virulence of many pathogenic bacteria. In addition, the capsule has some key biological features. However, few studies have explored the characteristics of the RA capsule. In this study, we mainly constructed a capsular mutants of RA by inactivating the wza gene using homologous recombination. We found that the mutant was failed to produce a capsule layer...
April 22, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28442346/identification-of-enzymes-involved-in-the-mevalonate-pathway-of-flavobacterium-johnsoniae
#20
Hajime Hayakawa, Fumiaki Sobue, Kento Motoyama, Tohru Yoshimura, Hisashi Hemmi
The mevalonate pathway is prevalent in eukaryotes, archaea, and a limited number of bacteria. This pathway yields the fundamental precursors for isoprenoid biosynthesis, i.e., isopentenyl diphosphate and dimethylally diphosphate. In the downstream part of the general eukaryote-type mevalonate pathway, mevalonate is converted into isopentenyl diphosphate by the sequential actions of mevalonate kinase, phosphomevalonate kinase, and diphosphomevalonte decarboxylase, while a partial lack of the putative genes of these enzymes is sometimes observed in archaeal and bacterial genomes...
April 22, 2017: Biochemical and Biophysical Research Communications
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