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https://www.readbyqxmd.com/read/28346939/a-b12-dependent-radical-sam-enzyme-involved-in-oxetanocin-a-biosynthesis
#1
Jennifer Bridwell-Rabb, Aoshu Zhong, He G Sun, Catherine L Drennan, Hung-Wen Liu
Oxetanocin A (OXT-A) is a potent antitumour, antiviral and antibacterial compound. Biosynthesis of OXT-A has been linked to a plasmid-borne Bacillus megaterium gene cluster that contains four genes: oxsA, oxsB, oxrA and oxrB. Here we show that both the oxsA and oxsB genes are required for the production of OXT-A. Biochemical analysis of the encoded proteins, a cobalamin (Cbl)-dependent S-adenosylmethionine (AdoMet) radical enzyme, OxsB, and an HD-domain phosphohydrolase, OxsA, reveals that OXT-A is derived from a 2'-deoxyadenosine phosphate in an OxsB-catalysed ring contraction reaction initiated by hydrogen atom abstraction from C2'...
March 27, 2017: Nature
https://www.readbyqxmd.com/read/28346912/optimizing-the-dose-of-erythropoietin-required-to-prevent-acute-ventilation-induced-cerebral-white-matter-injury-in-preterm-lambs
#2
Kyra Y Y Chan, Domenic A LaRosa, Mary Tolcos, Anqi Li, Valerie A Zahra, Graeme R Polglase, Samantha K Barton
Erythropoietin (EPO) is being trialed in preterm neonates for neuroprotection. We have recently demonstrated that a single high bolus dose (5,000 IU/kg) of recombinant human EPO amplified preterm lung and brain ventilation-induced injury. We aimed to determine the optimal dose of EPO to reduce ventilation-induced cerebral white matter inflammation and injury in preterm lambs. Lambs (0.85 gestation) were ventilated with an injurious strategy for 15 min followed by conventional ventilation for 105 min. Lambs were randomized to no treatment (VENT; n = 8) or received a bolus dose of EPO (EPREX®): 300 IU/kg (EPO 300; n = 5), 1,000 IU/kg (EPO 1,000; n = 5), or 3,000 IU/kg (EPO 3,000; n = 5)...
March 28, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28346745/emp10-encodes-a-mitochondrial-ppr-protein-that-affects-the-cis-splicing-of-nad2-intron-1-and-seed-development-in-maize
#3
Manjun Cai, L Shuzhen, Feng Sun, Qin Sun, Hailiang Zhao, Xuemei Ren, Yanxin Zhao, Baocai Tan, Zuxin Zhang, Fazhan Qiu
In higher plants, many mitochondrial genes contain group II-type introns that are removed from RNAs by splicing to produce mature transcripts that are then translated into functional proteins. However, the factors involved in the splicing of mitochondrial introns and their biological functions are not well understood in maize. Here, we isolated an empty pericarp 10 (emp10) mutant and identified the underlying gene by map-based cloning. Emp10 encodes a P-type mitochondria-targeted pentatricopeptide repeat (PPR) protein with 10 PPR motifs...
March 27, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28346714/discrepant-serological-assays-for-pneumococcus-in-renal-transplant-recipients
#4
Jay A Fishman, David N Iklé, Robert A Wilkinson
Vaccine immunoprotection for Streptococcus pneumoniae is mediated by opsonizing antibodies targeting serotype-specific capsular polysaccharides. Quantitative antibody levels (ELISA) and antibody-mediated opsonophagcytic assays (OPA) measure vaccine-induced protection; correlation of these assays in transplantation requires investigation. This study examines the laboratory assessment of antibody titers in vaccinated renal recipients. Streptococcus pneumoniae 19A is common in immunocompromised hosts and is represented in protein-conjugate vaccines (PCV) and polysaccharide vaccines (PSV)...
March 27, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28346704/the-chloroplast-rna-helicase-ise2-is-required-for-multiple-chloroplast-rna-processing-steps-in-arabidopsis-thaliana
#5
Krzysztof Bobik, Tyra N McCray, Ben Ernest, Jessica C Fernandez, Katharine A Howell, Thomas Lane, Margaret Staton, Tessa M Burch-Smith
INCREASED SIZE EXCLUSION LIMIT2 (ISE2) is a chloroplast-localized RNA helicase that is indispensable for proper plant development. Chloroplasts in leaves with reduced ISE2 expression have previously been shown to exhibit reduced thylakoid contents and increased stromal volume, indicative of defective development. It has recently been reported that ISE2 is required for the splicing of group II introns from chloroplast transcripts. The current study extends these findings, and presents evidence for ISE2's role in multiple aspects of chloroplast RNA processing beyond group II intron splicing...
March 27, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28346686/effects-of-catechins-and-their-related-compounds-on-cellular-accumulation-and-efflux-transport-of-mitoxantrone-in-caco-2-cell-monolayers
#6
Narumi Sugihara, Norihiko Kuroda, Fumiya Watanabe, Tominari Choshi, Jun Kamishikiryo, Makoto Seo
The ability of catechins and their related compounds to inhibit breast cancer resistance protein (BCRP) function in Caco-2 cell monolayers was investigated with mitoxantrone as a BCRP substrate. The gallate or pyrogallol moiety on the catechin structure seemed to promote increased cellular accumulation and inhibit efflux transport of mitoxantrone. The ability of gallate catechins such as (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin gallate (ECG) to increase cellular accumulation and inhibit efflux transport of mitoxantrone was greater than that of nongallate catechins...
March 27, 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28346409/the-metabolic-er-stress-sensor-ire1%C3%AE-suppresses-alternative-activation-of-macrophages-and-impairs-energy-expenditure-in-obesity
#7
Bo Shan, Xiaoxia Wang, Ying Wu, Chi Xu, Zhixiong Xia, Jianli Dai, Mengle Shao, Feng Zhao, Shengqi He, Liu Yang, Mingliang Zhang, Fajun Nan, Jia Li, Jianmiao Liu, Jianfeng Liu, Weiping Jia, Yifu Qiu, Baoliang Song, Jing-Dong J Han, Liangyou Rui, Sheng-Zhong Duan, Yong Liu
Obesity is associated with metabolic inflammation and endoplasmic reticulum (ER) stress, both of which promote metabolic disease progression. Adipose tissue macrophages (ATMs) are key players orchestrating metabolic inflammation, and ER stress enhances macrophage activation. However, whether ER stress pathways underlie ATM regulation of energy homeostasis remains unclear. Here, we identified inositol-requiring enzyme 1α (IRE1α) as a critical switch governing M1-M2 macrophage polarization and energy balance...
March 27, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28346363/rapid-and-low-cost-crp-measurement-by-integrating-a-paper-based-microfluidic-immunoassay-with-smartphone-crp-chip
#8
Meili Dong, Jiandong Wu, Zimin Ma, Hagit Peretz-Soroka, Michael Zhang, Paul Komenda, Navdeep Tangri, Yong Liu, Claudio Rigatto, Francis Lin
Traditional diagnostic tests for chronic diseases are expensive and require a specialized laboratory, therefore limiting their use for point-of-care (PoC) testing. To address this gap, we developed a method for rapid and low-cost C-reactive protein (CRP) detection from blood by integrating a paper-based microfluidic immunoassay with a smartphone (CRP-Chip). We chose CRP for this initial development because it is a strong biomarker of prognosis in chronic heart and kidney disease. The microfluidic immunoassay is realized by lateral flow and gold nanoparticle-based colorimetric detection of the target protein...
March 26, 2017: Sensors
https://www.readbyqxmd.com/read/28346358/genomic-evidence-for-bacterial-determinants-influencing-obesity-development
#9
Raphael D Isokpehi, Shaneka S Simmons, Matilda O Johnson, Marinelle Payton
Obesity is a major global public health problem requiring multifaceted interventional approaches including dietary interventions with probiotic bacteria. High-throughput genome sequencing of microbial communities in the mammalian gastrointestinal system continues to present diverse protein function information to understand the bacterial determinants that influence obesity development. The goal of the research reported in this article was to identify biological processes in probiotic bacteria that could influence the mechanisms for the extraction of energy from diet in the human gastrointestinal system...
March 26, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28346138/dilation-of-fusion-pores-by-crowding-of-snare-proteins
#10
Zhenyong Wu, Oscar D Bello, Sathish Thiyagarajan, Sarah Marie Auclair, Wensi Vennekate, Shyam S Krishnakumar, Ben O'Shaughnessy, Erdem Karatekin
Hormones and neurotransmitters are released through fluctuating exocytotic fusion pores that can flicker open and shut multiple times. Cargo release and vesicle recycling depend on the fate of the pore, which may reseal or dilate irreversibly. Pore nucleation requires zippering between vesicle-associated v- and target membrane t-SNAREs, but the mechanisms governing the subsequent pore dilation are not understood. Here, we probed dilation of single fusion pores using v-SNARE-reconstituted ~23 nm diameter discoidal nanolipoprotein particles (vNLPs) as fusion partners with cells ectopically expressing cognate, 'flipped' t-SNAREs...
March 27, 2017: ELife
https://www.readbyqxmd.com/read/28346135/polo-like-kinase-dependent-phosphorylation-of-the-synaptonemal-complex-protein-syp-4-regulates-double-strand-break-formation-through-a-negative-feedback-loop
#11
Saravanapriah Nadarajan, Talley J Lambert, Elisabeth Altendorfer, Jinmin Gao, Michael D Blower, Jennifer C Waters, Monica P Colaiácovo
The synaptonemal complex (SC) is an ultrastructurally conserved proteinaceous structure that holds homologous chromosomes together and is required for the stabilization of pairing interactions and the completion of crossover (CO) formation between homologs during meiosis I. Here, we identify a novel role for a central region component of the SC, SYP-4, in negatively regulating formation of recombination-initiating double-strand breaks (DSBs) via a feedback loop triggered by crossover designation in C. elegans...
March 27, 2017: ELife
https://www.readbyqxmd.com/read/28346094/drug-library-screening-for-the-identification-of-ionophores-that-correct-the-mistrafficking-disorder-associated-with-oxalosis-kidney-disease
#12
Shurong Hou, Franck Madoux, Louis Scampavia, Jo Ann Janovick, P Michael Conn, Timothy P Spicer
Primary hyperoxaluria is the underlying cause of oxalosis and is a life-threatening autosomal recessive disease, for which treatment may require dialysis or dual liver-kidney transplantation. The most common primary hyperoxaluria type 1 (PH1) is caused by genetic mutations of a liver-specific enzyme alanine:glyoxylate aminotransferase (AGT), which results in the misrouting of AGT from the peroxisomes to the mitochondria. Pharmacoperones are small molecules with the ability to modify misfolded proteins and route them correctly within the cells, which may present an effective strategy to treat AGT misrouting in PH1 disorders...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346055/a-to-i-editing-in-disease-is-not-fake-news
#13
Prajakta Bajad, Michael F Jantsch, Liam Keegan, Mary O'Connell
Adenosine deaminases acting on RNA (ADARs) are zinc-containing enzymes that deaminate adenosine bases to inosines within dsRNA regions in transcripts. In short, structured dsRNA hairpins individual adenosine bases may be targeted specifically and edited with up to one hundred percent efficiency, leading to the production of alternative protein variants. However, the majority of editing events occur within longer stretches of dsRNA formed by pairing of repetitive sequences. Here, many different adenosine bases are potential targets but editing efficiency is usually much lower...
March 27, 2017: RNA Biology
https://www.readbyqxmd.com/read/28346011/various-plus-unique-viral-protein-u-as-a-plurifunctional-protein-for-hiv-1-replication
#14
Andrew Soper, Guillermo Juarez-Fernandez, Hirofumi Aso, Miyu Moriwaki, Eri Yamada, Yusuke Nakano, Yoshio Koyanagi, Kei Sato
Human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome, encodes four accessory genes, one of which is viral protein U (Vpu). Recently, the study of Vpu has been of great interest. For instance, various cellular proteins are degraded (e.g. CD4) and down-modulated (e.g. tetherin) by Vpu. Vpu also antagonizes the function of tetherin and inhibits NF-κB. Moreover, Vpu is a viroporin forming ion channels and may represent a promising target for anti-HIV-1 drugs. In this review, we summarize the domains/residues that are responsible for Vpu's functions, describe the current understanding of the role of Vpu in HIV-1-infected cells, and review the effect of Vpu on HIV-1 in replication and pathogenesis...
April 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28346008/wnt-%C3%AE-catenin-signaling-is-required-for-distraction-osteogenesis-in-rats
#15
Xuemei Wang, En Luo, Ruiye Bi, Bin Ye, Jing Hu, Shujuan Zou
OVERVIEW: The Wnt signaling pathway plays crucial roles in embryonic skeletal development and postnatal bone regeneration. However, mechanisms of Wnt signaling functioning in distraction osteogenesis (DO) haven't been well characterized. MATERIALS AND METHODS: We established a DO model using Sprague-Dawley rat tibia. And a Wnt signaling blocking agent, recombinant rat Dickkopf-related protein 1 (rrDkk1), was locally applied in the distracted gap to study the role of Wnt signaling during DO process...
March 1, 2017: Connective Tissue Research
https://www.readbyqxmd.com/read/28345889/ape1-accelerates-turnover-of-hogg1-by-preventing-retrograde-binding-to-the-abasic-site-product
#16
Alexandre Esadze, Gaddiel Rodriguez, Shannen Lee Cravens, James T Stivers
A major product of oxidative DNA damage is 8-oxoguanine. In humans, 8-oxoguanine DNA Glycosylase (hOGG1) facilitates removal of these lesions, producing an abasic (AP) site in the DNA that is subsequently incised by AP-endonuclease 1 (APE1). APE1 stimulates turnover of several glycosylases by accelerating rate-limiting product release. However, there have been conflicting accounts of whether hOGG1 follows a similar mechanism. In pre-steady state kinetic measurements, we found that addition of APE1 had no effect on the rapid burst phase of 8-oxoguanine excision by hOGG1, but accelerated steady-state turnover (kcat) by ~10-fold...
March 27, 2017: Biochemistry
https://www.readbyqxmd.com/read/28345879/vibrational-probes-from-small-molecule-solvatochromism-theory-and-experiments-to-applications-in-complex-systems
#17
Bartosz Błasiak, Casey H Londergan, Lauren J Webb, Minhaeng Cho
The vibrational frequency of a chosen normal mode is one of the most accurately measurable spectroscopic properties of molecules in condensed phases. Accordingly, infrared absorption and Raman scattering spectroscopy have provided valuable information on both distributions and ensemble-average values of molecular vibrational frequencies, and these frequencies are now routinely used to investigate structure, conformation, and even absolute configuration of chemical and biological molecules of interest. Recent advancements in coherent time-domain nonlinear vibrational spectroscopy have allowed the study of heterogeneous distributions of local structures and thermally driven ultrafast fluctuations of vibrational frequencies...
March 27, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28345874/delivery-of-pesticides-to-plant-parasitic-nematodes-using-tobacco-mild-green-mosaic-virus-as-a-nanocarrier
#18
Paul L Chariou, Nicole F Steinmetz
Plant parasitic nematodes are a major burden to the global agricultural industry, causing a $157 billion loss each year in crop production worldwide. Effective treatment requires large doses of nematicides to be applied, putting the environment and human health at risk. Challenges are to treat nematodes that are located deep within the soil, feeding on the roots of plants. To attack the problem at its roots, we propose the use of tobacco mild green mosaic virus (TMGMV), an EPA-approved herbicide as a carrier to deliver nematicides...
March 27, 2017: ACS Nano
https://www.readbyqxmd.com/read/28345702/the-role-of-conformational-heterogeneity-in-regulating-the-apoptotic-activity-of-bax-protein
#19
Te-Yu Kao, Chia-Jung Tsai, Yu-Jing Lan, Yun-Wei Chiang
While activation of BAX is required for initiating mitochondria-mediated apoptosis, the underlying mechanisms remain unsettled. We studied conformations of BAX protein using pressure- and temperature-resolved ESR techniques and obtained the thermodynamic properties of the conformations. We show that inactive BAX is structurally heterogeneous and exists in equilibrium between two major populations of the conformations, UM and UM', of which the former is thermodynamically favored at room temperature. An increase in the population of UM', induced by either pressure or point mutations of BAX, renders BAX susceptible to oligomerization, which leads to cell death...
March 27, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28345667/the-toxicity-of-angiotensin-converting-enzyme-inhibitors-to-larvae-of-the-disease-vectors-aedes-aegypti-and-anopheles-gambiae
#20
Zatul-'Iffah Abu Hasan, Helen Williams, Nur M Ismail, Hidayatulfathi Othman, Gyles E Cozier, K Ravi Acharya, R Elwyn Isaac
The control of mosquitoes is threatened by the appearance of insecticide resistance and therefore new control chemicals are urgently required. Here we show that inhibitors of mosquito peptidyl dipeptidase, a peptidase related to mammalian angiotensin-converting enzyme (ACE), are insecticidal to larvae of the mosquitoes, Aedes aegypti and Anopheles gambiae. ACE inhibitors (captopril, fosinopril and fosinoprilat) and two peptides (trypsin-modulating oostatic factor/TMOF and a bradykinin-potentiating peptide, BPP-12b) were all inhibitors of the larval ACE activity of both mosquitoes...
March 27, 2017: Scientific Reports
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