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https://www.readbyqxmd.com/read/29786902/engineered-metalloenzymes-with-non-canonical-coordination-environments
#1
Takahiro Hayashi, Donald Hilvert, Anthony P Green
Nature employs a limited number of genetically encoded, metal coordinating residues to create metalloenzymes with diverse structures and functions. Engineered components of the cellular translation machinery can now be exploited to genetically encode non-canonical ligands with user-defined electronic and structural properties. This ability to efficiently install 'chemically programmed' ligands into proteins can provide powerful chemical probes of metalloenzyme mechanisms and presents excellent opportunities to create metalloprotein catalysts with augmented properties and novel activities...
May 22, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29786664/enable-2017-the-first-european-phd-and-post-doc-symposium-session-3-in-vitro-to-in-vivo-modeling-life-in-3d
#2
Gianmarco Di Mauro, Ambra Dondi, Giovanni Giangreco, Alexander Hogrebe, Elja Louer, Elisa Magistrati, Meeli Mullari, Gemma Turon, Wouter Verdurmen, Helena Xicoy Cortada, Sanja Zivanovic
The EUROPEAN ACADEMY FOR BIOMEDICAL SCIENCE (ENABLE) is an initiative funded by the European Union Horizon 2020 program involving four renowned European research institutes (Institute for Research in Biomedicine-IRB Barcelona, Spain; Radboud Institute for Molecular Life Sciences-RIMLS, the Netherlands; Novo Nordisk Foundation Center for Protein Research-NNF CPR, Denmark; European School of Molecular Medicine-SEMM, Italy) and an innovative science communication agency (Scienseed). With the aim to promote biomedical science of excellence in Europe, ENABLE organizes an annual three-day international event...
May 22, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29786657/eukaryotic-translation-initiation-factor-4a-down-regulation-mediates-interleukin-24-induced-apoptosis-through-inhibition-of-translation
#3
Xuelin Zhong, Leah Persaud, Hilal Muharam, Ashleigh Francis, Dibash Das, Bertal Huseyin Aktas, Moira Sauane
Dysregulated activity of helicase eIF4A drives transformation to and maintenance of cancer cell phenotype by reprogramming cellular translation. Interleukin 24 (IL-24) is a tumor-suppressing protein, which has the ability to inhibit angiogenesis, sensitize cancer cells to chemotherapy, and induce cancer cell-specific apoptosis. In this study, we found that eIF4A is inhibited by IL-24. Consequently, selective reduction of translation was observed for mRNAs harboring strong secondary structures in their 5'-untranslated regions (5'UTRs)...
May 22, 2018: Cancers
https://www.readbyqxmd.com/read/29786648/utilizing-optimized-tools-to-investigate-ptm-crosstalk-identifying-potential-ptm-crosstalk-of-acetylated-mitochondrial-proteins
#4
Henrick Horita, Andy Law, Kim Middleton
Post-translational modification (PTM) crosstalk is recognized as a major cell-regulatory mechanism, and studies of several proteins have validated the premise that PTMs work in concert. Previous work by our group investigated the potential PTM crosstalk on proteins in the EGFR-Ras-c-Fos axis by utilizing a comprehensive set of PTM reagents termed Signal-Seeker toolkits. In this study, these tools were used to investigate the potential PTM crosstalk that occurs in acetylated mitochondrial proteins in response to a mitochondrial stress-inducing agent hydrogen peroxide (H₂O₂)...
May 22, 2018: Proteomes
https://www.readbyqxmd.com/read/29786419/multifunctional-high-molecular-weight-post-translationally-modified-proteins-through-oxidative-cysteine-coupling-and-tyrosine-modification
#5
Brian M Seifried, James Cao, Bradley D Olsen
Glycoproteins and their mimics are challenging to produce via chemical or biological methods because of their long protein backbones and large number of polysaccharide side chains that form a densely grafted protein-polysaccharide brush architecture. Herein, we demonstrate a new approach to protein bioconjugate synthesis that can approach the molar mass and functionalization densities of natural glycoproteins such as mucins and aggrecans. In this method, a tyrosine-enriched protein sequence is engineered and synthesized in E...
May 22, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29785777/paradoxical-effect-of-baclofen-on-social-behavior-in-the-fragile-x-syndrome-mouse-model
#6
Shimriet Zeidler, Andreea S Pop, Israa A Jaafar, Helen de Boer, Ronald A M Buijsen, Celine E F de Esch, Ingeborg Nieuwenhuizen-Bakker, Renate K Hukema, Rob Willemsen
INTRODUCTION: Fragile X syndrome (FXS) is a common monogenetic cause of intellectual disability, autism spectrum features, and a broad range of other psychiatric and medical problems. FXS is caused by the lack of the fragile X mental retardation protein (FMRP), a translational regulator of specific mRNAs at the postsynaptic compartment. The absence of FMRP leads to aberrant synaptic plasticity, which is believed to be caused by an imbalance in excitatory and inhibitory network functioning of the synapse...
April 26, 2018: Brain and Behavior
https://www.readbyqxmd.com/read/29785510/measuring-translational-diffusion-of-15-n-enriched-biomolecules-in-complex-solutions-with-a-simplified-1-h-15-n-hmqc-filtered-best-sequence
#7
Shenggen Yao, Thomas G Meikle, Ashish Sethi, Frances Separovic, Jeffrey J Babon, David W Keizer
Pulsed-field gradient nuclear magnetic resonance has seen an increase in applications spanning a broad range of disciplines where molecular translational diffusion properties are of interest. The current study introduces and experimentally evaluates the measurement of translational diffusion coefficients of 15 N-enriched biomolecules using a 1 H-15 N HMQC-filtered band-selective excitation short transient (BEST) sequence as an alternative to the previously described SOFAST-XSTE sequence. The results demonstrate that accurate translational diffusion coefficients of 15 N-labelled peptides and proteins can be obtained using this alternative 1 H-15 N HMQC-filtered BEST sequence which is implementable on NMR spectrometers equipped with probes fitted with a single-axis field gradient, including most cryoprobes dedicated to bio-NMR...
May 21, 2018: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/29785487/rapid-monitoring-of-the-target-protein-expression-with-a-fluorescent-signal-based-on-a-dicistronic-construct-in-escherichia-coli
#8
Chang-Ye Hui, Yan Guo, Wen Zhang, Xian-Qing Huang
Real-time quantification of recombinant proteins is important in studies on fermentation engineering, cell engineering, etc. Measurement of the expression level of heterologous proteins in bacterial fermentation broth has traditionally relied on time-consuming and labor-intensive procedures, such as polyacrylamide gel electrophoresis, immunoblot analysis, and biological activity assays. We describe a simple, fast, and high sensitive assay for detecting heterologous proteins production in bacteria either at the overall level (fluorescence spectrophotometry) or at the individual level (fluorescence microscopic image) in this study...
May 21, 2018: AMB Express
https://www.readbyqxmd.com/read/29784884/the-effector-gene-xopae-of-xanthomonas-euvesicatoria-85-10-is-part-of-an-operon-and-encodes-an-e3-ubiquitin-ligase
#9
Georgy Popov, Bharat Bhusan Majhi, Guido Sessa
The type III effector XopAE from the Xanthomonas euvesicatoria strain 85-10 ( Xe 85-10) was previously shown to inhibit plant immunity and enhance pathogen-induced disease symptoms. Evolutionary analysis of 60 xopAE alleles ( AEal ) revealed that the xopAE locus is conserved in multiple Xanthomonas species. The majority of xopAE alleles (55 out of 60) encodes a single ORF ( xopAE ), while in 5 alleles, including AEal 37 of the Xe 85-10 strain, a frame-shift splits the locus into two ORFs ( hpaF and a truncated xopAE )...
May 21, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29784880/arginine-methylation-of-translocated-in-liposarcoma-tls-inhibits-its-binding-to-long-noncoding-rna-abrogating-tls-mediated-repression-of-cbp-p300-activity
#10
Wei Cui, Ryoma Yoneda, Naomi Ueda, Riki Kurokawa
Translocated in liposarcoma (TLS) is an RNA-binding protein and a transcription-regulatory sensor of DNA damage. TLS binds promoter-associated noncoding RNA (pncRNA) and inhibits histone acetyltransferase (HAT) activity of CREB-binding protein (CBP)/E1A-binding protein P300 (p300) on the cyclin D1 (CCND1) gene. Although post-translational modifications of TLS, such as arginine methylation, are known to regulate TLS's nucleocytoplasmic shuttling and assembly in stress granules, its interactions with RNAs remain poorly characterized...
May 21, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29784847/translation-elongation-factor-4-lepa-contributes-to-tetracycline-susceptibility-by-stalling-elongating-ribosomes
#11
Bin Liu, Chunlai Chen
Even though elongation factor 4 (EF4) is the third most conserved protein in bacteria, its physiological functions remain largely unknown and its proposed molecular mechanisms are conflicting among previous studies. In the present study we show that growth of an Escherichia coli strain is more susceptible to tetracycline than its EF4 knockout strain. In consistence with previous studies, our results suggested that EF4 affects ribosome biogenesis when tetracycline is present. Through ribosome profiling analysis, we discovered that EF4 causes 1-nucleotide shifting of ribosomal footprints on mRNA when cells have been exposed to tetracycline...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784786/two-ck1%C3%AE-transcripts-regulated-by-m6a-methylation-code-for-two-antagonistic-kinases-in-the-control-of-the-circadian-clock
#12
Jean-Michel Fustin, Rika Kojima, Kakeru Itoh, Hsin-Yi Chang, Ye Shiqi, Bowen Zhuang, Asami Oji, Shingo Gibo, Rajesh Narasimamurthy, David Virshup, Gen Kurosawa, Masao Doi, Ichiro Manabe, Yasushi Ishihama, Masahito Ikawa, Hitoshi Okamura
The N 6 -methylation of internal adenosines (m6A) in mRNA has been quantified and localized throughout the transcriptome. However, the physiological significance of m6A in most highly methylated mRNAs is unknown. It was demonstrated previously that the circadian clock, based on transcription-translation negative feedback loops, is sensitive to the general inhibition of m6A. Here, we show that the Casein Kinase 1 Delta mRNA ( Ck1δ ), coding for a critical kinase in the control of circadian rhythms, cellular growth, and survival, is negatively regulated by m6A...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29784649/small-molecular-inhibitors-targeting-protein-sumoylation-as-novel-anticancer-compounds
#13
Yanfang Yang, Zijing Xia, Xixi Wang, Xinyu Zhao, Zenghua Sheng, Yang Ye, Gu He, Liangxue Zhou, Hongxia Zhu, Ningzhi Xu, Shufang Liang
SUMOylation, one of post-translational modifications, is covalently modified on lysine residues of a target protein through an enzymatic cascade reaction similar to protein ubiquitination. Along with identification of many SUMOylated proteins, protein SUMOylation has been proven to regulate multiple biological activities including transcription, cell cycle, DNA repair and innate immunity. The dysregulation of protein SUMOylation and deSUMOylation modification is linked with carcinogenesis and tumor progression...
May 21, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29784395/development-a-hydrazide-functionalized-thermosensitive-polymer-based-homogeneous-system-for-highly-efficient-n-glycoprotein-glycopeptide-enrichment-from-human-plasma-exosome
#14
Haihong Bai, Yiting Pan, Lu Qi, Long Liu, Xinyuan Zhao, Hangyan Dong, Xiaoqiang Cheng, Weijie Qin, Xinghe Wang
As one of the most common post-translational modifications, protein N-glycosylation precipitates in many important biological processes and has closely correlations with the occurrence and progression of multiple diseases. Plasma exosomes secreted by cells contain various bioactive N-glycoproteins which may serve as potential biomarkers for early disease diagnosis and treatment. However, the protein N-glycosylation profile in human plasma exosome is largely unknown, due to the technical challenges in glycoprotein identification...
August 15, 2018: Talanta
https://www.readbyqxmd.com/read/29783951/the-transcriptomic-and-proteomic-responses-of-daphnia-pulex-to-changes-in-temperature-and-food-supply-comprise-environment-specific-and-clone-specific-elements
#15
Dörthe Becker, Yann Reydelet, Jacqueline A Lopez, Craig Jackson, John K Colbourne, Susan Hawat, Michael Hippler, Bettina Zeis, Rüdiger J Paul
BACKGROUND: Regulatory adjustments to acute and chronic temperature changes are highly important for aquatic ectotherms because temperature affects their metabolic rate as well as the already low oxygen concentration in water, which can upset their energy balance. This also applies to severe changes in food supply. Thus, we studied on a molecular level (transcriptomics and/or proteomics) the immediate responses to heat stress and starvation and the acclimation to different temperatures in two clonal isolates of the model microcrustacean Daphnia pulex from more or less stressful environments, which showed a higher (clone M) or lower (clone G) tolerance to heat and starvation...
May 21, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29783946/novel-flax-orbitide-derived-from-genetic-deletion
#16
Peta-Gaye Gillian Burnett, Lester Warren Young, Clara Marisa Olivia, Pramodkumar Dinkar Jadhav, Denis Paskal Okinyo-Owiti, Martin John Tarsisius Reaney
BACKGROUND: Flaxseed orbitides are homodetic plant cyclic peptides arising from ribosomal synthesis and post-translation modification (N to C cyclization), and lacking cysteine double bonds (Nat Prod Rep 30:108-160, 2013). Screening for orbitide composition was conducted on the flax core collection (FCC) grown at both Saskatoon, Saskatchewan and Morden, Manitoba over three growing seasons (2009-2011). Two flax (Linum usitatissimum L.) accessions 'Hollandia' (CN 98056) and 'Z 11637' (CN 98150) produce neither [1-9-NαC]-linusorb B2 (3) nor [1-9-NαC]-linusorb B3 (1)...
May 21, 2018: BMC Plant Biology
https://www.readbyqxmd.com/read/29783755/a-miniaturized-extruder-to-prototype-amorphous-solid-dispersions-selection-of-plasticizers-for-hot-melt-extrusion
#17
Matthias E Lauer, Reto Maurer, Anne T De Paepe, Cordula Stillhart, Laurence Jacob, Rajesh James, Yuki Kojima, Rene Rietmann, Tom Kissling, Joost A van den Ende, Sabine Schwarz, Olaf Grassmann, Susanne Page
Hot-melt extrusion is an option to fabricate amorphous solid dispersions and to enhance oral bioavailability of poorly soluble compounds. The selection of suitable polymer carriers and processing aids determines the dissolution, homogeneity and stability performance of this solid dosage form. A miniaturized extrusion device (MinEx) was developed and Hypromellose acetate succinate type L (HPMCAS-L) based extrudates containing the model drugs neurokinin-1 (NK1) and cholesterylester transfer protein (CETP) were manufactured, plasticizers were added and their impact on dissolution and solid-state properties were assessed...
May 19, 2018: Pharmaceutics
https://www.readbyqxmd.com/read/29783665/identification-of-novel-somatic-tp53-mutations-in-patients-with-high-grade-serous-ovarian-cancer-hgsoc-using-next-generation-sequencing-ngs
#18
Marica Garziera, Erika Cecchin, Vincenzo Canzonieri, Roberto Sorio, Giorgio Giorda, Simona Scalone, Elena De Mattia, Rossana Roncato, Sara Gagno, Elena Poletto, Loredana Romanato, Franca Sartor, Jerry Polesel, Giuseppe Toffoli
Somatic mutations in TP53 are a hallmark of high-grade serous ovarian cancer (HGSOC), although their prognostic and predictive value as markers is not well defined. Next-generation sequencing (NGS) can identify novel mutations with high sensitivity, that may be repurposed as potential druggable anti-cancer targets and aid in therapeutic decisions. Here, a commercial NGS cancer panel comprising 26 genes, including TP53 , was used to identify new genetic markers of platinum resistance and patient prognosis in a retrospective set of patients diagnosed with epithelial ovarian cancer...
May 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29783624/growth-responses-of-preterm-pigs-fed-formulas-with-different-protein-levels-and-supplemented-with-leucine-or-%C3%AE-hydroxyl-%C3%AE-methylbutyrate
#19
Randal K Buddington, Scott C Howard, Harold W Lee, Karyl K Buddington
Growth after preterm birth is an important determinant of long-term outcomes. Yet, many preterm infants suffer ex utero growth retardation. We evaluated effects of leucine and the metabolite, β-hydroxy β-methylbutyrate (HMB) on growth of preterm pigs, a previously-validated translational model for preterm infants. After 48 h of parenteral nutrition preterm pigs were fed for 6 to 7 days isocaloric formulas with different levels of protein (50 or 100 g/L) with leucine (10 g/L, 76 mM) or HMB (at 1.1 g/L, 4 mM) added to stimulate protein synthesis or with alanine (6...
May 18, 2018: Nutrients
https://www.readbyqxmd.com/read/29782946/delivery-of-the-improved-bmp-2-advanced-plasmid-dna-within-a-gene-activated-scaffold-accelerates-mesenchymal-stem-cell-osteogenesis-and-critical-size-defect-repair
#20
Rosanne M Raftery, Irene Mencía-Castaño, Simon Sperger, Gang Chen, Brenton Cavanagh, Georg Feichtinger, Heinz Redl, Ara Hacobian, Fergal J O'Brien
Gene-activated scaffolds have been shown to induce controlled, sustained release of functional transgene both in vitro and in vivo. Bone morphogenetic proteins (BMPs) are potent mediators of osteogenesis however we found that the delivery of plasmid BMP-2 (pBMP-2) alone was not sufficient to enhance bone formation. Therefore, the aim of this study was to assess if the use of a series of modified BMP-2 plasmids could enhance the functionality of a pBMP-2 gene-activated scaffold and ultimately improve bone regeneration when implanted into a critical sized bone defect in vivo...
May 18, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
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