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New Mass Ave. restaurants serve macarons, mac and cheese, brisket nachos, farm-to-table

40 restaurants in all fill the small, Downtown Indianapolis neighborhood

      




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House-ground burgers, sausage planned at new Mass Ave. restaurant Krueger's Tavern

The restaurant opening in January 2019 is from the owners of Bakersfield.

      




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Rihanna, Cardi B, John Oliver and more lash out at Trump after deadly mass shootings

Stars criticized the president after two mass shootings that occurred less than 24 hours apart in El Paso and Dayton, Ohio.




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Move over, Illuminati. The conspiracy against Trump’s economy is massive.

The credibility of statistics apparently depends on whether they’re beneficial.




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Google surfacing more local COVID news content to satisfy massive search demand

Local news publishers have struggled to monetize spike in consumer interest.

Please visit Search Engine Land for the full article.




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AT#112 - Travel to Boston, Massachusetts

Boston, Massachusetts




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AT#630 - Travel to Boston, Massachusetts

Hear about travel to Boston, Massachusetts as the Amateur Traveler talks to Lillie Marshall from AroundTheWorldL.com about her hometown.




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After Treating Barely Any Patients for a Massive $7.5 Million Each, 16 Emergency COVID Hospitals Are Standing Down

At a cost of $7.5 million a patient, they were 16 very expensive field hospitals. Yet, according to NPR, those hospitals are now “stand[ing] down.” You probably remember them from headlines early in the pandemic: makeshift medical centers being assembled at breakneck speed by companies contracted by the Army Corps of Engineers in anticipation of…

The post After Treating Barely Any Patients for a Massive $7.5 Million Each, 16 Emergency COVID Hospitals Are Standing Down appeared first on The Western Journal.




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Last night's massive boom over Puget Sound was likely exploding meteor

A massive boom heard Wednesday night over Puget Sound on the northwestern coast of Washington was most likely an exploding meteor. Or that's what They want us to believe anyway. The American Meteor Society registered a dozen reports. Video above. Keep your eyes on the upper left of the frame.

"The more I read the more inclined I am to believe this was a fireball (which is a meteor that is larger and brighter than normal)," the American Meteor Society's Bob Lunsford said. "I'm certain now that this was a meteoric event."

From KOMONews:

Most meteors' explosions are heard about a minute or two after they explode due to the time it takes the sound to reach the Earth's surface, Lunsford said. Sound travels at 767 mph in standard atmosphere conditions, indicating this fireball exploded some 35 miles away.

"If this was larger than normal then the sound could have originated from a higher altitude. So a delay of 3 minutes is entirely possible," Lunsford said. "Meteors become visible at a height of around 50 miles so your estimate is well within that range."

Lunsford said because there was a boom, it’s very likely there are small, rock-sized pieces of the meteor somewhere on the ground. When a meteor causes a boom, it’s “pretty far down” in the atmosphere.

Read the rest




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Transatlantic Cooperation to Prevent and Stop Mass Atrocities

Invitation Only Research Event

16 February 2015 - 1:00pm to 5:00pm

Chatham House, London

Event participants

Ambassador Lee Feinstein, Founding Dean, School of Global & International Studies, Indiana University
Xenia Wickett, Project Director, US; Dean, The Queen Elizabeth II Academy, Chatham House
Paul Arkwright, Director, Multilateral Policy, Foreign & Commonwealth Office
Dr Patricia Lewis, Research Director, International Security Programme, Chatham House
Jonathan Prentice, Director, London Office & Senior Adviser for European Advocacy, International Crisis Group
Sir John Holmes, Director, The Ditchley Foundation

The international community is in urgent need of successful, cooperative strategies for both preventing mass atrocities before they begin and stopping those in progress. As recent crises have highlighted, effective international cooperation to save lives and preserve peace and security remains largely aspirational. Participants will discuss current thinking on mass atrocity prevention and intervention, and identify how transatlantic cooperation in this space could be more effective.

Attendance at this event is by invitation only.

Department/project

Richard Gowing

Programme Administrator
+44 (0)20 7389 3270




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Mass Spectrometry of Human Leukocyte Antigen Class I Peptidomes Reveals Strong Effects of Protein Abundance and Turnover on Antigen Presentation

Michal Bassani-Sternberg
Mar 1, 2015; 14:658-673
Research




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Parallel Reaction Monitoring for High Resolution and High Mass Accuracy Quantitative, Targeted Proteomics

Amelia C. Peterson
Nov 1, 2012; 11:1475-1488
Technological Innovation and Resources




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In Vivo Identification of Human Small Ubiquitin-like Modifier Polymerization Sites by High Accuracy Mass Spectrometry and an in Vitro to in Vivo Strategy

Ivan Matic
Jan 1, 2008; 7:132-144
Research




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Quantitative, Multiplexed Assays for Low Abundance Proteins in Plasma by Targeted Mass Spectrometry and Stable Isotope Dilution

Hasmik Keshishian
Dec 1, 2007; 6:2212-2229
Research




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Time-resolved Mass Spectrometry of Tyrosine Phosphorylation Sites in the Epidermal Growth Factor Receptor Signaling Network Reveals Dynamic Modules

Yi Zhang
Sep 1, 2005; 4:1240-1250
Research




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Quantitative Mass Spectrometric Multiple Reaction Monitoring Assays for Major Plasma Proteins

Leigh Anderson
Apr 1, 2006; 5:573-588
Research




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The Paragon Algorithm, a Next Generation Search Engine That Uses Sequence Temperature Values and Feature Probabilities to Identify Peptides from Tandem Mass Spectra

Ignat V. Shilov
Sep 1, 2007; 6:1638-1655
Technology




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Parts per Million Mass Accuracy on an Orbitrap Mass Spectrometer via Lock Mass Injection into a C-trap

Jesper V. Olsen
Dec 1, 2005; 4:2010-2021
Technology




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Processivity of dextransucrases synthesizing very-high-molar-mass dextran is mediated by sugar-binding pockets in domain V [Glycobiology and Extracellular Matrices]

The dextransucrase DSR-OK from the Gram-positive bacterium Oenococcus kitaharae DSM17330 produces a dextran of the highest molar mass reported to date (∼109 g/mol). In this study, we selected a recombinant form, DSR-OKΔ1, to identify molecular determinants involved in the sugar polymerization mechanism and that confer its ability to produce a very-high-molar-mass polymer. In domain V of DSR-OK, we identified seven putative sugar-binding pockets characteristic of glycoside hydrolase 70 (GH70) glucansucrases that are known to be involved in glucan binding. We investigated their role in polymer synthesis through several approaches, including monitoring of dextran synthesis, affinity assays, sugar binding pocket deletions, site-directed mutagenesis, and construction of chimeric enzymes. Substitution of only two stacking aromatic residues in two consecutive sugar-binding pockets (variant DSR-OKΔ1-Y1162A-F1228A) induced quasi-complete loss of very-high-molar-mass dextran synthesis, resulting in production of only 10–13 kg/mol polymers. Moreover, the double mutation completely switched the semiprocessive mode of DSR-OKΔ1 toward a distributive one, highlighting the strong influence of these pockets on enzyme processivity. Finally, the position of each pocket relative to the active site also appeared to be important for polymer elongation. We propose that sugar-binding pockets spatially closer to the catalytic domain play a major role in the control of processivity. A deep structural characterization, if possible with large-molar-mass sugar ligands, would allow confirming this hypothesis.




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Is Massage Useful in the Management of Diabetes? A Systematic Review

Jeanette Ezzo
Oct 1, 2001; 14:
Articles




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Hershberger Named 2020 AMS Mass Media Fellow

The AMS is pleased to announce that Scott Hershberger has been chosen as the 2020 AMS Mass Media Fellow. Scott studied mathematics and physics at Washington University in St. Louis and will graduate in May 2020. He will be working at Scientific American this summer.

The Mass Media Science and Engineering Fellows program is organized by the American Association for the Advancement of Science (AAAS). This program is designed to improve public understanding of science and technology by placing advanced undergraduate, graduate and postgraduate science, mathematics and engineering students in media outlets nationwide. The fellows work for ten weeks over the summer as reporters, researchers, and production assistants alongside media professionals to sharpen their communication skills and increase their understanding of the editorial process by which events and ideas become news.

Now in its 45th year, this fellowship program has placed more than 700 fellows in media organizations nationwide as they research, write, and report today’s headlines. The program is designed to report science-related issues in the media in easy-to-understand ways so as to improve public understanding and appreciation for science and technology.

For more information on the AMS Mass Media Fellowship, visit the website.




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Surfaces that grip like gecko feet could be easily mass-produced

(Georgia Institute of Technology) The science behind sticky gecko's feet lets gecko adhesion materials pick up about anything. But cost-effective mass production of the materials was out of reach until now. A new method of making them could usher the spread of gecko-inspired grabbers to assembly lines and homes.




mass

Processivity of dextransucrases synthesizing very-high-molar-mass dextran is mediated by sugar-binding pockets in domain V [Glycobiology and Extracellular Matrices]

The dextransucrase DSR-OK from the Gram-positive bacterium Oenococcus kitaharae DSM17330 produces a dextran of the highest molar mass reported to date (∼109 g/mol). In this study, we selected a recombinant form, DSR-OKΔ1, to identify molecular determinants involved in the sugar polymerization mechanism and that confer its ability to produce a very-high-molar-mass polymer. In domain V of DSR-OK, we identified seven putative sugar-binding pockets characteristic of glycoside hydrolase 70 (GH70) glucansucrases that are known to be involved in glucan binding. We investigated their role in polymer synthesis through several approaches, including monitoring of dextran synthesis, affinity assays, sugar binding pocket deletions, site-directed mutagenesis, and construction of chimeric enzymes. Substitution of only two stacking aromatic residues in two consecutive sugar-binding pockets (variant DSR-OKΔ1-Y1162A-F1228A) induced quasi-complete loss of very-high-molar-mass dextran synthesis, resulting in production of only 10–13 kg/mol polymers. Moreover, the double mutation completely switched the semiprocessive mode of DSR-OKΔ1 toward a distributive one, highlighting the strong influence of these pockets on enzyme processivity. Finally, the position of each pocket relative to the active site also appeared to be important for polymer elongation. We propose that sugar-binding pockets spatially closer to the catalytic domain play a major role in the control of processivity. A deep structural characterization, if possible with large-molar-mass sugar ligands, would allow confirming this hypothesis.




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Researchers present a microbial strain capable of massive succinic acid production

(The Korea Advanced Institute of Science and Technology (KAIST)) A research team led by Distinguished Professor Sang-Yup Lee reported the production of a microbial strain capable of the massive production of succinic acid with the highest production efficiency to date. This strategy of integrating systems metabolic engineering with enzyme engineering will be useful for the production of industrially competitive bio-based chemicals.




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Tandem Mass Tag Approach Utilizing Pervanadate BOOST Channels Delivers Deeper Quantitative Characterization of the Tyrosine Phosphoproteome

Xien Yu Chua
Apr 1, 2020; 19:730-743
Technological Innovation and Resources




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A cross-linking mass spectrometry approach defines protein interactions in yeast mitochondria

Andreas Linden
Apr 24, 2020; 0:RA120.002028v1-mcp.RA120.002028
Research




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Selection of features with consistent profiles improves relative protein quantification in mass spectrometry experiments

Tsung-Heng Tsai
Mar 31, 2020; 0:RA119.001792v1-mcp.RA119.001792
Research




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Improving Identification of In-organello Protein-Protein Interactions Using an Affinity-enrichable, Isotopically Coded, and Mass Spectrometry-cleavable Chemical Crosslinker

Karl A. T. Makepeace
Apr 1, 2020; 19:624-639
Research




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A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients

Dorte B. Bekker-Jensen
Apr 1, 2020; 19:716-729
Technological Innovation and Resources




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Following the money in a massive “sextortion” spam scheme

Cryptocurrency profits from sextortion spam funneled into wallets tied to other cybercrime and dark web market activity.




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11C-(+)-PHNO Trapping Reversibility for Quantitative PET Imaging of Beta-Cell-Mass in Patients with Type-1 Diabetes




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Mass Spectrometry Based Immunopeptidomics Leads to Robust Predictions of Phosphorylated HLA Class I Ligands [Technological Innovation and Resources]

The presentation of peptides on class I human leukocyte antigen (HLA-I) molecules plays a central role in immune recognition of infected or malignant cells. In cancer, non-self HLA-I ligands can arise from many different alterations, including non-synonymous mutations, gene fusion, cancer-specific alternative mRNA splicing or aberrant post-translational modifications. Identifying HLA-I ligands remains a challenging task that requires either heavy experimental work for in vivo identification or optimized bioinformatics tools for accurate predictions. To date, no HLA-I ligand predictor includes post-translational modifications. To fill this gap, we curated phosphorylated HLA-I ligands from several immunopeptidomics studies (including six newly measured samples) covering 72 HLA-I alleles and retrieved a total of 2,066 unique phosphorylated peptides. We then expanded our motif deconvolution tool to identify precise binding motifs of phosphorylated HLA-I ligands. Our results reveal a clear enrichment of phosphorylated peptides among HLA-C ligands and demonstrate a prevalent role of both HLA-I motifs and kinase motifs on the presentation of phosphorylated peptides. These data further enabled us to develop and validate the first predictor of interactions between HLA-I molecules and phosphorylated peptides.




mass

Discovery of Species-unique Peptide Biomarkers of Bacterial Pathogens by Tandem Mass Spectrometry-based Proteotyping [Research]

Mass spectrometry (MS) and proteomics offer comprehensive characterization and identification of microorganisms and discovery of protein biomarkers that are applicable for diagnostics of infectious diseases. The use of biomarkers for diagnostics is widely applied in the clinic and the use of peptide biomarkers is increasingly being investigated for applications in the clinical laboratory. Respiratory-tract infections are a predominant cause for medical treatment, although, clinical assessments and standard clinical laboratory protocols are time-consuming and often inadequate for reliable diagnoses. Novel methods, preferably applied directly to clinical samples, excluding cultivation steps, are needed to improve diagnostics of infectious diseases, provide adequate treatment and reduce the use of antibiotics and associated development of antibiotic resistance. This study applied nano-liquid chromatography (LC) coupled with tandem MS, with a bioinformatics pipeline and an in-house database of curated high-quality reference genome sequences to identify species-unique peptides as potential biomarkers for four bacterial pathogens commonly found in respiratory tract infections (RTIs): Staphylococcus aureus; Moraxella catarrhalis; Haemophilus influenzae and Streptococcus pneumoniae. The species-unique peptides were initially identified in pure cultures of bacterial reference strains, reflecting the genomic variation in the four species and, furthermore, in clinical respiratory tract samples, without prior cultivation, elucidating proteins expressed in clinical conditions of infection. For each of the four bacterial pathogens, the peptide biomarker candidates most predominantly found in clinical samples, are presented. Data are available via ProteomeXchange with identifier PXD014522. As proof-of-principle, the most promising species-unique peptides were applied in targeted tandem MS-analyses of clinical samples and their relevance for identifications of the pathogens, i.e. proteotyping, was validated, thus demonstrating their potential as peptide biomarker candidates for diagnostics of infectious diseases.




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Guidance Document: Validation of a High-Performance Liquid Chromatography-Tandem Mass Spectrometry Immunopeptidomics Assay for the Identification of HLA Class I Ligands Suitable for Pharmaceutical Therapies [Commentary]

For more than two decades naturally presented, human leukocyte antigen (HLA)-restricted peptides (immunopeptidome) have been eluted and sequenced using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Since, identified disease-associated HLA ligands have been characterized and evaluated as potential active substances. Treatments based on HLA-presented peptides have shown promising results in clinical application as personalized T cell-based immunotherapy. Peptide vaccination cocktails are produced as investigational medicinal products under GMP conditions. To support clinical trials based on HLA-presented tumor-associated antigens, in this study the sensitive LC-MS/MS HLA class I antigen identification pipeline was fully validated for our technical equipment according to the current US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines.

The immunopeptidomes of JY cells with or without spiked-in, isotope labeled peptides, of peripheral blood mononuclear cells of healthy volunteers as well as a chronic lymphocytic leukemia and a bladder cancer sample were reliably identified using a data-dependent acquisition method. As the LC-MS/MS pipeline is used for identification purposes, the validation parameters include accuracy, precision, specificity, limit of detection and robustness.




mass

Tandem Mass Tag Approach Utilizing Pervanadate BOOST Channels Delivers Deeper Quantitative Characterization of the Tyrosine Phosphoproteome [Technological Innovation and Resources]

Dynamic tyrosine phosphorylation is fundamental to a myriad of cellular processes. However, the inherently low abundance of tyrosine phosphorylation in the proteome and the inefficient enrichment of phosphotyrosine(pTyr)-containing peptides has led to poor pTyr peptide identification and quantitation, critically hindering researchers' ability to elucidate signaling pathways regulated by tyrosine phosphorylation in systems where cellular material is limited. The most popular approaches to wide-scale characterization of the tyrosine phosphoproteome use pTyr enrichment with pan-specific, anti-pTyr antibodies from a large amount of starting material. Methods that decrease the amount of starting material and increase the characterization depth of the tyrosine phosphoproteome while maintaining quantitative accuracy and precision would enable the discovery of tyrosine phosphorylation networks in rarer cell populations. To achieve these goals, the BOOST (Broad-spectrum Optimization Of Selective Triggering) method leveraging the multiplexing capability of tandem mass tags (TMT) and the use of pervanadate (PV) boost channels (cells treated with the broad-spectrum tyrosine phosphatase inhibitor PV) selectively increased the relative abundance of pTyr-containing peptides. After PV boost channels facilitated selective fragmentation of pTyr-containing peptides, TMT reporter ions delivered accurate quantitation of each peptide for the experimental samples while the quantitation from PV boost channels was ignored. This method yielded up to 6.3-fold boost in pTyr quantification depth of statistically significant data derived from contrived ratios, compared with TMT without PV boost channels or intensity-based label-free (LF) quantitation while maintaining quantitative accuracy and precision, allowing quantitation of over 2300 unique pTyr peptides from only 1 mg of T cell receptor-stimulated Jurkat T cells. The BOOST strategy can potentially be applied in analyses of other post-translational modifications where treatments that broadly elevate the levels of those modifications across the proteome are available.




mass

A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients [Technological Innovation and Resources]

State-of-the-art proteomics-grade mass spectrometers can measure peptide precursors and their fragments with ppm mass accuracy at sequencing speeds of tens of peptides per second with attomolar sensitivity. Here we describe a compact and robust quadrupole-orbitrap mass spectrometer equipped with a front-end High Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) Interface. The performance of the Orbitrap Exploris 480 mass spectrometer is evaluated in data-dependent acquisition (DDA) and data-independent acquisition (DIA) modes in combination with FAIMS. We demonstrate that different compensation voltages (CVs) for FAIMS are optimal for DDA and DIA, respectively. Combining DIA with FAIMS using single CVs, the instrument surpasses 2500 peptides identified per minute. This enables quantification of >5000 proteins with short online LC gradients delivered by the Evosep One LC system allowing acquisition of 60 samples per day. The raw sensitivity of the instrument is evaluated by analyzing 5 ng of a HeLa digest from which >1000 proteins were reproducibly identified with 5 min LC gradients using DIA-FAIMS. To demonstrate the versatility of the instrument, we recorded an organ-wide map of proteome expression across 12 rat tissues quantified by tandem mass tags and label-free quantification using DIA with FAIMS to a depth of >10,000 proteins.




mass

Improving Identification of In-organello Protein-Protein Interactions Using an Affinity-enrichable, Isotopically Coded, and Mass Spectrometry-cleavable Chemical Crosslinker [Research]

An experimental and computational approach for identification of protein-protein interactions by ex vivo chemical crosslinking and mass spectrometry (CLMS) has been developed that takes advantage of the specific characteristics of cyanurbiotindipropionylsuccinimide (CBDPS), an affinity-tagged isotopically coded mass spectrometry (MS)-cleavable crosslinking reagent. Utilizing this reagent in combination with a crosslinker-specific data-dependent acquisition strategy based on MS2 scans, and a software pipeline designed for integrating crosslinker-specific mass spectral information led to demonstrated improvements in the application of the CLMS technique, in terms of the detection, acquisition, and identification of crosslinker-modified peptides. This approach was evaluated on intact yeast mitochondria, and the results showed that hundreds of unique protein-protein interactions could be identified on an organelle proteome-wide scale. Both known and previously unknown protein-protein interactions were identified. These interactions were assessed based on their known sub-compartmental localizations. Additionally, the identified crosslinking distance constraints are in good agreement with existing structural models of protein complexes involved in the mitochondrial electron transport chain.




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Mass spectrometry imaging and LC-MS reveal decreased cerebellar phosphoinositides in Niemann-Pick type C1-null mice [Research Articles]

Niemann-Pick disease, type C1 (NPC1) is a lipid storage disorder in which cholesterol and glycosphingolipids accumulate in late endosomal/lysosomal compartments because of mutations in the NPC1 gene. A hallmark of NPC1 is progressive neurodegeneration of the cerebellum as well as visceral organ damage; however, the mechanisms driving this disease pathology are not fully understood. Phosphoinositides are phospholipids that play distinct roles in signal transduction and vesicle trafficking. Here, we utilized consensus spectra analysis of MS imaging datasets and orthogonal LC–MS analyses to evaluate the spatial distribution of phosphoinositides and quantify them in cerebellar tissue from Npc1-null mice. Our results suggest significant depletion of multiple phosphoinositide species, including phosphatidylinositol (PI), phosphatidylinositol monophosphate (PIP), and bisphosphate (PIP2), in the cerebellum of the Npc1-null mice in both whole-tissue lysates and myelin-enriched fractions. Additionally, we observed altered levels of the regulatory enzyme phosphatidylinositol 4-kinase type 2 α (PI4K2A) in Npc1-null mice. In contrast, the levels of related kinases, phosphatases, and transfer proteins were unaltered in the Npc1-null mouse model as observed by Western blot analysis. Our discovery of phosphoinositide lipid biomarkers for NPC1 opens new perspectives on the pathophysiology underlying this fatal neurodegenerative disease.




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Fourier transform mass spectrometry [Invited]

This article provides an introduction to Fourier transform-based mass spectrometry (FTMS). The key performance characteristics of FTMS, mass accuracy and resolution, are presented in the view of how they impact the interpretation of measurements in proteomic applications. The theory and principles of operation of two types of mass analyzer, Fourier transform ion cyclotron resonance and Orbitrap, are described. Major benefits as well as limitations of FTMS technology are discussed in the context of practical sample analysis, and illustrated with examples included as figures in this text and in the accompanying slide set. Comparisons highlighting the performance differences between the two mass analyzers are made where deemed useful in assisting the user with choosing the most appropriate technology for his/her application. Recent developments of these high-performing mass spectrometers are mentioned to provide a future outlook.




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WITHDRAWN: Quantitative mass spectrometry analysis of PD-L1 protein expression, N-glycosylation and expression stoichiometry with PD-1 and PD-L2 in human melanoma [Research]

This article has been withdrawn by the authors. We discovered an error after this manuscript was published as a Paper in Press. Specifically, we learned that the structures of glycans presented for the PD-L1 peptide were drawn and labeled incorrectly. We wish to withdraw this article and submit a corrected version for review.




mass

Selection of features with consistent profiles improves relative protein quantification in mass spectrometry experiments [Research]

In bottom-up mass spectrometry-based proteomics, relative protein quantification is often achieved with data-dependent acquisition (DDA), data-independent acquisition (DIA), or selected reaction monitoring (SRM). These workflows quantify proteins by summarizing the abundances of all the spectral features of the protein (e.g., precursor ions, transitions or fragments) in a single value per protein per run. When abundances of some features are inconsistent with the overall protein profile (for technological reasons such as interferences, or for biological reasons such as post-translational modifications), the protein-level summaries and the downstream conclusions are undermined. We propose a statistical approach that automatically detects spectral features with such inconsistent patterns. The detected features can be separately investigated, and if necessary removed from the dataset. We evaluated the proposed approach on a series of benchmark controlled mixtures and biological investigations with DDA, DIA and SRM data acquisitions. The results demonstrated that it can facilitate and complement manual curation of the data. Moreover, it can improve the estimation accuracy, sensitivity and specificity of detecting differentially abundant proteins, and reproducibility of conclusions across different data processing tools. The approach is implemented as an option in the open-source R-based software MSstats.




mass

A cross-linking mass spectrometry approach defines protein interactions in yeast mitochondria [Research]

Protein cross-linking and the analysis of cross-linked peptides by mass spectrometry is currently receiving much attention. Not only is this approach applied to isolated complexes to provide information about spatial arrangements of proteins but it is also increasingly applied to entire cells and their organelles. As in quantitative proteomics, the application of isotopic labelling further makes it possible to monitor quantitative changes in the protein-protein interactions between different states of a system. Here, we cross-linked mitochondria from Saccharomyces cerevisiae grown on either glycerol- or glucose-containing medium to monitor protein-protein interactions under non-fermentative and fermentative conditions. We investigated qualitatively the protein-protein interactions of the 400 most abundant proteins applying stringent data-filtering criteria, i.e. a minimum of two cross-linked peptide spectrum matches and a cut-off in the spectrum scoring of the used search engine. The cross-linker BS3 proved to be equally suited for connecting proteins in all compartments of mitochondria when compared with its water-insoluble but membrane-permeable derivative DSS. We also applied quantitative cross-linking to mitochondria of both the growth conditions using stable-isotope labelled BS3. Significant differences of cross-linked proteins under glycerol and glucose conditions were detected, however, mainly due to the different copy numbers of these proteins in mitochondria under both the conditions. Results obtained from the glycerol condition indicate that the internal NADH:ubiquinone oxidoreductase Ndi1 is part of an electron transport chain supercomplex. We have also detected several hitherto uncharacterized proteins and identified their interaction partners. Among those, Min8 was found to be associated with cytochrome c oxidase. BN-PAGE analyses of min8 mitochondria suggest that Min8 promotes the incorporation of Cox12 into cytochrome c oxidase.




mass

Quantification of bile acids: a mass spectrometry platform for studying gut microbe connection to metabolic diseases [Research Articles]

Bile acids (BAs) serve multiple biological functions, ranging from the absorption of lipids and fat-soluble vitamins to serving as signaling molecules through the direct activation of dedicated cellular receptors. Synthesized by both host and microbial pathways, BAs are increasingly understood as participating in the regulation of numerous pathways relevant to metabolic diseases, including lipid and glucose metabolism, energy expenditure, and inflammation. Quantitative analyses of BAs in biological matrices can be problematic due to their unusual and diverse physicochemical properties, making optimization of a method that shows good accuracy, precision, efficiency of extraction, and minimized matrix effects across structurally distinct human and murine BAs challenging. Herein we develop and clinically validate a stable-isotope-dilution LC/MS/MS method for the quantitative analysis of numerous primary and secondary BAs in both human and mouse biological matrices. We also utilize this tool to investigate gut microbiota participation in the generation of structurally specific BAs in both humans and mice. We examine circulating levels of specific BAs and in a clinical case-control study of age- and gender-matched type 2 diabetes mellitus (T2DM) versus nondiabetics. BAs whose circulating levels are associated with T2DM include numerous 12α-hydroxyl BAs (taurocholic acid, taurodeoxycholic acid, glycodeoxycholic acid, deoxycholic acid, and 3-ketodeoxycholic acid), while taurohyodeoxycholic acid was negatively associated with diabetes. The LC/MS/MS-based platform described should serve as a robust, high-throughput investigative tool for studying the potential involvement of structurally specific BAs and the gut microbiome on both physiological and disease processes.




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Chữa đau nhức chân với bồn ngâm massage chân

Chữa đau nhức chân với bồn ngâm massage chân là một phương pháp được đánh giá rất cao hiện nay. Tuy nhiên thông tin về phương pháp này không phải ai cũng...




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The Impacts of the Demand for Woody Biomass for Power and Heat on Climate and Forests

23 February 2017

Although most renewable energy policy frameworks treat biomass as carbon-neutral at the point of combustion, biomass emits more carbon per unit of energy than most fossil fuels. 

Duncan Brack

Associate Fellow, Energy, Environment and Resources Programme

2017-02-15-woody-biomass-climate-forests-brack.jpg

Fuel composed of wood chips to be used for the UEM (Usine d’Electricité de Metz) biomass plant in Metz, eastern France. Photo: Getty Images.

Summary

  • The use of wood for electricity generation and heat in modern (non-traditional) technologies has grown rapidly in recent years, and has the potential to continue to do so.
  • The EU has been, and remains, the main global source of demand, as a result of its targets for renewable energy. This demand is largely met by its own forest resources and supplemented by imports from the US, Canada and Russia.
  • Countries outside the EU, including the US, China, Japan and South Korea, have the potential to increase the use of biomass (including agricultural residues as well as wood), but so far this has not taken place at scale, partly because of the falling costs of competing renewables such as solar PV and wind. However, the role of biomass as a system balancer, and its supposed ability, in combination with carbon capture and storage technology, to generate negative emissions, seem likely to keep it in contention in the future.
  • Although most renewable energy policy frameworks treat biomass as though it is carbon-neutral at the point of combustion, in reality this cannot be assumed, as biomass emits more carbon per unit of energy than most fossil fuels. Only residues that would otherwise have been burnt as waste or would have been left in the forest and decayed rapidly can be considered to be carbon-neutral over the short to medium term.
  • One reason for the perception of biomass as carbon-neutral is the fact that, under IPCC greenhouse gas accounting rules, its associated emissions are recorded in the land use rather than the energy sector. However, the different ways in which land use emissions are accounted for means that a proportion of the emissions from biomass may never be accounted for.
  • In principle, sustainability criteria can ensure that only biomass with the lowest impact on the climate are used; the current criteria in use in some EU member states and under development in the EU, however, do not achieve this as they do not account for changes in forest carbon stock.

Also see Woody Biomass for Power and Heat: Impacts on the Global Climate, which assesses the impact of the use of biomass for energy on greenhouse gas emissions, how these are accounted for under international climate accounting rules, and analyses the sustainability criteria currently in use and under development to minimise negative impacts.




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Serotonin Regulates Adult {beta}-Cell Mass by Stimulating Perinatal {beta}-Cell Proliferation

A sufficient β-cell mass is crucial for preventing diabetes, and perinatal β-cell proliferation is important in determining the adult β-cell mass. However, it is not yet known how perinatal β-cell proliferation is regulated. Here, we report that serotonin regulates β-cell proliferation through serotonin receptor 2B (HTR2B) in an autocrine/paracrine manner during the perinatal period. In β-cell–specific Tph1 knockout (Tph1 βKO) mice, perinatal β-cell proliferation was reduced along with the loss of serotonin production in β-cells. Adult Tph1 βKO mice exhibited glucose intolerance with decreased β-cell mass. Disruption of Htr2b in β-cells also resulted in decreased perinatal β-cell proliferation and glucose intolerance in adulthood. Growth hormone (GH) was found to induce serotonin production in β-cells through activation of STAT5 during the perinatal period. Thus, our results indicate that GH-GH receptor-STAT5-serotonin-HTR2B signaling plays a critical role in determining the β-cell mass by regulating perinatal β-cell proliferation, and defects in this pathway affect metabolic phenotypes in adults.




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Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats

G Xu
Dec 1, 1999; 48:2270-2276
Articles




mass

A Novel Model of Diabetic Complications: Adipocyte Mitochondrial Dysfunction Triggers Massive {beta}-Cell Hyperplasia

Obesity-associated type 2 diabetes mellitus (T2DM) entails insulin resistance and loss of β-cell mass. Adipose tissue mitochondrial dysfunction is emerging as a key component in the etiology of T2DM. Identifying approaches to preserve mitochondrial function, adipose tissue integrity, and β-cell mass during obesity is a major challenge. Mitochondrial ferritin (FtMT) is a mitochondrial matrix protein that chelates iron. We sought to determine whether perturbation of adipocyte mitochondria influences energy metabolism during obesity. We used an adipocyte-specific doxycycline-inducible mouse model of FtMT overexpression (FtMT-Adip mice). During a dietary challenge, FtMT-Adip mice are leaner but exhibit glucose intolerance, low adiponectin levels, increased reactive oxygen species damage, and elevated GDF15 and FGF21 levels, indicating metabolically dysfunctional fat. Paradoxically, despite harboring highly dysfunctional fat, transgenic mice display massive β-cell hyperplasia, reflecting a beneficial mitochondria-induced fat-to-pancreas interorgan signaling axis. This identifies the unique and critical impact that adipocyte mitochondrial dysfunction has on increasing β-cell mass during obesity-related insulin resistance.




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Leadership Visions: A Discussion with Mexican Foreign Minister Claudia Ruiz-Massieu

An MPI Leadership Visions discussion with the Foreign Minister of Mexico, Claudia Ruiz-Massieu, for her first public appearance in Washington, DC. 




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Watch: Escaped bull goes wandering on Massachusetts highway

A young bull went wandering on a Massachusetts highway after escaping from a trailer and was captured without causing any incidents, police said.