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Polypharmacy as a Risk Factor in the Treatment of Type 2 Diabetes

Roger P. Austin
Jan 1, 2006; 19:13-16
Pharmacy Update




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From DSME to DSMS: Developing Empowerment-Based Diabetes Self-Management Support

Martha Mitchell Funnell
Oct 1, 2007; 20:221-226
Articles




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Association of Self-Efficacy and Self-Care With Glycemic Control in Diabetes

Carla Moore Beckerle
Aug 1, 2013; 26:172-178
Feature Articles




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A Review of Volunteer-Based Peer Support Interventions in Diabetes

Tricia S. Tang
May 1, 2011; 24:85-98
From Research to Practice/Behavioral Interventions for Diabetes Self-Management




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Associations Between Self-Management Education and Comprehensive Diabetes Clinical Care

Tammie M. Johnson
Jan 1, 2010; 23:41-46
Feature Articles




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Interview-Based Customer Insights in Developing Countries

What are the opportunities and challenges of collecting consumer insights in developing countries—and how can the challenges be overcome?




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Impossible Foods: Fighting Climate Change with Plant-Based Meat

Can Impossible Foods change the way meat is produced on a large enough scale to make a serious inroad in the battle against climate change?




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Daniiboo releases ‘Drop It N Pop It’

Known for her creative dance moves and twerking style, dancer-turned-artiste Daniiboo dropped a new twerking song, titled ' Drop It N Pop It', in an attempt to put a smile on her fans' faces in a time of unprecedented uncertainty. The song is...




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People just wah hear sumpn different - Govana finds captive audience as ‘Convo Pt 2’ hits a million views

Back in January when dancehall artiste Govana released the track HAMANTS Convo, the storyline captivated listeners across the globe. For weeks, the song, which highlights infidelity in relationships, trended at number one on the local YouTube...




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What about entertainment? - Industry insider feels sector under-represented in COVID recovery task force

Last month, Prime Minister Andrew Holness announced the establishment of an Economic Recovery Task Force, chaired by Finance Minister Dr Nigel Clarke. The multisectoral task force, which is mandated to oversee Jamaica's economic recovery from...




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488 confirmed COVID-19 cases in Jamaica

The Ministry of Health and Wellness has reported ten new positive COVID-19 test results, pushing the tally of confirmed cases to 488. Among the ten new cases, eight are females, and two are males. Their ages range from four years to 39-years-...




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Bars may have to remove stools and tables - Holness hints at measures that could accompany reopening of pubs

It is possible that the next time you walk into a bar you may find that there is only standing room, and you are among a handful of persons allowed inside. Prime Minister Andrew Holness said that in addition to having a specific gathering rule,...




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Diabetics, asthma sufferers urged to take extra COVID caution

Persons with diabetes, cardiovascular disease, and conditions such as high blood pressure and asthma are being urged to be particularly careful as those comorbidities have been identified in persons with COVID-19 in Jamaica requiring hospital care...




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Fashion Brands Repurpose Resources to Offer Aid in the COVID-19 Crisis

Retail giants like Yoox Net-a-Porter Group and Brooks Brothers quickly pivoted to offer life-saving services.




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Proportionality in the Conduct of Hostilities: The Incidental Harm Side of the Assessment

10 December 2018

Clarification of international humanitarian law is important in ensuring compliance with the rule of proportionality, but a culture of compliance within armed forces and groups is also crucial.

Emanuela-Chiara Gillard

Associate Fellow, International Law Programme

2018-12-10-ilp-proportionality-paper.jpg

Members of civil right defence conduct a search and rescue operation on destroyed buildings after an airstrike was carried out over the city of Jisr al-Shughur in Idlib province in Syria, on 6 May 2018. Photo: Hadi Harrat/Anadolu Agency/Getty Images.

Summary

  • Military operations are taking place with increasing frequency in densely populated areas. Such operations result in loss of life and harm to civilians, as well as damage to civilian objects, (including infrastructure providing essential services). In order to protect civilians, it is imperative that armed forces and groups comply with the rules of international humanitarian law on the conduct of hostilities, including the rule of proportionality.
  • The rule of proportionality prohibits attacks which may be expected to cause incidental loss of civilian life, injury to civilians, damage to civilian objects or a combination thereof, which would be excessive in relation to the concrete and direct military advantage anticipated. This research paper analyses the key steps that belligerents must take to give effect to the rule, with a particular focus on one side of proportionality assessments – the expected incidental harm.
  • Those undertaking proportionality assessments before or during an attack must consider whether the expected harm will be caused by the attack, and whether that harm could be expected (that is, was it reasonably foreseeable).
  • For the purpose of proportionality assessments, injury to civilians includes disease, and there is no reason in principle to exclude mental harm, even though it is currently challenging to identify and quantify it. Damage to civilian objects includes damage to elements of the natural environment.
  • Once the incidental harm to be considered has been identified, a value or weight must be assigned to it. This is then balanced against the value or weight of the military advantage anticipated from the attack to determine whether the harm would be excessive.
  • In the determination of whether the expected incidental harm would be excessive compared to the anticipated military advantage, ‘excessive’ is a wide but not indeterminate standard.
  • Belligerents should develop methodologies so that those planning and deciding attacks are provided with all necessary information on expected incidental harm, and to assist them in assigning weight to the incidental harm to be considered.
  • If it becomes apparent that the rule of proportionality will be contravened, the attack in question must be cancelled or suspended.
  • Clarification of the law is important in ensuring compliance with the rule of proportionality, but a culture of compliance within armed forces and groups, inculcated by their leaders, is also crucial.




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Security and Prosperity in the Asia-Pacific: The Role of International Law

Research Event

27 March 2019 - 10:00am to 5:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Koji Tsuruoka, Ambassador of Japan to the United Kingdom
Ben Saul, Associate Fellow, International Law Programme, Chatham House; Challis Chair of International Law, Australian National University
Lee Chen Chen, Director, Singapore Institute of International Affairs
Aniruddha​ Rajput, Member, UN International Law Commission; Consultant, Withersworldwide

 

The rapid growth in the Asia-Pacific’s economic and political power has significant implications for global governance. Asia-Pacific countries such as Japan, India and China – and regional bodies such as ASEAN – are increasingly informing, influencing and seeking to shape international standards and norms.

This conference will bring together international law and policy experts to explore the political and legal dynamics affecting economic relations, security challenges and maritime governance in the region.

Given security and prosperity challenges within the region as well as the increasingly complex environment for global governance, to what extent is international law operating as a tool of cooperation in the Asia-Pacific? In which areas is it a source of friction?

And what are the broader implications for global governance including the development of international law?

Chanu Peiris

Programme Manager, International Law
+44 (0)20 7314 3686




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Human Rights Impact Assessment of Trade Agreements

Research Event

26 February 2019 - 6:00pm to 7:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

James Harrison, Reader and Associate Professor, University of Warwick School of Law
Richard James, Evaluation Co-ordinator, Directorate-General for Trade European Commission
Jennifer Zerk, Associate Fellow, International Law Programme, Chatham House
Chair: Andrea Shemberg, Chair, Global Business Initiative on Human Rights

The idea that trade agreements should be subject to human rights impact assessment has been gathering momentum in recent years. This idea springs from concern – particularly on the part of trade unions and civil society organizations – that states are not presently doing enough to anticipate and address the human rights-related issues that arise from their trading arrangements with other countries.

This meeting will coincide with the launch of a research paper on human rights impact assessment by Dr Jennifer Zerk. It will bring together experts from law, trade policy, human rights impact assessment practice and civil society to take stock of progress so far and consider the future prospects for human rights impact assessment as a risk-analysis and policymaking tool in the trade context.  

The meeting will explore the key risks and benefits of the human rights impact assessment of trade agreements. What legal, political and practical challenges have been encountered so far? In what ways could communication, stakeholder consultation and follow-up of findings be improved? And what is needed to build political and stakeholder support for these kinds of processes?  

This meeting will be followed by a reception. 

Chanu Peiris

Programme Manager, International Law
+44 (0)20 7314 3686




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Security and Prosperity in Asia: The Role of International Law

1 November 2019

The 'Security and Prosperity in Asia' conference looked at the impact of international law in the Asia-Pacific with a focus on regional economic and security issues such as the South China Sea disputes.

Security and Prosperity in Asia Cover Image.jpg

Singapore skyline at sunset, 2016. Photo: Getty Images.

About the Conference

At a time of geopolitical uncertainty and with multilateralism under pressure, this conference brought together diverse actors to explore the evolving role of international law on critical security and economic issues in the Asia-Pacific. From trade agreements to deep-sea mining, cyberwarfare to territorial disputes, the breadth of the discussion illustrated the growing reach of international law in the region.

Hosted by the International Law Programme and the Asia-Pacific Programme at Chatham House on 27 March 2019, the conference focused on three themes: trade and investment, maritime security and governance, and emerging security challenges. What trends are emerging in terms of engagement with international law in the region, and how can international standards play a greater role in encouraging collaboration and reducing tensions? And, with the eastward shift in geopolitical power, how will Asia-Pacific states shape the future of international law?




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Glucocerebrosidases catalyze a transgalactosylation reaction that yields a newly-identified brain sterol metabolite, galactosylated cholesterol [Glycobiology and Extracellular Matrices]

β-Glucocerebrosidase (GBA) hydrolyzes glucosylceramide (GlcCer) to generate ceramide. Previously, we demonstrated that lysosomal GBA1 and nonlysosomal GBA2 possess not only GlcCer hydrolase activity, but also transglucosylation activity to transfer the glucose residue from GlcCer to cholesterol to form β-cholesterylglucoside (β-GlcChol) in vitro. β-GlcChol is a member of sterylglycosides present in diverse species. How GBA1 and GBA2 mediate β-GlcChol metabolism in the brain is unknown. Here, we purified and characterized sterylglycosides from rodent and fish brains. Although glucose is thought to be the sole carbohydrate component of sterylglycosides in vertebrates, structural analysis of rat brain sterylglycosides revealed the presence of galactosylated cholesterol (β-GalChol), in addition to β-GlcChol. Analyses of brain tissues from GBA2-deficient mice and GBA1- and/or GBA2-deficient Japanese rice fish (Oryzias latipes) revealed that GBA1 and GBA2 are responsible for β-GlcChol degradation and formation, respectively, and that both GBA1 and GBA2 are responsible for β-GalChol formation. Liquid chromatography–tandem MS revealed that β-GlcChol and β-GalChol are present throughout development from embryo to adult in the mouse brain. We found that β-GalChol expression depends on galactosylceramide (GalCer), and developmental onset of β-GalChol biosynthesis appeared to be during myelination. We also found that β-GlcChol and β-GalChol are secreted from neurons and glial cells in association with exosomes. In vitro enzyme assays confirmed that GBA1 and GBA2 have transgalactosylation activity to transfer the galactose residue from GalCer to cholesterol to form β-GalChol. This is the first report of the existence of β-GalChol in vertebrates and how β-GlcChol and β-GalChol are formed in the brain.




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Deletion of fatty acid transport protein 2 (FATP2) in the mouse liver changes the metabolic landscape by increasing the expression of PPAR{alpha}-regulated genes [Lipids]

Fatty acid transport protein 2 (FATP2) is highly expressed in the liver, small intestine, and kidney, where it functions in both the transport of exogenous long-chain fatty acids and the activation of very-long-chain fatty acids. Here, using a murine model, we investigated the phenotypic impacts of deleting FATP2, followed by a transcriptomic analysis using unbiased RNA-Seq to identify concomitant changes in the liver transcriptome. WT and FATP2-null (Fatp2−/−) mice (5 weeks) were maintained on a standard chow diet for 6 weeks. The Fatp2−/− mice had reduced weight gain, lowered serum triglyceride, and increased serum cholesterol levels and attenuated dietary fatty acid absorption. Transcriptomic analysis of the liver revealed 258 differentially expressed genes in male Fatp2−/− mice and a total of 91 in female Fatp2−/− mice. These genes mapped to the following gene ontology categories: fatty acid degradation, peroxisome biogenesis, fatty acid synthesis, and retinol and arachidonic acid metabolism. Targeted RT-quantitative PCR verified the altered expression of selected genes. Of note, most of the genes with increased expression were known to be regulated by peroxisome proliferator–activated receptor α (PPARα), suggesting that FATP2 activity is linked to a PPARα-specific proximal ligand. Targeted metabolomic experiments in the Fatp2−/− liver revealed increases of total C16:0, C16:1, and C18:1 fatty acids; increases in lipoxin A4 and prostaglandin J2; and a decrease in 20-hydroxyeicosatetraenoic acid. We conclude that the expression of FATP2 in the liver broadly affects the metabolic landscape through PPARα, indicating that FATP2 provides an important role in liver lipid metabolism through its transport or activation activities.




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Determination of globotriaosylceramide analogs in the organs of a mouse model of Fabry disease [Lipids]

Fabry disease is a heritable lipid disorder caused by the low activity of α-galactosidase A and characterized by the systemic accumulation of globotriaosylceramide (Gb3). Recent studies have reported a structural heterogeneity of Gb3 in Fabry disease, including Gb3 isoforms with different fatty acids and Gb3 analogs with modifications on the sphingosine moiety. However, Gb3 assays are often performed only on the selected Gb3 isoforms. To precisely determine the total Gb3 concentration, here we established two methods for determining both Gb3 isoforms and analogs. One was the deacylation method, involving Gb3 treatment with sphingolipid ceramide N-deacylase, followed by an assay of the deacylated products, globotriaosylsphingosine (lyso-Gb3) and its analogs, by ultra-performance LC coupled to tandem MS (UPLC-MS/MS). The other method was a direct assay established in the present study for 37 Gb3 isoforms and analogs/isoforms by UPLC-MS/MS. Gb3s from the organs of symptomatic animals of a Fabry disease mouse model were mainly Gb3 isoforms and two Gb3 analogs, such as Gb3(+18) containing the lyso-Gb3(+18) moiety and Gb3(−2) containing the lyso-Gb3(−2) moiety. The total concentrations and Gb3 analog distributions determined by the two methods were comparable. Gb3(+18) levels were high in the kidneys (24% of total Gb3) and the liver (13%), and we observed Gb3(−2) in the heart (10%) and the kidneys (5%). These results indicate organ-specific expression of Gb3 analogs, insights that may lead to a deeper understanding of the pathophysiology of Fabry disease.




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MtrP, a putative methyltransferase in Corynebacteria, is required for optimal membrane transport of trehalose mycolates [Lipids]

Pathogenic bacteria of the genera Mycobacterium and Corynebacterium cause severe human diseases such as tuberculosis (Mycobacterium tuberculosis) and diphtheria (Corynebacterium diphtheriae). The cells of these species are surrounded by protective cell walls rich in long-chain mycolic acids. These fatty acids are conjugated to the disaccharide trehalose on the cytoplasmic side of the bacterial cell membrane. They are then transported across the membrane to the periplasm where they act as donors for other reactions. We have previously shown that transient acetylation of the glycolipid trehalose monohydroxycorynomycolate (hTMCM) enables its efficient transport to the periplasm in Corynebacterium glutamicum and that acetylation is mediated by the membrane protein TmaT. Here, we show that a putative methyltransferase, encoded at the same genetic locus as TmaT, is also required for optimal hTMCM transport. Deletion of the C. glutamicum gene NCgl2764 (Rv0224c in M. tuberculosis) abolished acetyltrehalose monocorynomycolate (AcTMCM) synthesis, leading to accumulation of hTMCM in the inner membrane and delaying its conversion to trehalose dihydroxycorynomycolate (h2TDCM). Complementation with NCgl2764 normalized turnover of hTMCM to h2TDCM. In contrast, complementation with NCgl2764 derivatives mutated at residues essential for methyltransferase activity failed to rectify the defect, suggesting that NCgl2764/Rv0224c encodes a methyltransferase, designated here as MtrP. Comprehensive analyses of the individual mtrP and tmaT mutants and of a double mutant revealed strikingly similar changes across several lipid classes compared with WT bacteria. These findings indicate that both MtrP and TmaT have nonredundant roles in regulating AcTMCM synthesis, revealing additional complexity in the regulation of trehalose mycolate transport in the Corynebacterineae.




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AIG1 and ADTRP are endogenous hydrolases of fatty acid esters of hydroxy fatty acids (FAHFAs) in mice [Metabolism]

Fatty acid esters of hydroxy fatty acids (FAHFAs) are a newly discovered class of signaling lipids with anti-inflammatory and anti-diabetic properties. However, the endogenous regulation of FAHFAs remains a pressing but unanswered question. Here, using MS-based FAHFA hydrolysis assays, LC-MS–based lipidomics analyses, and activity-based protein profiling, we found that androgen-induced gene 1 (AIG1) and androgen-dependent TFPI-regulating protein (ADTRP), two threonine hydrolases, control FAHFA levels in vivo in both genetic and pharmacologic mouse models. Tissues from mice lacking ADTRP (Adtrp-KO), or both AIG1 and ADTRP (DKO) had higher concentrations of FAHFAs particularly isomers with the ester bond at the 9th carbon due to decreased FAHFA hydrolysis activity. The levels of other lipid classes were unaltered indicating that AIG1 and ADTRP specifically hydrolyze FAHFAs. Complementing these genetic studies, we also identified a dual AIG1/ADTRP inhibitor, ABD-110207, which is active in vivo. Acute treatment of WT mice with ABD-110207 resulted in elevated FAHFA levels, further supporting the notion that AIG1 and ADTRP activity control endogenous FAHFA levels. However, loss of AIG1/ADTRP did not mimic the changes associated with pharmacologically administered FAHFAs on extent of upregulation of FAHFA levels, glucose tolerance, or insulin sensitivity in mice, indicating that therapeutic strategies should weigh more on FAHFA administration. Together, these findings identify AIG1 and ADTRP as the first endogenous FAHFA hydrolases identified and provide critical genetic and chemical tools for further characterization of these enzymes and endogenous FAHFAs to unravel their physiological functions and roles in health and disease.




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Certain ortho-hydroxylated brominated ethers are promiscuous kinase inhibitors that impair neuronal signaling and neurodevelopmental processes [Cell Biology]

The developing nervous system is remarkably sensitive to environmental signals, including disruptive toxins, such as polybrominated diphenyl ethers (PBDEs). PBDEs are an environmentally pervasive class of brominated flame retardants whose neurodevelopmental toxicity mechanisms remain largely unclear. Using dissociated cortical neurons from embryonic Rattus norvegicus, we found here that chronic exposure to 6-OH–BDE-47, one of the most prevalent hydroxylated PBDE metabolites, suppresses both spontaneous and evoked neuronal electrical activity. On the basis of our previous work on mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) (MEK) biology and our observation that 6-OH–BDE-47 is structurally similar to kinase inhibitors, we hypothesized that certain hydroxylated PBDEs mediate neurotoxicity, at least in part, by impairing the MEK–ERK axis of MAPK signal transduction. We tested this hypothesis on three experimental platforms: 1) in silico, where modeling ligand–protein docking suggested that 6-OH–BDE-47 is a promiscuous ATP-competitive kinase inhibitor; 2) in vitro in dissociated neurons, where 6-OH–BDE-47 and another specific hydroxylated BDE metabolite similarly impaired phosphorylation of MEK/ERK1/2 and activity-induced transcription of a neuronal immediate early gene; and 3) in vivo in Drosophila melanogaster, where developmental exposures to 6-OH–BDE-47 and a MAPK inhibitor resulted in offspring displaying similarly increased frequency of mushroom-body β–lobe midline crossing, a metric of axonal guidance. Taken together, our results support that certain ortho-hydroxylated PBDE metabolites are promiscuous kinase inhibitors and can cause disruptions of critical neurodevelopmental processes, including neuronal electrical activity, pre-synaptic functions, MEK–ERK signaling, and axonal guidance.




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WYSIWYG Web Builder 7.0 released!

We are pleased to announce a major new release with more than 150 new features and improvements!




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WYSIWYG Web Builder 8.0 released!

We are pleased to announce a major new release with more than 150 new features and improvements!




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WYSIWYG Web Builder 9.0 released!

We are pleased to announce a major new release with more than 150 new features and improvements!




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WYSIWYG Web Builder 10.0 released!

We are pleased to announce a major new release with more than 100 new features and improvements!




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WYSIWYG Web Builder 11.0 released!

We are pleased to announce a major new release with more than 150 new features and improvements!




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WYSIWYG Web Builder 12.0 released!

We are pleased to announce a major new release with more than 125 new features and improvements!




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Genetic Profile and Functional Proteomics of Anal Squamous Cell Carcinoma: Proposal for a Molecular Classification

Lucía Trilla-Fuertes
Apr 1, 2020; 19:690-700
Research




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A Quantitative Tri-fluorescent Yeast Two-hybrid System: From Flow Cytometry to In cellula Affinities

David Cluet
Apr 1, 2020; 19:701-715
Technological Innovation and Resources




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Phenotypic Adaption of Pseudomonas aeruginosa by Hacking Siderophores Produced by Other Microorganisms

Quentin Perraud
Apr 1, 2020; 19:589-607
Research




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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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Peptide-based interaction proteomics

Katrina Meyer
Apr 28, 2020; 0:R120.002034v1-mcp.R120.002034
Review




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The DNA sensor cGAS is decorated by acetylation and phosphorylation modifications in the context of immune signaling

Bokai Song
Apr 28, 2020; 0:RA120.001981v1-mcp.RA120.001981
Research




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Modulation of natural HLA-B*27:05 ligandome by ankylosing spondylitis-associated endoplasmic reticulum aminopeptidase 2 (ERAP2)

Elena Lorente
Apr 7, 2020; 0:RA120.002014v1-mcp.RA120.002014
Research




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HIGD2A is required for assembly of the COX3 module of human mitochondrial complex IV

Daniella H Hock
Apr 21, 2020; 0:RA120.002076v1-mcp.RA120.002076
Research




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Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9

Michael Plank
Apr 1, 2020; 19:655-671
Research




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Characterization of Prenylated C-terminal Peptides Using a Thiopropyl-based Capture Technique and LC-MS/MS

James A. Wilkins
Apr 13, 2020; 0:RA120.001944v1-mcp.RA120.001944
Research




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Flow-induced reorganization of laminin-integrin networks within the endothelial basement membrane uncovered by proteomics

Eelke P. Béguin
Apr 24, 2020; 0:RA120.001964v1-mcp.RA120.001964
Research




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Seminal Plasma Proteome as an Indicator of Sperm Dysfunction and Low Sperm Motility

Yunlei Li
Apr 20, 2020; 0:RA120.002017v1-mcp.RA120.002017
Research




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Investigation of inter- and intra-tumoral heterogeneity of glioblastoma using TOF-SIMS

Samvel K Gularyan
Apr 6, 2020; 0:RA120.001986v1-mcp.RA120.001986
Research




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Identification of an Unconventional Subpeptidome Bound to the Behcet's Disease-associated HLA-B*51:01 that is Regulated by Endoplasmic Reticulum Aminopeptidase 1 (ERAP1)

Liye Chen
May 1, 2020; 19:871-883
Research




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Immediate adaptation analysis implicates BCL6 as an EGFR-TKI combination therapy target in NSCLC

Yan Zhou Tran
Mar 31, 2020; 0:RA120.002036v1-mcp.RA120.002036
Research




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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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Characterization of signaling pathways associated with pancreatic {beta}-cell adaptive flexibility in compensation of obesity-linked diabetes in db/db mice

Taewook Kang
Apr 7, 2020; 0:RA119.001882v1-mcp.RA119.001882
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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Quantitative Profiling of the Human Substantia Nigra Proteome from Laser-capture Microdissected FFPE Tissue

Eva Griesser
May 1, 2020; 19:839-851
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