esea A proteomic approach to understand the clinical significance of acute myeloid leukemia-derived extracellular vesicles reflecting essential characteristics of leukemia [Research] By www.mcponline.org Published On :: 2020-11-30T16:35:18-08:00 Extracellular vesicle (EV) proteins from acute myeloid leukemia (AML) cell lines were analyzed using mass spectrometry. The analyses identified 2450 proteins, including 461 differentially expressed proteins (290 upregulated and 171 downregulated). CD53 and CD47 were upregulated and were selected as candidate biomarkers. The association between survival of patients with AML and the expression levels of CD53 and CD47 at diagnosis was analyzed using mRNA expression data from The Cancer Genome Atlas database. Patients with higher expression levels showed significantly inferior survival than those with lower expression levels. Enzyme-linked immunosorbent assay results of the expression levels of CD53 and CD47 from EVs in the bone marrow of patients with AML at diagnosis and at the time of complete remission with induction chemotherapy revealed that patients with downregulated CD53 and CD47 expression appeared to relapse less frequently. Network model analysis of EV proteins revealed several upregulated kinases, including LYN, CSNK2A1, SYK, CSK, and PTK2B. The potential cytotoxicity of several clinically applicable drugs that inhibit these kinases was tested in AML cell lines. The drugs lowered the viability of AML cells. The collective data suggest that AML-derived EVs could reflect essential leukemia biology. Full Article
esea The Mechanism of NEDD8 Activation of CUL5 Ubiquitin E3 Ligases [Research] By www.mcponline.org Published On :: 2020-12-02T10:35:15-08:00 Cullin RING E3 Ligases (CRLs) ubiquitylate hundreds of important cellular substrates. Here we have assembled and purified the Ankyrin repeat and SOCS Box protein 9 CUL5 RBX2 Ligase (ASB9-CRL) in vitro and show how it ubiquitylates one of its substrates, CKB. CRLs occasionally collaborate with RING between RING E3 ligases (RBRLs) and indeed, mass spectrometry analysis showed that CKB is specifically ubiquitylated by the ASB9-CRL-ARIH2-UBE2L3 complex. Addition of other E2s such as UBE2R1 or UBE2D2 contribute to polyubiquitylation but do not alter the sites of CKB ubiquitylation. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis revealed that CUL5 neddylation allosterically exposes its ARIH2 binding site, promoting high affinity binding, and it also sequesters the NEDD8 E2 (UBE2F) binding site on RBX2. Once bound, ARIH2 helices near the Ariadne domain active site are exposed, presumably relieving its autoinhibition. These results allow us to propose a model of how neddylation activates ASB-CRLs to ubiquitylate their substrates. Full Article
esea A proteomics-based assessment of inflammation signatures in endotoxemia [Research] By www.mcponline.org Published On :: 2020-12-07T09:35:24-08:00 We have previously shown that multimers of plasma pentraxin-3 (PTX3) were predictive of survival in patients with sepsis. To characterize the release kinetics and cellular source of plasma protein changes in sepsis, serial samples were obtained from healthy volunteers (n=10, 3 time-points) injected with low-dose endotoxin (LPS) and analyzed using data-independent acquisition (DIA) MS. The human plasma proteome response was compared to an LPS-induced endotoxemia model in mice. Proteomic analysis of human plasma revealed a rapid neutrophil degranulation signature, followed by a rise in acute phase proteins. Changes in circulating PTX3 correlated with increases in neutrophil-derived proteins following LPS injection. Time course analysis of the plasma proteome in mice showed a time-dependent increase in multimeric PTX3, alongside increases in neutrophil-derived myeloperoxidase (MPO) upon LPS treatment. The mechanisms of oxidation-induced multimerisation of PTX3 were explored in two genetic mouse models: MPO global knock-out mice and LysM CreNox2KO mice, in which NADPH oxidase 2 (Nox2) is only deficient in myeloid cells. Nox2 is the enzyme responsible for the oxidative burst in neutrophils. Increases in plasma multimeric PTX3 were not significantly different between wildtype and MPO or LysM CreNox2KO knock-out mice. Thus, PTX3 may already be stored and released in a multimeric form. Through in vivo neutrophil depletion and multiplexed vascular proteomics, PTX3 multimer deposition within the aorta was confirmed to be neutrophil-dependent. Proteomic analysis of aortas from LPS-injected mice returned PTX3 as the most upregulated protein, where multimeric PTX3 was deposited as early as 2 h post-LPS along with other neutrophil-derived proteins. In conclusion, the rise in multimeric PTX3 upon LPS injection correlates with neutrophil-related protein changes in plasma and in aortas. MPO and myeloid Nox2 are not required for the multimerisation of PTX3; instead, neutrophil extravasation is responsible for the LPS-induced deposition of multimeric PTX3 in the aorta. Full Article
esea A potential role for the Gsdf-eEF1{alpha} complex in inhibiting germ cell proliferation: A protein-interaction analysis in medaka (Oryzias latipes) from a proteomics perspective [Research] By www.mcponline.org Published On :: 2020-12-08T12:35:19-08:00 Gonadal soma-derived factor (gsdf) has been demonstrated to be essential for testicular differentiation in medaka (Oryzias latipes). To understand the protein dynamics of Gsdf in spermatogenesis regulation, we used a His-tag "pull-down" assay coupled with shotgun LC-MS/MS to identify a group of potential interacting partners for Gsdf, which included cytoplasmic dynein light chain 2, eukaryotic polypeptide elongation factor 1 alpha (eEF1α), and actin filaments in mature medaka testis. As for the interaction with TGFβ-dynein being critical for spermatogonial division in Drosophila melanogaster, the physical interactions of Gsdf-dynein and Gsdf-eEF1α were identified through a yeast 2-hybrid (Y2H) screening of an adult testis cDNA library using Gsdf as bait, which were verified by a paired Y2H assay. Co-immunoprecipitation of Gsdf and eEF1α was defined in adult testes as supporting the requirement of a Gsdf and eEF1α interaction in testis development. Proteomics analysis (data are available via ProteomeXchange with identifier PXD022153) and ultrastrutural observations showed that Gsdf deficiency activated eEF1α-mediated protein synthesis and ribosomal biogenesis, which in turn led to the differentiation of undifferentiated germ cells. Thus, our results provide a framework and new insight into the coordination of a Gsdf (TGFβ and eEF1α complex in the basic processes of germ cell proliferation, transcriptional and translational control of sexual RNA which may be fundamentally conserved across phyla during sexual differentiation. Full Article
esea In depth characterization of the Staphylococcus aureus phosphoproteome reveals new targets of Stk1 [Research] By www.mcponline.org Published On :: 2020-12-17T07:31:07-08:00 Staphylococcus aureus is a major cause of infections worldwide and infection results in a variety of diseases. As of no surprise, protein phosphorylation is an important game player in signaling cascades and has been shown to be involved in S. aureus virulence. Albeit long neglected, eukaryotic-type serine/threonine kinases in S. aureus have been implicated in this complex signaling cascades. Due to the sub-stoichiometric nature of protein phosphorylation and a lack of suitable analysis tools, the knowledge of these cascades is however, to date, still limited.Here, were apply an optimized protocol for efficient phosphopeptide enrichment via Fe3+-IMAC followed by LC-MS/MS to get a better understanding of the impact of protein phosphorylation on the complex signaling networks involved in pathogenicity. By profiling a serine/threonine kinase and phosphatase mutant from a methicillin-resistant S. aureus mutant library, we generated the most comprehensive phosphoproteome dataset of S. aureus to date, aiding a better understanding of signaling in bacteria. With the identification of 3800 class I p-sites we were able to increase the number of identifications by more than 21 times compared to recent literature. In addition, we were able to identify 74 downstream targets of the only reported eukaryotic-type Ser/Thr kinase of the S. aureus strain USA300, Stk1. This work allowed an extensive analysis of the bacterial phosphoproteome and indicates that Ser/Thr kinase signaling is far more abundant than previously anticipated in S. aureus. Full Article
esea Plasma proteomic data can contain personally identifiable, sensitive information and incidental findings [Research] By www.mcponline.org Published On :: 2020-12-17T07:31:07-08:00 The goal of clinical proteomics is to identify, quantify, and characterize proteins in body fluids or tissue to assist diagnosis, prognosis, and treatment of patients. In this way, it is similar to more mature omics technologies, such as genomics, that are increasingly applied in biomedicine. We argue that, similar to those fields, proteomics also faces ethical issues related to the kinds of information that is inherently obtained through sample measurement, although their acquisition was not the primary purpose. Specifically, we demonstrate the potential to identify individuals both by their characteristic, individual-specific protein levels and by variant peptides reporting on coding single nucleotide polymorphisms. Furthermore, it is in the nature of blood plasma proteomics profiling that it broadly reports on the health status of an individual – beyond the disease under investigation. Finally, we show that private and potentially sensitive information, such as ethnicity and pregnancy status, can increasingly be derived from proteomics data. Although this is potentially valuable not only to the individual, but also for biomedical research, it raises ethical questions similar to the incidental findings obtained through other omics technologies. We here introduce the necessity of - and argue for the desirability for - ethical and human rights-related issues to be discussed within the proteomics community. Those thoughts are more fully developed in our accompanying manuscript. Appreciation and discussion of ethical aspects of proteomic research will allow for deeper, better-informed, more diverse, and, most importantly, wiser guidelines for clinical proteomics. Full Article
esea Identification of novel serological autoantibodies in Takayasu arteritis patients using HuProt arrays [Research] By www.mcponline.org Published On :: 2020-12-17T13:35:20-08:00 To identify novel autoantibodies of Takayasu arteritis (TAK) using HuProt array-based approach. A two-phase approach was adopted. In Phase I, serum samples collected from 40 TAK patients, 15 autoimmune disease patients, and 20 healthy subjects were screened to identify TAK-specific autoantibodies using human protein (HuProt) arrays. In Phase II, the identified candidate autoantibodies were validated with TAK-focused arrays using an additional cohort comprised of 109 TAK patients, 110 autoimmune disease patients, and 96 healthy subjects. Subsequently, the TAK-specific autoantibodies validated in Phase II were further confirmed using Western blot analysis. We identified and validated eight autoantibodies as potential TAK-specific diagnostic biomarkers, including anti-SPATA7, -QDPR, -SLC25A2, -PRH2, -DIXDC1, -IL17RB, -ZFAND4, and -NOLC1 antibodies, with AUC of 0.803, 0.801, 0.780, 0.696, 0.695, 0.678, 0.635 and 0.613, respectively. SPATA7 could distinguish TAK from healthy and disease controls with 73.4% sensitivity at 85.4% specificity, while QDPR showed 71.6% sensitivity at 86.4% specificity. SLC25A22 showed the highest sensitivity of 80.7%, but at lower specificity of 67.0%. In addition, PRH2, IL17RB and NOLC1 showed good specificities of 88.3%, 85.9% and 86.9%, respectively, but at lower sensitivities (<50%). Finally, DIXDC1 and ZFAND4 showed moderate performance as compared with the other autoantibodies. Using a decision tree model, we could reach a specificity of 94.2% with AUC of 0.843, a significantly improved performance as compared to that by each individual biomarker. The performance of three autoantibodies, namely anti-SPATA7, -QDPR and -PRH2, were successfully confirmed with Western blot analysis. Using this two-phase strategy, we identified and validated eight novel autoantibodies as TAK–specific biomarker candidates, three of which could be readily adopted in a clinical setting. Full Article
esea Multi-sample mass spectrometry-based approach for discovering injury markers in chronic kidney disease [Research] By www.mcponline.org Published On :: 2020-12-20T09:35:16-08:00 Urinary proteomics studies have primarily focused on identifying markers of chronic kidney disease (CKD) progression. Here, we aimed to determine urinary markers of CKD renal parenchymal injury through proteomics analysis in animal kidney tissues and cells and in the urine of patients with CKD. Label-free quantitative proteomics analysis based on liquid chromatography-tandem mass spectrometry was performed on urine samples obtained from 6 normal controls and 9, 11, and 10 patients with CKD stages 1, 3, and 5, respectively, and on kidney tissue samples from a rat CKD model by 5/6 nephrectomy. Tandem mass tag-based quantitative proteomics analysis was performed for primary cultured glomerular endothelial cells (GECs) and proximal tubular epithelial cells (PTECs) before and after inducing 24-h hypoxia injury. Upon hierarchical clustering, out of 858 differentially expressed proteins (DEPs) in the urine of CKD patients, the levels of 416 decreased and 403 increased sequentially according to the disease stage, respectively. Among 2965 DEPs across 5/6 nephrectomized and sham-operated rat kidney tissues, 86 DEPs showed same expression patterns in the urine and kidney tissue. After cross-validation with two external animal proteome datasets, 38 DEPs were organized; only 10 DEPs, including serotransferrin, gelsolin, poly ADP-ribose polymerase 1, neuroblast differentiation-associated protein AHNAK, microtubule-associated protein 4, galectin-1, protein S, thymosin beta-4, myristoylated alanine-rich C-kinase substrate, and vimentin were finalized by screening human GECs and PTECs data. Among these ten potential candidates for universal CKD marker, validation analyses for protein S and galectin-1 were conducted. Galectin-1 was observed to have a significant inverse correlation with renal function as well as higher expression in glomerulus with chronic injury than protein S. This constitutes the first multi-sample proteomics study for identifying key renal-expressed proteins associated with CKD progression. The discovered proteins represent potential markers of chronic renal cell and tissue damage and candidate contributors to CKD pathophysiology. Full Article
esea Systematic identification of P. falciparum sporozoite membrane protein interactions reveals an essential role for the p24 complex in host infection [Research] By www.mcponline.org Published On :: 2020-12-22T08:35:40-08:00 Sporozoites are a motile form of malaria-causing Plasmodium falciparum parasites that migrate from the site of transmission in the dermis through the bloodstream to invade hepatocytes. Sporozoites interact with many cells within the host, but the molecular identity of these interactions and their role in the pathology of malaria is poorly understood. Parasite proteins that are secreted and embedded within membranes are known to be important for these interactions, but our understanding of how they interact with each other to form functional complexes is largely unknown. Here, we compile a library of recombinant proteins representing the repertoire of cell surface and secreted proteins from the P. falciparum sporozoite and use an assay designed to detect extracellular interactions to systematically identify complexes. We identify three protein complexes including an interaction between two components of the p24 complex that is involved in the trafficking of glycosylphosphatidylinositol (GPI)-anchored proteins through the secretory pathway. Plasmodium parasites lacking either gene are strongly inhibited in the establishment of liver stage infections. These findings reveal an important role for the p24 complex in malaria pathogenesis and show that the library of recombinant proteins represents a valuable resource to investigate P. falciparum sporozoite biology. Full Article
esea CMMB (Carboxylate Modified Magnetic Bead) -based isopropanol gradient peptide fractionation (CIF) enables rapid and robust off-line peptide mixture fractionation in bottom-up proteomics [Research] By www.mcponline.org Published On :: 2020-12-22T08:35:40-08:00 Deep proteome coverage in bottom-up proteomics requires peptide-level fractionation to simplify the complex peptide mixture before analysis by tandem mass spectrometry. By decreasing the number of co-eluting precursor peptide ions, fractionation effectively reduces the complexity of the sample leading to higher sample coverage and reduced bias towards high abundance precursors that are preferentially identified in data-dependent acquisition strategies. To achieve this goal, we report a bead-based off-line peptide fractionation method termed CIF or Carboxylate modified magnetic bead-based isopropanol gradient peptide fractionation. CIF is an extension of the SP3 (single-pot solid-phase-enhanced sample preparation) strategy and provides an effective but complementary approach to other commonly used fractionation methods including strong cation exchange (SCX) and reversed phase (RP)-based chromatography. We demonstrate that CIF is an effective offline separation strategy capable of increasing the depth of peptide analyte coverage both when used alone or as a second dimension of peptide fractionation in conjunction with high pH RP. These features make it ideally suited for a wide range of proteomic applications including the affinity purification of low abundance bait proteins. Full Article
esea Unraveling the MAX2 Protein Network in Arabidopsis thaliana: Identification of the Protein Phosphatase PAPP5 as a Novel MAX2 Interactor [Research] By www.mcponline.org Published On :: 2020-12-28T07:35:13-08:00 The F-box protein MORE AXILLARY GROWTH 2 (MAX2) is a central component in the signaling cascade of strigolactones (SLs) as well as of the smoke derived karrikins (KARs) and the so far unknown endogenous KAI2 ligand (KL). The two groups of molecules are involved in overlapping and unique developmental processes, and signal-specific outcomes are attributed to perception by the paralogous α/β-hydrolases DWARF14 (D14) for SL and KARRIKIN INSENSITIVE 2/ HYPOSENSITIVE TO LIGHT (KAI2/HTL) for KAR/KL. Additionally, depending on which receptor is activated, specific members of the SUPPRESSOR OF MAX2 1 (SMAX1) – LIKE (SMXL) family control KAR/KL and SL responses. As proteins that function in the same signal transduction pathway often occur in large protein complexes, we aimed at discovering new players of the MAX2, D14 and KAI2 protein network by tandem affinity purification using Arabidopsis cell cultures. When using MAX2 as a bait, various proteins were co-purified among which general components of the Skp1-Cullin-F-box complex and members of the CONSTITUTIVE PHOTOMORPHOGENIC 9 signalosome. Here, we report the identification of a novel interactor of MAX2, a type 5 serine/threonine protein phosphatase, designated PHYTOCHROME-ASSOCIATED PROTEIN PHOSPHATASE 5 (PAPP5). Quantitative affinity purification pointed at PAPP5 as being more present in KAI2 rather than D14 protein complexes. In agreement, mutant analysis suggests that PAPP5 modulates KAR/KL-dependent seed germination in suboptimal conditions and seedling development. Additionally, a phosphopeptide enrichment experiment revealed that PAPP5 might dephosphorylate MAX2 in vivo independently of the synthetic strigolactone analog, rac-GR24. Together, by analyzing the protein complexes to which MAX2, D14 and KAI2 belong, we revealed a new MAX2 interactor, PAPP5, that might act through dephosphorylation of MAX2 to control mainly KAR/KL- related phenotypes and, hence, provide another link with the light pathway. Full Article
esea Interspecies differences in proteome turnover kinetics are correlated with lifespans and energetic demands [Research] By www.mcponline.org Published On :: 2020-12-28T09:35:20-08:00 Cells continually degrade and replace damaged proteins. However, the high energetic demand of protein turnover generates reactive oxygen species (ROS) that compromise the long-term health of the proteome. Thus, the relationship between aging, protein turnover and energetic demand remains unclear. Here, we used a proteomic approach to measure rates of protein turnover within primary fibroblasts isolated from a number of species with diverse lifespans including the longest-lived mammal, the bowhead whale. We show that organismal lifespan is negatively correlated with turnover rates of highly abundant proteins. In comparison to mice, cells from long-lived naked mole rats have slower rates of protein turnover, lower levels of ATP production and reduced ROS levels. Despite having slower rates of protein turnover, naked mole rat cells tolerate protein misfolding stress more effectively than mouse cells. We suggest that in lieu of rapid constitutive turnover, long-lived species may have evolved more energetically efficient mechanisms for selective detection and clearance of damaged proteins. Full Article
esea Separation and identification of permethylated glycan isomers by reversed phase nanoLC-NSI-MS [Research] By www.mcponline.org Published On :: 2020-12-29T12:35:15-08:00 High performance liquid chromatography has been employed for decades to enhance detection sensitivity and quantification of complex analytes within biological mixtures. Among these analytes, glycans released from glycoproteins and glycolipids have been characterized as underivatized or fluorescently tagged derivatives by HPLC coupled to various detection methods. These approaches have proven extremely useful for profiling the structural diversity of glycoprotein and glycolipid glycosylation but require the availability of glycan standards and secondary orthogonal degradation strategies to validate structural assignments. A robust method for HPLC separation of glycans as their permethylated derivatives, coupled with in-line MSn fragmentation to assign structural features independent of standards, would significantly enhance the depth of knowledge obtainable from biological samples. Here, we report an optimized workflow for LC-MS analysis of permethylated glycans that includes sample preparation, mobile phase optimization, and MSn method development to resolve structural isomers on-the-fly. We report baseline separation and MSn fragmentation of isomeric N- and O-glycan structures, aided by supplementing mobile phases with Li+, which simplifies adduct heterogeneity and facilitates cross-ring fragmentation to obtain valuable monosaccharide linkage information. Our workflow has been adapted from standard proteomics-based workflows and, therefore, provides opportunities for laboratories with expertise in proteomics to acquire glycomic data with minimal deviation from existing buffer systems, chromatography media, and instrument configurations. Furthermore, our workflow does not require a mass spectrometer with high-resolution/accurate mass capabilities. The rapidly evolving appreciation of the biological significance of glycans for human health and disease requires the implementation of high-throughput methods to identify and quantify glycans harvested from sample sets of sufficient size to achieve appropriately powered statistical significance. The LC-MSn approach we report generates glycan isomeric separations, robust structural characterization, and is amenable to auto-sampling with associated throughput enhancements. Full Article
esea High-throughput and site-specific N-glycosylation analysis of human alpha-1-acid glycoprotein offers a great potential for new biomarker discovery [Research] By www.mcponline.org Published On :: 2020-12-29T12:35:15-08:00 Alpha-1-acid glycoprotein (AGP) is an acute phase glycoprotein in blood, which is primarily synthetized in the liver and whose biological role is not completely understood. It consists of 45% carbohydrates that are present in the form of five N-linked complex glycans. AGP N-glycosylation was shown to be changed in many different diseases and some changes appear to be disease-specific, thus it has a great diagnostic and prognostic potential. However, AGP glycosylation was mainly analyzed in small cohorts and without detailed site-specific glycan information. Here, we developed a cost-effective method for a high-throughput and site-specific N-glycosylation LC-MS analysis of AGP which can be applied on large cohorts, aid in search for novel disease biomarkers and enable better understanding of AGP’s role and function in health and disease. The method does not require isolation of AGP with antibodies and affinity chromatography, but AGP is enriched by acid precipitation from 5 μl of bloodplasma in a 96 well format. After trypsinization, AGP glycopeptides are purified using a hydrophilic interaction chromatography based solid-phase extraction and analyzed by RP-LC-ESI-MS. We used our method to show for the first time that AGP N-glycan profile is stable in healthy individuals (14 individuals in 3 time points), which is a requirement for evaluation of its diagnostic potential. Furthermore, we tested our method on a population including individuals with registered hyperglycemia in critical illness (59 cases and 49 controls), which represents a significantly increased risk of developing type 2 diabetes. Individuals at higher risk of diabetes presented increased N-glycan branching on AGP’s second glycosylation site and lower sialylation of N-glycans on AGP’s third and AGP1’s fourth glycosylation site. Although this should be confirmed on a larger prospective cohort, it indicates that site-specific AGP N-glycan profile could help distinguish individuals who are at risk of type 2 diabetes. Full Article
esea Global lysine acetylation and 2-hydroxyisobutyrylation reveal the metabolism conversion mechanism in Giardia lamblia [Research] By www.mcponline.org Published On :: 2020-12-29T13:35:14-08:00 Giardia lamblia (G. lamblia) disease is a zoonosis with a-infection rate affecting the general population of the world. Despite the constant possibility of damage due to their own metabolism, G. lamblia have survived and evolved to adapt to various environments. However, research on energy-metabolism conversion in G. lamblia is limited. This study aimed to reveal the dynamic metabolism-conversion mechanism in G. lamblia under sugar starvation by detecting global lysine acetylation and 2-hydroxyisobutyrylation sites combined with quantitative proteome analyses. A total of 2999 acetylation sites on 956 proteins and 8877 2-hydroxyisobutyryl sites on 1546 proteins were quantified under sugar starvation. Integrated Kac and Khib data revealed that modified proteins were associated with arginine biosynthesis, glycolysis/gluconeogenesis, and alanine, aspartate, and glutamate metabolism. These findings suggested that lysine acetylation and 2-hydroxyisobutyrylation were ubiquitous and provided deep insight into the metabolism-conversion mechanism in G. lamblia under sugar starvation. Overall, these results can help understand the biology of G. lamblia infections and reveal the evolution rule from prokaryote to eukaryote. Full Article
esea Ethical principles, opportunities and constraints in clinical proteomics [Research] By www.mcponline.org Published On :: 2021-01-04T06:35:18-08:00 Recent advances in MS-based proteomics have vastly increased the quality and scope of biological information that can be derived from human samples. These advances have rendered current workflows increasingly applicable in biomedical and clinical contexts. As proteomics is poised to take an important role in the clinic, associated ethical responsibilities increase in tandem with the impact on the health, privacy, and well-being of individuals. Here we conducted and report a systematic literature review of ethical issues in clinical proteomics. We add our perspectives from a background of bioethics, the results of our accompanying paper extracting individual-sensitive results from patient samples, and the literature addressing similar issues in genomics. The spectrum of potential issues ranges from patient re-identification to incidental findings of clinical significance. The latter can be divided into actionable and unactionable findings. Some of these have the potential to be employed in discriminatory or privacy-infringing ways. However, incidental findings may also have great positive potential. A plasma proteome profile, for instance, could inform on the general health or disease status of an individual regardless of the narrow diagnostic question that prompted it. We suggest that early discussion of ethical issues in clinical proteomics is important to ensure that eventual regulations reflect the considered judgment of the community as well as to anticipate opportunities and problems that may arise as the technology matures further. Full Article
esea Patients’ “gut feelings” about symptoms should be taken seriously, say researchers By www.bmj.com Published On :: Wednesday, November 23, 2016 - 06:31 Full Article
esea New research on 21st-century conflict By www.chathamhouse.org Published On :: Mon, 11 Apr 2022 16:47:14 +0000 New research on 21st-century conflict 25 April 2022 — 5:00PM TO 6:00PM Anonymous (not verified) 11 April 2022 Online This International Affairs webinar shares research on US special operations, urban warfare, and digital activism in recent conflicts. Given the ongoing Russian invasion of Ukraine, and continuing conflicts in Myanmar, Yemen, and other countries, it is important to understand the changing nature of conflict in the 21st century. In this webinar, authors from the March 2022 issue of International Affairs share research on the transformation of Western special forces, the impact of army size in urban warfare, and the use of social media and online activism in war. The speakers in this event drew on the following research: US Special Forces transformation: post-Fordism and the limits of networked warfare (https://doi.org/10.1093/ia/iiab213) Urban insurgency in the twenty-first century: smaller militaries and increased conflict in cities (https://doi.org/10.1093/ia/iiac007) Diasporas as cyberwarriors: infopolitics, participatory warfare and the 2020 Karabakh war (https://doi.org/10.1093/ia/iiac015) International Affairs was started at Chatham House in 1922 to communicate research to members who could not attend in person. Over the past 100 years, it has transformed into a journal that publishes academically rigorous and policy-relevant research. It is published for Chatham House by Oxford University Press. Read the latest issue here. Full Article
esea Five additional monkeys from S.C. research lab recovered; 13 remain at large By www.upi.com Published On :: Mon, 11 Nov 2024 22:01:15 -0500 An additional five rhesus macaque monkeys that escaped from a South Carolina research facility last week have been recovered, meaning about a dozen of the rhesus macaque primates remain at large. Full Article
esea Research Scientist II/Senior - Research Software Engineer By careers.hpcwire.com Published On :: Tue, 01 Oct 2024 02:15:13 EST This is a Remote Eligible open rank research software engineer position. The OIT (Office of Information Technology) department, Home | Office of Information Technology (oit.gatech.edu) at the Georgia Institute of Technology in Atlanta, Georgia invites applications for Partnership for Advanced Computing Environment (PACE) (pace.gatech.edu). This is a research faculty position, applications will be considered at all ranks. We seek a highly skilled and innovative Research Scientist to join our research software engineer team. The successful candidate will lead software lifecycle management with security and compliance efforts in PACE, in collaboration with other researchers, play a key role in supporting sensitive/regulated research projects while ensuring compliance with applicable regulations and security requirements. This position will also be responsible for the PACE software vulnerability management program. This role will closely work with the Research Facilitation and Cyberinfrastructure Teams to bring support to GT faculty on regulated research projects and evaluate underlying technologies. This role requires strong software engineering expertise, excellent communication skills, and the ability to bring innovative solutions to researchersâ projects and implement them to deliverable. Responsibilities ⢠Define and implement standard operating procedures to incorporate software vulnerability management ⢠Coordinate with other cyber security and research security personnel to satisfy software audit and compliance requirements ⢠Software Bill of Materials (SBOM) management, identify and address software vulnerability for the PACE software stack ⢠Take responsibility for the audit and compliance of restricted software/code (e.g. RSICC/NASA) ⢠Provide domain expertise on CUI (Controlled Unclassified Information) and regulated software ⢠Provide support on commercial/licensed software in the regulated environment ⢠Work in partnership with other GT Collegesâ IT groups to support the deployment of HPC scientific applications and workflows for researchers on PACE systems ⢠Closely work with other internal PACE units, including the Research Computing Facilitation (RCF) and Cyberinfrastructure (CI) teams, to address researchersâ needs ⢠Coordinate review and software access processes with other research cyber security personnel ⢠Implement best practices around research computing software vulnerability management ⢠Research and evaluate any new technologies in software vulnerability and closely monitor NIST regulations ⢠Author and publish scientific papers, reports, and presentations to communicate research results and findings to internal and external audiences Full Article
esea Accelerating Research Innovation with Qumulo’s File Data Platform By www.hpcwire.com Published On :: Thu, 10 Sep 2020 12:00:05 +0000 Large-scale scientific research labs and academic institutions are utilizing high performance computing to accelerate sequencing, simulations, and analytics for research, learning, and discovery. File data volumes are growing rapidly, and […] The post Accelerating Research Innovation with Qumulo’s File Data Platform appeared first on HPCwire. Full Article
esea QuEra and AIST Partner on Quantum-HPC Integration for Research and Industry By www.hpcwire.com Published On :: Fri, 25 Oct 2024 13:44:23 +0000 BOSTON, Oct. 25, 2024 — QuEra Computing, a leader in neutral-atom quantum computing, today announced that on September 6th, it signed a Memorandum of Understanding (MOU) with the National Institute of […] The post QuEra and AIST Partner on Quantum-HPC Integration for Research and Industry appeared first on HPCwire. Full Article
esea Highlights from GlobusWorld 2024: The Conference for Reimagining Research IT By www.hpcwire.com Published On :: Tue, 11 Jun 2024 19:51:38 +0000 The Globus user conference, now in its 22nd year, brought together over 180 researchers, system administrators, developers, and IT leaders from 55 top research computing centers, national labs, federal agencies, […] The post Highlights from GlobusWorld 2024: The Conference for Reimagining Research IT appeared first on HPCwire. Full Article Features AuroraGPT ChatGPT DOE Globus IRI ScienceBase USGS
esea CIQ Empowers Researchers to Innovate Faster with Fuzzball By www.hpcwire.com Published On :: Wed, 28 Aug 2024 20:57:30 +0000 RENO, Nev., Aug. 28, 2024 — Individual researchers focused on performing critical work in science and innovation can now converge on world-changing discoveries faster, owing to capabilities released today by […] The post CIQ Empowers Researchers to Innovate Faster with Fuzzball appeared first on HPCwire. Full Article
esea OSC Advances Marine Movement Research with Computational Tools for Bio-Inspired Robotics By www.hpcwire.com Published On :: Thu, 07 Nov 2024 15:50:27 +0000 COLUMBUS, Ohio, Nov. 7, 2024 — Alexander Hoover, an assistant professor in the Department of Mathematics and Statistics at Cleveland State University, has always been fascinated by marine organisms—the way […] The post OSC Advances Marine Movement Research with Computational Tools for Bio-Inspired Robotics appeared first on HPCwire. Full Article
esea Jülich Leads QSolid Quantum Prototype Toward Hybrid HPC Integration for Industry and Research By www.hpcwire.com Published On :: Mon, 11 Nov 2024 15:28:24 +0000 Nov. 11, 2024 — Forschungszentrum Jülich and its partners in the QSolid project have begun operating Germany’s first prototype quantum computer featuring optimized qubit quality. This prototype lays the groundwork […] The post Jülich Leads QSolid Quantum Prototype Toward Hybrid HPC Integration for Industry and Research appeared first on HPCwire. Full Article
esea Here's the Happiness Research that Stands Up to Scrutiny By www.scientificamerican.com Published On :: Wed, 31 Jan 2024 11:45:00 GMT From meditation to smiling, researchers take a second look at studies claiming to reveal what makes us happy Full Article Mind & Brain Psychology
esea Asexuality Research Has Reached New Heights. What Are We Learning? By www.scientificamerican.com Published On :: Fri, 23 Feb 2024 19:00:00 GMT A grassroots online movement has helped shift the way scientists think about asexuality. But much is still unknown. Full Article Health Mind & Brain Sexuality
esea IBM and NASA Launch Open-Source AI Model for Advanced Climate and Weather Research By www.hpcwire.com Published On :: Thu, 26 Sep 2024 04:00:22 +0000 IBM and NASA have developed a new AI foundation model for a wide range of climate and weather applications, with contributions from the Department of Energy’s Oak Ridge National Laboratory. […] The post IBM and NASA Launch Open-Source AI Model for Advanced Climate and Weather Research appeared first on HPCwire. Full Article Features AI climate foundation model Hugging Face IBM Watson JPL NASA Oak Ridge National Lab Prithvi-WxC weather
esea Research Insights, HPC Expertise, Meaningful Collaborations Abound at TACCSTER 2024 By www.hpcwire.com Published On :: Thu, 17 Oct 2024 15:23:31 +0000 It’s a wrap! The Texas Advanced Computing Center (TACC) at UT Austin welcomed more than 100 participants for the 7th annual TACC Symposium for Texas Researchers (TACCSTER). The event exists […] The post Research Insights, HPC Expertise, Meaningful Collaborations Abound at TACCSTER 2024 appeared first on HPCwire. Full Article Features star formation Storm Surge Modeling TACC TACCSTER-24
esea Pawsey Invites Australian Researchers to Advance Scientific Innovation Through the Pawsey Uptake Project By www.hpcwire.com Published On :: Wed, 20 Mar 2024 16:46:09 +0000 March 20, 2024 — The Pawsey Supercomputing Research Centre invites Australian-based research groups to join the Pawsey Uptake Project call. This initiative will provide teams with access to dedicated Pawsey […] The post Pawsey Invites Australian Researchers to Advance Scientific Innovation Through the Pawsey Uptake Project appeared first on HPCwire. Full Article
esea ENEA Chooses Lenovo for Supercomputer to Accelerate Sustainable Energy Research By www.hpcwire.com Published On :: Wed, 06 Nov 2024 16:08:19 +0000 MILAN, Nov. 6, 2024 — ENEA, Italy’s National Agency for New Technologies, Energy and Sustainable Economic Development, has selected Lenovo for the installation of an HPC system at the Portici […] The post ENEA Chooses Lenovo for Supercomputer to Accelerate Sustainable Energy Research appeared first on HPCwire. Full Article
esea Five additional monkeys from S.C. research lab recovered; 13 remain at large By www.upi.com Published On :: Mon, 11 Nov 2024 22:01:15 -0500 An additional five rhesus macaque monkeys that escaped from a South Carolina research facility last week have been recovered, meaning about a dozen of the rhesus macaque primates remain at large. Full Article
esea Preclinical research and development of a herbal antipyretic drug based on leaves of Ceiba pentandra (Malvaceae) By resources.medipacademy.com Published On :: 30 July 2022 11:32:03 Background: Faced with the limits of synthetic antipyretic substances, in particular their involvement in the occurrence of numerous and often serious adverse effects; the challenge is in search of new antipyretics especially from the African traditional pharmacopoeia. The objective of this study was to evaluate the antipyretic activity of an aqueous extract and a formulation of Ceiba pentandra, with a view to designing an herbal antipyretic drug. Methods: Trials of formulation of an antipyretic syrup with leaves extract of Ceiba pentandra were carried out. The antipyretic activity was investigated by the bewer's yeast induced pyrexia. Physicochemical and microbiological stability tests were carried out on the syrup. Results: It was found with the extract an antipyretic activity at doses of 125 mg/kg and 150 mg/kg. The effect was greater for the 125 mg/kg dose with inhibition percentages ranging from 27.58% to 71.25%. This antipyretic activity was early (from 30 minutes) and was preserved during the four hours of the experiment. The syrup dosed at 125 mg/kg gave an activity similar to that of the extract by significantly reducing the hyperthermia in the rats. Regarding the stability tests, the syrup remained stable both physico-chemically and microbiologically throughout the study period (28 days) both when exposed to low temperature (5 °±3 ° C) and at high temperature (40°±2° C). Conclusions: Ceiba pentandra leaves have antipyretic activity and could be used for the development of an herbal antipyretic drug. Full Article
esea NASA runs first engine tests on supersonic X-59 research aircraft By www.upi.com Published On :: Wed, 06 Nov 2024 16:04:00 -0500 NASA engineers fired the engines on the X-59 research aircraft in advance of planned test flights to determine if the aircraft can reduce sonic booms and make supersonic flight over land quieter. Full Article
esea Honesty Research May Be… Dishonest By feeds.feedblitz.com Published On :: Fri, 28 Jul 2023 19:37:34 +0000 A new report from NPR publishes a letter from The Hartford describing data they gave to Dan Ariely as having been fraudulently manipulated in a paper based on that data. The post Honesty Research May Be… Dishonest appeared first on Neuromarketing. Full Article Neuromarketing dan ariely dishonesty francesca gino fraud honesty replication
esea Your Brain on Zoom Calls: New Research By feeds.feedblitz.com Published On :: Thu, 14 Dec 2023 21:06:53 +0000 Yale scientists used brain imaging to compare face-to-face meetings with virtual sessions. The post Your Brain on Zoom Calls: New Research appeared first on Neuromarketing. Full Article Neuromarketing fNIRS meetings Zoom
esea Training Bias Out of Teachers: Research Shows Little Promise So Far By www.teachermagazine.org Published On :: 2020-11-17T17:11:00-05:00 After a summer of protests over racial injustice, school districts are embracing anti-bias programs. The problem is: Few studies show they work. Full Article Education
esea Kids Are Behind in Math Because of COVID-19. Here’s What Research Says Could Help By www.edweek.org Published On :: 2020-12-01T16:13:02-05:00 Previous studies can provide a window into why math learning is taking a big hit during the pandemic, and what educators can do about it. Full Article Education
esea Music and Brain Circuitry: Strategies for Strengthening Evidence-Based Research for Music-Based Interventions By www.jneurosci.org Published On :: 2022-11-09 Wen Grace ChenNov 9, 2022; 42:8498-8507Symposium and Mini-Symposium Full Article
esea FAO ranked 4th of 8000 research institutions around the world in 2017 By www.fao.org Published On :: Wed, 25 Jan 2017 00:00:00 GMT A recent release on the “Ranking Web of Research Centers” site ranks FAO as fourth among 8000 global research institutions in 2016 for use of its online information. [...] Full Article
esea How Smithsonian Researchers Are Studying Elephant Behavior By www.smithsonianmag.com Published On :: Thu, 31 Oct 2024 00:00:00 -0000 See how researchers at Smithsonian's National Zoo are trying to glean insight into elephant foraging behavior and more. Full Article
esea Researchers Discover the Oldest, Most Complete Skeleton Discovered in the New World By www.smithsonianmag.com Published On :: Thu, 31 Oct 2024 00:00:00 -0000 The 12,000 year old skeleton of a teenage girl was found in Hoyo Negro, an underwater cave system on the Yucatan Peninsula. Full Article
esea New Research Dispels the Myth That Ancient Cultures Had Universally Short Lifespans By www.smithsonianmag.com Published On :: Wed, 10 Jan 2018 20:56:31 +0000 Teeth are key to identifying elderly remains Full Article
esea A Mysterious Seismic Signal Lasted Nine Days Last Year. It Was a Mega-Tsunami Caused by Climate Change, Researchers Say By www.smithsonianmag.com Published On :: Mon, 16 Sep 2024 17:45:43 +0000 A melting glacier caused a mountain in Greenland to collapse into a narrow fjord, setting off an oscillating wave that rattled seismic detectors around the world Full Article
esea World's First Ultra-Precise Nuclear Clock Is Within Reach After Major Breakthrough, Researchers Say By www.smithsonianmag.com Published On :: Mon, 23 Sep 2024 16:53:18 +0000 The technology, enabled by thorium atoms, could keep time more accurately than atomic clocks and enable new discoveries about gravity, gravitational waves and dark matter Full Article
esea This Painting Was Thought to Be a Botticelli Copy. Now, Researchers Say It Was Made in His Studio By www.smithsonianmag.com Published On :: Mon, 07 Oct 2024 18:44:18 +0000 A new analysis suggests that the piece was created by several artists working in the Italian Renaissance painter's studio—and that Botticelli himself may have worked on important details Full Article
esea A Great White Shark Mysteriously Washed Ashore in Cape Cod, and Researchers Don't Know Why By www.smithsonianmag.com Published On :: Fri, 18 Oct 2024 20:54:39 +0000 Authorities have not yet identified the cause of death for the 12.5-foot-long shark, which was named Koala Full Article
esea Forty-Three Monkeys Are on the Loose in South Carolina After Escaping a Research Facility When a Door Was Left Unsecured By www.smithsonianmag.com Published On :: Fri, 08 Nov 2024 20:20:29 +0000 Once the first primate made a break, the 42 others followed suit in a simple case of monkey-see, monkey-do Full Article
esea KKK Halloween costumes symptom of growing far-right in Atlantic Canada, researcher says By www.cbc.ca Published On :: Sat, 09 Nov 2024 05:00:00 EST A researcher studying the rise of extremism in Atlantic Canada warns Ku Klux Klan Halloween costumes are just one example of an insidious effort by far-right groups to normalize hateful attitudes. Full Article News/Canada/Nova Scotia