| 1. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 11. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 12. |
- Thoma, B, et al.
(författare)
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An international, interprofessional investigation of the self-reported podcast listening habits of emergency clinicians: A METRIQ Study
- 2020
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Ingår i: CJEM. - : Springer Science and Business Media LLC. - 1481-8043 .- 1481-8035. ; 22:1, s. 112-117
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesPodcasts are increasingly being used for medical education. A deeper understanding of usage patterns would inform both producers and researchers of medical podcasts. We aimed to determine how and why podcasts are used by emergency medicine and critical care clinicians.MethodsAn international interprofessional sample (medical students, residents, physicians, nurses, physician assistants, and paramedics) was recruited through direct contact and a multimodal social media (Twitter and Facebook) campaign. Each participant completed a survey outlining how and why they utilize medical podcasts. Recruitment materials included an infographic and study website.Results390 participants from 33 countries and 4 professions (medicine, nursing, paramedicine, physician assistant) completed the survey. Participants most frequently listened to medical podcasts to review new literature (75.8%), learn core material (75.1%), and refresh memory (71.8%). The majority (62.6%) were aware of the ability to listen at increased speeds, but most (76.9%) listened at 1.0 x (normal) speed. All but 25 (6.4%) participants concurrently performed other tasks while listening. Driving (72.3%), exercising (39.7%), and completing chores (39.2%) were the most common. A minority of participants used active learning techniques such as pausing, rewinding, and replaying segments of the podcast. Very few listened to podcasts multiple times.ConclusionsAn international cohort of emergency clinicians use medical podcasts predominantly for learning. Their listening habits (rarely employing active learning strategies and frequently performing concurrent tasks) may not support this goal. Further exploration of the impact of these activities on learning from podcasts is warranted.
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| 13. |
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| 14. |
- Rheinbay, E, et al.
(författare)
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Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 102-
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of drivers of cancer has traditionally focused on protein-coding genes1–4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53, in the 3′ untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
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| 15. |
- Carlevaro-Fita, J, et al.
(författare)
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Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis
- 2020
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 56-
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Tidskriftsartikel (refereegranskat)abstract
- Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis.
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| 16. |
- Groß, M., et al.
(författare)
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Rubella vaccine–induced granulomas are a novel phenotype with incomplete penetrance of genetic defects in cytotoxicity
- 2022
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 149:1, s. 388-399
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Tidskriftsartikel (refereegranskat)abstract
- Background: Rubella virus–induced granulomas have been described in patients with various inborn errors of immunity. Most defects impair T-cell immunity, suggesting a critical role of T cells in rubella elimination. However, the molecular mechanism of virus control remains elusive. Objective: This study sought to understand the defective effector mechanism allowing rubella vaccine virus persistence in granulomas. Methods: Starting from an index case with Griscelli syndrome type 2 and rubella skin granulomas, this study combined an international survey with a literature search to identify patients with cytotoxicity defects and granuloma. The investigators performed rubella virus immunohistochemistry and PCR and T-cell migration assays. Results: This study identified 21 patients with various genetically confirmed cytotoxicity defects, who presented with skin and visceral granulomas. Rubella virus was demonstrated in all 12 accessible biopsies. Granuloma onset was typically before 2 years of age and lesions persisted from months to years. Granulomas were particularly frequent in MUNC13-4 and RAB27A deficiency, where 50% of patients at risk were affected. Although these proteins have also been implicated in lymphocyte migration, 3-dimensional migration assays revealed no evidence of impaired migration of patient T cells. Notably, patients showed no evidence of reduced control of concomitantly given measles, mumps, or varicella live-attenuated vaccine or severe infections with other viruses. Conclusions: This study identified lymphocyte cytotoxicity as a key effector mechanism for control of rubella vaccine virus, without evidence for its need in control of live measles, mumps, or varicella vaccines. Rubella vaccine–induced granulomas are a novel phenotype with incomplete penetrance of genetic disorders of cytotoxicity. © 2021 American Academy of Allergy, Asthma & Immunology
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| 17. |
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| 18. |
- Gurnett, D. A., et al.
(författare)
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A plasmapause-like density boundary at high latitudes in Saturn's magnetosphere
- 2010
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 37, s. L16806-
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the discovery of a well-defined plasma density boundary at high latitudes in Saturn's magnetosphere. The boundary separates a region of relatively high density at L less than about 8 to 15 from a region with densities nearly three orders of magnitude lower at higher L values. Magnetic field measurements show that strong field-aligned currents, probably associated with the aurora, are located just inside the boundary. Analyses of the anisotropy of energetic electrons show that the magnetic field lines are usually closed inside the boundary and open outside the boundary, although exceptions sometimes occur. The location of the boundary is also modulated at the similar to 10.6 to 10.8 hr rotational period of the planet. Many of these characteristics are similar to those predicted by Brice and Ioannidis for the plasmapause at a strongly magnetized, rapidly rotating planet such as Saturn.
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| 19. |
- Jones, G. H., et al.
(författare)
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The dust halo of Saturn's largest icy moon, Rhea
- 2008
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 319:5868, s. 1380-1384
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Tidskriftsartikel (refereegranskat)abstract
- Saturn's moon Rhea had been considered massive enough to retain a thin, externally generated atmosphere capable of locally affecting Saturn's magnetosphere. The Cassini spacecraft's in situ observations reveal that energetic electrons are depleted in the moon's vicinity. The absence of a substantial exosphere implies that Rhea's magnetospheric interaction region, rather than being exclusively induced by sputtered gas and its products, likely contains solid material that can absorb magnetospheric particles. Combined observations from several instruments suggest that this material is in the form of grains and boulders up to several decimetres in size and orbits Rhea as an equatorial debris disk. Within this disk may reside denser, discrete rings or arcs of material.
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| 20. |
- Khatri, Sumita B., et al.
(författare)
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Use of fractional exhaled nitric oxide to guide the treatment of asthma an official american thoracic society clinical practice guideline
- 2021
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 204:10, s. 97-109
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Tidskriftsartikel (refereegranskat)abstract
- Background: The fractional exhaled nitric oxide (FENO) test is a point-of-care test that is used in the assessment of asthma. Objective: To provide evidence-based clinical guidance on whether FENO testing is indicated to optimize asthma treatment in patients with asthma in whom treatment is being considered. Methods: An international, multidisciplinary panel of experts was convened to form a consensus document regarding a single question relevant to the use of FENO. The question was selected from three potential questions based on the greatest perceived impact on clinical practice and the unmet need for evidencebased answers related to this question. The panel performed systematic reviews of published randomized controlled trials between 2004 and 2019 and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework to develop recommendations. All panel members evaluated and approved the recommendations. Main Results: After considering the overall low quality of the evidence, the panel made a conditional recommendation for FENO-based care. In patients with asthma in whom treatment is being considered, we suggest that FENO is beneficial and should be used in addition to usual care. This judgment is based on a balance of effects that probably favors the intervention; the moderate costs and availability of resources, which probably favors the intervention; and the perceived acceptability and feasibility of the intervention in daily practice. Conclusions: Clinicians should consider this recommendation to measure FENO in patients with asthma in whom treatment is being considered based on current best available evidence.
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| 21. |
- Li, YL, et al.
(författare)
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Patterns of somatic structural variation in human cancer genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 112-
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Tidskriftsartikel (refereegranskat)abstract
- A key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments that range in size from kilobases to whole chromosomes1–7. Here we develop methods to group, classify and describe somatic structural variants, using data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumour types8. Sixteen signatures of structural variation emerged. Deletions have a multimodal size distribution, assort unevenly across tumour types and patients, are enriched in late-replicating regions and correlate with inversions. Tandem duplications also have a multimodal size distribution, but are enriched in early-replicating regions—as are unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy-number gains and frequent inverted rearrangements. One prominent structure consists of 2–7 templates copied from distinct regions of the genome strung together within one locus. Such cycles of templated insertions correlate with tandem duplications, and—in liver cancer—frequently activate the telomerase gene TERT. A wide variety of rearrangement processes are active in cancer, which generate complex configurations of the genome upon which selection can act.
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| 22. |
- Morooka, Michiko, et al.
(författare)
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The electron density of Saturn's magnetosphere
- 2009
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Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 27:7, s. 2971-2991
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated statistically the electron density below 5 cm(-3) in the magnetosphere of Saturn (7-80 R-S, Saturn radii) using 44 orbits of the floating potential data from the RPWS Langmuir probe (LP) onboard Cassini. The density distribution shows a clear dependence on the distance from the Saturnian rotation axis (root X-2 + Y-2) as well as on the distance from the equatorial plane (vertical bar Z vertical bar), indicating a disc-like structure. From the characteristics of the density distribution, we have identified three regions: the extension of the plasma disc, the magnetodisc region, and the lobe regions. The plasma disc region is at L<15, where L is the radial distance to the equatorial crossing of the dipole magnetic field line, and confined to vertical bar Z vertical bar <5 R-S. The magnetodisc is located beyond L=15, and its density has a large variability. The variability has quasi-periodic characteristics with a periodicity corresponding to the planetary rotation. For Z > 15 R-S, the magnetospheric density distribution becomes constant in Z. However, the density still varies quasi-periodically with the planetary rotation also in this region. In fact, the quasi-periodic variation has been observed all over the magnetosphere beyond L=15. The region above Z=15 R-S is identified as the lobe region. We also found that the magnetosphere can occasionally move latitudinally under the control of the density in the magnetosphere and the solar wind. From the empirical distributions of the electron densities obtained in this study, we have constructed an electron density model of the Saturnian nightside magnetosphere beyond 7 R-S. The obtained model can well reproduce the observed density distribution, and can thus be useful for magnetospheric modelling studies.
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| 23. |
- Reyna, Matthew A, et al.
(författare)
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Pathway and network analysis of more than 2500 whole cancer genomes
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
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| 24. |
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| 25. |
- Lennon, J. T., et al.
(författare)
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Priorities, opportunities, and challenges for integrating microorganisms into Earth system models for climate change prediction
- 2024
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Ingår i: mBio. - 2161-2129 .- 2150-7511.
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Tidskriftsartikel (refereegranskat)abstract
- Climate change jeopardizes human health, global biodiversity, and sustainability of the biosphere. To make reliable predictions about climate change, scientists use Earth system models (ESMs) that integrate physical, chemical, and biological processes occurring on land, the oceans, and the atmosphere. Although critical for catalyzing coupled biogeochemical processes, microorganisms have traditionally been left out of ESMs. Here, we generate a "top 10" list of priorities, opportunities, and challenges for the explicit integration of microorganisms into ESMs. We discuss the need for coarse-graining microbial information into functionally relevant categories, as well as the capacity for microorganisms to rapidly evolve in response to climate-change drivers. Microbiologists are uniquely positioned to collect novel and valuable information necessary for next-generation ESMs, but this requires data harmonization and transdisciplinary collaboration to effectively guide adaptation strategies and mitigation policy.
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| 26. |
- Roussos, E., et al.
(författare)
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Energetic electron observations of Rhea's magnetospheric interaction
- 2012
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Ingår i: Icarus. - : Elsevier BV. - 0019-1035 .- 1090-2643. ; 221:1, s. 116-134
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Tidskriftsartikel (refereegranskat)abstract
- Saturn's moon Rhea is thought to be a simple plasma absorber, however, energetic particle observations in its vicinity show a variety of unexpected and complex interaction features that do not conform with our current understanding about plasma absorbing interactions. Energetic electron data are especially interesting, as they contain a series of broad and narrow flux depletions on either side of the moon's wake. The association of these dropouts with absorption by dust and boulders orbiting within Rhea's Hill sphere was suggested but subsequently not confirmed, so in this study we review data from all four Cassini flybys of Rhea to date seeking evidence for alternative processes operating within the moon's interaction region. We focus on energetic electron observations, which we put in context with magnetometer, cold plasma density and energetic ion data. All flybys have unique features, but here we only focus on several structures that are consistently observed. The most interesting common feature is that of narrow dropouts in energetic electron fluxes, visible near the wake flanks. These are typically seen together with narrow flux enhancements inside the wake. A phase-space-density analysis for these structures from the first Rhea flyby (R1) shows that Liouville's theorem holds, suggesting that they may be forming due to rapid transport of energetic electrons from the magnetosphere to the wake, through narrow channels. A series of possibilities are considered to explain this transport process. We examined whether complex energetic electron drifts in the interaction region of a plasma absorbing moon (modeled through a hybrid simulation code) may allow such a transport. With the exception of several features (e.g. broadening of the central wake with increasing electron energy), most of the commonly observed interaction signatures in energetic electrons (including the narrow structures) were not reproduced. Additional dynamical processes, not simulated by the hybrid code, should be considered in order to explain the data. For the small scale features, the possibility that a flute (interchange) instability acts on the electrons is discussed. This instability is probably driven by strong gradients in the plasma pressure and the magnetic field magnitude: magnetometer observations show clearly signatures consistent with the (expected) plasma pressure loss due to ion absorption at Rhea. Another potential driver of the instability could have been gradients in the cold plasma density, which are, however, surprisingly absent from most crossings of Rhea's plasma wake. The lack of a density depletion in Rhea's wake suggests the presence of a local cold plasma source region. Hybrid plasma simulations show that this source cannot be the ionized component of Rhea's weak exosphere. It is probably related to accelerated photoelectrons from the moon's negatively charged surface, indicating that surface charging may play a very important role in shaping Rhea's magnetospheric interaction region. (C) 2012 Elsevier Inc. All rights reserved.
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| 27. |
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| 28. |
- Fischer, M Dominik, et al.
(författare)
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Expression profiling reveals metabolic and structural components of extraocular muscles
- 2002
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 9:2, s. 71-84
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Tidskriftsartikel (refereegranskat)abstract
- The extraocular muscles (EOM) are anatomically and physiologically distinct from other skeletal muscles. EOM are preferentially affected in mitochondrial myopathies, but spared in Duchenne's muscular dystrophy. The anatomical and pathophysiological properties of EOM have been attributed to their unique molecular makeup: an allotype. We used expression profiling to define molecular features of the EOM allotype. We found 346 differentially expressed genes in rat EOM compared with tibialis anterior, based on a twofold difference cutoff. Genes required for efficient, fatigue-resistant, oxidative metabolism were increased in EOM, whereas genes for glycogen metabolism were decreased. EOM also showed increased expression of genes related to structural components of EOM such as vessels, nerves, mitochondria, and neuromuscular junctions. Additionally, genes related to specialized functional roles of EOM such as the embryonic and EOM-specific myosin heavy chains and genes for muscle growth, development, and/or regeneration were increased. The EOM expression profile was validated using biochemical, structural, and molecular methods. Characterization of the EOM expression profile begins to define gene transcription patterns associated with the unique anatomical, metabolic, and pathophysiological properties of EOM.
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| 29. |
- Geahlen, J. H., et al.
(författare)
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Evolution of the human gastrokine locus and confounding factors regarding the pseudogenicity of GKN3
- 2013
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 45:15, s. 667-683
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Tidskriftsartikel (refereegranskat)abstract
- In a screen for genes expressed specifically in gastric mucous neck cells, we identified GKN3, the recently discovered third member of the gastrokine family. We present confirmatory mouse data and novel porcine data showing that mouse GKN3 expression is confined to mucous cells of the corpus neck and antrum base and is prominently expressed in metaplastic lesions. GKN3 was proposed originally to be expressed in some human populations and a pseudogene in others. To investigate that hypothesis, we studied human GKN3 evolution in the context of its paralogous genomic neighbors, GKN1 and GKN2. Haplotype analysis revealed that GKN3 mimics GKN2 in patterns of exonic SNP allocation, whereas GKN1 appeared to be more stringently selected. GKN3 showed signatures of both directional selection and population based selective sweeps in humans. One such selective sweep includes SNP rs10187256, originally identified as an ancestral tryptophan to premature STOP codon mutation. The derived (nonancestral) allele went to fixation in Asia. We show that another SNP, rs75578132, identified 5 bp downstream of rs10187256, exhibits a second selective sweep in almost all Europeans, some Latinos, and some Africans, possibly resulting from a reintroduction of European genes during African colonization. Finally, we identify a mutation that would destroy the splice donor site in the putative exon3-intron3 boundary, which occurs in all human genomes examined to date. Our results highlight a stomach-specific human genetic locus, which has undergone various selective sweeps across European, Asian, and African populations and thus reflects geographic and ethnic patterns in genome evolution.
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| 30. |
- Golding, H, et al.
(författare)
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CCR5 N-terminal region plays a critical role in HIV-1 inhibition by Toxoplasma gondii-derived cyclophilin-18
- 2005
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 280:33, s. 29570-29577
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Tidskriftsartikel (refereegranskat)abstract
- Molecular mimicry of chemokine ligands has been described for several pathogens. Toxoplasma gondii produces a protein, cyclophilin-18 (C-18), which binds to the human immunodeficiency virus (HIV) co-receptor CCR5 and inhibits fusion and infection of T cells and macrophages by R5 viruses but not by X4 viruses. We recently identified structural determinants of C-18 required for anti-HIV activity (Yarovinsky, F., Andersen, J. F., King, L. R., Caspar, P., Aliberti, J., Golding, H., and Sher, A. ( 2004) J. Biol. Chem. 279, 53635 - 53642). Here we have elucidated the fine specificity of CCR5 residues involved in binding and HIV inhibitory potential of C-18. To delineate the regions of CCR5 involved in C-18 binding, we analyzed C-18 inhibition of cells expressing CXCR4/CCR5 chimeric receptors and CCR5 with a truncated N terminus (Delta 2-19). These experiments identified a critical role for the N terminus of CCR5 in C-18 binding and anti-HIV activity. Studies with a large panel of CCR5 N-terminal peptides, including Tyr-sulfated analogues, truncated peptides, and alanine-scanning mutants, suggested that each of the 12 - 17 amino acids in the N terminus of CCR5 are essential for C-18 binding and inhibitory activity. Tyr sulfation did not improve C-18 reactivity. This finding is of interest because the same CCR5 N-terminal region was shown previously to play a key role in binding of HIV-1 envelope glycoproteins. The elucidation of the functional C-18-binding mechanism may help in the rational design of novel antiviral agents against HIV.
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| 31. |
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| 32. |
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| 33. |
- Zhou, X.-Z., et al.
(författare)
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Lunar dayside current in the terrestrial lobe: ARTEMIS observations
- 2014
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Ingår i: Journal of Geophysical Research - Space Physics. - : John Wiley & Sons. - 2169-9380 .- 2169-9402. ; 119:5, s. 3381-3391
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Tidskriftsartikel (refereegranskat)abstract
- We report Acceleration, Reconnection, Turbulence and Electrodynamics of Moon's Interaction with the Sun (ARTEMIS) dual-probe observations of two events in the terrestrial magnetotail lobe, both characterized by upward moving heavy ions of lunar origin at one of the probes that is magnetically connected with the dayside lunar surface. By treating magnetic measurements at the other probe as the unperturbed lobe fields, we obtain background-subtracted magnetic perturbations (most significantly in Bz) when the first probe moved in the dawn-dusk direction across flux tubes magnetically connected to the Moon. These magnetic perturbations indicate the presence of field-aligned current above the lunar surface. By examining possible carriers of field-aligned current, we find that lunar heavy ions and accompanying electrons both contribute considerably to the current. Observations of the field-aligned current also suggest that the charging process at the dayside lunar surface and the associated lobe plasma environment, which have traditionally been viewed as a one-dimensional current balance problem, are actually more complicated. These observations give the first insights into how heavy ions affect the lunar dayside environment in terms of multispecies plasma dynamics.
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| 34. |
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| 35. |
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| 36. |
- Öhrn, A., et al.
(författare)
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Calibration procedure for a neutron monitor at energies below 20 MeV
- 2008
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 592:3, s. 405-413
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Tidskriftsartikel (refereegranskat)abstract
- A liquid scintillation detector aimed for neutron energy and fluence measurements in the energy region below 20 MeV has been calibrated using monoenergetic and white spectrum neutron fields. Careful measurements of the proton light output function and the response matrix have been performed allowing for the application of unfolding techniques using existing codes. The response matrix is used to characterize monoenergetic neutron fields produced by the T(d,n) reaction at low deuteron energies.
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