| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Joffrin, E., et al.
(författare)
-
Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
- 2019
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
-
Forskningsöversikt (refereegranskat)abstract
- For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Fenstermacher, M.E., et al.
(författare)
-
DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
-
Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
|
|
| 12. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 13. |
- Tobias, Deirdre K, et al.
(författare)
-
Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
-
Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
-
Forskningsöversikt (refereegranskat)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
|
|
| 14. |
- Santangelo, James S., et al.
(författare)
-
Global urban environmental change drives adaptation in white clover
- 2022
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
-
Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
|
|
| 15. |
- Callaway, EM, et al.
(författare)
-
A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
-
Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
|
|
| 16. |
- Sumaila, U. Rashid, et al.
(författare)
-
WTO must ban harmful fisheries subsidies
- 2021
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 17. |
- Auffray, C., et al.
(författare)
-
COVID-19 and beyond : a call for action and audacious solidarity to all the citizens and nations, it is humanity’s fight
- 2020
-
Ingår i: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 9, s. 1130-18
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) belongs to a subgroup of coronaviruses rampant in bats for centuries. It caused the coronavirus disease 2019 (COVID-19) pandemic. Most patients recover, but a minority of severe cases experience acute respiratory distress or an inflammatory storm devastating many organs that can lead to patient death. The spread of SARS-CoV-2 was facilitated by the increasing intensity of air travel, urban congestion and human contact during the past decades. Until therapies and vaccines are available, tests for virus exposure, confinement and distancing measures have helped curb the pandemic. Vision: The COVID-19 pandemic calls for safeguards and remediation measures through a systemic response. Self-organizing initiatives by scientists and citizens are developing an advanced collective intelligence response to the coronavirus crisis. Their integration forms Olympiads of Solidarity and Health. Their ability to optimize our response to COVID-19 could serve as a model to trigger a global metamorphosis of our societies with far-reaching consequences for attacking fundamental challenges facing humanity in the 21st century. Mission: For COVID-19 and these other challenges, there is no alternative but action. Meeting in Paris in 2003, we set out to "rethink research to understand life and improve health." We have formed an international coalition of academia and industry ecosystems taking a systems medicine approach to understanding COVID-19 by thoroughly characterizing viruses, patients and populations during the pandemic, using openly shared tools. All results will be publicly available with no initial claims for intellectual property rights. This World Alliance for Health and Wellbeing will catalyze the creation of medical and health products such as diagnostic tests, drugs and vaccines that become common goods accessible to all, while seeking further alliances with civil society to bridge with socio-ecological and technological approaches that characterise urban systems, for a collective response to future health emergencies.
|
|
| 18. |
- Harrison, J.R., et al.
(författare)
-
Overview of new MAST physics in anticipation of first results from MAST Upgrade
- 2019
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
-
Forskningsöversikt (refereegranskat)abstract
- The mega amp spherical tokamak (MAST) was a low aspect ratio device (R/a = 0.85/0.65 ∼ 1.3) with similar poloidal cross-section to other medium-size tokamaks. The physics programme concentrates on addressing key physics issues for the operation of ITER, design of DEMO and future spherical tokamaks by utilising high resolution diagnostic measurements closely coupled with theory and modelling to significantly advance our understanding. An empirical scaling of the energy confinement time that favours higher power, lower collisionality devices is consistent with gyrokinetic modelling of electron scale turbulence. Measurements of ion scale turbulence with beam emission spectroscopy and gyrokinetic modelling in up-down symmetric plasmas find that the symmetry of the turbulence is broken by flow shear. Near the non-linear stability threshold, flow shear tilts the density fluctuation correlation function and skews the fluctuation amplitude distribution. Results from fast particle physics studies include the observation that sawteeth are found to redistribute passing and trapped fast particles injected from neutral beam injectors in equal measure, suggesting that resonances between the m = 1 perturbation and the fast ion orbits may be playing a dominant role in the fast ion transport. Measured D-D fusion products from a neutron camera and a charged fusion product detector are 40% lower than predictions from TRANSP/NUBEAM, highlighting possible deficiencies in the guiding centre approximation. Modelling of fast ion losses in the presence of resonant magnetic perturbations (RMPs) can reproduce trends observed in experiments when the plasma response and charge-exchange losses are accounted for. Measurements with a neutral particle analyser during merging-compression start-up indicate the acceleration of ions and electrons. Transport at the plasma edge has been improved through reciprocating probe measurements that have characterised a geodesic acoustic mode at the edge of an ohmic L-mode plasma and particle-in-cell modelling has improved the interpretation of plasma potential estimates from ball-pen probes. The application of RMPs leads to a reduction in particle confinement in L-mode and H-mode and an increase in the core ionization source. The ejection of secondary filaments following type-I ELMs correlates with interactions with surfaces near the X-point. Simulations of the interaction between pairs of filaments in the scrape-off layer suggest this results in modest changes to their velocity, and in most cases can be treated as moving independently. A stochastic model of scrape-off layer profile formation based on the superposition of non-interacting filaments is in good agreement with measured time-average profiles. Transport in the divertor has been improved through fast camera imaging, indicating the presence of a quiescent region devoid of filament near the X-point, extending from the separatrix to ψ n ∼ 1.02. Simulations of turbulent transport in the divertor show that the angle between the divertor leg on the curvature vector strongly influences transport into the private flux region via the interchange mechanism. Coherence imaging measurements show counter-streaming flows of impurities due to gas puffing increasing the pressure on field lines where the gas is ionised. MAST Upgrade is based on the original MAST device, with substantially improved capabilities to operate with a Super-X divertor to test extended divertor leg concepts. SOLPS-ITER modelling predicts the detachment threshold will be reduced by more than a factor of 2, in terms of upstream density, in the Super-X compared with a conventional configuration and that the radiation front movement is passively stabilised before it reaches the X-point. 1D fluid modelling reveals the key role of momentum and power loss mechanisms in governing detachment onset and evolution. Analytic modelling indicates that long legs placed at large major radius, or equivalently low at the target compared with the X-point are more amenable to external control. With MAST Upgrade experiments expected in 2019, a thorough characterisation of the sources of the intrinsic error field has been carried out and a mitigation strategy developed.
|
|
| 19. |
- Abazajian, Kevork, et al.
(författare)
-
CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
- 2022
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
-
Tidskriftsartikel (refereegranskat)abstract
- CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
|
|
| 20. |
|
|
| 21. |
- Quentin, Audrey G, et al.
(författare)
-
Non-structural carbohydrates in woody plants compared among laboratories.
- 2015
-
Ingår i: Tree physiology. - : Oxford University Press (OUP). - 1758-4469 .- 0829-318X. ; 35:11, s. 1146-1165
-
Tidskriftsartikel (refereegranskat)abstract
- Non-structural carbohydrates (NSC) in plant tissue are frequently quantified to make inferences about plant responses to environmental conditions. Laboratories publishing estimates of NSC of woody plants use many different methods to evaluate NSC. We asked whether NSC estimates in the recent literature could be quantitatively compared among studies. We also asked whether any differences among laboratories were related to the extraction and quantification methods used to determine starch and sugar concentrations. These questions were addressed by sending sub-samples collected from five woody plant tissues, which varied in NSC content and chemical composition, to 29 laboratories. Each laboratory analyzed the samples with their laboratory-specific protocols, based on recent publications, to determine concentrations of soluble sugars, starch and their sum, total NSC. Laboratory estimates differed substantially for all samples. For example, estimates for Eucalyptus globulus leaves (EGL) varied from 23 to 116 (mean = 56) mg g(-1) for soluble sugars, 6-533 (mean = 94) mg g(-1) for starch and 53-649 (mean = 153) mg g(-1) for total NSC. Mixed model analysis of variance showed that much of the variability among laboratories was unrelated to the categories we used for extraction and quantification methods (method category R(2) = 0.05-0.12 for soluble sugars, 0.10-0.33 for starch and 0.01-0.09 for total NSC). For EGL, the difference between the highest and lowest least squares means for categories in the mixed model analysis was 33 mg g(-1) for total NSC, compared with the range of laboratory estimates of 596 mg g(-1). Laboratories were reasonably consistent in their ranks of estimates among tissues for starch (r = 0.41-0.91), but less so for total NSC (r = 0.45-0.84) and soluble sugars (r = 0.11-0.83). Our results show that NSC estimates for woody plant tissues cannot be compared among laboratories. The relative changes in NSC between treatments measured within a laboratory may be comparable within and between laboratories, especially for starch. To obtain comparable NSC estimates, we suggest that users can either adopt the reference method given in this publication, or report estimates for a portion of samples using the reference method, and report estimates for a standard reference material. Researchers interested in NSC estimates should work to identify and adopt standard methods.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Hock, R, et al.
(författare)
-
High Mountain Areas
- 2019
-
Ingår i: IPCC Special Report on the Ocean and Cryosphere in a Changing Climate. - : IPCC - Intergovernmental Panel on Climate Change. ; , s. 131-202
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The cryosphere (including, snow, glaciers, permafrost, lake and river ice) is an integral element of high- mountain regions, which are home to roughly 10% of the global population. Widespread cryosphere changes affect physical, biological and human systems in the mountains and surrounding lowlands, with impacts evident even in the ocean. Building on the IPCC’s Fifth Assessment Report (AR5), this chapter assesses new evidence on observed recent and projected changes in the mountain cryosphere as well as associated impacts, risks and adaptation measures related to natural and human systems. Impacts in response to climate changes independently of changes in the cryosphere are not assessed in this chapter. Polar mountains are included in Chapter 3, except those in Alaska and adjacent Yukon, Iceland, and Scandinavia, which are included in this chapter.
|
|
| 25. |
- Metcalfe, N. B., et al.
(författare)
-
Solving the conundrum of intra-specific variation in metabolic rate: A multidisciplinary conceptual and methodological toolkit New technical developments are opening the door to an understanding of why metabolic rate varies among individual animals of a species
- 2023
-
Ingår i: Bioessays. - 0265-9247. ; 45:6
-
Tidskriftsartikel (refereegranskat)abstract
- Researchers from diverse disciplines, including organismal and cellular physiology, sports science, human nutrition, evolution and ecology, have sought to understand the causes and consequences of the surprising variation in metabolic rate found among and within individual animals of the same species. Research in this area has been hampered by differences in approach, terminology and methodology, and the context in which measurements are made. Recent advances provide important opportunities to identify and address the key questions in the field. By bringing together researchers from different areas of biology and biomedicine, we describe and evaluate these developments and the insights they could yield, highlighting the need for more standardisation across disciplines. We conclude with a list of important questions that can now be addressed by developing a common conceptual and methodological toolkit for studies on metabolic variation in animals.
|
|
| 26. |
- O'Gorman, Eoin J., et al.
(författare)
-
Impacts of Warming on the Structure and Functioning of Aquatic Communities : Individual-to Ecosystem-Level Responses
- 2012
-
Ingår i: Advances in Ecological Research, Vol 47. - : Elsevier. - 9780123983152 ; , s. 81-176
-
Bokkapitel (refereegranskat)abstract
- Environmental warming is predicted to rise dramatically over the next century, yet few studies have investigated its effects in natural, multi-species systems. We present data collated over an 8-year period from a catchment of geothermally heated streams in Iceland, which acts as a natural experiment on the effects of warming across different organisational levels and spatiotemporal scales. Body sizes and population biomasses of individual species responded strongly to temperature, with some providing evidence to support temperature size rules. Macroinvertebrate and meiofaunal community composition also changed dramatically across the thermal gradient. Interactions within the warm streams in particular were characterised by food chains linking algae to snails to the apex predator, brown trout These chains were missing from the colder systems, where snails were replaced by much smaller herbivores and invertebrate omnivores were the top predators. Trout were also subsidised by terrestrial invertebrate prey, which could have an effect analogous to apparent competition within the aquatic prey assemblage. Top-down effects by snails on diatoms were stronger in the warmer streams, which could account for a shallowing of mass-abundance slopes across the community. This may indicate reduced energy transfer efficiency from resources to consumers in the warmer systems and/or a change in predator-prey mass ratios. All the ecosystem process rates investigated increased with temperature, but with differing thermal sensitivities, with important implications for overall ecosystem functioning (e.g. creating potential imbalances in elemental fluxes). Ecosystem respiration rose rapidly with temperature, leading to increased heterotrophy. There were also indications that food web stability may be lower in the warmer streams.
|
|
| 27. |
- Roach, J C, et al.
(författare)
-
Genetic mapping at 3-kilobase resolution reveals inositol 1,4,5-triphosphate receptor 3 as a risk factor for type 1 diabetes in Sweden.
- 2006
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 79:4, s. 614-627
-
Tidskriftsartikel (refereegranskat)abstract
- We mapped the genetic influences for type 1 diabetes (T1D), using 2,360 single-nucleotide polymorphism (SNP) markers in the 4.4-Mb human major histocompatibility complex (MHC) locus and the adjacent 493 kb centromeric to the MHC, initially in a survey of 363 Swedish T1D cases and controls. We confirmed prior studies showing association with T1D in the MHC, most significantly near HLA-DR/DQ. In the region centromeric to the MHC, we identified a peak of association within the inositol 1,4,5-triphosphate receptor 3 gene (ITPR3; formerly IP3R3). The most significant single SNP in this region was at the center of the ITPR3 peak of association (P=1.7×10−4 for the survey study). For validation, we typed an additional 761 Swedish individuals. The P value for association computed from all 1,124 individuals was 1.30×10−6 (recessive odds ratio 2.5; 95% confidence interval [CI] 1.7–3.9). The estimated population-attributable risk of 21.6% (95% CI 10.0%–31.0%) suggests that variation within ITPR3 reflects an important contribution to T1D in Sweden. Two-locus regression analysis supports an influence of ITPR3 variation on T1D that is distinct from that of any MHC class II gene.
|
|
| 28. |
- Schweinsberg, Martin, et al.
(författare)
-
Same data, different conclusions : Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis
- 2021
-
Ingår i: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 165, s. 228-249
-
Tidskriftsartikel (refereegranskat)abstract
- In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists' gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for orga-nizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed.
|
|
| 29. |
- Zielinski, Brian L., et al.
(författare)
-
Patterns of Transcript Abundance of Eukaryotic Biogeochemically-Relevant Genes in the Amazon River Plume
- 2016
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:9
-
Tidskriftsartikel (refereegranskat)abstract
- The Amazon River has the largest discharge of all rivers on Earth, and its complex plume system fuels a wide array of biogeochemical processes, across a large area of the western tropical North Atlantic. The plume thus stimulates microbial processes affecting carbon sequestration and nutrient cycles at a global scale. Chromosomal gene expression patterns of the 2.0 to 156 mu m size-fraction eukaryotic microbial community were investigated in the Amazon River Plume, generating a robust dataset (more than 100 million mRNA sequences) that depicts the metabolic capabilities and interactions among the eukaryotic microbes. Combining classical oceanographic field measurements with metatranscriptomics yielded characterization of the hydrographic conditions simultaneous with a quantification of transcriptional activity and identity of the community. We highlight the patterns of eukaryotic gene expression for 31 biogeochemically significant gene targets hypothesized to be valuable within forecasting models. An advantage to this targeted approach is that the database of reference sequences used to identify the target genes was selectively constructed and highly curated optimizing taxonomic coverage, throughput, and the accuracy of annotations. A coastal diatom bloom highly expressed nitrate transporters and carbonic anhydrase presumably to support high growth rates and enhance uptake of low levels of dissolved nitrate and CO2. Diatom-diazotroph association (DDA: diatoms with nitrogen fixing symbionts) blooms were common when surface salinity was mesohaline and dissolved nitrate concentrations were below detection, and hence did not show evidence of nitrate utilization, suggesting they relied on ammonium transporters to aquire recently fixed nitrogen. These DDA blooms in the outer plume had rapid turnover of the photosystem D1 protein presumably caused by photodegradation under increased light penetration in clearer waters, and increased expression of silicon transporters as silicon became limiting. Expression of these genes, including carbonic anhydrase and transporters for nitrate and phosphate, were found to reflect the physiological status and biogeochemistry of river plume environments. These relatively stable patterns of eukaryotic transcript abundance occurred over modest spatiotemporal scales, with similarity observed in sample duplicates collected up to 2.45 km in space and 120 minutes in time. These results confirm the use of metatranscriptomics as a valuable tool to understand and predict microbial community function.
|
|
| 30. |
- Deadman, Mary E., et al.
(författare)
-
Specific amino acids of the glycosyltransferase LpsA direct the addition of glucose or galactose to the terminal inner core heptose of Haemophilus influenzae lipopolysaccharide via alternative linkages
- 2006
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 281:40, s. 29455-29467
-
Tidskriftsartikel (refereegranskat)abstract
- Lipopolysaccharide is the major glycolipid of the cell wall of the bacterium Haemophilus influenzae, a Gram-negative commensal and pathogen of humans. Lipopolysaccharide is both a virulence determinant and a target for host immune responses. Glycosyltransferases have high donor and acceptor substrate specificities that are generally limited to catalysis of one unique glycosidic linkage. The H. influenzae glycosyltransferase LpsA is responsible for the addition of a hexose to the distal heptose of the inner core of the lipopolysaccharide molecule and belongs to the glycosyltransferase family 25. The hexose added can be either glucose or galactose and linkage to the heptose can be either beta 1-2 or beta 1-3. Each H. influenzae strain uniquely produces only one of the four possible combinations of linked sugar in its lipopolysaccharide. We show that, in any given strain, a specific allelic variant of LpsA directs the anomeric linkage and the added hexose, glucose, or galactose. Site-directed mutagenesis of a single key amino acid at position 151 changed the hexose added in vivo from glucose to galactose or vice versa. By constructing chimeric lpsA gene sequences, it was shown that the 3' end of the gene directs the anomeric linkage (beta 1-2 or beta 1-3) of the added hexose. The lpsA gene is the first known example where interstrain variation in lipopolysaccharide core structure is directed by the specific sequence of a genetic locus encoding enzymes directing one of four alternative possible sugar additions from the inner core.
|
|
| 31. |
- Fox, Kate L., et al.
(författare)
-
Duplicate copies of lic1 direct the addition of multiple phosphocholine residues in the lipopolysaccharide of Haemophilus influenzae
- 2008
-
Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 76:2, s. 588-600
-
Tidskriftsartikel (refereegranskat)abstract
- The genes of the lic1 operon (lic1A to lic1D) are responsible for incorporation of phosphocholine (PCho) into the lipopolysaccharide (LPS) of Haemophilus influenzae. PCho plays a multifaceted role in the commensal and pathogenic lifestyles of a range of mucosal pathogens, including H. influenzae. Structural studies of the LPS of nontypeable H. influenzae (NTHI) have revealed that PCho can be linked to a hexose on any one of the oligosaccharide chain extensions from the conserved inner core triheptosyl backbone. In a collection of NTHI strains we found several strains in which there were two distinct but variant lic1D DNA sequences, genes predicted to encode the transferase responsible for directing the addition of PCho to LPS. The same isolates were also found to express concomitantly two PCho residues at distinct positions in their LPS. In one such NTHI isolate, isolate 1158, structural analysis of LPS from lic1 mutants confirmed that each of the two copies of lic1D directs the addition of PCho to a distinct location on the LPS. One position for PCho addition is a novel heptose, which is part of the oligosaccharide extension from the proximal heptose of the LPS inner core. Modification of the LPS by addition of two PCho residues resulted in increased binding of C-reactive protein and had consequential effects on the resistance of the organism to the killing effects of normal human serum compared to the effects of glycoforms containing one or no PCho. When bound, C-reactive protein leads to complement-mediated killing, indicating the potential biological significance of multiple PCho residues.
|
|
| 32. |
- Fox, K L, et al.
(författare)
-
Novel lipopolysaccharide biosynthetic genes containing tetranucleotide repeats in Haemophilus influenzae, identification of a gene for adding O-acetyl groups
- 2005
-
Ingår i: Molecular Microbiology. - : Wiley. - 0950-382X .- 1365-2958. ; 58:1, s. 207-216
-
Tidskriftsartikel (refereegranskat)abstract
- Many of the genes for lipopolysaccharide (LPS) biosynthesis in Haemophilus influenzae are phase variable. The mechanism of this variable expression involves slippage of tetranucleotide repeats located within the reading frame of these genes. Based on this, we hypothesized that tetranucleotide repeat sequences might be used to identify as yet unrecognized LPS biosynthetic genes. Synthetic oligonucleotides (20 bases), representing all previously reported LPS-related tetranucleotide repeat sequences in H. influenzae, were used to probe a collection of 25 genetically and epidemiologically diverse strains of non-typeable H. influenzae. A novel gene identified through this strategy was a homologue of oafA, a putative O-antigen LPS acetylase of Salmonella typhimurium, that was present in all 25 non-typeable H. influenzae, 19 of which contained multiple copies of the tetranucleotide 5'-GCAA. Using lacZ fusions, we showed that these tetranucleotide repeats could mediate phase variation of this gene. Structural analysis of LPS showed that a major site of acetylation was the distal heptose (HepIII) of the LPS inner-core. An oafA deletion mutant showed absence of O-acetylation of HepIII. When compared with wild type, oafA mutants displayed increased susceptibility to complement-mediated killing by human serum, evidence that O-acetylation of LPS facilitates resistance to host immune clearance mechanisms. These results provide genetic and structural evidence that H. influenzae oafA is required for phase variable O-acetylation of LPS and functional evidence to support the role of O-acetylation of LPS in pathogenesis.
|
|
| 33. |
- Graham, J, et al.
(författare)
-
Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes
- 2002
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 51:5, s. 1346-1355
-
Tidskriftsartikel (refereegranskat)abstract
- Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells were determined by logistic regression analysis in 971 incident patients with type 1 diabetes and 702 control subjects aged 0–34 years. GADAs were associated with HLA-DQ2 in young but not in older patients (P = 0.009). Autoantibodies to insulin were negatively associated with age (P < 0.0001) but positively associated with DQ8 (P = 0.03) and with INS VNTR (P = 0.04), supporting possible immune tolerance induction. ICA512/IA-2 were negatively associated with age (P < 0.0001) and with DQ2 (P < 0.0001) but positively associated with DQ8 (P = 0.04). Males were more likely than females to be negative for GADA (P < 0.0001), autoantibodies to islet cells (P = 0.04), and all four autoantibody markers (P = 0.004). The CTLA-4 3′ end microsatellite marker was not associated with any of the autoantibodies. We conclude that age and genetic factors such as HLA-DQ and INS VNTR need to be combined with islet autoantibody markers when evaluating the risk for type 1 diabetes development.
|
|
| 34. |
- Hood, D W, et al.
(författare)
-
Genetic basis for expression of the major globotetraose-containing lipopolysaccharide from H-influenzae strain Rd (RM118)
- 2001
-
Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 11:11, s. 957-967
-
Tidskriftsartikel (refereegranskat)abstract
- A genetic basis for the biosynthetic assembly of the globotetraose containing lipopolysaccharide (LPS) of Haemophilus influenzae strain RM118 (Rd) was determined by structural analysis of LPS derived from mutant strains. We have previously shown that the parent strain RM118 elaborates a population of LPS molecules made up of a series of related glycoforms differing in the degree of oligosaccharide chain extension from the distal heptose residue of a conserved phosphorylated inner-core element, L-alpha -D-Hepp-(1-->2)-L-alpha -D-Hepp-(1-->3)-[beta -D-Glcp-(1-->4)-]-L-alpha -D-Hepp-(1-->5)-alpha -Kdo. The fully extended LPS glycoform expresses the globotetraose structure, beta -D-GalpNAc-(1-->3)-alpha -D-Galp(1-->4)-beta -D-Galp-(1-->4)-beta -D-Glcp. A fingerprinting strategy was employed to establish the structure of LPS from strains mutated in putative glycosyltransferase genes compared to the parent strain. This involved glycose and linkage analysis on intact LPS samples and analysis of O-deacylated LPS samples by electrospray ionization mass spectrometry and 1D H-1-nuclear magnetic resonance spectroscopy. Four genes, lpsA, lic2A, lgtC, and lgtD, were required for sequential addition of the glycoses to the terminal inner-core heptose to give the globotetraose structure. lgtC and lgtD were shown to encode glycosyltransferases by enzymatic assays with synthetic acceptor molecules. This is the first genetic blueprint determined for H. influenzae LPS oligosaccharide biosynthesis, identifying genes Involved in the addition of each glycose residue.
|
|
| 35. |
- Kutlu, Burak, et al.
(författare)
-
Detailed transcriptome atlas of the pancreatic beta cell
- 2009
-
Ingår i: BMC Medical Genomics. - : Springer Science and Business Media LLC. - 1755-8794. ; 2, s. 3-
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gene expression patterns provide a detailed view of cellular functions. Comparison of profiles in disease vs normal conditions provides insights into the processes underlying disease progression. However, availability and integration of public gene expression datasets remains a major challenge. The aim of the present study was to explore the transcriptome of pancreatic islets and, based on this information, to prepare a comprehensive and open access inventory of insulin-producing beta cell gene expression, the Beta Cell Gene Atlas (BCGA). METHODS: We performed Massively Parallel Signature Sequencing (MPSS) analysis of human pancreatic islet samples and microarray analyses of purified rat beta cells, alpha cells and INS-1 cells, and compared the information with available array data in the literature. RESULTS: MPSS analysis detected around 7600 mRNA transcripts, of which around a third were of low abundance. We identified 2000 and 1400 transcripts that are enriched/depleted in beta cells compared to alpha cells and INS-1 cells, respectively. Microarray analysis identified around 200 transcription factors that are differentially expressed in either beta or alpha cells. We reanalyzed publicly available gene expression data and integrated these results with the new data from this study to build the BCGA. The BCGA contains basal (untreated conditions) gene expression level estimates in beta cells as well as in different cell types in human, rat and mouse pancreas. Hierarchical clustering of expression profile estimates classify cell types based on species while beta cells were clustered together. CONCLUSION: Our gene atlas is a valuable source for detailed information on the gene expression distribution in beta cells and pancreatic islets along with insulin producing cell lines. The BCGA tool, as well as the data and code used to generate the Atlas are available at the T1Dbase website (T1DBase.org).
|
|
| 36. |
- Livingston, P. O., et al.
(författare)
-
Selection of GM2, fucosyl GM1, globo H and polysialic acid as targets on small cell lung cancers for antibody mediated immunotherapy
- 2005
-
Ingår i: Cancer Immunol Immunother. ; 54:10
-
Tidskriftsartikel (refereegranskat)abstract
- Glycolipids GM2, GD2, GD3, fucosyl GM1, sialyl Lewis a (sLe(a)) and globo H, and polysialic acid on embryonal NCAM, are cell-surface antigens expressed on small cell lung cancer (SCLC) biopsy specimens. They are all candidates for inclusion in a polyvalent, antibody-inducing vaccine or for adoptive therapy with monoclonal antibodies (mAbs) against SCLC. To identify the minimum optimal combination of target antigens on SCLC and to confirm that antibodies against this combination might be able to mediate complement activation and lysis in the majority of cases, we tested ten SCLC cell lines with fluorescence activated cell sorter (FACS) and complement dependent cytotoxicity (CDC) assays using mAbs against these seven target antigens individually or pooled in different combinations. We find that (1) none of these mAbs demonstrated strong FACS reactivity with more than 6 of the 10 cell lines, (2) no mAb had strong CDC reactivity with more than 4 of the cell lines, (3) when the mAbs were pooled, nine cell lines were strongly positive by FACS and nine cell lines were strongly positive by CDC, and (4) mAbs against GM2, FucGM1, globo H and polysialic acid was the minimum optimal combination for inducing FACS reactivity. The addition of mAbs against sLe(a), GD2 and GD3 had no additional impact by FACS and only minimal additional impact in CDC assays. H345, the only cell line that had less than 30% CDC with the four mAb pool was strongly positive by FACS. To understand the lack of correlation between FACS and CDC in the case of H345, the ten cell lines were screened for expression of complement resistance factors CD55 and CD59. Three cell lines were strongly positive for CD55 and eight were strongly positive for CD59. Overall, no correlation was seen between expression of either of these factors on the ten cell lines and sensitivity to CDC. In the case of H345 however, complement resistance of H345 is demonstrated to be mediated primarily by CD59, and in the presence of mAb against CD59, the four mAb MEM-43 pool induced strong (94%) CDC. CD59 inhibits membrane attack complex formation but not activation of earlier complement components. Consequently, all ten cell lines are good targets for complement activation by the four antibody pool and for elimination by effector mechanisms including complement mediated inflammation and opsonization. These findings support our plan to develop a tetravalent vaccine against SCLC targeting GM2, fucosyl GM1, globo H and polysialic acid.
|
|
| 37. |
- Lopes, Miguel, et al.
(författare)
-
Temporal profiling of cytokine-induced genes in pancreatic beta-cells by meta-analysis and network inference
- 2014
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 103:4, s. 264-275
-
Tidskriftsartikel (refereegranskat)abstract
- Type I Diabetes (T1D) is an autoimmune disease where local release of cytokines such as IL-1 beta and IFN-gamma contributes to beta-cell apoptosis. To identify relevant genes regulating this process we performed a meta-analysis of 8 datasets of beta-cell gene expression after exposure to IL-1 beta and IFN-gamma. Two of these datasets are novel and contain time-series expressions in human islet cells and rat INS-1E cells. Genes were ranked according to their differential expression within and after 24 h from exposure, and characterized by function and prior knowledge in the literature. A regulatory network was then inferred from the human time expression datasets, using a time-series extension of a network inference method. The two most differentially expressed genes previously unknown in T1D literature (RIPK2 and ELF3) were found to modulate cytokine-induced apoptosis. The inferred regulatory network is thus supported by the experimental validation, providing a proof-of-concept for the proposed statistical inference approach.
|
|
| 38. |
- Lundström, Susanna L., et al.
(författare)
-
Application of capillary electrophoresis mass spectrometry and liquid chromatography multiple-step tandem electrospray mass spectrometry to profile glycoform expression during Haemophilus influenzae pathogenesis in the chinchilla model of experimental otitis media
- 2008
-
Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 76:7, s. 3255-3267
-
Tidskriftsartikel (refereegranskat)abstract
- Otitis media caused by nontypeable Haemophilus influenzae (NTHi) is a common and recurrent bacterial infection of childhood. The structural variability and diversity of H. influenzae lipopolysaccharide (LPS) glycoforms are known to play a significant role in the commensal and disease-causing behavior of this pathogen. In this study, we determined LPS glycoform populations from NTHi strain 1003 during the course of experimental otitis media in the chinchilla model of infection by mass spectrometric techniques. Building on an established structural model of the major LPS glycoforms expressed by this NTHi strain in vitro (M. Mansson, W. Hood, J. Li, J. C. Richards, E. R. Moxon, and E. K. Schweda, Eur. J. Biochem. 269:808-818, 2002), minor isomeric glycoform populations were determined by liquid chromatography multiple-step tandem electrospray mass spectrometry (LC-ESI-MSn). Using capillary electrophoresis ESI-MS (CE-ESI-MS), we determined glycoform profiles for bacteria from direct middle ear fluid (MEF) samples. The LPS glycan profiles were essentially the same when the MEF samples of 7 of 10 animals were passaged on solid medium (chocolate agar). LC-ESI-MSn provided a sensitive method for determining the isomeric distribution of LPS glycoforms in MEF and passaged specimens. To investigate changes in LPS glycoform distribution during the course of infection, MEF samples were analyzed at 2, 5, and 9 days postinfection by CE-ESI-MS following minimal passage on chocolate agar. As previously observed, sialic acid-containing glycoforms were detected during the early stages of infection, but a trend toward more-truncated and less-complex LPS glycoforms that lacked sialic acid was found as disease progressed.
|
|
| 39. |
- Lundström, Susanna L., et al.
(författare)
-
Novel globoside-like oligosaccharide expression patterns in nontypeable Haemophilus influenzae lipopolysaccharide
- 2007
-
Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 274:18, s. 4886-4903
-
Tidskriftsartikel (refereegranskat)abstract
- We report the novel pattern of lipopolysaccharide (LPS) expressed by two disease-associated nontypeable Haemophilus influenzae strains, 1268 and 1200. The strains express the common structural motifs of H. influenzae; globotetraose [beta-D-GalpNAc-(1 -> 3)-alpha-D-Galp-(1 -> 4)-beta-D-Galp-(1 -> 4)-beta-d-Glcp] and its truncated versions globoside [alpha-D-Galp-(1 -> 4)-beta-D-Galp-(1 -> 4)-beta-D-Glcp] and lactose [beta-D-Galp-(1 -> 4)-beta-D-Glcp] linked to the terminal heptose (HepIII) and the corresponding structures with an alpha-D-Glcp as the reducing sugar linked to the middle heptose (HepII) in the same LPS molecule. Previously these motifs had been found linked only to either the proximal heptose (HepI) or HepIII of the triheptosyl inner-core moiety l-alpha-D-Hepp-(1 -> 2)-[PEtn -> 6]-l-alpha-D-Hepp-(1 -> 3)-l-alpha-D-Hepp-(1 -> 5)-[PPEtn -> 4]-alpha-Kdo-(2 -> 6)-lipid A. This novel finding was obtained by structural studies of LPS using NMR techniques and ESI-MS on O-deacylated LPS and core oligosaccharide material, as well as electrospray ionization-multiple-step tandem mass spectrometry on permethylated dephosphorylated oligosaccharide material. A lpsA mutant of strain 1268 expressed LPS of reduced complexity that facilitated unambiguous structural determination. Using capillary electrophoresis-ESI-MS/MS we identified sialylated glycoforms that included sialyllactose as an extension from HepII, this is a further novel finding for H. influenzae LPS. In addition, each LPS was found to carry phosphocholine and O-linked glycine. Nontypeable H. influenzae strain 1200 expressed identical LPS structures to 1268 with the difference that strain 1200 LPS had acetates substituting HepIII, whereas strain 1268 LPS has glycine at the same position.
|
|
| 40. |
- Lundström, Susanna L., et al.
(författare)
-
Structural analysis of the lipopolysaccharide from nontypeable Haemophilus influenzae strain R2846
- 2008
-
Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 47:22, s. 6025-6038
-
Tidskriftsartikel (refereegranskat)abstract
- We here report the lipopolysaccharide (LPS) structures expressed by nontypeable Haemophilus influenzae R2846, a strain whose complete genome sequence has recently been obtained. Results were obtained by using NMR techniques and ESI-MS on O-deacylated LPS and core oligosaccharide material (OS) as well as ESI-MSn on permethylated dephosphorylated OS. A beta-D-Glcp-(1 -> 4)-D-alpha-D-Hepp-(1 -> 6)-beta-D-Glcp-(1 -> 4) unit was found linked to the proximal heptose (HepI) of the conserved triheptosyl inner-core moiety, L-alpha-D-Hepp-(1 -> 2)-[PEtn -> 6]-L-alpha-D-Hepp-(1 -> 3)-L-alpha-D-Hepp-(1 -> 5)-[PPEtn -> 4]-alpha-Kdo-(2 -> 6)-lipid A. The beta-D-Glcp (GlcI) linked to HepI was also branched with oligosaccharide extensions from O-4 and O-6. O-4 of GlcI was substituted with sialyllacto-N-neotetraose [alpha-Neu5Ac-(2 -> 3)-beta-D-Galp-(1 -> 4)-beta-GlcpNAc-(1 -> 3)-beta-D-Galp-(1 -> 4)-beta-D-Glcp-(1 ->] and the related structure [(PEtn -> 6)-alpha-D-GalpNAc-(1 -> 6)-beta-D-Galp-(1 -> 4)-beta-D-GlcpNAc-(1 -> 3)-beta-D-Galp-(1 -> 4)-beta-Glcp-(1-]. The distal heptose (HepIII) was substituted at O-2 by beta-D-Gal. Phosphate, phosphoethanolamine, phosphocholine, acetate, and glycine were found to substitute the core oligosaccharide. Two heptosyltransferase genes, losB1 and losB2, have been identified from the R2846 genome sequence and are candidates to add the noncore heptose to the LPS. Mutant strain R2846losB1 did not show DD-heptose in the extension from HepI but still contained minor quantities of LD-heptose at the same position, indicating that the losB1 gene is required to add DD-heptose to Glcl. The LPS from strain R2846losB1/losB2 expressed no noncore heptose, consistent with losB2 directing the addition of LD-heptose.
|
|
| 41. |
- Moser, Othmar, et al.
(författare)
-
Glucose management for exercise using continuous glucose monitoring (CGM) and intermittently scannedCGM(isCGM) systems in type 1 diabetes: position statement of the European Association for the Study of Diabetes (EASD) and of the International Society for Pediatric and Adolescent Diabetes (ISPAD) endorsed byJDRFand supported by the American Diabetes Association (ADA)
- 2020
-
Ingår i: PEDIATRIC DIABETES. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 21:8, s. 1375-1393
-
Tidskriftsartikel (refereegranskat)abstract
- Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin-dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (ie, before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes.
|
|
| 42. |
- Pelletier, Stefan, et al.
(författare)
-
Vanadium oxide and a sharp onset of cold-trapping on a giant exoplanet
- 2023
-
Ingår i: Nature. - 0028-0836. ; 619:7970, s. 491-494
-
Tidskriftsartikel (refereegranskat)abstract
- The abundance of refractory elements in giant planets can provide key insights into their formation histories1. Owing to the low temperatures of the Solar System giants, refractory elements condense below the cloud deck, limiting sensing capabilities to only highly volatile elements2. Recently, ultra-hot giant exoplanets have allowed for some refractory elements to be measured, showing abundances broadly consistent with the solar nebula with titanium probably condensed out of the photosphere3,4. Here we report precise abundance constraints of 14 major refractory elements on the ultra-hot giant planet WASP-76b that show distinct deviations from proto-solar and a sharp onset in condensation temperature. In particular, we find nickel to be enriched, a possible sign of the accretion of the core of a differentiated object during the evolution of the planet. Elements with condensation temperatures below 1,550 K otherwise closely match those of the Sun5 before sharply transitioning to being strongly depleted above 1,550 K, which is well explained by nightside cold-trapping. We further unambiguously detect vanadium oxide on WASP-76b, a molecule long suggested to drive atmospheric thermal inversions6, and also observe a global east–west asymmetry7 in its absorption signals. Overall, our findings indicate that giant planets have a mostly stellar-like refractory elemental content and suggest that temperature sequences of hot Jupiter spectra can show abrupt transitions wherein a mineral species is either present or completely absent if a cold trap exists below its condensation temperature8.
|
|
| 43. |
- Sanchez-Bezanilla, S., et al.
(författare)
-
Growth Hormone Increases BDNF and mTOR Expression in Specific Brain Regions after Photothrombotic Stroke in Mice
- 2022
-
Ingår i: Neural Plasticity. - : Hindawi Limited. - 2090-5904 .- 1687-5443. ; 2022
-
Tidskriftsartikel (refereegranskat)abstract
- Aims. We have shown that growth hormone (GH) treatment poststroke increases neuroplasticity in peri-infarct areas and the hippocampus, improving motor and cognitive outcomes. We aimed to explore the mechanisms of GH treatment by investigating how GH modulates pathways known to induce neuroplasticity, focusing on association between brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR) in the peri-infarct area, hippocampus, and thalamus. Methods. Recombinant human growth hormone (r-hGH) or saline was delivered (0.25 mu l/hr, 0.04 mg/day) to mice for 28 days, commencing 48 hours after photothrombotic stroke. Protein levels of pro-BDNF, total-mTOR, phosphorylated-mTOR, total-p70S6K, and phosporylated-p70S6K within the peri-infarct area, hippocampus, and thalamus were evaluated by western blotting at 30 days poststroke. Results. r-hGH treatment significantly increased pro-BDNF in peri-infarct area, hippocampus, and thalamus (p < 0.01). r-hGH treatment significantly increased expression levels of total-mTOR in the peri-infarct area and thalamus (p < 0.05). r-hGH treatment significantly increased expression of total-p70S6K in the hippocampus (p < 0.05). Conclusion. r-hGH increases pro-BDNF within the peri-infarct area and regions that are known to experience secondary neurodegeneration after stroke. Upregulation of total-mTOR protein expression in the peri-infarct and thalamus suggests that this might be a pathway that is involved in the neurorestorative effects previously reported in these animals and warrants further investigation. These findings suggest region-specific mechanisms of action of GH treatment and provide further understanding for how GH treatment promotes neurorestorative effects after stroke.
|
|
| 44. |
- Thornton, R. B., et al.
(författare)
-
Panel 7 – Pathogenesis of otitis media – A review of the literature between 2015 and 2019
- 2020
-
Ingår i: International Journal of Pediatric Otorhinolaryngology. - : Elsevier BV. - 0165-5876. ; 130:S1
-
Forskningsöversikt (refereegranskat)abstract
- Objective: To perform a comprehensive review of the literature from July 2015 to June 2019 on the pathogenesis of otitis media. Bacteria, viruses and the role of the microbiome as well as the host response are discussed. Directions for future research are also suggested. Data sources: PubMed database of the National Library of Medicine. Review methods: PubMed was searched for any papers pertaining to OM pathogenesis between July 2015 and June 2019. If in English, abstracts were assessed individually for their relevance and included in the report. Members of the panel drafted the report based on these searches and on new data presented at the 20th International Symposium on Recent Advances in Otitis Media. Conclusions: The main themes that arose in OM pathogenesis were around the need for symptomatic viral infections to develop disease. Different populations potentially having different mechanisms of pathogenesis. Novel bacterial otopathogens are emerging and need to be monitored. Animal models need to continue to be developed and used to understand disease pathogenesis. Implications for Practice: The findings in the pathogenesis panel have several implications for both research and clinical practice. The most urgent areas appear to be to continue monitoring the emergence of novel otopathogens, and the need to develop prevention and preventative therapies that do not rely on antibiotics and protect against the development of the initial OM episode.
|
|
