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Sökning: WFRF:(Withers B)

  • Resultat 1-11 av 11
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1.
  • Babic, M, et al. (författare)
  • NK cell receptor NKG2D enforces proinflammatory features and pathogenicity of Th1 and Th17 cells
  • 2020
  • Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 217:8
  • Tidskriftsartikel (refereegranskat)abstract
    • NKG2D is a danger sensor expressed on different subsets of innate and adaptive lymphocytes. Despite its established role as a potent activator of the immune system, NKG2D-driven regulation of CD4+ T helper (Th) cell–mediated immunity remains unclear. In this study, we demonstrate that NKG2D modulates Th1 and proinflammatory T-bet+ Th17 cell effector functions in vitro and in vivo. In particular, NKG2D promotes higher production of proinflammatory cytokines by Th1 and T-bet+ Th17 cells and reinforces their transcription of type 1 signature genes, including Tbx21. Conditional deletion of NKG2D in T cells impairs the ability of antigen-specific CD4+ T cells to promote inflammation in vivo during antigen-induced arthritis and experimental autoimmune encephalomyelitis, indicating that NKG2D is an important target for the amelioration of Th1- and Th17-mediated chronic inflammatory diseases.
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2.
  • Greco, R, et al. (författare)
  • Hematopoietic stem cell transplantation for autoimmune diseases in the time of COVID-19: EBMT guidelines and recommendations
  • 2021
  • Ingår i: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 56:7, s. 1493-1508
  • Tidskriftsartikel (refereegranskat)abstract
    • Coronavirus disease-19 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), represents one of the biggest challenges of 21st century, threatening public health around the globe. Increasing age and presence of co-morbidities are reported risk factors for severe disease and mortality, along with autoimmune diseases (ADs) and immunosuppressive treatments such as haematopoietic stem cell transplantation (HSCT), which are also associated with adverse outcomes. We review the impact of the pandemic on specific groups of patients with neurological, rheumatological, and gastroenterological indications, along with the challenges delivering HSCT in adult and pediatric populations. Moving forward, we developed consensus-based guidelines and recommendations for best practice and quality of patient care in order to support clinicians, scientists, and their multidisciplinary teams, as well as patients and their carers. These guidelines aim to support national and international organizations related to autoimmune diseases and local clinical teams delivering HSCT. Areas of unmet need and future research questions are also highlighted. The waves of the COVID-19 pandemic are predicted to be followed by an “endemic” phase and therefore an ongoing risk within a “new normality”. These recommendations reflect currently available evidence, coupled with expert opinion, and will be revised according to necessary modifications in practice.
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3.
  • Withers, Sarah B., et al. (författare)
  • Eosinophils are key regulators of perivascular adipose tissue and vascular functionality
  • 2017
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity impairs the relaxant capacity of adipose tissue surrounding the vasculature (PVAT) and has been implicated in resultant obesity-related hypertension and impaired glucose intolerance. Resident immune cells are thought to regulate adipocyte activity. We investigated the role of eosinophils in mediating normal PVAT function. Healthy PVAT elicits an anti-contractile effect, which was lost in mice deficient in eosinophils, mimicking the obese phenotype, and was restored upon eosinophil reconstitution. Ex vivo studies demonstrated that the loss of PVAT function was due to reduced bioavailability of adiponectin and adipocyte-derived nitric oxide, which was restored after eosinophil reconstitution. Mechanistic studies demonstrated that adiponectin and nitric oxide are released after activation of adipocyte-expressed β3 adrenoceptors by catecholamines, and identified eosinophils as a novel source of these mediators. We conclude that adipose tissue eosinophils play a key role in the regulation of normal PVAT anti-contractile function.
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4.
  • Andrews, David J., et al. (författare)
  • MARSIS Observations of Field-Aligned Irregularities and Ducted Radio Propagation in the Martian Ionosphere
  • 2018
  • Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 123:8, s. 6251-6263
  • Tidskriftsartikel (refereegranskat)abstract
    • Knowledge of Mars's ionosphere has been significantly advanced in recent years by observations from Mars Express and lately Mars Atmosphere and Volatile EvolutioN. A topic of particular interest are the interactions between the planet's ionospheric plasma and its highly structured crustal magnetic fields and how these lead to the redistribution of plasma and affect the propagation of radio waves in the system. In this paper, we elucidate a possible relationship between two anomalous radar signatures previously reported in observations from the Mars Advanced Radar for Subsurface and Ionospheric Sounding instrument on Mars Express. Relatively uncommon observations of localized, extreme increases in the ionospheric peak density in regions of radial (cusp-like) magnetic fields and spread echo radar signatures are shown to be coincident with ducting of the same radar pulses at higher altitudes on the same field lines. We suggest that these two observations are both caused by a high electric field (perpendicular to B) having distinctly different effects in two altitude regimes. At lower altitudes, where ions are demagnetized and electrons magnetized, and recombination dominantes, a high electric field causes irregularities, plasma turbulence, electron heating, slower recombination, and ultimately enhanced plasma densities. However, at higher altitudes, where both ions and electrons are magnetized and atomic oxygen ions cannot recombine directly, the high electric field instead causes frictional heating, a faster production of molecular ions by charge exchange, and so a density decrease. The latter enables ducting of radar pulses on closed field lines, in an analogous fashion to interhemispheric ducting in the Earth's ionosphere.
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5.
  • Flores-Langarica, A., et al. (författare)
  • CD103 + CD11b + mucosal classical dendritic cells initiate long-term switched antibody responses to flagellin
  • 2018
  • Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 11:3, s. 681-692
  • Tidskriftsartikel (refereegranskat)abstract
    • Antibody responses induced at mucosal and nonmucosal sites demonstrate a significant level of autonomy. Here, we demonstrate a key role for mucosal interferon regulatory factor-4 (IRF4)-dependent CD103 + CD11b + (DP), classical dendritic cells (cDCs) in the induction of T-dependent immunoglobulin G (IgG) and immunoglobulin A (IgA) responses in the mesenteric lymph node (MLN) following systemic immunization with soluble flagellin (sFliC). In contrast, IRF8-dependent CD103 + CD11b ' (SP) are not required for these responses. The lack of this response correlated with a complete absence of sFliC-specific plasma cells in the MLN, small intestinal lamina propria, and surprisingly also the bone marrow (BM). Many sFliC-specific plasma cells accumulating in the BM of immunized wild-type mice expressed α 4 β 7 +, suggesting a mucosal origin. Collectively, these results suggest that mucosal DP cDC contribute to the generation of the sFliC-specific plasma cell pool in the BM and thus serve as a bridge linking the mucosal and systemic immune system.
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6.
  • Jakosky, B. M., et al. (författare)
  • MAVEN observations of the response of Mars to an interplanetary coronal mass ejection
  • 2015
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 350:6261
  • Tidskriftsartikel (refereegranskat)abstract
    • Coupling between the lower and upper atmosphere, combined with loss of gas from the upper atmosphere to space, likely contributed to the thin, cold, dry atmosphere of modern Mars. To help understand ongoing ion loss to space, the Mars Atmosphere and Volatile Evolution (MAVEN) spacecraft made comprehensive measurements of the Mars upper atmosphere, ionosphere, and interactions with the Sun and solar wind during an interplanetary coronal mass ejection impact in March 2015. Responses include changes in the bow shock and magnetosheath, formation of widespread diffuse aurora, and enhancement of pick-up ions. Observations and models both show an enhancement in escape rate of ions to space during the event. Ion loss during solar events early in Mars history may have been a major contributor to the long-term evolution of the Mars atmosphere.
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8.
  • Matthie, J, et al. (författare)
  • Analytic assessment of the various bioimpedance methods used to estimate body water
  • 1998
  • Ingår i: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 84:5, s. 1801-1816
  • Tidskriftsartikel (refereegranskat)abstract
    • Knowledge of patient fluid distribution would be useful clinically. Both single-frequency (SF) and impedance modeling approaches are proposed. The high intercorrelation between body water compartments makes determining the best approach difficult. This study was conducted to evaluate the merits of an SF approach. Mathematical simulation was performed to determine the effect of tissue change on resistance and reactance. Dilution results were reanalyzed, and resistance and parallel reactance were used to predict the intracellular water for two groups. Results indicated that the amount of intracellular and extracellular water conduction at any SF can vary with tissue change, and reactance at any SF is affected by all tissue parameters. Modeling provided a good prediction of dilution intracellular and extracellular water, but an SF method did not. Intracellular, extracellular, and total body water were equally predicted at all frequencies by SF resistance and parallel reactance. Extracellular and intracellular water are best measured through modeling, because only at the zero and infinite frequencies are the results sensitive only to extracellular and intracellular water. At all other frequencies there are other effects.
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10.
  • Parreiras, Lucas S., et al. (författare)
  • Engineering and two-stage evolution of a lignocellulosic hydrolysate-tolerant Saccharomyces cerevisiae strain for anaerobic fermentation of xylose from AFEX pretreated corn stover
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:9
  • Tidskriftsartikel (refereegranskat)abstract
    • The inability of the yeast Saccharomyces cerevisiae to ferment xylose effectively under anaerobic conditions is a major barrier to economical production of lignocellulosic biofuels. Although genetic approaches have enabled engineering of S. cerevisiae to convert xylose efficiently into ethanol in defined lab medium, few strains are able to ferment xylose from lignocellulosic hydrolysates in the absence of oxygen. This limited xylose conversion is believed to result from small molecules generated during biomass pretreatment and hydrolysis, which induce cellular stress and impair metabolism. Here, we describe the development of a xylose-fermenting S. cerevisiae strain with tolerance to a range of pretreated and hydrolyzed lignocellulose, including Ammonia Fiber Expansion (AFEX)-pretreated corn stover hydrolysate (ACSH). We genetically engineered a hydrolysate-resistant yeast strain with bacterial xylose isomerase and then applied two separate stages of aerobic and anaerobic directed evolution. The emergent S. cerevisiae strain rapidly converted xylose from lab medium and ACSH to ethanol under strict anaerobic conditions. Metabolomic, genetic and biochemical analyses suggested that a missense mutation in GRE3, which was acquired during the anaerobic evolution, contributed toward improved xylose conversion by reducing intracellular production of xylitol, an inhibitor of xylose isomerase. These results validate our combinatorial approach, which utilized phenotypic strain selection, rational engineering and directed evolution for the generation of a robust S. cerevisiae strain with the ability to ferment xylose anaerobically from ACSH.
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11.
  • Steuwer, Axel, et al. (författare)
  • A combined approach to microstructure mapping of an Al-Li AA2199 friction stir weld
  • 2011
  • Ingår i: Acta Materialia. - : Elsevier BV. - 1873-2453 .- 1359-6454. ; 59:8, s. 3002-3011
  • Tidskriftsartikel (refereegranskat)abstract
    • A wide range of complementary techniques are used to build up a detailed picture of the microstructural zones found in friction stir welds (FSW) in an advanced AA2199 Al-Li alloy. Neutron and synchrotron X-ray diffraction, transmission electron microscopy, differential scanning calorimetry, small angle X-ray scattering, scanning electron microscopy, electron backscatter diffraction (EBSD) and hardness mapping are brought together to build up a detailed two-dimensional picture of the grain morphology, precipitate type, size, volume fraction and matrix solute content across the weld cross section and to explain the general lack of a W-shaped hardness profile across FSW in third-generation Al-Li-Cu Mg alloys. Dissolution of the age-hardening phases occurred in different regions of the weld, depending on their respective solvus temperatures, with 5' dissolving within the heat-affected zone and T-1 coarsening in the thermo-mechanically affected zone before going into solution in the weld nugget. Changes to the precipitate distribution, and especially to the T1 phase, are linked to a significant reduction in hardness (strength) and unstrained lattice parameter across the weld zone. It was also possible to show that the low recovery of nugget zone hardness is primarily due to its poor natural ageing response. (C) 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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