| 1. |
- Jakosky, B. M., et al.
(författare)
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MAVEN observations of the response of Mars to an interplanetary coronal mass ejection
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 350:6261
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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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| 2. |
- Lillis, Robert J., et al.
(författare)
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MOSAIC: A satellite constellation to enable groundbreaking mars climate system science and prepare for human exploration
- 2021
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Ingår i: Planetary Science Journal. - : Institute of Physics (IOP). - 2632-3338. ; 2:5
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Tidskriftsartikel (refereegranskat)abstract
- The Martian climate system has been revealed to rival the complexity of Earth's. Over the last 20 yr, a fragmented and incomplete picture has emerged of its structure and variability; we remain largely ignorant of many of the physical processes driving matter and energy flow between and within Mars' diverse climate domains. Mars Orbiters for Surface, Atmosphere, and Ionosphere Connections (MOSAIC) is a constellation of ten platforms focused on understanding these climate connections, with orbits and instruments tailored to observe the Martian climate system from three complementary perspectives. First, low-circular near-polar Sun-synchronous orbits (a large mothership and three smallsats spaced in local time) enable vertical profiling of wind, aerosols, water, and temperature, as well as mapping of surface and subsurface ice. Second, elliptical orbits sampling all of Mars' plasma regions enable multipoint measurements necessary to understand mass/energy transport and ion-driven escape, also enabling, with the polar orbiters, dense radio occultation coverage. Last, longitudinally spaced areostationary orbits enable synoptic views of the lower atmosphere necessary to understand global and mesoscale dynamics, global views of the hydrogen and oxygen exospheres, and upstream measurements of space weather conditions. MOSAIC will characterize climate system variability diurnally and seasonally, on meso-, regional, and global scales, targeting the shallow subsurface all the way out to the solar wind, making many first-of-their-kind measurements. Importantly, these measurements will also prepare for human exploration and habitation of Mars by providing water resource prospecting, operational forecasting of dust and radiation hazards, and ionospheric communication/positioning disruptions.
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| 3. |
- Raffan, Eleanor, et al.
(författare)
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A Deletion in the Canine POMC Gene Is Associated with Weight and Appetite in Obesity-Prone Labrador Retriever Dogs
- 2016
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 23:5, s. 893-900
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Tidskriftsartikel (refereegranskat)abstract
- Sequencing of candidate genes for obesity in Labrador retriever dogs identified a 14 bp deletion in pro-opiomelanocortin (POMC) with an allele frequency of 12%. The deletion disrupts the b-MSH and beta-endorphin coding sequences and is associated with body weight (per allele effect of 0.33 SD), adiposity, and greater food motivation. Among other dog breeds, the deletion was only found in the closely related flat-coat retriever (FCR), where it is similarly associated with body weight and food motivation. The mutation is significantly more common in Labrador retrievers selected to become assistance dogs than pets. In conclusion, the deletion in POMC is a significant modifier of weight and appetite in Labrador retrievers and FCRs and may influence other behavioral traits.
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| 4. |
- Parreiras, Lucas S., et al.
(författare)
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Engineering and two-stage evolution of a lignocellulosic hydrolysate-tolerant Saccharomyces cerevisiae strain for anaerobic fermentation of xylose from AFEX pretreated corn stover
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:9
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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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| 5. |
- Andrews, David J., et al.
(författare)
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MARSIS Observations of Field-Aligned Irregularities and Ducted Radio Propagation in the Martian Ionosphere
- 2018
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Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 123:8, s. 6251-6263
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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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| 6. |
- Mousavy Gharavy, S. Neda, et al.
(författare)
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Sexually dimorphic roles for the type 2 diabetes-associated C2cd4b gene in murine glucose homeostasis
- 2021
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Ingår i: Diabetologia. - : Springer Nature. - 0012-186X .- 1432-0428. ; 64:4, s. 850-864
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Variants close to the VPS13C/C2CD4A/C2CD4B locus are associated with altered risk of type 2 diabetes in genome-wide association studies. While previous functional work has suggested roles for VPS13C and C2CD4A in disease development, none has explored the role of C2CD4B. Methods CRISPR/Cas9-induced global C2cd4b-knockout mice and zebrafish larvae with c2cd4a deletion were used to study the role of this gene in glucose homeostasis. C2 calcium dependent domain containing protein (C2CD)4A and C2CD4B constructs tagged with FLAG or green fluorescent protein were generated to investigate subcellular dynamics using confocal or near-field microscopy and to identify interacting partners by mass spectrometry. Results Systemic inactivation of C2cd4b in mice led to marked, but highly sexually dimorphic changes in body weight and glucose homeostasis. Female C2cd4b mice displayed unchanged body weight compared with control littermates, but abnormal glucose tolerance (AUC, p = 0.01) and defective in vivo, but not in vitro, insulin secretion (p = 0.02). This was associated with a marked decrease in follicle-stimulating hormone levels as compared with wild-type (WT) littermates (p = 0.003). In sharp contrast, male C2cd4b null mice displayed essentially normal glucose tolerance but an increase in body weight (p < 0.001) and fasting blood glucose (p = 0.003) after maintenance on a high-fat and -sucrose diet vs WT littermates. No metabolic disturbances were observed after global inactivation of C2cd4a in mice, or in pancreatic beta cell function at larval stages in C2cd4a null zebrafish. Fasting blood glucose levels were also unaltered in adult C2cd4a-null fish. C2CD4B and C2CD4A were partially localised to the plasma membrane, with the latter under the control of intracellular Ca2+. Binding partners for both included secretory-granule-localised PTPRN2/phogrin. Conclusions/interpretation Our studies suggest that C2cd4b may act centrally in the pituitary to influence sex-dependent circuits that control pancreatic beta cell function and glucose tolerance in rodents. However, the absence of sexual dimorphism in the impact of diabetes risk variants argues for additional roles for C2CD4A or VPS13C in the control of glucose homeostasis in humans. Data availability The datasets generated and/or analysed during the current study are available in the Biorxiv repository (www. biorxiv.org/content/10.1101/2020.05.18.099200v1). RNA-Seq (GSE152576) and proteomics (PXD021597) data have been deposited to GEO (www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE152576) and ProteomeXchange (www.ebi.ac.uk/pride/ archive/projects/PXD021597) repositories, respectively.
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| 7. |
- Nawaf, Maher G., et al.
(författare)
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Concurrent OX40 and CD30 Ligand Blockade Abrogates the CD4-Driven Autoimmunity Associated with CTLA4 and PD1 Blockade while Preserving Excellent Anti-CD8 Tumor Immunity
- 2017
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 199:3, s. 974-981
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Tidskriftsartikel (refereegranskat)abstract
- Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans, their widespread implementation for cancer immunotherapy has been hampered by significant off-target autoimmune side effects that can be lethal. Our work has shown that absence of OX40 and CD30 costimulatory signals prevents CD4 T cell-driven autoimmunity in Foxp3-deficient mice, suggesting a novel way to block these side effects. In this study, we show that excellent antitumor CD8 T cell responses can be achieved in Foxp3(KO) mice deficient in OX40 and CD30 signals, particularly in the presence of concurrent PD1 blockade. Furthermore, excellent antitumor immune responses can also be achieved using combinations of Abs that block CTLA4, PD1, OX40, and CD30 ligands, without CD4 T cell-driven autoimmunity. By dissociating autoimmune side effects from anticancer immune responses, this potentially shifts this antitumor approach to patients with far less advanced disease.
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| 8. |
- Vogt, Marissa F., et al.
(författare)
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Electron densities in the ionosphere of Mars : A comparison of MARSIS and radio occultation measurements
- 2016
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Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 121:10, s. 10241-10257
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Tidskriftsartikel (refereegranskat)abstract
- Radio occultation electron densities measurements from the Mariner 9 and Viking spacecraft, which orbited Mars in the 1970s, have recently become available in a digital format. These data are highly complementary to the radio occultation electron density profiles from Mars Global Surveyor, which were restricted in solar zenith angle and altitude. Wehave compiled data from the Mariner 9, Viking, and Mars Global Surveyor radio occultation experiments for comparison to electron density measurements made by Mars AdvancedRadar for SubsurfaceandIonosphere Sounding (MARSIS), the topside radar sounder on Mars Express, and MARSIS-based empirical density models. Wefind that the electron densities measured by radio occultation are in generally good agreement with the MARSIS data and model, especially near the altitude of the peak electron density but that the MARSIS data and model display a larger plasma scale height than the radio occultation profiles at altitudes between the peak density and 200 km. Consequently, the MARSIS-measured and model electron densities are consistently larger than radio occultation densities at altitudes similar to 200-300 km. Finally, we have analyzed transitions in the topside ionosphere, at the boundary between the photochemically controlled and transport-controlled regions, and identified the average transition altitude, or altitude at which a change in scale height occurs. The average transition altitude is similar to 200 km in the Mariner 9 and Viking radio occultation profiles and in profiles of the median MARSIS radar sounding electron densities.
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| 9. |
- Withers, David R., et al.
(författare)
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The Survival of Memory CD4(+) T Cells within the Gut Lamina Propria Requires OX40 and CD30 Signals
- 2009
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 183:8, s. 5079-5084
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Tidskriftsartikel (refereegranskat)abstract
- Although CD4(+) memory T cells reside within secondary lymphoid tissue, the major reservoir of these cells is in the lamina propria of the intestine. In this study, we demonstrate that, in the absence of signals through both OX40 and CD30, CD4(+) T cells are comprehensively depleted from the lamina propria. Deficiency in either CD30 or OX40 alone reduced CD4(+) T cell numbers, however, in mice deficient in both OX40 and CD30, CD4(+) T cell loss was greatly exacerbated. This loss of CD4(+) T cells was not due to a homing defect because CD30 x OX40-deficient OTH cells were not impaired in their ability to express CCR9 and alpha(4)beta(7) or traffic to the small intestine. There was also no difference in the priming of wild-type (WT) and CD30 x OX40-deficient OTH cells in the mesenteric lymph node after oral immunization. However, following oral immunization, CD30 x OX40-deficient OTH cells trafficked to the lamina propria but failed to persist compared with WT OTH cells. This was not due to reduced levels of Bcl-2 or Bcl-XL, because expression of these was comparable between wT and double knockout OTH cells. Collectively, these data demonstrate that signals through CD30 and OX40 are required for the survival of CD4(+) T cells within the small intestine lamina propria. The Journal of Immunology, 2009, 183: 5079-5084.
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