65 research outputs found
A Novel Function for 15-Lipoxygenases in Cholesterol Homeostasis and CCL17 Production in Human Macrophages
Arachidonate 15-lipoxygenase (ALOX15) and arachidonate 15-lipoxygenase, type B (ALOX15B) catalyze the dioxygenation of polyunsaturated fatty acids and are upregulated in human alternatively activated macrophages (AAMs) induced by Th2 cytokine interleukin-4 (IL-4) and/or interleukin-13. Known primarily for roles in bioactive lipid mediator synthesis, 15-lipoxygenases (15-LOXs) have been implicated in various macrophage functions including efferocytosis and ferroptosis. Using a combination of inhibitors and siRNAs to suppress 15-LOX isoforms, we studied the role of 15-LOXs in cellular cholesterol homeostasis and immune function in naïve and AAMs. Silencing or inhibiting the 15-LOX isoforms impaired sterol regulatory element binding protein (SREBP)-2 signaling by inhibiting SREBP-2 processing into mature transcription factor and reduced SREBP-2 binding to sterol regulatory elements and subsequent target gene expression. Silencing ALOX15B reduced cellular cholesterol and the cholesterol intermediates desmosterol, lanosterol, 24,25-dihydrolanosterol, and lathosterol as well as oxysterols in IL-4-stimulated macrophages. In addition, attenuating both 15-LOX isoforms did not generally affect IL-4 gene expression but rather uniquely impacted IL-4-induced CCL17 production in an SREBP-2-dependent manner resulting in reduced T cell migration to macrophage conditioned media. In conclusion, we identified a novel role for ALOX15B, and to a lesser extent ALOX15, in cholesterol homeostasis and CCL17 production in human macrophages
The Influence of Object Relative Size on Priming and Explicit Memory
We investigated the effects of object relative size on priming and explicit memory for color photos of common objects. Participants were presented with color photos of pairs of objects displayed in either appropriate or inappropriate relative sizes. Implicit memory was assessed by speed of object size ratings whereas explicit memory was assessed by an old/new recognition test. Study-to-test changes in relative size reduced both priming and explicit memory and had large effects for objects displayed in large vs. small size at test. Our findings of substantial size-specific influences on priming with common objects under some but not other conditions are consistent with instance views of object perception and priming but inconsistent with structural description views
Ejecta Evolution Following a Planned Impact into an Asteroid: The First Five Weeks
The impact of the DART spacecraft into Dimorphos, moon of the asteroid
Didymos, changed Dimorphos' orbit substantially, largely from the ejection of
material. We present results from twelve Earth-based facilities involved in a
world-wide campaign to monitor the brightness and morphology of the ejecta in
the first 35 days after impact. After an initial brightening of ~1.4
magnitudes, we find consistent dimming rates of 0.11-0.12 magnitudes/day in the
first week, and 0.08-0.09 magnitudes/day over the entire study period. The
system returned to its pre-impact brightness 24.3-25.3 days after impact
through the primary ejecta tail remained. The dimming paused briefly eight days
after impact, near in time to the appearance of the second tail. This was
likely due to a secondary release of material after re-impact of a boulder
released in the initial impact, through movement of the primary ejecta through
the aperture likely played a role.Comment: 16 pages, 5 Figures, accepted in the Astrophysical Journal Letters
(ApJL) on October 16, 202
A Honey Bee Hexamerin, HEX 70a, Is Likely to Play an Intranuclear Role in Developing and Mature Ovarioles and Testioles
Insect hexamerins have long been known as storage proteins that are massively synthesized by the larval fat body and secreted into hemolymph. Following the larval-to-pupal molt, hexamerins are sequestered by the fat body via receptor-mediated endocytosis, broken up, and used as amino acid resources for metamorphosis. In the honey bee, the transcript and protein subunit of a hexamerin, HEX 70a, were also detected in ovaries and testes. Aiming to identify the subcellular localization of HEX 70a in the female and male gonads, we used a specific antibody in whole mount preparations of ovaries and testes for analysis by confocal laser-scanning microscopy. Intranuclear HEX 70a foci were evidenced in germ and somatic cells of ovarioles and testioles of pharate-adult workers and drones, suggesting a regulatory or structural role. Following injection of the thymidine analog EdU we observed co-labeling with HEX 70a in ovariole cell nuclei, inferring possible HEX 70a involvement in cell proliferation. Further support to this hypothesis came from an injection of anti-HEX 70a into newly ecdysed queen pupae where it had a negative effect on ovariole thickening. HEX 70a foci were also detected in ovarioles of egg laying queens, particularly in the nuclei of the highly polyploid nurse cells and in proliferating follicle cells. Additional roles for this storage protein are indicated by the detection of nuclear HEX 70a foci in post-meiotic spermatids and spermatozoa. Taken together, these results imply undescribed roles for HEX 70a in the developing gonads of the honey bee and raise the possibility that other hexamerins may also have tissue specific functions
Ejecta Evolution Following a Planned Impact into an Asteroid: The First Five Weeks
The impact of the Double Asteroid Redirection Test spacecraft into Dimorphos, moon of the asteroid Didymos, changed Dimorphos’s orbit substantially, largely from the ejection of material. We present results from 12 Earth-based facilities involved in a world-wide campaign to monitor the brightness and morphology of the ejecta in the first 35 days after impact. After an initial brightening of ∼1.4 mag, we find consistent dimming rates of 0.11–0.12 mag day−1 in the first week, and 0.08–0.09 mag day−1 over the entire study period. The system returned to its pre-impact brightness 24.3–25.3 days after impact though the primary ejecta tail remained. The dimming paused briefly eight days after impact, near in time to the appearance of the second tail. This was likely due to a secondary release of material after re-impact of a boulder released in the initial impact, though movement of the primary ejecta through the aperture likely played a role
Achievement of the planetary defense investigations of the Double Asteroid Redirection Test (DART) mission
NASA's Double Asteroid Redirection Test (DART) mission was the first to demonstrate asteroid deflection, and the mission's Level 1 requirements guided its planetary defense investigations. Here, we summarize DART's achievement of those requirements. On 2022 September 26, the DART spacecraft impacted Dimorphos, the secondary member of the Didymos near-Earth asteroid binary system, demonstrating an autonomously navigated kinetic impact into an asteroid with limited prior knowledge for planetary defense. Months of subsequent Earth-based observations showed that the binary orbital period was changed by –33.24 minutes, with two independent analysis methods each reporting a 1σ uncertainty of 1.4 s. Dynamical models determined that the momentum enhancement factor, β, resulting from DART's kinetic impact test is between 2.4 and 4.9, depending on the mass of Dimorphos, which remains the largest source of uncertainty. Over five dozen telescopes across the globe and in space, along with the Light Italian CubeSat for Imaging of Asteroids, have contributed to DART's investigations. These combined investigations have addressed topics related to the ejecta, dynamics, impact event, and properties of both asteroids in the binary system. A year following DART's successful impact into Dimorphos, the mission has achieved its planetary defense requirements, although work to further understand DART's kinetic impact test and the Didymos system will continue. In particular, ESA's Hera mission is planned to perform extensive measurements in 2027 during its rendezvous with the Didymos–Dimorphos system, building on DART to advance our knowledge and continue the ongoing international collaboration for planetary defense
Efferocytosis potentiates the expression of arachidonate 15-lipoxygenase (ALOX15) in alternatively activated human macrophages through LXR activation.
A Novel Function for 15-Lipoxygenases in Cholesterol Homeostasis and CCL17 Production in Human Macrophages
Hypoxia Potentiates Palmitate-induced Pro-inflammatory Activation of Primary Human Macrophages.
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