The APOE4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). The contribution of microglial APOE4 to AD pathogenesis is unknown, although APOE has the most enriched ...gene expression in neurodegenerative microglia (MGnD). Here, we show in mice and humans a negative role of microglial APOE4 in the induction of the MGnD response to neurodegeneration. Deletion of microglial APOE4 restores the MGnD phenotype associated with neuroprotection in P301S tau transgenic mice and decreases pathology in APP/PS1 mice. MGnD-astrocyte cross-talk associated with β-amyloid (Aβ) plaque encapsulation and clearance are mediated via LGALS3 signaling following microglial APOE4 deletion. In the brains of AD donors carrying the APOE4 allele, we found a sex-dependent reciprocal induction of AD risk factors associated with suppression of MGnD genes in females, including LGALS3, compared to individuals homozygous for the APOE3 allele. Mechanistically, APOE4-mediated induction of ITGB8-transforming growth factor-β (TGFβ) signaling impairs the MGnD response via upregulation of microglial homeostatic checkpoints, including Inpp5d, in mice. Deletion of Inpp5d in microglia restores MGnD-astrocyte cross-talk and facilitates plaque clearance in APP/PS1 mice. We identify the microglial APOE4-ITGB8-TGFβ pathway as a negative regulator of microglial response to AD pathology, and restoring the MGnD phenotype via blocking ITGB8-TGFβ signaling provides a promising therapeutic intervention for AD.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
We use the first-year Dark Energy Survey (DES) data down to previously unprobed photometric depths to search for stellar systems in the Galactic halo, therefore complementing the previous analysis of ...the same data carried out by our group earlier this year. Our search is based on a matched filter algorithm that produces stellar density maps consistent with stellar population models of various ages, metallicities, and distances over the survey area. The most conspicuous density peaks in these maps have been identified automatically and ranked according to their significance and recurrence for different input models. We report the discovery of one additional stellar system besides those previously found by several authors using the same first-year DES data. The object is compact, and consistent with being dominated by an old and metal-poor population. DES 1 is found at high significance and appears in the DES images as a compact concentration of faint blue point sources. Assuming different spatial profile parameterizations, the best-fitting heliocentric distance and total absolute magnitude in the range of 77.6–87.1 kpc and −3.00 ≲ M
V
≲ −2.21, respectively. The half-light radius of this object, r
h ∼ 10 pc and total luminosity are consistent with it being a low-mass halo cluster. It is also found to have a very elongated shape (ϵ ∼ 0.57). In addition, our deeper probe of DES first-year data confirms the recently reported satellite galaxy candidate Horologium II as a significant stellar overdensity. We also infer its structural properties and compare them to those reported in the literature.
The mechanisms by which AML1/ETO (A/E) fusion protein induces leukemogenesis in acute myeloid leukemia (AML) without mutagenic events remain elusive. Here we show that interactions between A/E and ...hypoxia-inducible factor 1α (HIF1α) are sufficient to prime leukemia cells for subsequent aggressive growth. In agreement with this, HIF1α is highly expressed in A/E-positive AML patients and strongly predicts inferior outcomes, regardless of gene mutations. Co-expression of A/E and HIF1α in leukemia cells causes a higher cell proliferation rate in vitro and more serious leukemic status in mice. Mechanistically, A/E and HIF1α form a positive regulatory circuit and cooperate to transactivate DNMT3a gene leading to DNA hypermethylation. Pharmacological or genetic interventions in the A/E-HIF1α loop results in DNA hypomethylation, a re-expression of hypermethylated tumor-suppressor p15(INK4b) and the blockage of leukemia growth. Thus high HIF1α expression serves as a reliable marker, which identifies patients with a poor prognosis in an otherwise prognostically favorable AML group and represents an innovative therapeutic target in high-risk A/E-driven leukemia.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Significant efforts have been devoted to assess the effects of conservation tillage (no-tillage NT and straw returning) on greenhouse gas (GHG) emissions, global warming potential (GWP), greenhouse ...gas intensity (GHGI), and net economic budget in crop growing seasons. However, only a few studies have evaluated the effects conservation tillage on the net ecosystem economic budget (NEEB) in a rice–wheat cropping system. Therefore, a split-plot field experiment was performed to comprehensively evaluate the effects of tillage practices (i.e., conventional intensive tillage CT and NT) and straw returning methods (i.e., straw returning or removal of preceding crop) on the soil total organic carbon (TOC), GHG emissions, GWP, GHGI, and NEEB of sandy loam soil in a rice–wheat cropping system in central China. Conservation tillage did not affect rice and wheat grain yields. Compared with CT and straw removal, NT and straw returning significantly increased the TOC of 0–5 cm soil layer by 2.9% and 7.8%, respectively. However, the TOC of 0–20 cm soil layer was not affected by tillage practices and straw returning methods. NT did not also affect the N2O emissions during the rice and wheat seasons; NT significantly decreased the annual CH4 emissions by 7.5% and the annual GWP by 7.8% compared with CT. Consequently, GHGI under NT was reduced by 8.1%. Similar to NT, straw returning did not affect N2O emissions during the rice and wheat seasons. Compared with straw removal, straw returning significantly increased annual CH4 emissions by 35.0%, annual GWP by 32.0%, and annual GHGI by 31.1%. Straw returning did not also affect NEEB; by contrast, NT significantly increased NEEB by 15.6%. NT without straw returning resulted in the lowest GWP, the lowest GHGI, and the highest NEEB among all treatments. This finding suggested that NT without straw returning may be applied as a sustainable technology to increase economic and environmental benefits. Nevertheless, environmentally straw returning methods should be considered in future studies.
•Effects of conservation tillage on GHG emissions and NEEB in rice-wheat cropping systems were investigated.•NT significantly decreased annual GWP and GHGI, but increased NEEB compared with CT.•Straw returning significantly increased annual GWP and GHGI, but did not affect NEEB compared with straw removal.•NT with straw removal may be a sustainable technology to increase economic and environmental benefits.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The OSIRIS-REx Visible and InfraRed Spectrometer (OVIRS) onboard the Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer (OSIRIS-REx) spacecraft detected ~3.4-μm ...absorption features indicative of carbonates and organics on near-Earth asteroid (101955) Bennu. We apply a Kolmogorov-Smirnov similarity test to OVIRS spectra of Bennu and laboratory spectra of minerals to categorize 3.4-μm features observed on Bennu as representing either carbonates or organics. Among the 15,585 spectra acquired by OVIRS during high-resolution (4 to 9 m/spectrum footprint) reconnaissance observations of select locations on Bennu's surface, we find 544 spectral matches with carbonates and 245 spectral matches with organics (total of 789 high-confidence spectral matches). We map the locations of these matches and characterize features of Bennu's surface using corresponding image data. Image data are used to quantitatively characterize the albedo within each spectrometer footprint. We find no apparent relationships between spectral classification and surface morphological expression, and we find no correlation between carbon species classification and other spectral properties such as slope or band depth. This suggests either that carbonates and organics are ubiquitous across the surface of Bennu, independent of surface features (consistent with findings from laboratory studies of carbonaceous chondrites), or that the observations do not have the spatial resolution required to resolve differences. However, we find more organic spectral matches at certain locations, including the site from which the OSIRIS-REx mission collected a sample, than at others. Higher concentrations of organics may be explained if these materials have been more recently exposed to surface alteration processes, perhaps by recent crater formation.
•OSIRIS-REx target asteroid 101955 Bennu contains organics and carbonates.•Spectra of regions on Bennu show features similar to laboratory meteorite spectra that contain organics.•These detections of organics and carbonates are not correlated with surface features such as craters or boulders.•Bennu expresses more carbonate-like spectra than organic-like spectra.•Organics and carbonates are mixed below the spatial resolution of the OSIRIS-REx Visual InfraRed Spectrometer, OVIRS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hydrostatic pressure (HP) effects on corrosion process of X70 steel in 3.5% NaCl solution have been investigated by situ electrochemical impedance spectroscopy (EIS), immersion tests and Raman ...spectra. These results indicate HP affects the corrosion behavior of the X70 steel during the whole immersion period. At the initial immersion, HP promotes the electrochemical reaction of corrosion process. Pitting initiation rate and propagation are both promoted by HP, corrosion rate increases with HP at the initial immersion period. At the stable immersion period, inner layer corrosion product is complete at 0.1 MPa, obvious cracks can be observed at 10 MPa. HP promotes Cl− transport and adsorption on the rust layer, corrosion rate slightly increases with HP.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Crescent‐shaped electron distributions perpendicular to the magnetic field are an important indicator of the electron diffusion region in magnetic reconnection. They can be formed by the electron ...finite gyroradius effect at plasma boundaries or by demagnetized electron motion. In this study, we present Magnetospheric Multiscale mission observations of electron crescents at the flank magnetopause on 20 September 2017, where reconnection signatures are not observed. These agyrotropic electron distributions are generated by electron gyromotion at the thin electron‐scale magnetic boundaries of a magnetic minimum after magnetic curvature scattering. The variation of their angular range in the perpendicular plane is in good agreement with predictions. Upper hybrid waves are observed to accompany the electron crescents at all four Magnetospheric Multiscale spacecraft as a result of the beam‐plasma instability associated with these agyrotropic electron distributions. This study suggests electron crescents can be more frequently formed at the magnetopause.
Plain Language Summary
In this study, we present Magnetospheric Multiscale mission observations of electron crescents at the flank magnetopause and these agyrotropic electron distributions are formed at thin electron‐scale magnetic boundaries after electron pitch angle scattering by the curved magnetic field. These results suggest that agyrotropic electron distributions can be more frequently formed at the magnetopause: (1) magnetic reconnection is not necessary, although electron crescents are taken as one of the observational signatures of the electron diffusion region, and (2) agyrotropic electron distributions can cover a large local time range to the flank magnetopause. In addition, upper hybrid waves accompanied with the electron crescents are observed as a result of the beam‐plasma interaction associated with these agyrotropic electron distributions. This suggests that high‐frequency waves play a role in electron dynamics through wave‐particle interactions.
Key Points
Agyrotropic electron crescents are found in a nonreconnecting current sheet at the flank magnetopause
These electron distributions are generated by finite gyroradius effect after magnetic curvature scattering
The observed electron crescents can excite upper hybrid waves
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
New particle formation (NPF) is a significant source of atmospheric
particles, affecting climate and air quality. Understanding the mechanisms
involved in urban aerosols is important to develop ...effective mitigation
strategies. However, NPF rates reported in the polluted boundary layer span
more than 4 orders of magnitude, and the reasons behind this variability are the subject of intense scientific debate. Multiple atmospheric vapours have been
postulated to participate in NPF, including sulfuric acid, ammonia, amines
and organics, but their relative roles remain unclear. We investigated NPF
in the CLOUD chamber using mixtures of anthropogenic vapours that simulate
polluted boundary layer conditions. We demonstrate that NPF in polluted
environments is largely driven by the formation of sulfuric acid–base
clusters, stabilized by the presence of amines, high ammonia concentrations
and lower temperatures. Aromatic oxidation products, despite their extremely
low volatility, play a minor role in NPF in the chosen urban environment but
can be important for particle growth and hence for the survival of newly
formed particles. Our measurements quantitatively account for NPF in highly
diverse urban environments and explain its large observed variability. Such
quantitative information obtained under controlled laboratory conditions
will help the interpretation of future ambient observations of NPF rates in
polluted atmospheres.
Lymphocytes provide optimal responses against pathogens with minimal inflammatory pathology. However, the intrinsic mechanisms regulating these responses are unknown. Here, we report that deletion of ...both transcription factors Egr2 and Egr3 in lymphocytes resulted in a lethal autoimmune syndrome with excessive serum proinflammatory cytokines but also impaired antigen receptor-induced proliferation of B and T cells. Egr2- and Egr3-defective B and T cells had hyperactive signal transducer and activator of transcription-1 (STAT1) and STAT3 while antigen receptor-induced activation of transcription factor AP-1 was severely impaired. We discovered that Egr2 and/or Egr3 directly induced expression of suppressor of cytokine signaling-1 (SOCS1) and SOCS3, inhibitors of STAT1 and STAT3, and also blocked the function of Batf, an AP-1 inhibitor, in B and T cells. Thus, Egr2 and Egr3 regulate B and T cell function in adaptive immune responses and homeostasis by promoting antigen receptor signaling and controlling inflammation.
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► Deletion of Egr2 and Egr3 in lymphocytes results in a lethal autoimmune syndrome ► Deficiency in both Egr2 and Egr3 impairs antigen receptor-induced proliferation ► Egr2 and Egr3 are required for AP-1 activity by blocking Batf ► Egr2 and Egr3 induce expression of SOCS1 and SOCS3
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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