Abstract
Existing weather forecasting models are based on physics and use supercomputers to evolve the atmosphere into the future. Better physics-based forecasts require improved atmospheric models, ...which can be difficult to discover and develop, or increasing the resolution underlying the simulation, which can be computationally prohibitive. An emerging class of weather models based on neural networks overcome these limitations by learning the required transformations from data instead of relying on hand-coded physics and by running efficiently in parallel. Here we present a neural network capable of predicting precipitation at a high resolution up to 12 h ahead. The model predicts raw precipitation targets and outperforms for up to 12 h of lead time state-of-the-art physics-based models currently operating in the Continental United States. The results represent a substantial step towards validating the new class of neural weather models.
Aim
As one of the most diverse and economically important families on Earth, ground beetles (Carabidae) are viewed as a key barometer of climate change. Recent meta‐analyses provide equivocal ...evidence on abundance changes of terrestrial insects. Generalizations from traits (e.g., body size, diets, flights) provide insights into understanding community responses, but syntheses for the diverse Carabidae have not yet emerged. We aim to determine how habitat and trait syndromes mediate risks from contemporary and future climate change on the Carabidae community.
Location
North America.
Time period
2012–2100.
Major taxa studied
Ground beetles (Carabidae).
Methods
We synthesized the abundance and trait data for 136 species from the National Ecological Observatory Network (NEON) and additional raw data from studies across North America with remotely sensed habitat characteristics in a generalized joint attribute model. Combined Light Detection and RAnging (LiDAR) and hyperspectral imagery were used to derive habitat at a continental scale. We evaluated climate risks on the joint response of species and traits by expanding climate velocity to response velocity given habitat change.
Results
Habitat contributes more variations in species abundance and community‐weighted mean traits compared to climate. Across North America, grassland fliers benefit from open habitats in hot, dry climates. By contrast, large‐bodied, burrowing omnivores prefer warm‐wet climates beneath closed canopies. Species‐specific abundance changes predicted by the fitted model under future shared socioeconomic pathways (SSP) scenarios are controlled by climate interactions with habitat heterogeneity. For example, the mid‐size, non‐flier is projected to decline across much of the continent, but the magnitudes of declines are reduced or even reversed where canopies are open. Conversely, temperature dominates the response of the small, frequent flier Agonoleptus conjunctus, causing projected change to be more closely linked to regional temperature changes.
Main conclusions
Carabidae community reorganization under climate change is being governed by climate–habitat interactions (CHI). Species‐specific responses to CHI are explained by trait syndromes. The fact that habitat mediates warming impacts has immediate application to critical habitat designation for carabid conservation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This Special Issue, entitled "Personalized Medicine for Liver Disease: From Molecular Mechanisms to Potential Targeted Therapies", includes 11 publications from colleagues working on various liver ...diseases including non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), hepatocellular carcinoma (HCC), primary biliary cholangitis (PBC), as well as various treatment modalities including pharmacotherapies and liver transplantation ....
Abstract
The anomalous microwave emission (AME) still lacks a conclusive explanation. This excess of emission, roughly between 10 and 50 GHz, tends to defy attempts to explain it as synchrotron or ...free–free emission. The overlap with frequencies important for cosmic microwave background explorations, combined with a strong correlation with interstellar dust, drive cross-disciplinary collaboration between interstellar medium and observational cosmology. The apparent relationship with dust has prompted a “spinning dust” hypothesis. The typical peak frequency range of the AME profile implicates spinning grains on the order of 1 nm. This points to polycyclic aromatic hydrocarbons (PAHs). We use data from the AKARI/Infrared Camera (IRC), due to its thorough PAH-band coverage, to compare AME from the Planck Collaboration astrophysical component separation product with infrared dust emission in the λ Orionis AME-prominent region. We look also at infrared dust emission from other mid-infrared and far-infrared bands. The results and discussion contained here apply to an angular scale of approximately 1°. We find that dust mass certainly correlates with AME, and that PAH-related emission in the AKARI/IRC 9 μm band correlates slightly more strongly. Using hierarchical Bayesian inference and full-dust spectral energy distribution (SED) modeling we argue that AME in λ Orionis correlates more strongly with PAH mass than with total dust mass, lending support for a spinning PAH hypothesis within this region. We emphasize that future efforts to understand AME should focus on individual regions, and a detailed comparison of the PAH features with the variation of the AME SED.
Life-history traits influence colonization, persistence, and extinction of species on islands and are important aspects of theories predicting the geographical distribution and evolution of species. ...We used data collected from a large freshwater lake (1,413 km2) in central Canada to test the effects of island area and isolation on species richness and abundance of carabid beetles as a function of body size, wing length, and breeding season. A total of 10,018 individual beetles from 37 species were collected during the frost-free period of 2013 using transects of pitfall traps on 30 forested islands ranging in area from 0.2 to 980.7 ha. Life-history traits improved the predictive ability and significantly modified the shape of species-area and abundance-area curves. Abundance and richness of small-bodied (< 13.9 mm), macropterous (winged), and spring-breeding species decreased with island area and increased with isolation. In contrast, richness and abundance of larger-bodied (> 14.0 mm) and flightless species increased with area, but not isolation. Body size of female Carabus taedatus Fabricius, the largest-bodied species, was positively related to island area, while body size on the adjacent mainland was most similar to that on smaller islands. Overall, species with large body size and low dispersal ability, as indicated by flightlessness, were most sensitive to reductions in area. We suggest that large-bodied, flightless species are rare on small islands because habitat is less suitable for them and immigration rates are lower because they depend on freshwater drift for dispersal to islands.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hepatocellular Carcinoma (HCC) is the 5th most common cause of cancer‐related death in the United States with an estimated 32,000 annual deaths. The standard of care for HCC as established by the ...IMBrave150 trial is a combination of the PD‐L1 inhibitor, Atezolizumab, and an antiangiogenic, Bevacizumab. While this combination extends overall survival to 19.2 months in unresectable HCC, only 52% of patients survive to 18 months. Furthermore, objective response rates are around 32% and hence clarifying underlying mechanisms regulating the immune response in HCC oncogenesis might strengthen immunotherapy efficacy. Especially important is to identify response rates of these agents in specific molecular subclasses of HCC may help in better patient selection. The oncogene ꞵ‐catenin is consistently mutated and activated among 30% of HCC patients. The Wnt/ꞵ‐catenin pathway has been approached as a target for precision medicine in HCC. We recently modeled HCCs with ꞵ‐catenin mutations in mice up to 69% genetic similarity. Here, we combine hydrodynamic tail vein injections with the Sleeping Beauty Transposase which is a non‐viral method of expressing genes of interest. Our model co‐expresses an S45Y point mutant of ꞵ‐catenin with the tyrosine kinase receptor MET (B+M). This combination represents ~10% of patient HCCs and provides a clinically relevant tool for the investigation of personalized HCC therapeutics.
A recent study demonstrated HCCs driven by a Δ90‐truncation mutant of ꞵ‐catenin in combination with the Myc oncogene are shown to lack sufficient immune cell surveillance. These HCCs have poor cytotoxic T cell and dendritic cell recruitment while responding poorly to checkpoint inhibitors. Since activating point mutations in CTNNB1 gene are common in patient HCCs, we asked whether poor immune surveillance extends to HCC models harboring point mutations. We first checked and found the presence of CD45+, F4/80+, and CD11b+ cells both 2 and 4 weeks after B+M tumor induction. This indicates the presence of both adaptive and innate immune cells in the B+M tumor microenvironment. We next asked whether checkpoint inhibition will effectively reduce tumor burden in the B+M model. Therefore, we treated B+M mice with either IgG or anti‐PD1 monoclonal antibodies 4 weeks after tumor induction. Tissues were harvested 3.5 weeks after treatment. We found a modest 20% reduction in liver weight to body weight ratio, a measure of tumor burden, in B+M mice treated with anti‐PD1 compared to IgG controls. Our results demonstrate that HCCs with missense ꞵ‐catenin mutations do respond albeit marginally to checkpoint inhibitors. In the future, combination of checkpoint inhibitors with other inhibitors will be tested in these models to determine their efficacy in treating ꞵ‐catenin‐mutated HCCs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Hepatocellular carcinoma (HCC) is the 5th most common cause of cancer‐related death in the United States with an estimated 32,000 annual deaths. Roughly 30% of HCC cases demonstrate mutations in the ...CTNNB1 oncogene that encodes a form of the ꞵ‐catenin protein that cannot be degraded. Recently, we developed a mouse model of HCC that genetically represents ~9‐12% of all human HCCs. Here, we combine hydrodynamic tail vein injections with the Sleeping Beauty Transposase – a non‐viral method of expressing genes of interest. Our model uses a clinically observed mutant of ꞵ‐catenin‐(T41A) that is co‐expressed with a mutant form of the nuclear factor erythroid 2–related factor 2 (Nrf2‐G31A) in the livers of wild‐type mice (B+N). This system results in microscopic HCC within 3 weeks and evident macroscopic disease by 7 weeks after induction.
ꞵ‐catenin activation can be identified by the expression of its downstream target gene Glutamine Synthetase (GS) in the liver. Patient HCCs with ꞵ‐catenin mutations strongly correlate with GS expression. The evolution and function of GS in b‐catenin‐mutated HCC, remains unclear. Also, there is a gap in the knowledge whether elevated GS expression correlates with HCC biology, which were all subjects of the current study. B+N mouse model of HCC was examined temporally for development of HCC along with GS expression. B+N mice develop HCCs with heterogeneous GS expression in the form of GS‐high and GS‐low to GS‐negative foci. We next asked whether GS expression is associated with cell proliferation or death in the B+N model. We stained tissues for TUNEL and PCNA to mark cell apoptosis and proliferation, respectively in 7‐ and 9.5 weeks post‐injection livers, which were then correlated to GS staining of HCC nodules. While we found no correlation between apoptosis and GS, we found nodules with lower GS expression to have higher proliferation and vice versa. Finally, we asked if eliminating GS expression from B+N HCCs will impact tumor burden. Five weeks after B+N tumor induction in GS‐floxed mice, these animals were injected with AAV8‐TBG‐Cre virus to delete Glul,and mice were harvested after 2‐ or 4.5‐weeks. We found B+N mice with Glul deletion show increased liver weight to body weight ratio, a measurement of HCC burden, compared to controls. The livers of these mice were enriched for GS‐negative tumors. Together, our data suggests that HCC nodules with lower GS expression may outperform GS‐positive foci, and thus are more aggressive compared to the nodules with higher GS expression, which may be more differentiated. The mechanisms of GS heterogeneity and elucidation of its functional significance may help select the most effective targeted therapies for HCC patients with ꞵ‐catenin mutations.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Micro-X-ray absorption near-edge structure (µ-XANES) spectroscopy has been used by several recent studies to determine the oxidation state and coordination of iron in silicate glasses. Here, we ...present new results from Fe µ-XANES analyses on a set of 19 Fe-bearing felsic glasses and 9 basaltic glasses with known, independently determined, iron oxidation state. Some of these glasses were measured previously via Fe XANES (7 rhyolitic, 9 basaltic glasses; Cottrell et al. 2009), while most felsic reference glasses (12) were analyzed for the first time. The main purpose of this study was to understand how small changes in glass composition, especially at the evolved end of silicate melt compositions occurring in nature, may affect a calibration of the Fe µ-XANES method. We performed Fe µ-XANES analyses at different synchrotron radiation sources Advanced Photon Source (APS), Argonne, U.S.A., and Angstromquelle Karlsruhe (ANKA), Germany and compared our results to existing calibrations obtained at other synchrotron radiation sources worldwide. The compiled results revealed that changes in instrumentation have a negligible effect on the correlation between the centroid energy of the Fe pre-edge peak and the Fe oxidation state in the glasses. Oxidation of the glasses during extended exposure (up to 50 min) to the X-ray beam was not observed. Based on the new results and literature data we determined a set of equations for different glass compositions, which can be applied for the calculation of the iron valence ratio (Fe3+/ΣFe) in glasses by using XANES spectra collected at different synchrotron beamlines. For instance, the compiled felsic reference material data demonstrated that the correlation between the centroid energy of the Fe pre-edge peak CFe (eV) and the Fe3+/ΣFe ratio of felsic glasses containing 60.9 to 77.5 wt% SiO2 and 1.3 to 5.7 wt% FeOtot can be accurately described by a single linear trend, if the spectra were collected at 13-ID-E beamline at APS and for 0.3 ≤ Fe3+/ΣFe ≤ 0.85: CFeeV = 0.012395 (±0.00026217) × Fe3+/ΣFe + 7112.1 (±0.014525);R2 = 0.987. Based on this equation, the Fe oxidation state of felsic glasses can be estimated at an absolute uncertainty of ±2.4% Fe3+/ΣFe.In general, the differences between the calibrations for felsic and mafic glasses were small and the compiled data set (i.e., results collected at four different beamlines on 79 reference glass materials) is well described by a single second-order polynomial equation.
Ultramafic xenoliths from southeastern Arizona, USA, provide evidence for Cu‐isotope heterogeneity in the lithospheric mantle. We report new data on Type I (Cr‐, Mg‐rich) peridotites, but also the ...first Cu‐isotope data for Fe‐Ti‐Al‐rich Type II pyroxenite (±amphibole) xenoliths. Whole rock δ65Cu values of the pyroxenites and cryptically metasomatized Type I lherzolites range to isotopically heavier compositions than asthenospheric mantle (i.e., up to +1.44‰ and +1.12‰, respectively, vs. ∼0‰ ± 0.2‰). Copper leached from the xenoliths using aqua regia, assumed to be hosted in interstitial sulfides, is even more variable (δ65Cu −0.78 to +3.88‰), indicating considerable isotopic heterogeneity within individual samples. Host basalts have low δ65Cu (−0.23‰ to −1.30‰), so basalt—xenolith interactions are not responsible for the compositional variations observed. While mass‐dependent fractionation may be partly responsible, metasomatism by fluids derived from recycled crustal materials is the predominant control on isotopic variations observed. Amphibole megacrysts and amphiboles separated from Type II amphibole‐bearing clinopyroxenite have normal, mantle‐like 18O/16O ratios but H‐isotope compositions (δ2HSMOW −82‰ to −45‰) that range between that of nominally anhydrous mantle (−80 ± 10‰) and seawater (0‰). Host basalts are also enriched in 34S relative to depleted asthenospheric mantle, having δ34SCDT values up to +8‰, i.e., compositions commonly attributed to a component of recycled seawater or hydrated oceanic crust. These new data suggest that formation of Type II metasomes in the lithospheric mantle beneath the Basin and Range Province was associated with subduction of the Farallon plate and not alkali basalt magmatism associated with Basin and Range extension.
Plain Language Summary
The Cu‐isotope composition of Earth's mantle is believed to be homogenous, with δ65Cu varying between −0.2‰ and +0.2‰ (where δ65Cu is the 65Cu/63Cu ratio relative to the NIST976 copper standard). However, samples of the lithospheric mantle entrained as inclusions in Plio‐Pleistocene age basalts from SE Arizona, USA, record a much wider compositional range of −0.78‰ to +3.88‰. The greatest compositional range (−0.08‰ to +1.44‰) is observed in Fe‐, Ti‐, and Al‐rich pyroxenites (±amphibole) that formed by fractional crystallization of basaltic melts in the mantle. While mass‐dependent fractionation in the mantle may be responsible for some of the isotopic variation, metasomatism during subduction, by fluids derived from recycled crustal materials, is proposed as the dominant mechanism. These new data also suggest that formation of enriched veins in the lithospheric mantle beneath the Basin and Range is associated with subduction of the Farallon plate, and not the alkali basalt magmatism caused by Basin and Range extension, as had previously been proposed.
Key Points
The Cu‐isotope composition of lithospheric mantle is heterogeneous
Metasomatism of this mantle by fluids/melts derived from crustal materials recycled via seduction is the principal source of the heterogeneity
Fe‐Al‐rich pyroxenites, representative of geochemically enriched mantle metasomes, exhibit greater isotopic variation than metasomatized peridotites
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Tau hyperphosphorylation, mostly at serine (Ser) or threonine (Thr) residues, plays a key role in the pathogenesis of Alzheimer disease (AD) and other tauopathies. Rodent studies show ...similar hyperphosphorylation in the developing brain, which may be involved in regulating axonal growth and plasticity, but detailed human studies are lacking. Here, we examine tau phosphorylation by immunohistochemistry and immunoblotting in human fetal and adult autopsy brain tissue. Of the 20 cases with sufficient tissue preservation, 18 (90%) showed positive staining for S214 (pSer214), with the majority also positive for CP13 (pSer202), and PHF-1 (pSer396/pSer404). AT8 (pSer202/pThr205) and RZ3 (pThr231) were largely negative while PG5 (pSer409) was negative in all cases. Immunoblotting showed tau monomers with a similar staining pattern. We also observed phospho-tau aggregates in the fetal molecular layer, staining positively for S214, CP13, and PHF1 and negative for thioflavin S. These corresponded to high-molecular weight (∼150 kD) bands seen on Western blots probed with S214, PHF1, and PG5. We therefore conclude that fetal phosphorylation overlaps with AD in some residues, while others (e.g. T231, S409) appear to be unique to AD, and that tau is capable of forming nontoxic aggregates in the developing brain. These findings suggest that the fetal brain is resilient to formation of toxic aggregates, the mechanism for which may yield insights into the pathogenesis of tau aggregation and toxicity in the aging brain.
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