The impact of the seasonal mean background state on the physical processes responsible for better Madden‐Julian Oscillation (MJO) propagation and prediction was investigated using 20 year European ...Centre for Medium‐Range Weather Forecasts (ECMWF) reforecast data sets. While the reforecast captures the MJO propagating signal in the circulation field, the outgoing longwave radiation and column‐integrated moist static energy (MSE) anomalies show a weaker signal than the reanalysis when the MJO detours and propagates in the southern Maritime Continent. By comparing individual MSE budget terms, it is found that the predicted positive MSE tendency to the east of the MJO convection center is weaker than the reanalysis due to the weaker horizontal MSE advection. The dry bias in the seasonal mean lower tropospheric moisture is a key factor that weakens the horizontal MSE advection, and thus deteriorates the MJO propagation in the reforecasts. Therefore, improvements in the mean state could further extend the MJO prediction and associated subseasonal weather phenomena over the globe.
Key Points
In the ECMWF reforecast, the MJO‐associated convection and MSE anomalies show a faster and weaker propagating signal than the reanalysis
The weak predicted MSE tendency to the east of the MJO convection is due to the weak horizontal MSE advection
The dry bias in seasonal mean tropospheric moisture field is a key factor that weakens the horizontal MSE advection
Glioblastoma (GBM), the most severe and common brain tumor in adults, is characterized by multiple somatic mutations and aberrant activation of inflammatory responses. Immune cell infiltration and ...subsequent inflammation cause tumor growth and resistance to therapy. Somatic loss-of-function mutations in the gene encoding tumor suppressor protein p53 (TP53) are frequently observed in various cancers. However, numerous studies suggest that TP53 regulates malignant phenotypes by gain-of-function (GOF) mutations. Here we demonstrate that a TP53 GOF mutation promotes inflammation in GBM. Ectopic expression of a TP53 GOF mutant induced transcriptomic changes, which resulted in enrichment of gene signatures related to inflammation and chemotaxis. Bioinformatics analyses revealed that a gene signature, upregulated by the TP53 GOF mutation, is associated with progression and shorter overall survival in GBM. We also observed significant correlations between the TP53 GOF mutation signature and inflammation in the clinical database of GBM and other cancers. The TP53 GOF mutant showed upregulated C-C motif chemokine ligand 2 (CCL2) and tumor necrosis factor alpha (TNFA) expression via nuclear factor kappa B (NFκB) signaling, consequently increasing microglia and monocyte-derived immune cell infiltration. Additionally, TP53 GOF mutation and CCL2 and TNFA expression correlated positively with tumor-associated immunity in patients with GBM. Taken together, our findings suggest that the TP53 GOF mutation plays a crucial role in inflammatory responses, thereby deteriorating prognostic outcomes in patients with GBM.
This study assesses the CMIP5 decadal hindcast/forecast simulations of seven state‐of‐the‐art ocean‐atmosphere coupled models. Each decadal prediction consists of simulations over a 10 year period ...each of which are initialized every five years from climate states of 1960/1961 to 2005/2006. Most of the models overestimate trends, whereby the models predict less warming or even cooling in the earlier decades compared to observations and too much warming in recent decades. All models show high prediction skill for surface temperature over the Indian, North Atlantic and western Pacific Oceans where the externally forced component and low‐frequency climate variability is dominant. However, low prediction skill is found over the equatorial and North Pacific Ocean. The Atlantic Multidecadal Oscillation (AMO) index is predicted in most of the models with significant skill, while the Pacific Decadal Oscillation (PDO) index shows relatively low predictive skill. The multi‐model ensemble has in general better‐forecast quality than the single‐model systems for global mean surface temperature, AMO and PDO.
Key Points
CMIP5 models overestimate trend for global mean surface temperature
The multi‐model ensemble mean has better‐forecast quality than single‐model
The Atlantic Multi‐decadal Oscillation index is well predicted in all models
The year-to-year changes in atmospheric rivers (ARs) and moisture transport over the northeast Pacific and western North America are investigated during December to February (DJF) from 1979/80 to ...2015/16. Changes in AR frequency, intensity, and landfall characteristics are compared between three ENSO phases: central Pacific El Niño (CPEN), eastern Pacific El Niño (EPEN), and La Niña (NINA). During EPEN events, the subtropical jet extends to the south and east with an anomalous cyclonic flow around a deeper Aleutian Low. More moisture is transported towards North America and AR frequency is increased over western North America. In CPEN events, the Aleutian low shifts further southward relative to its position in EPEN, resulting in an increase in the frequency and intensity of landfalling ARs over the southwestern US. In NINA events, the landfalling AR frequency is reduced associated with anomalous anticyclonic circulation over the eastern North Pacific. We diagnose the contribution of multiple factors to the seasonal mean moisture transport using moisture budgets. During the three ENSO phases, the change in low-frequency circulation (dynamical process) is the leading contributor to the seasonal mean moisture flux divergence, while the contributions of the synoptic anomalies and the change in moisture anomaly (thermodynamic process) are not significant along the west coast of North America.
Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain; however, the roles of GABA in antimicrobial host defenses are largely unknown. Here we demonstrate that ...GABAergic activation enhances antimicrobial responses against intracellular bacterial infection. Intracellular bacterial infection decreases GABA levels in vitro in macrophages and in vivo in sera. Treatment of macrophages with GABA or GABAergic drugs promotes autophagy activation, enhances phagosomal maturation and antimicrobial responses against mycobacterial infection. In macrophages, the GABAergic defense is mediated via macrophage type A GABA receptor (GABA
R), intracellular calcium release, and the GABA type A receptor-associated protein-like 1 (GABARAPL1; an Atg8 homolog). Finally, GABAergic inhibition increases bacterial loads in mice and zebrafish in vivo, suggesting that the GABAergic defense plays an essential function in metazoan host defenses. Our study identified a previously unappreciated role for GABAergic signaling in linking antibacterial autophagy to enhance host innate defense against intracellular bacterial infection.
Glioblastoma (GBM) is a complex disease with extensive molecular and transcriptional heterogeneity. GBM can be subcategorized into four distinct subtypes; tumors that shift towards the mesenchymal ...phenotype upon recurrence are generally associated with treatment resistance, unfavorable prognosis, and the infiltration of pro-tumorigenic macrophages.
We explore the transcriptional regulatory networks of mesenchymal-associated tumor-associated macrophages (MA-TAMs), which drive the malignant phenotypic state of GBM, and identify macrophage receptor with collagenous structure (MARCO) as the most highly differentially expressed gene. MARCO
TAMs induce a phenotypic shift towards mesenchymal cellular state of glioma stem cells, promoting both invasive and proliferative activities, as well as therapeutic resistance to irradiation. MARCO
TAMs also significantly accelerate tumor engraftment and growth in vivo. Moreover, both MA-TAM master regulators and their target genes are significantly correlated with poor clinical outcomes and are often associated with genomic aberrations in neurofibromin 1 (NF1) and phosphoinositide 3-kinases/mammalian target of rapamycin/Akt pathway (PI3K-mTOR-AKT)-related genes. We further demonstrate the origination of MA-TAMs from peripheral blood, as well as their potential association with tumor-induced polarization states and immunosuppressive environments.
Collectively, our study characterizes the global transcriptional profile of TAMs driving mesenchymal GBM pathogenesis, providing potential therapeutic targets for improving the effectiveness of GBM immunotherapy.
We introduce the design and implementation of a new array, the Korea Biobank Array (referred to as KoreanChip), optimized for the Korean population and demonstrate findings from GWAS of blood ...biochemical traits. KoreanChip comprised >833,000 markers including >247,000 rare-frequency or functional variants estimated from >2,500 sequencing data in Koreans. Of the 833 K markers, 208 K functional markers were directly genotyped. Particularly, >89 K markers were presented in East Asians. KoreanChip achieved higher imputation performance owing to the excellent genomic coverage of 95.38% for common and 73.65% for low-frequency variants. From GWAS (Genome-wide association study) using 6,949 individuals, 28 associations were successfully recapitulated. Moreover, 9 missense variants were newly identified, of which we identified new associations between a common population-specific missense variant, rs671 (p.Glu457Lys) of ALDH2, and two traits including aspartate aminotransferase (P = 5.20 × 10
) and alanine aminotransferase (P = 4.98 × 10
). Furthermore, two novel missense variants of GPT with rare frequency in East Asians but extreme rarity in other populations were associated with alanine aminotransferase (rs200088103; p.Arg133Trp, P = 2.02 × 10
and rs748547625; p.Arg143Cys, P = 1.41 × 10
). These variants were successfully replicated in 6,000 individuals (P = 5.30 × 10
and P = 1.24 × 10
). GWAS results suggest the promising utility of KoreanChip with a substantial number of damaging variants to identify new population-specific disease-associated rare/functional variants.
The authors examine the predictability and prediction skill of the Madden–Julian oscillation (MJO) of two ocean–atmosphere coupled forecast systems of ECMWF Variable Resolution Ensemble Prediction ...System (VarEPS) and NCEP Climate Forecast System, version 2 (CFSv2). The VarEPS hindcasts possess five ensemble members for the period 1993–2009 and the CFSv2 hindcasts possess three ensemble members for the period 2000–09. Predictability and prediction skill are estimated by the bivariate correlation coefficient between the observed and predicted Wheeler–Hendon real-time multivariate MJO index (RMM). MJO predictability is beyond 32 days lead time in both hindcasts, while the prediction skill is about 27 days in VarEPS and 21 days in CFSv2 as measured by the bivariate correlation exceeding 0.5. Both predictability and prediction skill of MJO are enhanced by averaging ensembles. Results show clearly that forecasts initialized with (or targeting) strong MJOs possess greater prediction skill compared to those initialized with (or targeting) weak or nonexistent MJOs. The predictability is insensitive to the initial MJO phase (or forecast target phase), although the prediction skill varies with MJO phases.
A few common model issues are identified. In both hindcasts, the MJO propagation speed is slower and the MJO amplitude is weaker than observed. Also, both ensemble forecast systems are underdispersive, meaning that the growth rate of ensemble error is greater than the growth rate of the ensemble spread by lead time.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The seasonal prediction skill for the Northern Hemisphere winter is assessed using retrospective predictions (1982–2010) from the ECMWF System 4 (Sys4) and National Center for Environmental ...Prediction (NCEP) CFS version 2 (CFSv2) coupled atmosphere–ocean seasonal climate prediction systems. Sys4 shows a cold bias in the equatorial Pacific but a warm bias is found in the North Pacific and part of the North Atlantic. The CFSv2 has strong warm bias from the cold tongue region of the eastern Pacific to the equatorial central Pacific and cold bias in broad areas over the North Pacific and the North Atlantic. A cold bias in the Southern Hemisphere is common in both reforecasts. In addition, excessive precipitation is found in the equatorial Pacific, the equatorial Indian Ocean and the western Pacific in Sys4, and in the South Pacific, the southern Indian Ocean and the western Pacific in CFSv2. A dry bias is found for both modeling systems over South America and northern Australia. The mean prediction skill of 2 meter temperature (2mT) and precipitation anomalies are greater over the tropics than the extra-tropics and also greater over ocean than land. The prediction skill of tropical 2mT and precipitation is greater in strong El Nino Southern Oscillation (ENSO) winters than in weak ENSO winters. Both models predict the year-to-year ENSO variation quite accurately, although sea surface temperature trend bias in CFSv2 over the tropical Pacific results in lower prediction skill for the CFSv2 relative to the Sys4. Both models capture the main ENSO teleconnection pattern of strong anomalies over the tropics, the North Pacific and the North America. However, both models have difficulty in forecasting the year-to-year winter temperature variability over the US and northern Europe.
Two distinctly different forms of tropical Pacific Ocean warming are shown to have substantially different impacts on the frequency and tracks of North Atlantic tropical cyclones. The eastern Pacific ...warming (EPW) is identical to that of the conventional El Niño, whereas the central Pacific warming (CPW) has maximum temperature anomalies located near the dateline. In contrast to EPW events, CPW episodes are associated with a greater-than-average frequency and increasing landfall potential along the Gulf of Mexico coast and Central America. Differences are shown to be associated with the modulation of vertical wind shear in the main development region forced by differential teleconnection patterns emanating from the Pacific. The CPW is more predictable than the EPW, potentially increasing the predictability of cyclones on seasonal time scales.
PDF
