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Pentad (5-day averaged) forecast skill over the Arctic region in boreal winter is evaluated for the subseasonal to seasonal prediction (S2S) systems from three operational centers: the European Centre for Medium-Range Weather Forecasts (ECMWF), the U.S. National Centers for Environmental Prediction (NCEP), and Environment and Climate Change Canada (ECCC). The results indicate that for a lead time longer than about 10 days the forecast skill of 2-m air temperature and 500-hPa geopotential height in the Arctic area is low compared to the tropical and midlatitude regions. The three S2S systems have comparable forecast skill in the northern polar region. Relatively high skill is observed in the Arctic sector north of the Bering Strait in pentads 4–6. Possible sources of S2S predictability in the polar region are explored. The polar forecast skill is found to be dependent on the phase of the Arctic Oscillation (AO) in the initial condition; that is, forecasts initialized with the negative AO are more skillful than those starting from the positive AO. This is likely due to the influence of the stratospheric polar vortex. The tropical MJO is found to also influence the prediction skill in the polar region. Forecasts starting from MJO phases 6–7, which correspond to suppressed convection in the equatorial eastern Indian Ocean and enhanced convection in the tropical western Pacific, tend to be more skillful than those initialized from other MJO phases. To improve the polar prediction on the subseasonal time scale, it is important to have a well-represented stratosphere and tropical MJO and their associated teleconnections in the model.

Using observational pentad data of the recent 34 Northern Hemisphere extended winters, subseasonal variability of surface air temperature (SAT) over North America is analyzed. The four leading modes of subseasonal SAT variability, that are identified with an empirical orthogonal function (EOF) analysis, account for about 60% of the total variance. The first (EOF1) and second (EOF2) modes are independent of other modes, and thus are likely controlled by distinct processes. The third (EOF3) and fourth (EOF4) modes, however, tend to have a phase shift to each other in space and time, indicating that part of their variability is related to a common process and represent a propagating pattern over North America. Lagged regression analysis is conducted to identify the precursors of large-scale atmospheric circulation for each mode a few pentads in advance, and to understand the processes that influence the subseasonal SAT variability and the predictability signal sources. EOF1 is found to be closely related to the Pacific-North American (PNA) circulation pattern and at least part of its variability is preceded by the East Asian cold surge. The cold surge leads to low-level convergence and enhanced convection in the tropical central Pacific which in turn induces the PNA. EOF2 tends to oscillate at a period of about 70 days, and is influenced by the low-frequency component of the Madden–Julian Oscillation (MJO). On the other hand, EOF3 and EOF4 are connected to the high-frequency part of the MJO which has a period range of 30–50 days. These findings would help understanding the mechanisms of subseasonal surface air temperature variability in North America and improving weather predictions on a subseasonal time scale.

The placenta is crucial for a successful pregnancy and the health of both the fetus and the pregnant woman. However, how the human trophoblast lineage is regulated, including the categorization of the placental cell subtypes is poorly understood. Here we performed single-cell RNA sequencing (RNA-seq) on sorted placental cells from first- and second-trimester human placentas. New subtypes of cells of the known cytotrophoblast cells (CTBs), extravillous trophoblast cells (EVTs), Hofbauer cells, and mesenchymal stromal cells were identified and cell-type-specific gene signatures were defined. Functionally, this study revealed many previously unknown functions of the human placenta. Notably, 102 polypeptide hormone genes were found to be expressed by various subtypes of placental cells, which suggests a complex and significant role of these hormones in regulating fetal growth and adaptations of maternal physiology to pregnancy. These results document human placental trophoblast differentiation at single-cell resolution and thus advance our understanding of human placentation during the early stage of pregnancy.

The maternal‐foetal interface is an immune‐privileged site where the semi‐allogeneic embryo is protected from attacks by the maternal immune system. Uterine macrophages are key players in establishing and maintaining pregnancy, and the dysregulation of the M1‐M2 subpopulation balance causes abortion. We separated two distinct mouse uterine macrophage subpopulations during early pregnancy, CD45+F4/80+CD206− M1‐like (M1) and CD45+F4/80+CD206+ M2‐like (M2) cells. The M1 preponderance was significantly exaggerated at 6 hours after lipopolysaccharide (LPS) treatment, and adoptive transfer of M2 macrophages partially rescued LPS‐induced abortion. RNA sequencing analysis of mouse uterine M2 versus M1 revealed 1837 differentially expressed genes (DEGs), among which 629 was up‐regulated and 1208 was down‐regulated. Histone deacetylase 9 (Hdac9) was one of the DEGs and validated to be significantly up‐regulated in uterine M2 as compared with M1. Remarkably, this differential expression profile between M1 and M2 was also evident in primary splenic macrophages and in vitro polarized murine peritoneal, bone marrow–derived and RAW 264.7 macrophages. In Hdac9/HDAC9 knockout RAW 264.7 and human THP‐1–derived macrophages, the expression of M1 differentiation markers was unchanged or decreased whereas M2 markers were increased compared with the wild‐type cells, and these effects were unrelated to compromised proliferation. Furthermore, Hdac9/HDAC9 ablation significantly enhanced the phagocytosis of fluorescent microspheres in M2 Raw 264.7 cells yet decreased the capacity of THP‐1‐derived M1 macrophages. The above results demonstrate that Hdac9/HDAC9 deficiency exaggerates M2 macrophage polarization in mouse and human macrophages, which may provide clues for our understanding of the epigenetic regulation on macrophage M1/M2 polarization in maternal‐foetal tolerance.

Although 5-methylcytosine (m 5 C) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the single-nucleotide resolution landscape of messenger RNA m 5 C modifications in human urothelial carcinoma of the bladder (UCB). We identify numerous oncogene RNAs with hypermethylated m 5 C sites causally linked to their upregulation in UCBs and further demonstrate YBX1 as an m 5 C ‘reader’ recognizing m 5 C-modified mRNAs through the indole ring of W65 in its cold-shock domain. YBX1 maintains the stability of its target mRNA by recruiting ELAVL1. Moreover, NSUN2 and YBX1 are demonstrated to drive UCB pathogenesis by targeting the m 5 C methylation site in the HDGF 3′ untranslated region. Clinically, a high coexpression of NUSN2, YBX1 and HDGF predicts the poorest survival. Our findings reveal an unprecedented mechanism of RNA m 5 C-regulated oncogene activation, providing a potential therapeutic strategy for UCB. Chen et al. provide an m 5 C landscape in bladder cancer and show m 5 C enrichment at oncogene mRNAs that promotes tumour progression. They identify YBX1 as the m 5 C ‘reader’ that recruits ELAVL1 to stabilize mRNAs.

The fast development of single-particle cryogenic electron microscopy (cryo-EM) has made it more feasible to obtain the 3D structure of well-behaved macromolecules with a molecular weight higher than 300 kDa at ~3 Å resolution. However, it remains a challenge to obtain the high-resolution structures of molecules smaller than 200 kDa using single-particle cryo-EM. In this work, we apply the Cs-corrector-VPP-coupled cryo-EM to study the 52 kDa streptavidin (SA) protein supported on a thin layer of graphene and embedded in vitreous ice. We are able to solve both the apo-SA and biotin-bound SA structures at near-atomic resolution using single-particle cryo-EM. We demonstrate that the method has the potential to determine the structures of molecules as small as 39 kDa. It remains a challenge to obtain high-resolution structures of molecules smaller than 200 kDa using single particle cryo-EM. Here, the authors apply the Cs-corrector-VPP coupled cryo-EM and solve structures of the 52 kDa streptavidin (SA) protein at near-atomic resolution.

Global teleconnections associated with the Asian summer monsoon convective activities are investigated based on monthly data of 29 Northern Hemisphere summers defined as June–September (JJAS). Two distinct teleconnection patterns are identified that are associated respectively with variabilities of the Indian summer monsoon and the western North Pacific summer monsoon. The Indian summer monsoon convective activity is associated with a global pattern that has a far-reaching connection in both hemispheres, whereas the western North Pacific summer monsoon convective activity is connected to a Southern Hemisphere wave train that influences the high-latitude South Pacific and South America. A global primitive equation model is utilized to assess the cause of the global circulation anomalies. The model responses to anomalous heatings of both monsoon systems match the general features of the observed circulation anomalies well, and they are mainly controlled by linear processes. The response patterns are largely determined by the summertime large-scale background mean flow and the location of the heating anomaly relative to the upper easterly jet in the monsoon region.

Metal-free and controlled synthesis of sulfur-containing polymer is still a big challenge in polymer chemistry. Here, we report a metal-free, living copolymerization of carbonyl sulfide (COS) with epoxides via the cooperative catalysis of organic Lewis pairs including bases (e.g.: phosphazene, amidine, and guanidine) and thioureas as hydrogen-bond donors, afford well-defined poly(monothiocarbonate)s with 100% alternating degree, >99% tail-to-head content, controlled molecular weights (up to 98.4 kg/mol), and narrow molecular weight distributions (1.13–1.23). The effect of the types of Lewis pairs on the copolymerization of COS with several epoxides is investigated. The turnover frequencies (TOFs) of these Lewis pairs are as high as 112 h −1 at 25 °C. Kinetic and mechanistic results suggest that the supramolecular specific recognition of thiourea to epoxide and base to COS promote the copolymerization cooperatively. This strategy provides commercially available Lewis pairs for metal-free synthesis of sulfur-containing polymers with precise structure. Sulfur-containing polymers are useful commodities, but there is still a big challenge to produce such polymers in a controlled fashion. Here the authors show a metal-free living copolymerization between carbonyl sulfide and epoxides via cooperative catalysis.

In this study, a new index is defined to capture the prominent northward propagation of the intraseasonal oscillation (ISO) in boreal summer in the East Asian and western North Pacific (EAWNP) region. It is based on the first two modes of empirical orthogonal function (EOF) analysis of the combined fields of daily anomalies of zonally averaged outgoing longwave radiation (OLR) and 850-hPa zonal wind (U850) in the EAWNP region. These two EOFs are well separated from the rest of the modes, and their principal components (PCs) capture the intraseasonal variability. They are nearly in quadrature in both space and time and their combination reasonably well represents the northward propagation of the ISO. As no future information beyond the current date is required as in conventional time filtering, this ISO index can be used in real-time applications. This index is applied to the output of the 24-yr historical hindcast experiment using the Global Environmental Multiscale (GEM) model of Environment Canada to evaluate the forecast skill of the ISO of the EAWNP summer monsoon.

In this paper we report a thermodynamic database which was developed by using the CALPHAD approach. The TCHEA1 database includes 15 chemical elements (Al, Co, Cr, Cu, Fe, Hf, Mn, Mo, Nb, Ni, Ta, Ti, V, W and Zr). It is suitable for the study of Bcc and Fcc HEA systems. The database is constructed based on the thermodynamic assessment of all binary systems and many key ternary systems where almost all possible metastable and stable phases are considered. It is extensively demonstrated in the present work that TCHEA1 gives satisfactory prediction on the phase equilibria in various HEA systems (quaternary to ennead) and wide temperature ranges (liquidus to subsolidus). Thermodynamic stability calculations of simple solid solutions (Bcc and Fcc) and intermetallics (sigma, Laves, μ-phase etc.) are validated against the available experimental information in as-cast or as-annealed state. Such CALPHAD database focusing on the modelling of Gibbs energy rather than entropy makes reliable predictions of thermodynamic equilibrium and phase transformation, no matter whether the alloy/system has high entropy or not. Cases with miscibility gap in liquid and solid solutions and second-order phase transition at low temperatures are demonstrated. With the volume data included, TCHEA1 is capable to predict the density and thermal expansion coefficient of HEAs as well. This thermodynamic database is also applicable in process simulations when used together with compatible kinetic databases.