Overestimate of Committed Warming

Palaeoclimate variations are an essential component in constraining future projections of climate change as a function of increasing anthropogenic greenhouse gases. The Earth System Sensitivity (ESS) describes the multi-millennial response of Earth (in terms of global mean temperature) to a doubling of CO2 concentrations. A recent study used a correlation of inferred temperatures and radiative forcing from greenhouse gases over the past 800,000 years to estimate the ESS from present day CO2 is about 9 degrees C, and to imply a long-term commitment of 3-7 degrees C even if greenhouse gas levels remain at present-day concentrations. However, we demonstrate that the methodology of ref. 2 does not reliably estimate the ESS in the presence of orbital forcing of ice age cycles and therefore conclude that the inferred present-day committed warming is considerably overestimated

Cancer-Associated Fibroblasts Neutralize the Anti-tumor Effect of CSF1 Receptor Blockade by Inducing PMN-MDSC Infiltration of Tumors.

Tumor-associated macrophages (TAM) contribute to all aspects of tumor progression. Use of CSF1R inhibitors to target TAM is therapeutically appealing, but has had very limited anti-tumor effects. Here, we have identified the mechanism that limited the effect of CSF1R targeted therapy. We demonstrated that carcinoma-associated fibroblasts (CAF) are major sources of chemokines that recruit granulocytes to tumors. CSF1 produced by tumor cells caused HDAC2-mediated downregulation of granulocyte-specific chemokine expression in CAF, which limited migration of these cells to tumors. Treatment with CSF1R inhibitors disrupted this crosstalk and triggered a profound increase in granulocyte recruitment to tumors. Combining CSF1R inhibitor with a CXCR2 antagonist blocked granulocyte infiltration of tumors and showed strong anti-tumor effects

Octahedral rotation-induced ferroelectricity in cation ordered perovskites

Increasing demands for electric field-tunable electric, magnetic, and orbital (EMO) materials has renewed interests in ferroelectricity and its coupling to EMO properties in complex perovskite oxides. The historic design strategy to achieve a spontaneous polarization involves the incorporation of second-order Jahn-Teller (SOJT) active cations. The challenge, however, is that this mechanism is limited to specific chemistries and the polar distortions that arise are largely decoupled from EMO properties, limiting their use as field-tunable multifunctional technology materials. Here we report the crystal-chemistry criteria which circumvents those restrictions and enables the rational design of new materials displaying octahedral rotation-induced ferroelectricity - an innovative route to realize electric polarization without the need for SOJT cations - from non-polar building blocks. The strategy exploits the centric octahedral rotation patterns, which strongly couple to EMO properties, and cation ordering commonly observed in non-polar $AB$O$_3$ perovskites. By uniting switchable electric polarizations to the connectivity of the transition-metal oxygen octahedra, electric-field control over materials properties is possible.Comment: Supplementary information available upon reques

The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8α+ dendritic cells

Human BDCA3+ dendritic cells (DCs) were suggested to be homologous to mouse CD8α+ DCs. We demonstrate that human BDCA3+ DCs are more efficient than their BDCA1+ counterparts or plasmacytoid DCs (pDCs) in cross-presenting antigen and activating CD8+ T cells, which is similar to mouse CD8α+ DCs as compared with CD11b+ DCs or pDCs, although with more moderate differences between human DC subsets. Yet, no specific marker was known to be shared between homologous DC subsets across species. We found that XC chemokine receptor 1 (XCR1) is specifically expressed and active in mouse CD8α+, human BDCA3+, and sheep CD26+ DCs and is conserved across species. The mRNA encoding the XCR1 ligand chemokine (C motif) ligand 1 (XCL1) is selectively expressed in natural killer (NK) and CD8+ T lymphocytes at steady-state and is enhanced upon activation. Moreover, the Xcl1 mRNA is selectively expressed at high levels in central memory compared with naive CD8+ T lymphocytes. Finally, XCR1−/− mice have decreased early CD8+ T cell responses to Listeria monocytogenes infection, which is associated with higher bacterial loads early in infection. Therefore, XCR1 constitutes the first conserved specific marker for cell subsets homologous to mouse CD8α+ DCs in higher vertebrates and promotes their ability to activate early CD8+ T cell defenses against an intracellular pathogenic bacteria