Klotho controls the brain-immune system interface in the choroid plexus.

Located within the brain's ventricles, the choroid plexus produces cerebrospinal fluid and forms an important barrier between the central nervous system and the blood. For unknown reasons, the choroid plexus produces high levels of the protein klotho. Here, we show that these levels naturally decline with aging. Depleting klotho selectively from the choroid plexus via targeted viral vector-induced knockout in Klotho flox/flox mice increased the expression of multiple proinflammatory factors and triggered macrophage infiltration of this structure in young mice, simulating changes in unmanipulated old mice. Wild-type mice infected with the same Cre recombinase-expressing virus did not show such alterations. Experimental depletion of klotho from the choroid plexus enhanced microglial activation in the hippocampus after peripheral injection of mice with lipopolysaccharide. In primary cultures, klotho suppressed thioredoxin-interacting protein-dependent activation of the NLRP3 inflammasome in macrophages by enhancing fibroblast growth factor 23 signaling. We conclude that klotho functions as a gatekeeper at the interface between the brain and immune system in the choroid plexus. Klotho depletion in aging or disease may weaken this barrier and promote immune-mediated neuropathogenesis

Matching as Nonparametric Preprocessing for Reducing Model Dependence in Parametric Causal Inference

Although published works rarely include causal estimates from more than a few model specifications, authors usually choose the presented estimates from numerous trial runs readers never see. Given the often large variation in estimates across choices of control variables, functional forms, and other modeling assumptions, how can researchers ensure that the few estimates presented are accurate or representative? How do readers know that publications are not merely demonstrations that it is \emph{possible} to find a specification that fits the author's favorite hypothesis? And how do we evaluate or even define statistical properties like unbiasedness or mean squared error when no unique model or estimator even exists? Matching methods, which offer the promise of causal inference with fewer assumptions, constitute one possible way forward, but crucial results in this fast-growing methodological literature are often grossly misinterpreted. We explain how to avoid these misinterpretations and propose a unified approach that makes it possible for researchers to preprocess data with matching (such as with the easy-to-use software we offer) and then to apply the best parametric techniques they would have used anyway. This procedure makes parametric models produce more accurate and considerably less model-dependent causal inferences.Governmen

The Supreme Court During Crisis: How War Affects only Non-War Cases

Does the U.S. Supreme Court curtail rights and liberties when the nation’s security is under threat? In hundreds of articles and books, and with renewed fervor since September 11, 2001, members of the legal community have warred over this question. Yet, not a single large-scale, quantitative study exists on the subject. Using the best data available on the causes and outcomes of every civil rights and liberties case decided by the Supreme Court over the past six decades and employing methods chosen and tuned especially for this problem, our analyses demonstrate that when crises threaten the nation’s security, the justices are substantially more likely to curtail rights and liberties than when peace prevails. Yet paradoxically, and in contradiction to virtually every theory of crisis jurisprudence, war appears to affect only cases that are unrelated to the war. For these cases, the effect of war and other international crises is so substantial, persistent, and consistent that it may surprise even those commentators who long have argued that the Court rallies around the flag in times of crisis. On the other hand, we find no evidence that cases most directly related to the war are affected. We attempt to explain this seemingly paradoxical evidence with one unifying conjecture: Instead of balancing rights and security in high stakes cases directly related to the war, the justices retreat to ensuring the institutional checks of the democratic branches. Since rights-oriented and process-oriented dimensions seem to operate in different domains and at different times, and often suggest different outcomes, the predictive factors that work for cases unrelated to the war fail for cases related to the war. If this conjecture is correct, federal judges should consider giving less weight to legal principles established during wartime for ordinary cases, and attorneys should see it as their responsibility to distinguish cases along these lines.Governmen

The Structure of Nuclear Star Clusters in Nearby Late-type Spiral Galaxies from Hubble Space Telescope Wide Field Camera 3 Imaging

We obtained Hubble Space Telescope/Wide Field Camera 3 imaging of a sample of ten of the nearest and brightest nuclear clusters residing in late-type spiral galaxies, in seven bands that span the near-ultraviolet to the near-infrared. Structural properties of the clusters were measured by fitting two-dimensional surface brightness profiles to the images using GALFIT. The clusters exhibit a wide range of structural properties. For six of the ten clusters in our sample, we find changes in the effective radius with wavelength, suggesting radially varying stellar populations. In four of the objects, the effective radius increases with wavelength, indicating the presence of a younger population which is more concentrated than the bulk of the stars in the cluster. However, we find a general decrease in effective radius with wavelength in two of the objects in our sample, which may indicate extended, circumnuclear star formation. We also find a general trend of increasing roundness of the clusters at longer wavelengths, as well as a correlation between the axis ratios of the NCs and their host galaxies. These observations indicate that blue disks aligned with the host galaxy plane are a common feature of nuclear clusters in late-type galaxies, but are difficult to detect in galaxies that are close to face-on. In color-color diagrams spanning the near-UV through the near-IR, most of the clusters lie far from single-burst evolutionary tracks, showing evidence for multi-age populations. Most of the clusters have integrated colors consistent with a mix of an old population (> 1 Gyr) and a young population (~100-300 Myr). The wide wavelength coverage of our data provides a sensitivity to populations with a mix of ages that would not be possible to achieve with imaging in optical bands only.Comment: Corrected a typo in author name and affiliation for MC and corrected a typo in the conclusio

Malaria parasite translocon structure and mechanism of effector export.

The putative Plasmodium translocon of exported proteins (PTEX) is essential for transport of malarial effector proteins across a parasite-encasing vacuolar membrane into host erythrocytes, but the mechanism of this process remains unknown. Here we show that PTEX is a bona fide translocon by determining structures of the PTEX core complex at near-atomic resolution using cryo-electron microscopy. We isolated the endogenous PTEX core complex containing EXP2, PTEX150 and HSP101 from Plasmodium falciparum in the 'engaged' and 'resetting' states of endogenous cargo translocation using epitope tags inserted using the CRISPR-Cas9 system. In the structures, EXP2 and PTEX150 interdigitate to form a static, funnel-shaped pseudo-seven-fold-symmetric protein-conducting channel spanning the vacuolar membrane. The spiral-shaped AAA+ HSP101 hexamer is tethered above this funnel, and undergoes pronounced compaction that allows three of six tyrosine-bearing pore loops lining the HSP101 channel to dissociate from the cargo, resetting the translocon for the next threading cycle. Our work reveals the mechanism of P. falciparum effector export, and will inform structure-based design of drugs targeting this unique translocon

Effect of biochars pyrolyzed in N2 and CO2, and feedstock on microbial community in metal(loid)s contaminated soils

Little is known about the effects of applying amendments on soil for immobilizing metal(loid)s on the soil microbial community. Alterations in the microbial community were examined after incubation of treated contaminated soils. One soil was contaminated with Pb and As, a second soil with Cd and Zn. Red pepper stalk (RPS) and biochars produced from RPS in either N2 atmosphere (RPSN) or CO2 atmosphere (RPSC) were applied at a rate of 2.5% to the two soils and incubated for 30 days. Bacterial communities of control and treated soils were characterized by sequencing 16S rRNA genes using the Illumina MiSeq sequencing. In both soils, bacterial richness increased in the amended soils, though somewhat differently between the treatments. Evenness values decreased significantly, and the final overall diversities were reduced. The neutralization of pH, reduced available concentrations of Pb or Cd, and supplementation of available carbon and surface area could be possible factors affecting the community changes. Biochar amendments caused the soil bacterial communities to become more similar than those in the not amended soils. The bacterial community structures at the phylum and genus levels showed that amendment addition might restore the normal bacterial community of soils, and cause soil bacterial communities in contaminated soils to normalize and stabilize