Infection programs sustained lymphoid stromal cell responses and shapes lymph node remodeling upon secondary challenge

Published: January 10, 2017Lymph nodes (LNs) are constructed of intricate networks of endothelial and mesenchymal stromal cells. How these lymphoid stromal cells (LSCs) regulate lymphoid tissue remodeling and contribute to immune responses remains poorly understood. We performed a comprehensive functional and transcriptional analysis of LSC responses to skin viral infection and found that LSC subsets responded robustly, with different kinetics for distinct pathogens. Recruitment of cells to inflamed LNs induced LSC expansion, while B cells sustained stromal responses in an antigen-independent manner. Infection induced rapid transcriptional responses in LSCs. This transcriptional program was transient, returning to homeostasis within 1 month of infection, yet expanded fibroblastic reticular cell networks persisted for more than 3 months after infection, and this altered LN composition reduced the magnitude of LSC responses to subsequent heterologous infection. Our results reveal the complexity of LSC responses during infection and suggest that amplified networks of LN stromal cells support successive immune responses.Julia L. Gregory, Anne Walter, Yannick O. Alexandre, Jyh Liang Hor, Ruijie Liu, Joel Z. Ma, Sapna Devi, Nobuko Tokuda, Yuji Owada, Laura K. Mackay, Gordon K. Smyth, William R. Heath, and Scott N. Muelle

Study of the plutino object (208996) 2003 AZ84 from stellar occultations: size, shape and topographic features

We present results derived from four stellar occultations by the plutino object (208996) 2003~AZ$_{84}$, detected at January 8, 2011 (single-chord event), February 3, 2012 (multi-chord), December 2, 2013 (single-chord) and November 15, 2014 (multi-chord). Our observations rule out an oblate spheroid solution for 2003~AZ$_{84}$'s shape. Instead, assuming hydrostatic equilibrium, we find that a Jacobi triaxial solution with semi axes $(470 \pm 20) \times (383 \pm 10) \times (245 \pm 8)$~km % axis ratios $b/a= 0.82 \pm 0.05$ and $c/a= 0.52 \pm 0.02$, can better account for all our occultation observations. Combining these dimensions with the rotation period of the body (6.75~h) and the amplitude of its rotation light curve, we derive a density $\rho=0.87 \pm 0.01$~g~cm$^{-3}$ a geometric albedo $p_V= 0.097 \pm 0.009$. A grazing chord observed during the 2014 occultation reveals a topographic feature along 2003~AZ$_{84}$'s limb, that can be interpreted as an abrupt chasm of width $\sim 23$~km and depth $> 8$~km or a smooth depression of width $\sim 80$~km and depth $\sim 13$~km (or an intermediate feature between those two extremes)

Serial femtosecond zero dose crystallography captures a water‐free distal heme site in a dye‐decolourising peroxidase to reveal a catalytic role for an arginine in FeIV=O formation

Obtaining structures of intact redox states of metal centres derived from zero dose X‐ray crystallography can advance our mechanistic understanding of metalloenzymes. In dye‐decolourising heme peroxidases (DyPs), controversy exists regarding the mechanistic role of the distal heme residues, aspartate and arginine, in the heterolysis of peroxide to form the catalytic intermediate compound I (Fe IV =O and a porphyrin cation radical). Using serial femtosecond X‐ray (SFX) crystallography, we have determined the pristine structures of the Fe III and Fe IV =O redox states of a B‐type DyP. These structures reveal a water‐free distal heme site, which together with the presence of an asparagine, infer the use of the distal arginine as a catalytic base. A combination of mutagenesis and kinetic studies corroborate such a role. Our SFX approach thus provides unique insight into how the distal heme site of DyPs can be tuned to select aspartate or arginine for the rate enhancement of peroxide heterolysis

First Results from KamLAND: Evidence for Reactor Anti-Neutrino Disappearance

KamLAND has been used to measure the flux of $\bar{\nu}_e$'s from distant nuclear reactors. In an exposure of 162 ton$\cdot$yr (145.1 days) the ratio of the number of observed inverse $\beta$-decay events to the expected number of events without disappearance is $0.611\pm 0.085 {\rm (stat)} \pm 0.041 {\rm (syst)}$ for $\bar{\nu}_e$ energies $>$ 3.4 MeV. The deficit of events is inconsistent with the expected rate for standard $\bar{\nu}_e$ propagation at the 99.95% confidence level. In the context of two-flavor neutrino oscillations with CPT invariance, these results exclude all oscillation solutions but the `Large Mixing Angle' solution to the solar neutrino problem using reactor $\bar{\nu}_e$ sources.Comment: 6 pages, 6 figure

Measurement of Neutrino Oscillation with KamLAND: Evidence of Spectral Distortion

We present results of a study of neutrino oscillation based on a 766 ton-year exposure of KamLAND to reactor anti-neutrinos. We observe 258 \nuebar\ candidate events with energies above 3.4 MeV compared to 365.2 events expected in the absence of neutrino oscillation. Accounting for 17.8 expected background events, the statistical significance for reactor \nuebar disappearance is 99.998%. The observed energy spectrum disagrees with the expected spectral shape in the absence of neutrino oscillation at 99.6% significance and prefers the distortion expected from \nuebar oscillation effects. A two-neutrino oscillation analysis of the KamLAND data gives \DeltaMSq = 7.9$^{+0.6}_{-0.5}\times10^{-5}$ eV$^2$. A global analysis of data from KamLAND and solar neutrino experiments yields \DeltaMSq = 7.9$^{+0.6}_{-0.5}\times10^{-5}$ eV$^2$ and \ThetaParam = 0.40$^{+0.10}_{-0.07}$, the most precise determination to date.Comment: 5 pages, 4 figures; submitted to Phys.Rev.Letter

Search for the Invisible Decay of Neutrons with KamLAND

The Kamioka Liquid scintillator Anti-Neutrino Detector (KamLAND) is used in a search for single neutron or two neutron intra-nuclear disappearance that would produce holes in the $\it{s}$-shell energy level of $^{12}$C nuclei. Such holes could be created as a result of nucleon decay into invisible modes ($inv$), e.g. $n \to 3\nu$ or $nn \to 2\nu$. The de-excitation of the corresponding daughter nucleus results in a sequence of space and time correlated events observable in the liquid scintillator detector. We report on new limits for one- and two-neutron disappearance: $\tau(n\to inv)> 5.8\times 10^{29}$ years and $\tau (nn \to inv)> 1.4 \times 10^{30}$ years at 90% CL. These results represent an improvement of factors of $\sim$3 and $>10^4$ over previous experiments.Comment: 5 pages, 3 figure

Midkine is a NF-κB-inducible gene that supports prostate cancer cell survival

BackgroundMidkine is a heparin-binding growth factor that is over-expressed in various human cancers and plays important roles in cell transformation, growth, survival, migration, and angiogenesis. However, little is known about the upstream factors and signaling mechanisms that regulate midkine gene expression.MethodsTwo prostate cancer cell lines LNCaP and PC3 were studied for their expression of midkine. Induction of midkine expression in LNCaP cells by serum, growth factors and cytokines was determined by Western blot analysis and/or real-time quantitative reverse-transcription - polymerase chain reaction (RT-PCR). The cell viability was determined by the trypan blue exclusion assay when the LNCaP cells were treated with tumor necrosis factor alpha (TNFalpha) and/or recombinant midkine. When the LNCaP cells were treated with recombinant midkine, activation of intracellular signalling pathways was determined by Western blot analysis. Prostate tissue microarray slides containing 129 cases (18 normal prostate tissues, 40 early stage cancers, and 71 late stage cancers) were assessed for midkine expression by immunohistochemical staining.ResultsWe identified that fetal bovine serum, some growth factors (epidermal growth factor, androgen, insulin-like growth factor-I, and hepatocyte growth factor) and cytokines (TNFalpha and interleukin-1beta) induced midkine expression in a human prostate cancer cell line LNCaP cells. TNFalpha also induced midkine expression in PC3 cells. TNFalpha was the strongest inducer of midkine expression via nuclear factor-kappa B pathway. Midkine partially inhibited TNFalpha-induced apoptosis in LNCaP cells. Knockdown of endogenous midkine expression by small interfering RNA enhanced TNFalpha-induced apoptosis in LNCaP cells. Midkine activated extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase pathways in LNCaP cells. Furthermore, midkine expression was significantly increased in late stage prostate cancer, which coincides with previously reported high serum levels of TNFalpha in advanced prostate cancer.ConclusionThese findings provide the first demonstration that midkine expression is induced by certain growth factors and cytokines, particularly TNFalpha, which offers new insight into understanding how midkine expression is increased in the late stage prostate cancer

Physical properties of Centaur (60558) 174P/Echeclus from stellar occultations

The Centaur (60558) Echeclus was discovered on March 03, 2000, orbiting between the orbits of Jupiter and Uranus. After exhibiting frequent outbursts, it also received a comet designation, 174P. If the ejected material can be a source of debris to form additional structures, studying the surroundings of an active body like Echeclus can provide clues about the formation scenarios of rings, jets, or dusty shells around small bodies. Stellar occultation is a handy technique for this kind of investigation, as it can, from Earth-based observations, detect small structures with low opacity around these objects. Stellar occultation by Echeclus was predicted and observed in 2019, 2020, and 2021. We obtain upper detection limits of rings with widths larger than 0.5 km and optical depth of $\tau$ = 0.02. These values are smaller than those of Chariklo's main ring; in other words, a Chariklo-like ring would have been detected. The occultation observed in 2020 provided two positive chords used to derive the triaxial dimensions of Echeclus based on a 3D model and pole orientation available in the literature. We obtained $a = 37.0\pm0.6$ km, $b = 28.4 \pm 0.5$ km, and $c= 24.9 \pm 0.4$ km, resulting in an area-equivalent radius of $30.0 \pm 0.5$ km. Using the projected limb at the occultation epoch and the available absolute magnitude ($\rm{H}_{\rm{v}} = 9.971 \pm 0.031$), we calculate an albedo of $p_{\rm{v}} = 0.050 \pm 0.003$. Constraints on the object's density and internal friction are also proposed.Comment: Corrected and typeset versio

Laser-induced transient magnons in Sr₃Ir₂O₇ throughout the Brillouin zone

Although ultrafast manipulation of magnetism holds great promise for new physical phenomena and applications, targeting specific states is held back by our limited understanding of how magnetic correlations evolve on ultrafast timescales. Using ultrafast resonant inelastic X-ray scattering we demonstrate that femtosecond laser pulses can excite transient magnons at large wavevectors in gapped antiferromagnets and that they persist for several picoseconds, which is opposite to what is observed in nearly gapless magnets. Our work suggests that materials with isotropic magnetic interactions are preferred to achieve rapid manipulation of magnetism