A phospholipase D2 inhibitor, CAY10594, ameliorates acetaminophen-induced acute liver injury by regulating the phosphorylated-GSK-3 beta/JNK axis

We examined the role of phospholipase D2 (PLD2) on acetaminophen (APAP)-induced acute liver injury using a PLD2 inhibitor (CAY10594). 500 mg/kg of APAP challenge caused acute liver damage. CAY10594 administration markedly blocked the acute liver injury in a dose-dependent manner, showing almost complete inhibition with 8 mg/kg of CAY10594. During the pathological progress of acute liver injury, GSH levels are decreased, and this is significantly recovered upon the administration of CAY10594 at 6 hours post APAP challenge. GSK-3 beta (Serine 9)/JNK phosphorylation is mainly involved in APAPinduced liver injury. CAY10594 administration strongly blocked GSK-3 beta (Serine 9)/JNK phosphorylation in the APAP-induced acute liver injury model. Consistently, sustained JNK activation in the cytosol and mitochondria from hepatocytes were also decreased in CAY10594-treated mice. Many types of immune cells are also implicated in APAP-induced liver injury. However, neutrophil and monocyte populations were not different between vehicle- and CAY10594-administered mice which are challenged with APAP. Therapeutic administration of CAY10594 also significantly attenuated liver damage caused by the APAP challenge, eliciting an enhanced survival rate. Taken together, these results indicate that PLD2 is involved in the intrinsic response pathway of hepatocytes driving the pathogenesis of APAP-induced acute liver injury, and PLD2 may therefore represent an important therapeutic target for patients with drug-induced liver injury.11Ysciescopu

Synthesis, structure and magnetic properties ofβ-MnO2nanorods

We present synthesis, structure and magnetic properties of structurally well-ordered single-crystalline β-MnO2nanorods of 50–100 nm diameter and several µm length. Thorough structural characterization shows that the basic β-MnO2material is covered by a thin surface layer (∼2.5 nm) of α-Mn2O3phase with a reduced Mn valence that adds its own magnetic signal to the total magnetization of the β-MnO2nanorods. The relatively complicated temperature-dependent magnetism of the nanorods can be explained in terms of a superposition of bulk magnetic properties of spatially segregated β-MnO2and α-Mn2O3constituent phases and the soft ferromagnetism of the thin interface layer between these two phases

Factor XIIIA-expressing inflammatory monocytes promote lung squamous cancer through fibrin cross-linking

Lung cancer is the leading cause of cancer-related deaths worldwide, and lung squamous carcinomas (LUSC) represent about 30% of cases. Molecular aberrations in lung adenocarcinomas have allowed for effective targeted treatments, but corresponding therapeutic advances in LUSC have not materialized. However, immune checkpoint inhibitors in sub-populations of LUSC patients have led to exciting responses. Using computational analyses of The Cancer Genome Atlas, we identified a subset of LUSC tumors characterized by dense infiltration of inflammatory monocytes (IMs) and poor survival. With novel, immunocompetent metastasis models, we demonstrated that tumor cell derived CCL2-mediated recruitment of IMs is necessary and sufficient for LUSC metastasis. Pharmacologic inhibition of IM recruitment had substantial anti-metastatic effects. Notably, we show that IMs highly express Factor XIIIA, which promotes fibrin cross-linking to create a scaffold for LUSC cell invasion and metastases. Consistently, human LUSC samples containing extensive cross-linked fibrin in the microenvironment correlated with poor survival

Shrinking a large dataset to identify variables associated with increased risk of Plasmodium falciparum infection in Western Kenya

Large datasets are often not amenable to analysis using traditional single-step approaches. Here, our general objective was to apply imputation techniques, principal component analysis (PCA), elastic net and generalized linear models to a large dataset in a systematic approach to extract the most meaningful predictors for a health outcome. We extracted predictors for Plasmodium falciparum infection, from a large covariate dataset while facing limited numbers of observations, using data from the People, Animals, and their Zoonoses (PAZ) project to demonstrate these techniques: data collected from 415 homesteads in western Kenya, contained over 1500 variables that describe the health, environment, and social factors of the humans, livestock, and the homesteads in which they reside. The wide, sparse dataset was simplified to 42 predictors of P. falciparum malaria infection and wealth rankings were produced for all homesteads. The 42 predictors make biological sense and are supported by previous studies. This systematic data-mining approach we used would make many large datasets more manageable and informative for decision-making processes and health policy prioritization

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Saethre-Chotzen syndrome : cranofacial anomalies caused by genetic changes in the TWIST gene

In this thesis, one of the most frequently occurring and most variable craniosynostosis syndromes was investigated; Saethre-Chotzen syndrome. Craniosynostosis is the premature obliteration of cranial sutures in the developing embryo. It can also occur in the first few months of life. Saethre-Chotzen syndrome is, besides craniosynostosis, characterized by specific facial and limb abnormalities, of which the most frequently reported are ptosis, prominent crus helicis, cutaneous syndactyly of digit 2 and 3 on both hands and feet, and broad halluces. Saethre-Chotzen syndrome has been linked to the TWIST gene on chromosome 7p21.1. Mutations in and variably sized deletions of this gene can be found in patients with clinical features of Saethre-Chotzen syndrome. The latter, TWIST deletions, often also include part of the surrounding chromosome 7p and are reported to be associated with mental retardation. In Saethre-Chotzen patients, in whom neither a mutation nor a deletion of TWIST had been found, the FGFR3 P250R mutation was in some cases detected. This mutation has specifically been linked to Muenke syndrome that is characterized by unior bicoronal synostosis and slight facial dysmorphology. However, a Saethre-Chotzen like phenotype can also result from this mutation. Because of the possible overlap of Saethre-Chotzen with Muenke syndrome, these syndromes were studied in order to provide clinical criteria that discriminate between the two (chapter 4). Many phenotypic features occur in both syndromes. In addition, although unicoronal synostosis occurs slightly more frequently in Muenke syndrome, unicoronal and bicoronal synostosis are seen in both syndromes. The discrimination between Saethre-Chotzen and Muenke is often not made easily and the associated genes, TWIST and FGFR3, respectively, are simultaneously tested for pathogenic m

W boson polarization measurement in the ttbar dilepton channel using the CDF II Detector

We present a measurement of $W$ boson polarization in top-quark decays in $t\bar{t}$ events with decays to dilepton final states using $5.1 {\rm fb^{-1}}$ of integrated luminosity in $p\bar{p}$ collisions collected by the CDF II detector at the Tevatron. A simultaneous measurement of the fractions of longitudinal ($f_0$) and right-handed ($f_+$) $W$ bosons yields the results $f_0 = 0.71 ^{+0.18}_{-0.17} {\rm (stat)} \pm 0.06 {\rm (syst)}$ and $f_+ = -0.07 \pm 0.09 {\rm (stat)} \pm 0.03 {\rm (syst)}$. Combining this measurement with our previous result based on single lepton final states, we obtain $f_0 = 0.84 \pm 0.09 {\rm (stat)} \pm 0.05 {\rm (syst)}$ and $f_{+} = -0.16 \pm 0.05 {\rm (stat)} \pm 0.04 {\rm (syst)}$. The results are consistent with standard model expectation.Comment: Published in Phys. Lett.

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society

Erratum: "A Gravitational-wave Measurement of the Hubble Constant Following the Second Observing Run of Advanced LIGO and Virgo" (2021, ApJ, 909, 218)

[no abstract available