Carrier dynamics and infrared-active phonons in c-axis oriented RuSr2_2GdCu2_2O8_8 film

The conductivity spectra of c-axis oriented thin RuSr$_2$GdCu$_2$O$_8$ film on SrTiO$_3$ substrate, prepared by pulsed-laser deposition, are obtained from the analysis of the reflectivity spectra over broad frequency range and temperatures between 10 and 300 K. The free charge carriers are found to be strongly overdamped with their scattering rate (1.0 eV at room temperature) exceeding the plasma frequency (0.55 eV). Four phonon lines are identified in the experimental spectra and assigned to the specific oxygen related in-plane polarized vibrations based on the comparison with the results of a lattice dynamics shell model calculations.Comment: 3 pages, 4 figure

Potential for Supernova Neutrino Detection in MiniBooNE

The MiniBooNE detector at Fermilab is designed to search for $\nu_\mu \to \nu_e$ oscillation appearance at $E_\nu \sim 1 {\rm GeV}$ and to make a decisive test of the LSND signal. The main detector (inside a veto shield) is a spherical volume containing 0.680 ktons of mineral oil. This inner volume, viewed by 1280 phototubes, is primarily a \v{C}erenkov medium, as the scintillation yield is low. The entire detector is under a 3 m earth overburden. Though the detector is not optimized for low-energy (tens of MeV) events, and the cosmic-ray muon rate is high (10 kHz), we show that MiniBooNE can function as a useful supernova neutrino detector. Simple trigger-level cuts can greatly reduce the backgrounds due to cosmic-ray muons. For a canonical Galactic supernova at 10 kpc, about 190 supernova $\bar{\nu}_e + p \to e^+ + n$ events would be detected. By adding MiniBooNE to the international network of supernova detectors, the possibility of a supernova being missed would be reduced. Additionally, the paths of the supernova neutrinos through Earth will be different for MiniBooNE and other detectors, thus allowing tests of matter-affected mixing effects on the neutrino signal.Comment: Added references, version to appear in PR

Genomic RNA Elements Drive Phase Separation of the SARS-CoV-2 Nucleocapsid

We report that the SARS-CoV-2 nucleocapsid protein (N-protein) undergoes liquid-liquid phase separation (LLPS) with viral RNA. N-protein condenses with specific RNA genomic elements under physiological buffer conditions and condensation is enhanced at human body temperatures (33°C and 37°C) and reduced at room temperature (22°C). RNA sequence and structure in specific genomic regions regulate N-protein condensation while other genomic regions promote condensate dissolution, potentially preventing aggregation of the large genome. At low concentrations, N-protein preferentially crosslinks to specific regions characterized by single-stranded RNA flanked by structured elements and these features specify the location, number, and strength of N-protein binding sites (valency). Liquid-like N-protein condensates form in mammalian cells in a concentration-dependent manner and can be altered by small molecules. Condensation of N-protein is RNA sequence and structure specific, sensitive to human body temperature, and manipulatable with small molecules, and therefore presents a screenable process for identifying antiviral compounds effective against SARS-CoV-2

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer's disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer's disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer's disease and other tau-mediated neurodegenerative diseases

Inflammatory biomarkers in Alzheimer's disease plasma

Introduction: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a \u201cHoly Grail\u201d of AD research and intensively sought; however, there are no well-established plasma markers. Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed. Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APO\u3b54 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71). Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation