Maternal separation is associated with strain-specific responses to stress and epigenetic alterations to<i>Nr3c1</i>,<i>Avp</i>, and<i>Nr4a1</i>in mouse

Stressful events early in life have been widely linked to behavioral phenotypes and have been implicated in the development of psychiatric disorders. Using a maternal separation paradigm, we investigated phenotypic and epigenetic changes following early life stress in two inbred strains of mice, C57BL/6J and DBA/2J. We found an increase in the corticosterone response to stress in male, C57BL/6J mice that had undergone maternal separation compared to controls. In addition, early life stress induced a number of mild but significant behavioral changes, many of which were sex and strain dependent. Following maternal separation anxiety was decreased in males but increased in DBA/2J females, DBA/2J males displayed reduced exploration of a novel object, and baseline activity was altered in males of both strains. Finally, we examined DNA methylation levels in the hippocampus across promoter regions of Nr3c1, Avp, and Nr4a1, and found altered levels at several CpG sites in maternally separated male mice compared to controls. This study contributes to a growing body of recent literature suggesting that epigenetic changes may mediate the impact of early life stress on behavior. In particular, we establish that the phenotypic and epigenetic responses to an adverse environment differ as a function of genetic background. Using a maternal separation paradigm, we investigated phenotypic and epigenetic changes following early life stress in two inbred strains of mice, C57BL/6J and DBA/2J. We found an increase in the corticosterone response to stress in male, C57BL/6J mice that had undergone maternal separation, and early life stress induced a number of mild but significant behavioral changes, many of which were dependent on genetic background. © 2012 The Authors. Published by Wiley Periodicals, Inc

Versatile Sarcosine Biosensing Schemes Utilizing Layer-by-Layer Construction of Carbon Nanotube-Chitosan Composite Films

Layer-by-layer composite films of carbon nanotubes (CNTs) within a chitosan matrix with sarcosine oxidase enzyme and capped with Nafion have been developed and optimized as a versatile 1st generation amperometric sarcosine biosensing platform that operates successfully both as an isolated sarcosine sensor as well as a functional component within a creatinine sensor. Accurate measurement of sarcosine in urine and creatinine in blood may help with early diagnosis of diseases such as prostate cancer and renal failure, respectively. In this study, each material within the film is systematically optimized toward sarcosine sensitivity, including a critical evaluation of different CNTs effect on sensing performance. Films featuring carboxylic acid–modified single–walled carbon nanotubes and strategic enzyme doping were shown to be most effective sarcosine sensing platforms, exhibiting excellent sensitivity (~0.5 μA/mM), a linear response (≤ 0.75 mM), fast response time (8 s), low limits of detection (~6 μM), as well as both continuous use stability (7 days) and effective shelf life (\u3e 12 days). Operation of the sarcosine sensor was demonstrated in a urine matrix, detecting sarcosine at physiologically relevant concentrations and successfully quantifying sarcosine-spiked urine samples with high percent recovery and low relative error. The sarcosine sensing platform was also adapted to a 1st generation creatinine biosensing scheme in which the sarcosine enzymatic reaction is critical to a trienzymatic cascade event. The creatinine sensor yielded sensitivity of ~0.6 μA/mM, similar sensing performance parameters to the sarcosine sensor, and was effectively operated in blood serum at physiologically relevant creatinine concentrations. The demonstrated functionality of these sensors in their respective biological fluids at physiological concentrations of the analyte species suggests potential clinical application as diagnostic tools

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

Stau Search in IceCube

The tau lepton’s supersymmetric partner, the stau, appears in some models as the next-to-lightest supersymmetric particle. Their deacy process into the lightest superpartner is usually suppressed by supersymmetry breaking, which makes it a long-lived particle. In this scenario, its signature is a long, minimally ionizing track when traveling through the IceCube detector. Independent of their primary energy, the stau tracks appear like low-energy muons in the detector. A potential signal of staus would thus be an excess over muon tracks induced by atmospheric muon neutrinos. Our analysis focuses on the region around the horizon as here the ratio between stau signal and atmospheric background is largest. We will present the first sensitivity to constrain the stau mass using IceCube and demonstrate the potential of this analysis with future improvements

Non-standard neutrino interactions in IceCube

Non-standard neutrino interactions (NSI) may arise in various types of new physics. Their existence would change the potential that atmospheric neutrinos encounter when traversing Earth matter and hence alter their oscillation behavior. This imprint on coherent neutrino forward scattering can be probed using high-statistics neutrino experiments such as IceCube and its low-energy extension, DeepCore. Both provide extensive data samples that include all neutrino flavors, with oscillation baselines between tens of kilometers and the diameter of the Earth. DeepCore event energies reach from a few GeV up to the order of 100 GeV - which marks the lower threshold for higher energy IceCube atmospheric samples, ranging up to 10 TeV. In DeepCore data, the large sample size and energy range allow us to consider not only flavor-violating and flavor-nonuniversal NSI in the μ−τ sector, but also those involving electron flavor. The effective parameterization used in our analyses is independent of the underlying model and the new physics mass scale. In this way, competitive limits on several NSI parameters have been set in the past. The 8 years of data available now result in significantly improved sensitivities. This improvement stems not only from the increase in statistics but also from substantial improvement in the treatment of systematic uncertainties, background rejection and event reconstruction

IceCube Search for Earth-traversing ultra-high energy Neutrinos

The search for ultra-high energy neutrinos is more than half a century old. While the hunt for these neutrinos has led to major leaps in neutrino physics, including the detection of astrophysical neutrinos, neutrinos at the EeV energy scale remain undetected. Proposed strategies for the future have mostly been focused on direct detection of the first neutrino interaction, or the decay shower of the resulting charged particle. Here we present an analysis that uses, for the first time, an indirect detection strategy for EeV neutrinos. We focus on tau neutrinos that have traversed Earth, and show that they reach the IceCube detector, unabsorbed, at energies greater than 100 TeV for most trajectories. This opens up the search for ultra-high energy neutrinos to the entire sky. We use ten years of IceCube data to perform an analysis that looks for secondary neutrinos in the northern sky, and highlight the promise such a strategy can have in the next generation of experiments when combined with direct detection techniques