Assessment of Feeding Behavior in Laboratory Mice

The global obesity epidemic has heightened the need for an improved understanding of how body weight is controlled, and research using mouse models is critical to this effort. In this perspective, we provide a conceptual framework for investigation of feeding behavior in this species, with an emphasis on factors that influence study design, data interpretation, and relevance to feeding behavior in humans. Although we focus on the mouse, the principles presented can be applied to most other animal models. This document represents the current consensus view of investigators from the National Institutes of Health (NIH)-funded Mouse Metabolic Phenotyping Centers (MMPCs)

A study of long-term potentiation in transgenic mice over-expressing mutant forms of both amyloid precursor protein and presenilin-1

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Synaptic transmission and long-term potentiation (LTP) in the CA1 region of hippocampal slices have been studied during ageing of a double transgenic mouse strain relevant to early-onset familial Alzheimer's disease (AD). This strain, which over-expresses both the 695 amino acid isoform of human amyloid precursor protein (APP) with K670N and M671L mutations and presenilin 1 with the A246E mutation, has accelerated amyloidosis and plaque formation. There was a decrease in synaptic transmission in both wildtype and transgenic mice between 2 and 9 months of age. However, preparing slices from 14 month old animals in kynurenic acid (1 mM) counteracted this age-related deficit. Basal transmission and paired-pulse facilitation was similar between the two groups at all ages (2, 6, 9 and 14 months) tested. Similarly, at all ages LTP, induced either by theta burst stimulation or by multiple tetani, was normal. These data show that a prolonged, substantially elevated level of Aβ are not sufficient to cause deficits in the induction or expression of LTP in the CA1 hippocampal region.Published versio

Contactless photoconductivity-detected electron spin resonance of P donors in isotopically purified Si

Coherence times of electron spins bound to phosphorus donors have been measured, using a standard Hahn echo technique, to be up to 20 ms in isotopically pure silicon with [P]$= 10^{14}$ cm$^{-3}$ and at temperatures $\leq 4$K. Although such times are exceptionally long for electron spins in the solid state, they are nevertheless limited by donor electron spin-spin interactions. Suppressing such interactions requires even lower donor concentrations, which lie below the detection limit for typical electron spin resonance (ESR) spectrometers. Here we describe an alternative method for phosphorus donor ESR detection, exploiting the spin-to-charge conversion provided by the optical donor bound exciton transition. We characterise the method and its dependence on laser power and use it to measure a coherence time of $T_2 = 130$ms for one of the purest silicon samples grown to-date ([P]$= 5\times 10^{11}$cm$^{-3}$). We then benchmark this result using an alternative application of the donor bound exciton transition: optically polarising the donor spins before using conventional ESR detection at 1.7~K for a sample with [P]$= 4\times10^{12}$cm$^{-3}$, and measuring in this case a $T_2$ of 350 ms

Mitotic stress is an integral part of the oncogene-induced senescence program that promotes multinucleation and cell cycle arrest

Oncogene-induced senescence (OIS) is a tumor suppression mechanism that blocks cell proliferation in response to oncogenic signaling. OIS is frequently accompanied by multinucleation; however, the origin of this is unknown. Here, we show that multinucleate OIS cells originate mostly from failed mitosis. Prior to senescence, mutant H-RasV12 activation in primary human fibroblasts compromised mitosis, concordant with abnormal expression of mitotic genes functionally linked to the observed mitotic spindle and chromatin defects. Simultaneously, H-RasV12 activation enhanced survival of cells with damaged mitoses, culminating in extended mitotic arrest and aberrant exit from mitosis via mitotic slippage. ERK-dependent transcriptional upregulation of Mcl1 was, at least in part, responsible for enhanced survival and slippage of cells with mitotic defects. Importantly, mitotic slippage and oncogene signaling cooperatively induced senescence and key senescence effectors p21 and p16. In summary, activated Ras coordinately triggers mitotic disruption and enhanced cell survival to promote formation of multinucleate senescent cells

Redox-responsive branched-bottlebrush polymers for \u3ci\u3ein vivo\u3c/i\u3e MRI and fluorescence imaging

Stimuli-responsive multimodality imaging agents have broad potential in medical diagnostics. Herein, we report the development of a new class of branched-bottlebrush polymer dual-modality organic radical contrast agents—ORCAFluors—for combined magnetic resonance and near-infrared fluorescence imaging in vivo. These nitroxide radical-based nanostructures have longitudinal and transverse relaxation times that are on par with commonly used heavy-metal-based magnetic resonance imaging (MRI) contrast agents. Furthermore, these materials display a unique compensatory redox response: fluorescence is partially quenched by surrounding nitroxides in the native state; exposure to ascorbate or ascorbate/glutathione leads to nitroxide reduction and a concomitant 2- to 3.5-fold increase in fluorescence emission. This behaviour enables correlation of MRI contrast, fluorescence intensity and spin concentration with tissues known to possess high concentrations of ascorbate in mice. Our in vitro and in vivo results, along with our modular synthetic approach, make ORCAFluors a promising new platform for multimodality molecular imaging

Decoherence mechanisms of 209Bi donor electron spins in isotopically pure 28Si

Bismuth (209Bi) is the deepest Group V donor in silicon and possesses the most extreme characteristics such as a 9/2 nuclear spin and a 1.5 GHz hyperfine coupling. These lead to several potential advantages for a Si:Bi donor electron spin qubit compared to the more common phosphorus donor. Previous studies on Si:Bi have been performed using natural silicon where linewidths and electron spin coherence times are limited by the presence of 29Si impurities. Here we describe electron spin resonance (ESR) and electron nuclear double resonance (ENDOR) studies on 209Bi in isotopically pure 28Si. ESR and ENDOR linewidths, transition probabilities and coherence times are understood in terms of the spin Hamiltonian parameters showing a dependence on field and mI of the 209Bi nuclear spin. We explore various decoherence mechanisms applicable to the donor electron spin, measuring coherence times up to 700 ms at 1.7 K at X-band, comparable with 28Si:P. The coherence times we measure follow closely the calculated field-sensitivity of the transition frequency, providing a strong motivation to explore 'clock' transitions where coherence lifetimes could be further enhanced.Comment: 5 pages, 4 figure

Measuring Five Dimensions of Religiosity Across Adolescence

This paper theorizes and tests a latent variable model of adolescent religiosity in which five dimensions of religiosity are interrelated: religious beliefs, religious exclusivity, external religiosity, private practice, and religious salience. Research often theorizes overlapping and independent influences of single items or dimensions of religiosity on outcomes such as adolescent sexual behavior, but rarely operationalizes the dimensions in a measurement model accounting for their associations with each other and across time. We use longitudinal structural equation modeling (SEM) with latent variables to analyze data from two waves of the National Study of Youth and Religion. We test our hypothesized measurement model as compared to four alternate measurement models and find that our proposed model maintains superior fit. We then discuss the associations between the five dimensions of religiosity we measure and how these change over time. Our findings suggest how future research might better operationalize multiple dimensions of religiosity in studies of the influence of religion in adolescence