161 research outputs found
Evidence of a metabolic memory to early-life dietary restriction in male C57BL/6 mice
<p>Background: Dietary restriction (DR) extends lifespan and induces beneficial metabolic effects in many animals. What is far less clear is whether animals retain a metabolic memory to previous DR exposure, that is, can early-life DR preserve beneficial metabolic effects later in life even after the resumption of ad libitum (AL) feeding. We examined a range of metabolic parameters (body mass, body composition (lean and fat mass), glucose tolerance, fed blood glucose, fasting plasma insulin and insulin-like growth factor 1 (IGF-1), insulin sensitivity) in male C57BL/6 mice dietary switched from DR to AL (DR-AL) at 11 months of age (mid life). The converse switch (AL-DR) was also undertaken at this time. We then compared metabolic parameters of the switched mice to one another and to age-matched mice maintained exclusively on an AL or DR diet from early life (3 months of age) at 1 month, 6 months or 10 months post switch.</p>
<p>Results: Male mice dietary switched from AL-DR in mid life adopted the metabolic phenotype of mice exposed to DR from early life, so by the 10-month timepoint the AL-DR mice overlapped significantly with the DR mice in terms of their metabolic phenotype. Those animals switched from DR-AL in mid life showed clear evidence of a glycemic memory, with significantly improved glucose tolerance relative to mice maintained exclusively on AL feeding from early life. This difference in glucose tolerance was still apparent 10 months after the dietary switch, despite body mass, fasting insulin levels and insulin sensitivity all being similar to AL mice at this time.</p>
<p>Conclusions: Male C57BL/6 mice retain a long-term glycemic memory of early-life DR, in that glucose tolerance is enhanced in mice switched from DR-AL in mid life, relative to AL mice, even 10 months following the dietary switch. These data therefore indicate that the phenotypic benefits of DR are not completely dissipated following a return to AL feeding. The challenge now is to understand the molecular mechanisms underlying these effects, the time course of these effects and whether similar interventions can confer comparable benefits in humans.</p>
Effect of casopitant, a novel NK-1 antagonist, on the pharmacokinetics of dolasetron and granisetron
Summary of the NuSTEC Workshop on Shallow- and Deep-Inelastic Scattering
The NuSTEC workshop (https://indico.cern.ch/event/727283) held at L'Aquila in October 2018 was devoted to neutrino-nucleus scattering in the kinematic region where hadronic systems with invariant masses above the resonance are produced: the so-called shallow- and deep-inelastic scattering regime. Not only is the physics in this kinematic region quite intriguing, it is also important for current and future oscillation experiments with accelerator and atmospheric neutrinos. For the benefit of the community, links to the presentations are accompanied by annotations from the speakers
Morphological and Functional Changes in the Retina after Chronic Oxygen-Induced Retinopathy
The mouse model of oxygen-induced retinopathy (OIR) has been widely used for studies of retinopathy of prematurity (ROP). This disorder, characterized by abnormal vascularization of the retina, tends to occur in low birth weight neonates after exposure to high supplemental oxygen. Currently, the incidence of ROP is increasing because of increased survival of these infants due to medical progress. However, little is known about changes in the chronic phase after ROP. Therefore, in this study, we examined morphological and functional changes in the retina using a chronic OIR model. Both the a- and b-waves in the OIR model recovered in a time-dependent manner at 4 weeks (w), 6 w, and 8 w, but the oscillatory potential (OP) amplitudes remained depressed following a return to normoxic conditions. Furthermore, decrease in the thicknesses of the inner plexiform layer (IPL) and inner nuclear layer (INL) at postnatal day (P) 17, 4 w, and 8 w and hyperpermeability of blood vessels were observed in conjunction with the decrease in the expression of claudin-5 and occludin at 8 w. The chronic OIR model revealed the following: (1) a decrease in OP amplitudes, (2) morphological abnormalities in the retinal cells (limited to the IPL and INL) and blood vessels, and (3) an increase in retinal vascular permeability via the impairment of the tight junction proteins. These findings suggest that the experimental animal model used in this study is suitable for elucidating the pathogenesis of ROP and may lead to the development of potential therapeutic agents for ROP treatment
Measurement of the Production Cross Section and Search for Anomalous and Couplings in Collisions at TeV
This Letter describes the current most precise measurement of the boson
pair production cross section and most sensitive test of anomalous
and couplings in collisions at a center-of-mass energy of 1.96
TeV. The candidates are reconstructed from decays containing two charged
leptons and two neutrinos, where the charged leptons are either electrons or
muons. Using data collected by the CDF II detector from 3.6 fb of
integrated luminosity, a total of 654 candidate events are observed with an
expected background contribution of events. The measured total
cross section is pb, which is in good agreement
with the standard model prediction. The same data sample is used to place
constraints on anomalous and couplings.Comment: submitted to Phys. Rev. Let
Developmental axon pruning mediated by BDNF-p75NTR–dependent axon degeneration
The mechanisms that regulate the pruning of mammalian axons are just now being elucidated. Here, we describe a mechanism by which, during developmental sympathetic axon competition, winning axons secrete brain-derived neurotrophic factor (BDNF) in an activity-dependent fashion, which binds to the p75 neurotrophin receptor (p75NTR) on losing axons to cause their degeneration and, ultimately, axon pruning. Specifically, we found that pruning of rat and mouse sympathetic axons that project to the eye requires both activity-dependent BDNF and p75NTR. p75NTR and BDNF are also essential for activity-dependent axon pruning in culture, where they mediate pruning by directly causing axon degeneration. p75NTR, which is enriched in losing axons, causes axonal degeneration by suppressing TrkA-mediated signaling that is essential for axonal maintenance. These data provide a mechanism that explains how active axons can eliminate less-active, competing axons during developmental pruning by directly promoting p75NTR-mediated axonal degeneration
Attosecond imaging of molecular electronic wavepackets
International audienceA strong laser field may tunnel ionize a molecule from several orbitals simultaneously, forming an attosecond electron–hole wavepacket. Both temporal and spatial information on this wavepacket can be obtained through the coherent soft X-ray emission resulting from the laser-driven recollision of the liberated electron with the core. By characterizing the emission from aligned N 2 molecules, we demonstrate the attosecond contributions of the two highest occupied molecular orbitals. We determine conditions where they are disentangled in the real and imaginary parts of the emission dipole moment. This allows us to carry out a tomographic reconstruction of both orbitals with angstrom spatial resolution. Their coherent superposition provides experimental images of the attosecond wavepacket created in the ionization process. Our results open the prospect of imaging ultrafast intramolecular dynamics combining attosecond and angstrom resolutions
Age and Diet Affect Gene Expression Profiles in Canine Liver Tissue
BACKGROUND: The liver plays a central role in nutrient and xenobiotic metabolism, but its functionality declines with age. Senior dogs suffer from many of the chronic hepatic diseases as elderly humans, with age-related alterations in liver function influenced by diet. However, a large-scale molecular analysis of the liver tissue as affected by age and diet has not been reported in dogs. METHODOLOGY/PRINCIPAL FINDINGS: Liver tissue samples were collected from six senior (12-year old) and six young adult (1-year old) female beagles fed an animal protein-based diet (APB) or a plant protein-based diet (PPB) for 12 months. Total RNA in the liver tissue was extracted and hybridized to Affymetrix GeneChip® Canine Genome Arrays. Using a 2.0-fold cutoff and false discovery rate <0.10, our results indicated that expression of 234 genes was altered by age, while 137 genes were differentially expressed by diet. Based on functional classification, genes affected by age and/or diet were involved in cellular development, nutrient metabolism, and signal transduction. In general, gene expression suggested that senior dogs had an increased risk of the progression of liver disease and dysfunction, as observed in aged humans and rodents. In particular for aged liver, genes related to inflammation, oxidative stress, and glycolysis were up-regulated, whereas genes related to regeneration, xenobiotic metabolism, and cholesterol trafficking were down-regulated. Diet-associated changes in gene expression were more common in young adult dogs (33 genes) as compared to senior dogs (3 genes). CONCLUSION: Our results provide molecular insight pertaining to the aged canine liver and its predisposition to disease and abnormalities. Therefore, our data may aid in future research pertaining to age-associated alterations in hepatic function or identification of potential targets for nutritional management as a means to decrease incidence of age-dependent liver dysfunction
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