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  • 1
    Article
    Article
    In: Current Opinion in Endocrinology, Diabetes and Obesity, 2010, Vol.17(5), pp.453-459
    Description: PURPOSE OF REVIEW: The environmental obesogen hypothesis postulates chemical pollutants that are able to promote obesity by altering homeostatic metabolic set-points, disrupting appetite controls, perturbing lipid homeostasis to promote adipocyte hypertrophy, or stimulating adipogenic pathways that enhance adipocyte hyperplasia during development or in adults. This review focuses on recent experimental advances for candidate obesogens that target nuclear hormone receptors when a direct link between exposure, modulation of transcriptional networks and adipogenic phenotypes can be rationalized. RECENT FINDINGS: Various endocrine disrupting chemicals can disrupt hormonal signaling relevant to adipose tissue biology. In this review, progress on one identified obesogen, the organotin tributyltin, will be outlined to highlight principles and novel insights into its high-affinity nuclear hormone receptor-mediated mechanism, its effects on adipocyte biology, its potential to promote long-term obesogenic changes and its epidemiological relevance. When appropriate, important results for other suspected obesogenic ligands, including bisphenol A, phthalates, polybrominated diphenyl ethers and perfluoro-compounds, will highlight corroborating principles. SUMMARY: These examples serve to provide perspective on the potential harm that man-made obesogenic pollutants pose to human health, focus attention on areas in which knowledge remains inadequate and prompt a re-evaluation of the causative risk factors driving the current changes in obesity rates.
    Keywords: Adipocytes–Drug Effects ; Adipose Tissue–Metabolism ; Animals–Drug Effects ; Appetite Regulation–Metabolism ; Benzhydryl Compounds–Drug Effects ; Endocrine Disruptors–Metabolism ; Environmental Exposure–Toxicity ; Environmental Pollutants–Adverse Effects ; Female–Metabolism ; Fluorocarbons–Toxicity ; Halogenated Diphenyl Ethers–Metabolism ; Homeostasis–Toxicity ; Humans–Metabolism ; Male–Toxicity ; Mice–Drug Effects ; Obesity–Chemically Induced ; Ppar Gamma–Epidemiology ; Phenols–Metabolism ; Phenotype–Agonists ; Phthalic Acids–Metabolism ; Receptors, Cytoplasmic and Nuclear–Toxicity ; Retinoid X Receptors–Metabolism ; Transcription, Genetic–Toxicity ; Trialkyltin Compounds–Metabolism ; Trialkyltin Compounds–Agonists ; Trialkyltin Compounds–Drug Effects ; Trialkyltin Compounds–Metabolism ; Trialkyltin Compounds–Toxicity ; Benzhydryl Compounds ; Endocrine Disruptors ; Environmental Pollutants ; Fluorocarbons ; Halogenated Diphenyl Ethers ; Ppar Gamma ; Phenols ; Phthalic Acids ; Receptors, Cytoplasmic and Nuclear ; Retinoid X Receptors ; Trialkyltin Compounds ; Tributyltin ; Phthalic Acid ; Bisphenol A;
    ISSN: 1752-296X
    E-ISSN: 17522978
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  • 2
    Language: English
    In: PLoS ONE, 01 January 2015, Vol.10(7), p.e0131839
    Description: Degenerative joint disease and associated pain are common in cats, particularly in older cats. There is a need for treatment options, however evaluation of putative therapies is limited by a lack of suitable, validated outcome measures that...
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 3
    In: Cerebral Cortex, 2011, Vol. 21(11), pp.2482-2497
    Description: During natural vision, primates perform frequent saccadic eye movements, allowing only a narrow time window for processing the visual information at each location. Individual neurons may contribute only with a few spikes to the visual processing during each fixation, suggesting precise spike timing as a relevant mechanism for information processing. We recently found in V1 of monkeys freely viewing natural images, that fixation-related spike synchronization occurs at the early phase of the rate response after fixation-onset, suggesting a specific role of the first response spikes in V1. Here, we show that there are strong local field potential (LFP) modulations locked to the onset of saccades, which continue into the successive fixation periods. Visually induced spikes, in particular the first spikes after the onset of a fixation, are locked to a specific epoch of the LFP modulation. We suggest that the modulation of neural excitability, which is reflected by the saccade-related LFP changes, serves as a corollary signal enabling precise timing of spikes in V1 and thereby providing a mechanism for spike synchronization.
    Keywords: Free Viewing ; Local Field Potential ; Phase Locking ; Primary Visual Cortex ; Spike Synchrony
    ISSN: 1047-3211
    E-ISSN: 1460-2199
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  • 4
    In: EMBO Journal, 18 August 2014, Vol.33(16), pp.1740-1750
    Description: Development of the early embryo is thought to be mainly driven by maternal gene products and post‐transcriptional gene regulation. Here, we used metabolic labeling to show that can be transferred by sperm into the oocyte upon fertilization. To identify genes with paternal expression in the embryo, we performed crosses of males and females from divergent strains. RNA sequencing of s and small s in the 1‐cell hybrid embryo revealed that about one hundred sixty paternal s are reproducibly expressed in the embryo and that about half of all assayed endogenous sis and pis are also of paternal origin. Together, our results suggest an unexplored paternal contribution to early development. This paper establishes significant paternal contributions in zygotes, a result with major bearings on their potential functional relevance. Metabolic labeling of males shows that male RNA is transferred into the oocyte upon fertilization. We performed a cross of hybrid strains and sequenced RNA from the 1‐cell‐fertilized embryo. Computational analyses of these data allow to quantify maternal and paternal RNA in the fertilized embryo. We discover numerous mRNAs and different classes of non‐coding RNAs of paternal origin in the fertilized embryo. This paper establishes significant paternal contributions in zygotes, a result with major bearings on their potential functional relevance.
    Keywords: Embryogenesis ; Epigenetic Inheritance ; Paternal ; Transgenerational Inheritance
    ISSN: 0261-4189
    E-ISSN: 1460-2075
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  • 5
    Language: English
    In: PLoS ONE, 2012, Vol.7(2), p.e31508
    Description: Macrophage inflammatory protein-1α (CCL3) plays a well-known role in infectious and viral diseases; however, its contribution to atherosclerotic lesion formation and lipid metabolism has not been determined. Low density lipoprotein receptor deficient (LDLR −/− ) mice were transplanted with bone marrow from CCL3 −/− or C57BL/6 wild type donors. After 6 and 12 weeks on western diet (WD), recipients of CCL3 −/− marrow demonstrated lower plasma cholesterol and triglyceride concentrations compared to recipients of C57BL/6 marrow. Atherosclerotic lesion area was significantly lower in female CCL3 −/− recipients after 6 weeks and in male CCL3 −/− recipients after 12 weeks of WD feeding ( P 〈0.05). Surprisingly, male CCL3 −/− recipients had a 50% decrease in adipose tissue mass after WD-feeding, and plasma insulin, and leptin levels were also significantly lower. These results were specific to CCL3, as LDLR −/− recipients of monocyte chemoattractant protein −/− (CCL2) marrow were not protected from the metabolic consequences of high fat feeding. Despite these improvements in LDLR −/− recipients of CCL3 −/− marrow in the bone marrow transplantation (BMT) model, double knockout mice, globally deficient in both proteins, did not have decreased body weight, plasma lipids, or atherosclerosis compared with LDLR −/− controls. Finally, there were no differences in myeloid progenitors or leukocyte populations, indicating that changes in body weight and plasma lipids in CCL3 −/− recipients was not due to differences in hematopoiesis. Taken together, these data implicate a role for CCL3 in lipid metabolism in hyperlipidemic mice following hematopoietic reconstitution.
    Keywords: Research Article ; Biology ; Medicine ; Immunology ; Diabetes And Endocrinology
    E-ISSN: 1932-6203
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  • 6
    Language: English
    In: Journal of the American Veterinary Medical Association, 01 December 2012, Vol.241(11), pp.1445-7
    Keywords: Behavior, Animal -- Drug Effects ; Cat Diseases -- Drug Therapy ; Cats -- Physiology ; Urination -- Drug Effects
    ISSN: 00031488
    E-ISSN: 1943-569X
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  • 7
    Language: English
    In: The Journal of neuroscience : the official journal of the Society for Neuroscience, 10 August 2016, Vol.36(32), pp.8329-40
    Description: The computational role of spike time synchronization at millisecond precision among neurons in the cerebral cortex is hotly debated. Studies performed on data of limited size provided experimental evidence that low-order correlations occur in relation to behavior. Advances in electrophysiological technology to record from hundreds of neurons simultaneously provide the opportunity to observe coordinated spiking activity of larger populations of cells. We recently published a method that combines data mining and statistical evaluation to search for significant patterns of synchronous spikes in massively parallel spike trains (Torre et al., 2013). The method solves the computational and multiple testing problems raised by the high dimensionality of the data. In the current study, we used our method on simultaneous recordings from two macaque monkeys engaged in an instructed-delay reach-to-grasp task to determine the emergence of spike synchronization in relation to behavior. We found a multitude of synchronous spike patterns aligned in both monkeys along a preferential mediolateral orientation in brain space. The occurrence of the patterns is highly specific to behavior, indicating that different behaviors are associated with the synchronization of different groups of neurons ("cell assemblies"). However, pooled patterns that overlap in neuronal composition exhibit no specificity, suggesting that exclusive cell assemblies become active during different behaviors, but can recruit partly identical neurons. These findings are consistent across multiple recording sessions analyzed across the two monkeys. Neurons in the brain communicate via electrical impulses called spikes. How spikes are coordinated to process information is still largely unknown. Synchronous spikes are effective in triggering a spike emission in receiving neurons and have been shown to occur in relation to behavior in a number of studies on simultaneous recordings of few neurons. We recently published a method to extend this type of investigation to larger data. Here, we apply it to simultaneous recordings of hundreds of neurons from the motor cortex of macaque monkeys performing a motor task. Our analysis reveals groups of neurons selectively synchronizing their activity in relation to behavior, which sheds new light on the role of synchrony in information processing in the cerebral cortex.
    Keywords: Cell Assemblies ; Massively Parallel Spike Trains ; Motor Cortex ; Spike Synchrony ; Temporal Coding ; Action Potentials -- Physiology ; Hand Strength -- Physiology ; Motor Cortex -- Physiology ; Neurons -- Physiology ; Range of Motion, Articular -- Physiology
    ISSN: 02706474
    E-ISSN: 1529-2401
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  • 8
    Language: English
    In: Brain Research, 24 January 2012, Vol.1434, pp.34-46
    Description: Humans and other primates move their eyes several times per second to foveate at different locations of a visual scene. What features of a scene guide eye movements in natural vision? We recorded eye movements of three monkeys during free exploration of natural scenes and propose a simple model to explain their dynamics. We use the spatial clustering of fixation positions to define the monkeys' subjective regions-of-interest (ROI) in natural scenes. For most images the subjective ROIs match significantly the computed saliency of the natural scene, except when the image contains human or primate faces. We also investigated the temporal sequence of eye movements by computing the probability that a fixation will be made inside or outside of the ROI, given the current fixation position. We fitted a Markov chain model to the sequence of fixation positions, and find that fixations made inside a ROI are more likely to be followed by another fixation in the same ROI. This is true, independent of the image saliency in the area of the ROI. Our results show that certain regions in a natural scene are explored locally before directing the focus to another local region. This strategy could allow for quick integration of the visual features that constitute an object, and efficient segmentation of objects from other objects and the background during free viewing of natural scenes.
    Keywords: Eye Movement ; Scan Path ; Fixation Map ; Natural Vision ; Monkey ; Anatomy & Physiology
    ISSN: 0006-8993
    E-ISSN: 1872-6240
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  • 9
    Language: English
    In: PLoS ONE, 01 January 2017, Vol.12(1), p.e0169576
    Description: Accelerometry is used as an objective measure of physical activity in humans and veterinary species. In cats, one important use of accelerometry is in the study of therapeutics designed to treat degenerative joint disease (DJD) associated pain,...
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 10
    In: Journal of Veterinary Internal Medicine, July 2016, Vol.30(4), pp.1138-1148
    Description: Byline: M.E. Gruen, A.E. Thomson, E.H. Griffith, H. Paradise, D.P. Gearing, B.D.X. Lascelles Keywords: Client-specific outcome measures; Feline musculoskeletal pain index; Osteoarthritis Background Neutralizing antibodies against nerve growth factor (NGF) are analgesic in rodent models, naturally occurring degenerative joint disease (DJD) pain in dogs, and chronic pain in humans. Objectives To evaluate the efficacy of a fully felinized anti-NGF antibody (NV-02) for the treatment of DJD pain and mobility impairment in cats. Animals Thirty-four client-owned cats with DJD-associated pain and mobility impairment. Methods In a placebo-controlled, pilot, masked clinical study, cats were randomized to a single treatment with NV-02 (0.4 mg/kg SC [n = 11] or 0.8 mg/kg SC [n = 12]) or placebo (saline, SC [n = 11]). Activity was measured objectively. Additionally, owners completed clinical metrology instruments (client-specific outcome measures [CSOM] and feline musculoskeletal pain index [FMPI]) on days 0 (screening), 14 (baseline), 35, 56, and 77. A repeated-measures model was used to evaluate the objective activity data. Results NV-02 significantly increased objectively measured activity overall (P = .017) and at 2 (P = .035), 3 (P = .007), 4 (P = .006), 5 (P = .007), and 6 (P = .017) weeks after treatment. CSOM scores (P = .035) and pain (P = .024) showed a significant effect of treatment 3 weeks after administration. In the treatment group, 83% of the owners correctly identified the treatment administered compared with 45% of owners in the placebo group (P = .013). No treatment-related adverse effects were identified. Conclusions These pilot data demonstrate a 6-week duration positive analgesic effect of this fully felinized anti-NGF antibody in cats suffering from DJD-associated pain. Article Note: Work was conducted at North Carolina State University, Comparative Pain Research Program, College of Veterinary Medicine.
    Keywords: Client‐Specific Outcome Measures ; Feline Musculoskeletal Pain Index ; Osteoarthritis
    ISSN: 0891-6640
    E-ISSN: 1939-1676
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