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The central administration of C75, a fatty acid synthase inhibitor, activates sympathetic outflow and thermogenesis in interscapular brown adipose tissue.The present work investigated the participation of interscapular brown adipose tissue (IBAT), which is an important site for thermogenesis, in the anti-obesity effects of C75, a synthetic inhibitor of fatty acid synthase (FAS). We report that a single intracerebroventricular (i.c.v.) injection of C75 induced hypophagia and weight loss in fasted male Wistar rats. Furthermore, C75 induced a rapid increase in core body temperature and an increase in heat dissipation. In parallel, C75 stimulated IBAT thermogenesis, which was evidenced by a marked increase in the IBAT temperature that preceded the rise in the core body temperature and an increase in the mRNA levels of uncoupling protein-1. As with C75, an i.c.v. injection of cerulenin, a natural FAS inhibitor, increased the core body and IBAT temperatures. The sympathetic IBAT denervation attenuated all of the thermoregulatory effects of FAS inhibitors as well as the C75 effect on weight loss and hypophagia. C75 induced the expression of Fos in the paraventricular nucleus, preoptic area, dorsomedial nucleus, ventromedial nucleus, and raphé pallidus, all of which support a central role of FAS in regulating IBAT thermogenesis. These data indicate a role for IBAT in the increase in body temperature and hypophagia that is induced by FAS inhibitors and suggest new mechanisms explaining the weight loss induced by these compounds.
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Rare Control of SIVmac239 Infection in a Vaccinated Rhesus Macaque.Effector memory T cell (T) responses display potent antiviral properties and have been linked to stringent control of simian immunodeficiency virus (SIV) replication. Since recurrent antigen stimulation drives the differentiation of CD8 T cells toward the T phenotype, in this study we incorporated a persistent herpesviral vector into a heterologous prime/boost/boost vaccine approach to maximize the induction of T responses. This new regimen resulted in CD8 T-biased responses in four rhesus macaques, three of which controlled viral replication to <1,000 viral RNA copies/ml of plasma for more than 6 months after infection with SIVmac239. Over the course of this study, we made a series of interesting observations in one of these successful controller animals. Indeed, in vivo elimination of CD8αβ T cells using a new CD8β-depleting antibody did not abrogate virologic control in this monkey. Only after its CD8α lymphocytes were depleted did SIV rebound, suggesting that CD8αα but not CD8αβ cells were controlling viral replication. By 2 weeks postinfection (PI), the only SIV sequences that could be detected in this animal harbored a small in-frame deletion in nef affecting six amino acids. Deep sequencing of the SIVmac239 challenge stock revealed no evidence of this polymorphism. However, sequencing of the rebound virus following CD8α depletion at week 38.4 PI again revealed only the six-amino acid deletion in nef. While any role for immunological pressure on the selection of this deleted variant remains uncertain, our data provide anecdotal evidence that control of SIV replication can be maintained without an intact CD8αβ T cell compartment.
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Quantitative Detection of Trace Malachite Green in Aquiculture Water Samples by Extractive Electrospray Ionization Mass Spectrometry.Exposure to malachite green (MG) may pose great health risks to humans; thus, it is of prime importance to develop fast and robust methods to quantitatively screen the presence of malachite green in water. Herein the application of extractive electrospray ionization mass spectrometry (EESI-MS) has been extended to the trace detection of MG within lake water and aquiculture water, due to the intensive use of MG as a biocide in fisheries. This method has the advantage of obviating offline liquid-liquid extraction or tedious matrix separation prior to the measurement of malachite green in native aqueous medium. The experimental results indicate that the extrapolated detection limit for MG was ~3.8 μg·L(-1) (S/N = 3) in lake water samples and ~0.5 μg·L(-1) in ultrapure water under optimized experimental conditions. The signal intensity of MG showed good linearity over the concentration range of 10-1000 μg·L(-1). Measurement of practical water samples fortified with MG at 0.01, 0.1 and 1.0 mg·L(-1) gave a good validation of the established calibration curve. The average recoveries and relative standard deviation (RSD) of malachite green in lake water and Carassius carassius fish farm effluent water were 115% (6.64% RSD), 85.4% (9.17% RSD) and 96.0% (7.44% RSD), respectively. Overall, the established EESI-MS/MS method has been demonstrated suitable for sensitive and rapid (<2 min per sample) quantitative detection of malachite green in various aqueous media, indicating its potential for online real-time monitoring of real life samples.
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Feasibility and usefulness of three-dimensional optical coherence tomography guidance for optimal side branch treatment in coronary bifurcation stenting.For the treatment of coronary bifurcation lesions, optimal guidewire (GW) recrossing after main vessel stenting is important for good stent apposition at the side branch (SB) orifice in kissing balloon inflation (KBI).
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Occurrence of multi-class surfactants in urban wastewater: contribution of a healthcare facility to the pollution transported into the sewerage system.Healthcare facility discharges, by their nature, are often considered as non-domestic effluent, which can provide significant pollution comparatively to other domestic sources. In this context, a total of 12 monthly sampling campaigns were collected from a healthcare facility as well as the output of a sewerage system of Site Pilote de Bellecombe (SIPIBEL) observatory. This study focuses more specifically on 12 surfactants and biocides: four anionics, four cationic, two non-ionic, one zwitterionic, and one dispersive agent, among the most commonly used commercial surfactants. Particular attention was also provided to routine wastewater quality parameters. Both effluents were heavily contaminated by most anionic surfactants; they displayed median concentrations up to 1 to 2 mg/L for linear alkylbenzene sulfonates and between 10 and 100 μg/L for other sodium sulfate congeners (lauryl and laureth). Overall, for the majority of surfactants, the healthcare facility contribution to the total flux reaching the wastewater treatment plant ranges between 5 and 9%.
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Botulinum toxin for the treatment of strabismus.The use of botulinum toxin as an investigative and treatment modality for strabismus is well reported in the medical literature. However, it is unclear how effective it is in comparison to other treatment options for strabismus.
Tissue Pre Treatment Kit Tissue Pre Treatment Kit Rabbit Anti-Clostridium b Goat Anti-C. botulinum To Mouse Anti-Clostridium bo Mouse Anti-Clostridium bo Rabbit Anti-C. botulinum Mouse Anti-C. botulinum T Mouse Anti-C. botulinum T Rabbit Anti-C. botulinum Rabbit Anti-C. botulinum Rabbit Anti-C. botulinum
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Assessment of oral and lung bioaccessibility of Cd and Pb from smelter-impacted dust.Soil and dust contamination by metals engenders significant environmental and health problems in northern France where a lead smelter was in activity for more than a century. This study aims to examine the long-term effects of the smelter, 10 years after its closedown, on the presence of metal in sidewalk dust for a better assessment of the local population's exposure to Cd and Pb. The investigation included: (i) the metal distribution in different dust particle sizes and (ii) the assessment of metal bioaccessibility via ingestion and inhalation of dust. Seventy-two sidewalk dust samples were collected using a dust-sampling vacuum. The samples were sieved to collect different particle sizes from 0.3 to 1000 μm. The unified bioaccessibility method (UBM) was employed to evaluate the oral bioaccessibility of metals in the different particle sizes. The pulmonary bioaccessible fraction of Cd and Pb via the finest particles was extracted with lung-simulating solution (artificial lysosomal fluid). Ten years after the smelter closedown, (i) a strong relationship was observed between the concentrations of metals in dust and the distance to the former smelter, whatever the particle size; (ii) both total and oral bioaccessible concentrations of metals were high in the finest fraction (0.3-5 μm) and decreased when the particle size increased; (iii) a higher oral bioaccessibility of Cd and Pb was measured in the gastric phase (on average 43% for both metals for all particle sizes) and compared to the gastrointestinal phase (on average 16% for both metals for all particle sizes); and (iv) metal bioaccessibility via inhalation of dust was relatively high (on average 74 and 69%, for Cd and Pb, respectively). The results of the present study suggest that this environmental compartment may be a sensitive and effective indicator of anthropogenic metal contamination and the human exposure in urban areas.
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Ameliorative Effects of Selenium on Cadmium-Induced Injury in the Chicken Ovary: Mechanisms of Oxidative Stress and Endoplasmic Reticulum Stress in Cadmium-Induced Apoptosis.Despite the well-established toxicity of cadmium (Cd) to animals and the ameliorative effects of selenium (Se), some specific mechanisms in the chicken ovary are not yet clarified. To explore the mechanism by which the toxicity effect of Cd is induced and explore the effect of supranutritional Se on Cd toxicity in female bird reproduction, forty-eight 50-day-old Isa Brown female chickens were divided randomly into four groups. Group I (control group) was fed the basic diet containing 0.2 mg/kg Se. Group II (Se-treated group) was fed the basic diet supplemented with sodium selenite (NaSeO), and the total Se content was 2 mg/kg. Group III (Se + Cd-treated group) was fed the basic diet supplemented with NaSeO; the total Se content was 2 mg/kg, and it was supplemented with 150 mg/kg cadmium chloride (CdCl). Group IV (Cd-treated group) was with the basic diet supplemented with 150 mg/kg CdCl. The Cd, estradiol (E2), and progestogen (P4) contents changed after subchronic Cd exposure in chicken ovarian tissue; subsequently, oxidative stress occurred and activated the endoplasmic reticulum (ER) pathway to induce apoptosis. Further, Se decreased the accumulation of Cd in ovarian tissue, increased the E2 and P4 contents, alleviated oxidative stress, and reduced apoptosis via the ER stress pathway. The present results demonstrated that Cd could induce apoptosis via the ER stress pathway in chicken ovarian tissue and that Se had a significant antagonistic effect. These results are potentially valuable for finding a strategy to prevent Cd poisoning.
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On-wafer probing-kit for RF characterization of silicon photonic integrated transceivers.A wafer-level and high-efficiency radio frequency (RF) testing of a photonic device is highly desired in the fabrication and characterization of large-scale photonic integration circuits. In this work, we propose on-wafer probing kit designs, and demonstrate a damage-free, self-calibrated RF characterization of an integrated silicon photonic transceiver with a heterodyne mixing approach. Reduced or even free of fiber coupling off chip operation can be achieved with the on-wafer probing-kit to extract the frequency responses of broadband modulators and photodetectors in the photonic integration transceiver, with no requirement of electro-optical or opto-electrical calibration. A proof-of-concept probing kit is designed and fabricated with an on-chip electroabsorption modulator (EAM) and photodetectors by heterogeneously integrated III-V material on silicon substrate. On-wafer RF measurements with the self-calibration method are experimentally demonstrated with an accuracy analysis compared with the conventional swept-frequency method. The on-wafer and full-electrical test nature of the probing kit significantly advances performance monitoring of photonic integration circuits during chip fabrication, and promisingly offers predictable outcome and yield analysis before packaging.
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Beyond Oncolytics: E1B55K-Deleted Adenovirus as a Vaccine Delivery Vector.Type 5 human adenoviruses (Ad5) deleted of genes encoding the early region 1B 55-kDa (E1B55K) protein including Onyx-015 (dl1520) and H101 are best known for their oncolytic potential. As a vaccine vector the E1B55K deletion may allow for the insertion of a transgene nearly 1,000 base pairs larger than now possible. This has the potential of extending the application for which the vectors are clinically known. However, the immune priming ability of E1B55K-deleted vectors is unknown, undermining our ability to gauge their usefulness in vaccine applications. For this reason, we created an E1B55K-deleted Ad5 vector expressing full-length single chain HIVBaLgp120 attached to a flexible linker and the first two domains of rhesus CD4 (rhFLSC) in exchange for the E3 region. In cell-based experiments the E1B55K-deleted vector promoted higher levels of innate immune signals including chemokines, cytokines, and the NKG2D ligands MIC A/B compared to an E1B55K wild-type vector expressing the same immunogen. Based on these results we evaluated the immune priming ability of the E1B55K-deleted vector in mice. The E1B55K-deleted vector promoted similar levels of Ad5-, HIVgp120, and rhFLSC-specific cellular and humoral immune responses as the E1B55K wild-type vector. In pre-clinical HIV-vaccine studies the wild-type vector has been employed as part of a very effective prime-boost strategy. This study demonstrates that E1B55K-deleted adenoviruses may serve as effective vaccine delivery vectors.
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