736 research outputs found

    Magnetoresistance of metallic perovskite oxide LaNiO3δ_{3-\delta}

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    We report a study of the magnetoresistance (MR) of the metallic perovskite oxide LaNiO3δ_{3-\delta} as a function of the oxygen stoichiometry δ\delta (δ\delta \leq 0.14), magnetic field (H 6T\leq 6T) and temperature (1.5K \leq T \leq 25K). We find a strong dependence of the nature of MR on the oxygen stoichiometry. The MR at low temperatures change from positive to negative as the sample becomes more oxygen deficient (i.e, δ\delta increases). Some of the samples which are more resistive, show a resistivity minima at TminT_{min} \approx 20K. We find that in these samples the MR is positive at T > TminT_{min} and negative for T < TminT_{min}. We conclude that in the absence of strong magnetic interaction, the negative MR in these oxides can arise from weak localisation effects.Comment: 10 pages in REVTeX format, 4 eps fig

    Macrophage regulation of the “second brain”: CD163 intestinal macrophages interact with inhibitory interneurons to regulate colonic motility - evidence from the Cx3cr1-Dtr rat model

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    Intestinal macrophages are well-studied for their conventional roles in the immune response against pathogens and protecting the gut from chronic inflammation. However, these macrophages may also have additional functional roles in gastrointestinal motility under typical conditions. This is likely to occur via both direct and indirect influences on gastrointestinal motility through interaction with myenteric neurons that contribute to the gut-brain axis, but this mechanism is yet to be properly characterised. The CX3CR1 chemokine receptor is expressed in the majority of intestinal macrophages, so we used a conditional knockout Cx3cr1-Dtr (diphtheria toxin receptor) rat model to transiently ablate these cells. We then utilized ex vivo video imaging to evaluate colonic motility. Our previous studies in brain suggested that Cx3cr1-expressing cells repopulate by 7 days after depletion in this model, so we performed our experiments at both the 48 hr (macrophage depletion) and 7-day (macrophage repopulation) time points. We also investigated whether inhibitory neuronal input driven by nitric oxide from the enteric nervous system is required for the regulation of colonic motility by intestinal macrophages. Our results demonstrated that CD163-positive resident intestinal macrophages are important in regulating colonic motility in the absence of this major inhibitory neuronal input. In addition, we show that intestinal macrophages are indispensable in maintaining a healthy intestinal structure. Our study provides a novel understanding of the interplay between the enteric nervous system and intestinal macrophages in colonic motility. We highlight intestinal macrophages as a potential therapeutic target for gastrointestinal motility disorders when inhibitory neuronal input is suppressed

    Conductivity landscape of highly oriented pyrolytic graphite surface containing ribbons and edges

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    We present an extensive study on electrical spectroscopy of graphene ribbons and edges of highly oriented pyrolytic graphite (HOPG) using atomic force microscope (AFM). We have addressed in the present study two main issues, (1) How does the electrical property of the graphite (graphene) sheet change when the graphite layer is displaced by shear forces? and (2) How does the electrical property of the graphite sheet change across a step edge? While addressing these two issues we observed, (1) variation of conductance among the graphite ribbons on the surface of HOPG. The top layer always exhibits more conductance than the lower layers, (2) two different monolayer ribbons on the same sheet of graphite shows different conductance, (3) certain ribbon/sheet edges show sharp rise in current, (4) certain ribbons/sheets on the same edge shows both presence and absense of the sharp rise in the current, (5) some lower layers at the interface near a step edge shows a strange dip in the current/conductance (depletion of charge). We discuss possible reasons for such rich conducting landscape on the surface of graphite.Comment: 13 pages, 9 figures. For better quality figures please contact autho

    A CEP215-HSET complex links centrosomes with spindle poles and drives centrosome clustering in cancer.

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    Numerical centrosome aberrations underlie certain developmental abnormalities and may promote cancer. A cell maintains normal centrosome numbers by coupling centrosome duplication with segregation, which is achieved through sustained association of each centrosome with a mitotic spindle pole. Although the microcephaly- and primordial dwarfism-linked centrosomal protein CEP215 has been implicated in this process, the molecular mechanism responsible remains unclear. Here, using proteomic profiling, we identify the minus end-directed microtubule motor protein HSET as a direct binding partner of CEP215. Targeted deletion of the HSET-binding domain of CEP215 in vertebrate cells causes centrosome detachment and results in HSET depletion at centrosomes, a phenotype also observed in CEP215-deficient patient-derived cells. Moreover, in cancer cells with centrosome amplification, the CEP215-HSET complex promotes the clustering of extra centrosomes into pseudo-bipolar spindles, thereby ensuring viable cell division. Therefore, stabilization of the centrosome-spindle pole interface by the CEP215-HSET complex could promote survival of cancer cells containing supernumerary centrosomes.S.C. is supported by UK Medical Research Council (MC_U105185859). This work was made possible by funding from Cancer Research UK (C14303/A17197). We acknowledge the support of the University of Cambridge and Hutchison Whampoa Ltd.This is the final version of the article. It first appeared from Nature Publishing Group via https://doi.org/10.1038/ncomms1100

    Reassessing candidate eccentric binary black holes: Results with a model including higher-order modes

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    The detection of eccentricity from a gravitational wave signal is expected to help distinguish between formation channels for a given binary. In this study, we reassess all previously-reported binary black holes with previous claims of possible eccentricity as well as a few binaries with more interesting source parameters, for the first time using a model (TEOBResumSGeneral) which accounts for the full eccentricity range possible and incorporates higher-order gravitational emission critical to model emission from highly eccentric orbits. We estimate the eccentricity of these five events. For the first time, we present marginal evidence of eccentricity for one of the events: GW190929. Contrary to previous work with different settings, we do not find evidence supporting eccentric orbits for the same systems. We find the incorporation of eccentricity in our analyses dramatically shifts the posterior in multiple parameters for several events, features could negatively impact other analyses

    TAML/H2O2 oxidative degradation of metaldehyde: Pursuing better water treatment for the most persistent pollutants.

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    The extremely persistent molluscicide, metaldehyde, widely used on farms and gardens, is often detected in drinking water sources of various countries at concentrations of regulatory concern. Metaldehyde contamination restricts treatment options. Conventional technologies for remediating dilute organics in drinking water, activated carbon and ozone, are insufficiently effective against metaldehyde. Some treatment plants have resorted to effective, but more costly UV/H2O2. Here we have examined if TAML/H2O2 can decompose metaldehyde under laboratory conditions to guide development of a better real world option. TAML/H2O2 slowly degrades metaldehyde to acetaldehyde and acetic acid. Nuclear magnetic resonance spectroscopy ((1)H NMR) was used to monitor the degradation-the technique requires a high metaldehyde concentration (60 ppm). Within the pH range of 6.5-9, the reaction rate is greatest at pH 7. Under optimum conditions, one aliquot of TAML 1a (400 nM) catalyzed 5% degradation over 10 hours with a turnover number of 40. Five sequential TAML aliquots (2 μM overall) effected a 31% removal over 60 hours. TAML/H2O2 degraded metaldehyde steadily over many hours, highlighting an important long-service property. The observation of metaldehyde decomposition under mild conditions provides a further indication that TAML catalysis holds promise for advancing water treatment. These results have turned our attention to more aggressive TAML activators in development, which we expect will advance the observed technical performance

    Gastrointestinal dysfunction in patients and mice expressing the autism-associated R451C mutation in neuroligin-3

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    Gastrointestinal (GI) problems constitute an important comorbidity in many patients with autism. Multiple mutations in the neuroligin family of synaptic adhesion molecules are implicated in autism, however whether they are expressed and impact GI function via changes in the enteric nervous system is unknown. We report the GI symptoms of two brothers with autism and an R451C mutation in Nlgn3 encoding the synaptic adhesion protein, neuroligin-3. We confirm the presence of an array of synaptic genes in the murine GI tract and investigate the impact of impaired synaptic protein expression in mice carrying the human neuroligin-3 R451C missense mutation (NL3R451C ). Assessing in vivo gut dysfunction, we report faster small intestinal transit in NL3R451C compared to wild-type mice. Using an ex vivo colonic motility assay, we show increased sensitivity to GABAA receptor modulation in NL3R451C mice, a well-established Central Nervous System (CNS) feature associated with this mutation. We further show increased numbers of small intestine myenteric neurons in NL3R451C mice. Although we observed altered sensitivity to GABAA receptor modulators in the colon, there was no change in colonic neuronal numbers including the number of GABA-immunoreactive myenteric neurons. We further identified altered fecal microbial communities in NL3R451C mice. These results suggest that the R451C mutation affects small intestinal and colonic function and alter neuronal numbers in the small intestine as well as impact fecal microbes. Our findings identify a novel GI phenotype associated with the R451C mutation and highlight NL3R451C mice as a useful preclinical model of GI dysfunction in autism. LAY SUMMARY: People with autism commonly experience gastrointestinal problems, however the cause is unknown. We report gut symptoms in patients with the autism-associated R451C mutation encoding the neuroligin-3 protein. We show that many of the genes implicated in autism are expressed in mouse gut. The neuroligin-3 R451C mutation alters the enteric nervous system, causes gastrointestinal dysfunction, and disrupts gut microbe populations in mice. Gut dysfunction in autism could be due to mutations that affect neuronal communication.This work was supported by an Idea Development Award from the United States Department of Defense’s Congressionally Directed Medical Research Programs (CDMRP) Autism Research Program (AR110134) to E.L.H.-Y. and J.C.B.; the Victorian Government through the Operational Infrastructure Scheme, National Health and Medical Research Council (NHMRC) project grants (APP566642 to J.C.B. and APP1047674 to E.L.H.-Y.) and the Royal Melbourne Hospital Neuroscience Foundation. E.L.H.-Y. also received an ARC Future Fellowship (FT160100126) and an RMIT Vice Chancellor’s Senior Research Fellowship which supported G.K.B. and S.H. T.S., P.U., and N.Y. were funded by grants RO1AI100914, P30-DK56338, and U01-AI24290 awards to Baylor College of Medicine funded from the National Institute of Allergy and Infectious Diseases and National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health (T.C.S.)

    First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

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    Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far
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