745 research outputs found

    Implementation of a Simplified Regional Citrate Anticoagulation Protocol for Post-Dilution Continuous Hemofiltration Using a Bicarbonate Buffered, Calcium Containing Replacement Solution

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    This service development program and open access publication of this manuscript have been supported by an unrestricted education grant from Nikkiso Europe GmbH, Hannover, Germany

    Evidence for a nuclear compartment of transcription and splicing located at chromosome domain boundaries

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    The nuclear topography of splicing snRNPs, mRNA transcripts and chromosome domains in various mammalian cell types are described. The visualization of splicing snRNPs, defined by the Sm antigen, and coiled bodies, revealed distinctly different distribution patterns in these cell types. Heat shock experiments confirmed that the distribution patterns also depend on physiological parameters. Using a combination of fluorescencein situ hybridization and immunodetection protocols, individual chromosome domains were visualized simultaneously with the Sm antigen or the transcript of an integrated human papilloma virus genome. Three-dimensional analysis of fluorescence-stained target regions was performed by confocal laser scanning microscopy. RNA transcripts and components of the splicing machinery were found to be generally excluded from the interior of the territories occupied by the individual chromosomes. Based on these findings we present a model for the functional compartmentalization of the cell nucleus. According to this model the space between chromosome domains, including the surface areas of these domains, defines a three-dimensional network-like compartment, termed the interchromosome domain (ICD) compartment, in which transcription and splicing of mRNA occurs

    JWST's PEARLS: TN J1338-1942 -- I. Extreme jet triggered star-formation in a z=4.11 luminous radio galaxy

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    We present the first JWST observations of the z = 4.11 luminous radio galaxy TN J1338–1942, obtained as part of the ‘Prime Extragalactic Areas for Reionization and Lensing Science’ (‘PEARLS’) project. Our NIRCam observations, designed to probe the key rest-frame optical continuum and emission line features at this redshift, enable resolved spectral energy distribution modelling that incorporates both a range of stellar population assumptions and radiative shock models. With an estimated stellar mass of log10(M/M) ∼ 10.9, TN J1338–1942 is confirmed to be one of the most massive galaxies known at this epoch. Our observations also reveal extremely high equivalent-width nebular emission coincident with the luminous AGN jets that is best fit by radiative shocks surrounded by extensive recent star formation. We estimate the total star-formation rate (SFR) could be as high as ∼ 1600 M yr−1 , with the SFR that we attribute to the jet induced burst conservatively 500 M yr−1. The mass-weighted age of the star-formation, tmass < 4 Myr, is consistent with the likely age of the jets responsible for the triggered activity and significantly younger than that measured in the core of the host galaxy. The extreme scale of the potential jet-triggered star-formation activity indicates the potential importance of positive AGN feedback in the earliest stages of massive galaxy formation, with our observations also illustrating the extraordinary prospects for detailed studies of high-redshift galaxies with JWST.KJD acknowledges funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement number 892117 (HIZRAD) and support from the STFC through an Ernest Rutherford Fellowship (grant number ST/W003120/1). RAW, SHC, and RAJ acknowledge support from NASA JWST Interdisciplinary Scientist grants NAG5-12460, NNX14AN10G, and 80NSSC18K0200 from GSFC. Work by CJC acknowledges support from the European Research Council (ERC) Advanced Investigator Grant EPOCHS (788113). BLF thanks the Berkeley Center for Theoretical Physics for their hospitality during the writing of this paper. MAM acknowledges the support of a National Research Council of Canada Plaskett Fellowship, and the Australian Research Council center of Excellence for All Sky Astrophysics in 3 Dimensions (ASTRO 3D), through project number CE17010001. CNAW acknowledges funding from the JWST/NIRCam contract NASS-0215 to the University of Arizona. TAH is supported by an appointment to the NASA Postdoctoral Program (NPP) at NASA Goddard Space Flight Center, administered by Oak Ridge Associated Universities under contract with NASA.Peer reviewe

    Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior

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    Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.Fil: Hutchison, M. A.. National Institutes of Health; Estados UnidosFil: Gu, X.. National Institutes of Health; Estados UnidosFil: Adrover, Martín Federico. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lee, M. R.. National Institutes of Health; Estados UnidosFil: Hnasko, T. S.. University of California at San Diego; Estados UnidosFil: Alvarez, V. A.. National Institutes of Health; Estados UnidosFil: Lu, W.. National Institutes of Health; Estados Unido

    An Atomic-resolution nanomechanical mass sensor

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    Mechanical resonators are widely used as inertial balances to detect small quantities of adsorbed mass through shifts in oscillation frequency[1]. Advances in lithography and materials synthesis have enabled the fabrication of nanoscale mechanical resonators[2, 3, 4, 5, 6], which have been operated as precision force[7], position[8, 9] and mass sensors[10, 11, 12, 13, 14, 15]. Here we demonstrate a room-temperature, carbon-nanotube-based nanomechanical resonator with atomic mass resolution. This device is essentially a mass spectrometer with a mass sensitivity of 1.3 times 10^-25 kg Hz^-1/2 or, equivalently, 0.40 gold atoms Hz^-1/2. Using this extreme mass sensitivity, we observe atomic mass shot noise, which is analogous to the electronic shot noise[16, 17] measured in many semiconductor experiments. Unlike traditional mass spectrometers, nanomechanical mass spectrometers do not require the potentially destructive ionization of the test sample, are more sensitive to large molecules, and could eventually be incorporated on a chip

    The Distribution of Toxoplasma gondii Cysts in the Brain of a Mouse with Latent Toxoplasmosis: Implications for the Behavioral Manipulation Hypothesis

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    reportedly manipulates rodent behavior to enhance the likelihood of transmission to its definitive cat host. The proximate mechanisms underlying this adaptive manipulation remain largely unclear, though a growing body of evidence suggests that the parasite-entrained dysregulation of dopamine metabolism plays a central role. Paradoxically, the distribution of the parasite in the brain has received only scant attention. at six months of age and examined 18 weeks later. The cysts were distributed throughout the brain and selective tropism of the parasite toward a particular functional system was not observed. Importantly, the cysts were not preferentially associated with the dopaminergic system and absent from the hypothalamic defensive system. The striking interindividual differences in the total parasite load and cyst distribution indicate a probabilistic nature of brain infestation. Still, some brain regions were consistently more infected than others. These included the olfactory bulb, the entorhinal, somatosensory, motor and orbital, frontal association and visual cortices, and, importantly, the hippocampus and the amygdala. By contrast, a consistently low incidence of tissue cysts was recorded in the cerebellum, the pontine nuclei, the caudate putamen and virtually all compact masses of myelinated axons. Numerous perivascular and leptomeningeal infiltrations of inflammatory cells were observed, but they were not associated with intracellular cysts. distribution stems from uneven brain colonization during acute infection and explains numerous behavioral abnormalities observed in the chronically infected rodents. Thus, the parasite can effectively change behavioral phenotype of infected hosts despite the absence of well targeted tropism
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