218 research outputs found
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Perinatal Lead (Pb) Exposure Results in Sex-Specific Effects on Food Intake, Fat, Weight, and Insulin Response across the Murine Life-Course
Developmental lead (Pb) exposure has been associated with lower body weight in human infants and late onset obesity in mice. We determined the association of perinatal Pb exposure in mice with changes in obesity-related phenotypes into adulthood. Mice underwent exposure via maternal drinking water supplemented with 0 (control), 2.1 (low), 16 (medium), or 32 (high) ppm Pb-acetate two weeks prior to mating through lactation. Offspring were phenotyped at ages 3, 6, and 9 months for energy expenditure, spontaneous activity, food intake, body weight, body composition, and at age 10 months for glucose tolerance. Data analyses were stratified by sex and adjusted for litter effects. Exposed females and males exhibited increased energy expenditure as compared to controls (p<0.0001 for both). In females, horizontal activity differed significantly from controls (p = 0.02) over the life-course. Overall, food intake increased in exposed females and males (p<0.0008 and p<0.0001, respectively) with significant linear trends at 9 months in females (p = 0.01) and 6 months in males (p<0.01). Body weight was significantly increased in males at the medium and high exposures (p = 0.001 and p = 0.006). Total body fat differed among exposed females and males (p<0.0001 and p<0.0001, respectively). Insulin response was significantly increased in medium exposure males (p<0.05). Perinatal Pb exposure at blood lead levels between 4.1 ”g/dL and 32 ”g/dL is associated with increased food intake, body weight, total body fat, energy expenditure, activity, and insulin response in mice. Physiological effects of developmental Pb exposure persist and vary according to sex and age
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Zebrafish behavioural profiling identifies GABA and serotonin receptor ligands related to sedation and paradoxical excitation.
Anesthetics are generally associated with sedation, but some anesthetics can also increase brain and motor activity-a phenomenon known as paradoxical excitation. Previous studies have identified GABAA receptors as the primary targets of most anesthetic drugs, but how these compounds produce paradoxical excitation is poorly understood. To identify and understand such compounds, we applied a behavior-based drug profiling approach. Here, we show that a subset of central nervous system depressants cause paradoxical excitation in zebrafish. Using this behavior as a readout, we screened thousands of compounds and identified dozens of hits that caused paradoxical excitation. Many hit compounds modulated human GABAA receptors, while others appeared to modulate different neuronal targets, including the human serotonin-6 receptor. Ligands at these receptors generally decreased neuronal activity, but paradoxically increased activity in the caudal hindbrain. Together, these studies identify ligands, targets, and neurons affecting sedation and paradoxical excitation in vivo in zebrafish
Prebiotic-Induced Anti-tumor Immunity Attenuates Tumor Growth
Growing evidence supports the importance of gut microbiota in the control of tumor growth and response to therapy. Here, we select prebiotics that can enrich bacterial taxa that promote anti-tu- mor immunity. Addition of the prebiotics inulin or mucin to the diet of C57BL/6 mice induces anti-tu- mor immune responses and inhibition of BRAF mutant melanoma growth in a subcutaneously implanted syngeneic mouse model. Mucin fails to inhibit tumor growth in germ-free mice, indicating that the gut microbiota is required for the activation of the anti-tumor immune response. Inulin and mucin drive distinct changes in the microbiota, as inulin, but not mucin, limits tumor growth in synge- neic mouse models of colon cancer and NRAS mutant melanoma and enhances the efficacy of a MEK inhibitor against melanoma while delaying the emergence of drug resistance. We highlight the importance of gut microbiota in anti-tumor immunity and the potential therapeutic role for prebiotics in this process
Disk-Jet Connection in the Radio Galaxy 3C 120
We present the results of extensive multi-frequency monitoring of the radio
galaxy 3C 120 between 2002 and 2007 at X-ray, optical, and radio wave bands, as
well as imaging with the Very Long Baseline Array (VLBA). Over the 5 yr of
observation, significant dips in the X-ray light curve are followed by
ejections of bright superluminal knots in the VLBA images. Consistent with
this, the X-ray flux and 37 GHz flux are anti-correlated with X-ray leading the
radio variations. This implies that, in this radio galaxy, the radiative state
of accretion disk plus corona system, where the X-rays are produced, has a
direct effect on the events in the jet, where the radio emission originates.
The X-ray power spectral density of 3C 120 shows a break, with steeper slope at
shorter timescale and the break timescale is commensurate with the mass of the
central black hole based on observations of Seyfert galaxies and black hole
X-ray binaries. These findings provide support for the paradigm that black hole
X-ray binaries and active galactic nuclei are fundamentally similar systems,
with characteristic time and size scales linearly proportional to the mass of
the central black hole. The X-ray and optical variations are strongly
correlated in 3C 120, which implies that the optical emission in this object
arises from the same general region as the X-rays, i.e., in the accretion
disk-corona system. We numerically model multi-wavelength light curves of 3C
120 from such a system with the optical-UV emission produced in the disk and
the X-rays generated by scattering of thermal photons by hot electrons in the
corona. From the comparison of the temporal properties of the model light
curves to that of the observed variability, we constrain the physical size of
the corona and the distances of the emitting regions from the central BH.Comment: Accepted for publication in the Astrophysical Journal. 28 pages, 21
figures, 2 table
Design and implementation of a noise temperature measurement system for the Hydrogen Intensity and Real-time Analysis eXperiment (HIRAX)
This paper describes the design, implementation, and verification of a
test-bed for determining the noise temperature of radio antennas operating
between 400-800MHz. The requirements for this test-bed were driven by the HIRAX
experiment, which uses antennas with embedded amplification, making system
noise characterization difficult in the laboratory. The test-bed consists of
two large cylindrical cavities, each containing radio-frequency (RF) absorber
held at different temperatures (300K and 77K), allowing a measurement of system
noise temperature through the well-known 'Y-factor' method. The apparatus has
been constructed at Yale, and over the course of the past year has undergone
detailed verification measurements. To date, three preliminary noise
temperature measurement sets have been conducted using the system, putting us
on track to make the first noise temperature measurements of the HIRAX feed and
perform the first analysis of feed repeatability.Comment: 19 pages, 12 figure
S-adenosylmethionine and S-adenosylhomocysteine levels in the aging brain of APP/PS1 Alzheimer mice
Hyperhomocysteinemia and factors of homocysteine metabolism, S-adenosylhomocysteine (AdoHcy) and S-adenosylmethionine (AdoMet), may play a role in Alzheimerâs disease (AD). With liquid-chromatography-tandem-mass-spectrometry AdoMet and AdoHcy were determined in brains of 8- and 15-month-old APP/PS1 Alzheimer mice, and their possible roles in AD brains investigated. The finding that AdoMet levels do not differ between the genotypes in (young) 8-month-old mice, but are different in (older) 15-month-old APP/PS1 mice compared to their wild-type littermates, suggests that alterations in AdoMet are a consequence of AD pathology rather than a cause. During aging, AdoMet levels decreased in the brains of wild-type mice, whereas AdoHcy levels diminished in both wild type and APP/PS1 mice. The finding that AdoMet levels in APP/PS1 mice are not decreased during aging (in contrast to wild-type mice), is probably related to less demand due to neurodegeneration. No effect of the omega-3 fatty acid docosahexaenoic acid (DHA) or cholesterol-enriched diets on AdoMet or AdoHcy levels were found
LSST: from Science Drivers to Reference Design and Anticipated Data Products
(Abridged) We describe here the most ambitious survey currently planned in
the optical, the Large Synoptic Survey Telescope (LSST). A vast array of
science will be enabled by a single wide-deep-fast sky survey, and LSST will
have unique survey capability in the faint time domain. The LSST design is
driven by four main science themes: probing dark energy and dark matter, taking
an inventory of the Solar System, exploring the transient optical sky, and
mapping the Milky Way. LSST will be a wide-field ground-based system sited at
Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m
effective) primary mirror, a 9.6 deg field of view, and a 3.2 Gigapixel
camera. The standard observing sequence will consist of pairs of 15-second
exposures in a given field, with two such visits in each pointing in a given
night. With these repeats, the LSST system is capable of imaging about 10,000
square degrees of sky in a single filter in three nights. The typical 5
point-source depth in a single visit in will be (AB). The
project is in the construction phase and will begin regular survey operations
by 2022. The survey area will be contained within 30,000 deg with
, and will be imaged multiple times in six bands, ,
covering the wavelength range 320--1050 nm. About 90\% of the observing time
will be devoted to a deep-wide-fast survey mode which will uniformly observe a
18,000 deg region about 800 times (summed over all six bands) during the
anticipated 10 years of operations, and yield a coadded map to . The
remaining 10\% of the observing time will be allocated to projects such as a
Very Deep and Fast time domain survey. The goal is to make LSST data products,
including a relational database of about 32 trillion observations of 40 billion
objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures
available from https://www.lsst.org/overvie
Toxicity of Sediment-Associated Pesticides to Chironomus dilutus and Hyalella azteca
Two hundred sediment samples were collected and their toxicity evaluated to aquatic species in a previous study in the agriculturally dominated Central Valley of California, United States. Pyrethroid insecticides were the main contributors to the observed toxicity. However, mortality in approximately one third of the toxic samples could not be explained solely by the presence of pyrethroids in the matrices. Hundreds of pesticides are currently used in the Central Valley of California, but only a few dozen are analyzed in standard environmental monitoring. A significant amount of unexplained sediment toxicity may be due to pesticides that are in widespread use that but have not been routinely monitored in the environment, and even if some of them were, the concentrations harmful to aquatic organisms are unknown. In this study, toxicity thresholds for nine sediment-associated pesticides including abamectin, diazinon, dicofol, fenpropathrin, indoxacarb, methyl parathion, oxyfluorfen, propargite, and pyraclostrobin were established for two aquatic species, the midge Chironomus dilutus and the amphipod Hyalella azteca. For midges, the median lethal concentration (LC50) of the pesticides ranged from 0.18 to 964Â ÎŒg/g organic carbon (OC), with abamectin being the most toxic and propargite being the least toxic pesticide. A sublethal growth endpoint using average individual ash-free dry mass was also measured for the midges. The noâobservable effect concentration values for growth ranged from 0.10 to 633Â ÎŒg/g OC for the nine pesticides. For the amphipods, fenpropathrin was the most toxic, with an LC50 of 1â2Â ÎŒg/g OC. Abamectin, diazinon, and methyl parathion were all moderately toxic (LC50s 2.8â26Â ÎŒg/g OC). Dicofol, indoxacarb, oxyfluorfen, propargite, and pyraclostrobin were all relatively nontoxic, with LC50s greater than the highest concentrations tested. The toxicity information collected in the present study will be helpful in decreasing the frequency of unexplained sediment toxicity in agricultural waterways
Gene Expression Profiles of Sporadic Canine Hemangiosarcoma Are Uniquely Associated with Breed
The role an individual's genetic background plays on phenotype and biological behavior of sporadic tumors remains incompletely understood. We showed previously that lymphomas from Golden Retrievers harbor defined, recurrent chromosomal aberrations that occur less frequently in lymphomas from other dog breeds, suggesting spontaneous canine tumors provide suitable models to define how heritable traits influence cancer genotypes. Here, we report a complementary approach using gene expression profiling in a naturally occurring endothelial sarcoma of dogs (hemangiosarcoma). Naturally occurring hemangiosarcomas of Golden Retrievers clustered separately from those of non-Golden Retrievers, with contributions from transcription factors, survival factors, and from pro-inflammatory and angiogenic genes, and which were exclusively present in hemangiosarcoma and not in other tumors or normal cells (i.e., they were not due simply to variation in these genes among breeds). Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) was among genes preferentially enriched within known pathways derived from gene set enrichment analysis when characterizing tumors from Golden Retrievers versus other breeds. Heightened VEGFR1 expression in these tumors also was apparent at the protein level and targeted inhibition of VEGFR1 increased proliferation of hemangiosarcoma cells derived from tumors of Golden Retrievers, but not from other breeds. Our results suggest heritable factors mold gene expression phenotypes, and consequently biological behavior in sporadic, naturally occurring tumors
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