We report a first search for weakly interacting massive particles (WIMPs) using the background rejection capabilities of SuperCDMS. An exposure of 577 kg days was analyzed for WIMPs with mass <30 ...GeV/c(2), with the signal region blinded. Eleven events were observed after unblinding. We set an upper limit on the spin-independent WIMP-nucleon cross section of 1.2×10(-42) cm(2) at 8 GeV/c(2). This result is in tension with WIMP interpretations of recent experiments and probes new parameter space for WIMP-nucleon scattering for WIMP masses <6 GeV/c(2).
Dark matter particle annihilation or decay can produce monochromatic gamma-ray lines and contribute to the diffuse gamma-ray background. Flux upper limits are presented for gamma-ray spectral lines ...from 7 to 200 GeV and for the diffuse gamma-ray background from 4.8 GeV to 264 GeV obtained from two years of Fermi Large Area Telescope data integrated over most of the sky. We give cross-section upper limits and decay lifetime lower limits for dark matter models that produce gamma-ray lines or contribute to the diffuse spectrum, including models proposed as explanations of the PAMELA and Fermi cosmic-ray data.
Protein arginine methyltransferases (PRMTs) are a family of enzymes involved in gene regulation and protein/histone modifications. PRMT8 is primarily expressed in the central nervous system, ...specifically within the cellular membrane and synaptic vesicles. Recently, PRMT8 has been described to play key roles in neuronal signaling such as a regulator of dendritic arborization, synaptic function and maturation, and neuronal differentiation and plasticity. Here, we examined the role of PRMT8 in response to hypoxia-induced stress in brain metabolism. Our results from liquid chromatography mass spectrometry, mitochondrial oxygen consumption rate, and protein analyses indicate that PRMT8(-/-) knockout mice presented with altered membrane phospholipid composition, decreased mitochondrial stress capacity, and increased neuroinflammatory markers, such as tumor necrosis factor alpha and ionized calcium binding adaptor molecule 1 (Iba1, a specific marker for microglia/macrophage activation) after hypoxic stress. Furthermore, adenovirus-based overexpression of PRMT8 reversed the changes in membrane phospholipid composition, mitochondrial stress capacity, and neuroinflammatory markers. Together, our findings establish PRMT8 as an important regulatory component of membrane phospholipid composition, short-term memory function, mitochondrial function, and neuroinflammation in response to hypoxic stress.
•We previously discovered palmitic acid methyl ester (a C16:0 saturated fatty acid) is a novel and potent vasodilator.•We investigated the therapeutic potential of palmitic acid methyl ester against ...cardiac arrest-induced brain injury and neurological deficits.•We found that post-treatment of palmitic acid methyl ester after cardiac arrest can enhance cerebral blood flow and neuronal cell survival ultimately improving functional learning/memory.
We previously discovered that palmitic acid methyl ester (PAME) is a potent vasodilator first identified and released from the superior cervical ganglion and remain understudied. Thus, we investigated PAME's role in modulating cerebral blood flow (CBF) and neuroprotection after 6 min of cardiac arrest (model of global cerebral ischemia). Our results suggest that PAME can enhance CBF under normal physiological conditions, while administration of PAME (0.02 mg/kg) immediately after cardiopulmonary resuscitation can also enhance CBF in vivo. Additionally, functional learning and spatial memory assessments (via T-maze) 3 days after asphyxial cardiac arrest (ACA) suggest that PAME-treated rats have improved learning and memory recovery versus ACA alone. Furthermore, improved neuronal survival in the CA1 region of the hippocampus were observed in PAME-treated, ACA-induced rats. Altogether, our findings suggest that PAME can enhance CBF, alleviate neuronal cell death, and promote functional outcomes in the presence of ACA.
Cerebral ischemia is one of the leading causes of morbidity and mortality worldwide. Although stroke (a form of cerebral ischemia)-related costs are expected to reach 240.67 billion dollars by 2030, ...options for treatment against cerebral ischemia/stroke are limited. All therapies except anti-thrombolytics (i.e., tissue plasminogen activator) and hypothermia have failed to reduce neuronal injury, neurological deficits, and mortality rates following cerebral ischemia, which suggests that development of novel therapies against stroke/cerebral ischemia are urgently needed. Here, we discuss the possible mechanism(s) underlying cerebral ischemia-induced brain injury, as well as current and future novel therapies (i.e., growth factors, nicotinamide adenine dinucleotide, melatonin, resveratrol, protein kinase C isozymes, pifithrin, hypothermia, fatty acids, sympathoplegic drugs, and stem cells) as it relates to cerebral ischemia.
Opacity Buildup in Impulsive Relativistic Sources Granot, Jonathan; Cohen-Tanugi, Johann; do Couto e Silva, Eduardo
Astrophysical journal/The Astrophysical journal,
04/2008, Volume:
677, Issue:
1
Journal Article
Peer reviewed
Open access
Opacity effects in relativistic sources of high-energy gamma-rays, such as gamma-ray bursts (GRBs) or blazars, can probe the Lorentz factor of the outflow as well as the distance of the emission site ...from the source and, thus, help constrain the composition of the outflow (protons, pairs, magnetic field) and the emission mechanism. Most previous works consider the opacity in steady state. Here we study time-dependent effects of the opacity to pair production in impulsive relativistic sources. We present a simple, yet rich, semianalytic model for the time and energy dependence of the optical depth, image, in which a thin spherical shell expands ultrarelativistically and emits isotropically in its own rest frame over a finite range of radii, image. This is particularly relevant for GRB internal shocks. We find that for impulsive sources, while the instantaneous spectrum has an exponential cutoff above the photon energy image where image, the time-integrated spectrum has a power-law high-energy tail above the photon energy image where image is the duration of the emission episode. Furthermore, photons with image should arrive mainly near the onset of the spike or flare corresponding to the short emission episode, since in impulsive sources it takes time to build up the (target) photon field, and thus, image initially increases with time and image correspondingly decreases with time, so that photons of energy image are able to escape the source mainly very early on while image. As the source approaches a quasi-steady state, the time- integrated spectrum develops an exponential cutoff, while the power-law tail becomes increasingly suppressed.
Alzheimer's disease (AD) is the leading cause of mortality, disability, and long‐term care burden in the United States, with women comprising the majority of AD diagnoses. While AD‐related dementia ...is associated with tau and amyloid beta accumulation, concurrent derangements in cerebral blood flow have been observed alongside these proteinopathies in humans and rodent models. The homeostatic production of nitric oxide synthases (NOS) becomes uncoupled in AD which leads to decreased NO‐mediated vasodilation and oxidative stress via the production of peroxynitrite (ONOO−∙) superoxide species. Here, we investigate the role of the novel protein arginine methyltransferase 4 (PRMT4) enzyme function and its downstream product asymmetric dimethyl arginine (ADMA) as it relates to NOS dysregulation and cerebral blood flow in AD. ADMA (type‐1 PRMT product) has been shown to bind NOS as a noncanonic ligand causing enzymatic dysfunction. Our results from RT‐qPCR and protein analyses suggest that aged (9−12 months) female mice bearing tau‐ and amyloid beta‐producing transgenic mutations (3xTg‐AD) express higher levels of PRMT4 in the hippocampus when compared to age‐ and sex‐matched C57BL6/J mice. In addition, we performed studies to quantify the expression and activity of different NOS isoforms. Furthermore, laser speckle contrast imaging analysis was indicative that 3xTg‐AD mice have dysfunctional NOS activity, resulting in reduced production of NO metabolites, enhanced production of free‐radical ONOO−, and decreased cerebral blood flow. Notably, the aforementioned phenomena can be reversed via pharmacologic PRMT4 inhibition. Together, these findings implicate the potential importance of PRMT4 signaling in the pathogenesis of Alzheimer's‐related cerebrovascular derangement.
The methylation of arginine residues by protein arginine methyltransferases (PRMTs) is a type of post-translational modification which is important for numerous cellular processes, including mRNA ...splicing, DNA repair, signal transduction, protein interaction, and transport. PRMTs have been extensively associated with various pathologies, including cancer, inflammation, and immunity response. However, the role of PRMTs has not been well described in vascular and neurological function. Aberrant expression of PRMTs can alter its metabolic products, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA). Increased ADMA levels are recognized as an independent risk factor for cardiovascular disease and mortality. Recent studies have provided considerable advances in the development of small-molecule inhibitors of PRMTs to study their function under normal and pathological states. In this review, we aim to elucidate the particular roles of PRMTs in vascular and neuronal function as a potential target for cardiovascular and neurological diseases.
We present observations of the young supernova remnant (SNR) RX J1713.7--3946 with the Fermi Large Area Telescope (LAT). We clearly detect a source positionally coincident with the SNR. The source is ...extended with a best-fit extension of 055 ? 004 matching the size of the non-thermal X-ray and TeV gamma-ray emission from the remnant. The positional coincidence and the matching extended emission allow us to identify the LAT source with SNR RX J1713.7--3946. The spectrum of the source can be described by a very hard power law with a photon index of Delta *G = 1.5 ? 0.1 that coincides in normalization with the steeper H.E.S.S.-detected gamma-ray spectrum at higher energies. The broadband gamma-ray emission is consistent with a leptonic origin as the dominant mechanism for the gamma-ray emission.
We present the detections of 18 solar flares detected in high-energy gamma-rays (above 100 MeV) with the Fermi Large Area Telescope (LAT) during its first 4 yr of operation. This work suggests that ...particle acceleration up to very high energies in solar flares is more common than previously thought, occurring even in modest flares, and for longer durations. We then describe the detailed temporal, spatial, and spectral characteristics of the first two long-lasting events; the 2011 March 7 flare, a moderate (M3.7) impulsive flare followed by slowly varying gamma-ray emission over 13 hr, and the 2011 June 7 M2.5 flare. We compare the Fermi LAT data with X-ray and proton data measurements from GOES and RHESSI. We argue that the gamma-rays are more likely produced through pion decay than electron bremsstrahlung, and we find that flic energy spectrum of the proton distribution softens during the extended emission of the 2011 March 7 flare.
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