Synaptically evoked glutamate transporter currents in Spinal Dorsal Horn Astrocytes

<p>Abstract</p> <p>Background</p> <p>Removing and sequestering synaptically released glutamate from the extracellular space is carried out by specific plasma membrane transporters that are primarily located in astrocytes. Glial glutamate transporter function can be monitored by recording the currents that are produced by co-transportation of Na⁺ions with the uptake of glutamate. The goal of this study was to characterize glutamate transporter function in astrocytes of the spinal cord dorsal horn in real time by recording synaptically evoked glutamate transporter currents.</p> <p>Results</p> <p>Whole-cell patch clamp recordings were obtained from astrocytes in the spinal substantia gelatinosa (SG) area in spinal slices of young adult rats. Glutamate transporter currents were evoked in these cells by electrical stimulation at the spinal dorsal root entry zone in the presence of bicuculline, strychnine, DNQX and D-AP5. Transporter currents were abolished when synaptic transmission was blocked by TTX or Cd²⁺. Pharmacological studies identified two subtypes of glutamate transporters in spinal astrocytes, GLAST and GLT-1. Glutamate transporter currents were graded with stimulus intensity, reaching peak responses at 4 to 5 times activation threshold, but were reduced following low-frequency (0.1 – 1 Hz) repetitive stimulation.</p> <p>Conclusion</p> <p>These results suggest that glutamate transporters of spinal astrocytes could be activated by synaptic activation, and recording glutamate transporter currents may provide a means of examining the real time physiological responses of glial cells in spinal sensory processing, sensitization, hyperalgesia and chronic pain.</p

Radio pulsar populations

The goal of this article is to summarize the current state of play in the field of radio pulsar statistics. Simply put, from the observed sample of objects from a variety of surveys with different telescopes, we wish to infer the properties of the underlying sample and to connect these with other astrophysical populations (for example supernova remnants or X-ray binaries). The main problem we need to tackle is the fact that, like many areas of science, the observed populations are often heavily biased by a variety of selection effects. After a review of the main effects relevant to radio pulsars, I discuss techniques to correct for them and summarize some of the most recent results. Perhaps the main point I would like to make in this article is that current models to describe the population are far from complete and often suffer from strong covariances between input parameters. That said, there are a number of very interesting conclusions that can be made concerning the evolution of neutron stars based on current data. While the focus of this review will be on the population of isolated Galactic pulsars, I will also briefly comment on millisecond and binary pulsars as well as the pulsar content of globular clusters and the Magellanic Clouds.Comment: 16 pages, 6 figures, to appear in Proceedings of ICREA Workshop on The High-Energy Emission from Pulsars and their Systems, Sant Cugat, Spain, 2010 April 12-16 (Springer

Binary and Millisecond Pulsars at the New Millennium

We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

Biological characteristics and treatment outcomes of metastatic or recurrent neuroendocrine tumors: tumor grade and metastatic site are important for treatment strategy

<p>Abstract</p> <p>Background</p> <p>Studies about the biology, treatment pattern, and treatment outcome of metastatic/recurrent neuroendocrine tumor (NET) have been few.</p> <p>Methods</p> <p>We enrolled patients with metastatic/recurrent NET diagnosed between January 1996 and July 2007 and retrospectively analyzed.</p> <p>Results</p> <p>A total of 103 patients were evaluated. Twenty-six patients (25.2%) had pancreatic NET, 27 (26.2%) had gastrointestinal NET, 2 (1.9%) had lung NET, 28 (27.2%) had NET from other sites, and 20 (19.4%) had NET from unknown origin. The liver was the most common metastatic site (68.9%). Thirty-four patients had grade 1 disease, 1 (1.0%) had grade 2 disease, 15 (14.6%) had grade 3 disease, 9 (8.7%) had large cell disease, and 7 (6.8%) had small cell disease.</p> <p>Sixty-six patients received systemic treatment (interferon, somatostatin analogues or chemotherapy), 64 patients received local treatment (TACE, radiofrequency ablation, metastasectomy, etc.). Thirty-six patients received both systemic and local treatments.</p> <p>Median overall survival (OS) was 29.0 months (95% confidence interval, 25.0-33.0) in the103 patients. OS was significantly influenced by grade (<it>p </it>= .001). OS was 43.0, 23.0, and 29.0 months in patients who received local treatment only, systemic treatment only, and both treatments, respectively (<it>p </it>= .245). The median time-to-progression (TTP) was 6.0 months. Overall response rate was 34.0% and disease-control rate was 64.2%. TTP was influenced by the presence of liver metastasis (<it>p </it>= .011).</p> <p>Conclusions</p> <p>OS of metastatic/recurrent NET was different according to tumor grade. TTP was different according to metastasis site. Therefore, development of optimal treatment strategy based on the characteristics of NET is warranted.</p

P-Type ATPase TAT-2 Negatively Regulates Monomethyl Branched-Chain Fatty Acid Mediated Function in Post-Embryonic Growth and Development in C. elegans

Monomethyl branched-chain fatty acids (mmBCFAs) are essential for Caenorhabditis elegans growth and development. To identify factors acting downstream of mmBCFAs for their function in growth regulation, we conducted a genetic screen for suppressors of the L1 arrest that occurs in animals depleted of the 17-carbon mmBCFA C17ISO. Three of the suppressor mutations defined an unexpected player, the P-type ATPase TAT-2, which belongs to the flippase family of proteins that are implicated in mediating phospholipid bilayer asymmetry. We provide evidence that TAT-2, but not other TAT genes, has a specific role in antagonizing the regulatory activity of mmBCFAs in intestinal cells. Interestingly, we found that mutations in tat-2 also suppress the lethality caused by inhibition of the first step in sphingolipid biosynthesis. We further showed that the fatty acid side-chains of glycosylceramides contain 20%–30% mmBCFAs and that this fraction is greatly diminished in the absence of mmBCFA biosynthesis. These results suggest a model in which a C17ISO-containing sphingolipid may mediate the regulatory functions of mmBCFAs and is negatively regulated by TAT-2 in intestinal cells. This work indicates a novel connection between a P-type ATPase and the critical regulatory function of a specific fatty acid

Glial Hsp70 Protects K+ Homeostasis in the Drosophila Brain during Repetitive Anoxic Depolarization

Neural tissue is particularly vulnerable to metabolic stress and loss of ion homeostasis. Repetitive stress generally leads to more permanent dysfunction but the mechanisms underlying this progression are poorly understood. We investigated the effects of energetic compromise in Drosophila by targeting the Na+/K+-ATPase. Acute ouabain treatment of intact flies resulted in subsequent repetitive comas that led to death and were associated with transient loss of K+ homeostasis in the brain. Heat shock pre-conditioned flies were resistant to ouabain treatment. To control the timing of repeated loss of ion homeostasis we subjected flies to repetitive anoxia while recording extracellular [K+] in the brain. We show that targeted expression of the chaperone protein Hsp70 in glial cells delays a permanent loss of ion homeostasis associated with repetitive anoxic stress and suggest that this is a useful model for investigating molecular mechanisms of neuroprotection

The NANOGrav 15 yr Data Set: Search for Transverse Polarization Modes in the Gravitational-wave Background

\ua9 2024. The Author(s). Published by the American Astronomical Society.Recently we found compelling evidence for a gravitational-wave background with Hellings and Downs (HD) correlations in our 15 yr data set. These correlations describe gravitational waves as predicted by general relativity, which has two transverse polarization modes. However, more general metric theories of gravity can have additional polarization modes, which produce different interpulsar correlations. In this work, we search the NANOGrav 15 yr data set for evidence of a gravitational-wave background with quadrupolar HD and scalar-transverse (ST) correlations. We find that HD correlations are the best fit to the data and no significant evidence in favor of ST correlations. While Bayes factors show strong evidence for a correlated signal, the data does not strongly prefer either correlation signature, with Bayes factors ∼2 when comparing HD to ST correlations, and ∼1 for HD plus ST correlations to HD correlations alone. However, when modeled alongside HD correlations, the amplitude and spectral index posteriors for ST correlations are uninformative, with the HD process accounting for the vast majority of the total signal. Using the optimal statistic, a frequentist technique that focuses on the pulsar-pair cross-correlations, we find median signal-to-noise ratios of 5.0 for HD and 4.6 for ST correlations when fit for separately, and median signal-to-noise ratios of 3.5 for HD and 3.0 for ST correlations when fit for simultaneously. While the signal-to-noise ratios for each of the correlations are comparable, the estimated amplitude and spectral index for HD are a significantly better fit to the total signal, in agreement with our Bayesian analysis

How to Detect an Astrophysical Nanohertz Gravitational Wave Background

\ua9 2023. The Author(s). Published by the American Astronomical Society.Analyses of pulsar timing data have provided evidence for a stochastic gravitational wave background in the nanohertz frequency band. The most plausible source of this background is the superposition of signals from millions of supermassive black hole binaries. The standard statistical techniques used to search for this background and assess its significance make several simplifying assumptions, namely (i) Gaussianity, (ii) isotropy, and most often, (iii) a power-law spectrum. However, a stochastic background from a finite collection of binaries does not exactly satisfy any of these assumptions. To understand the effect of these assumptions, we test standard analysis techniques on a large collection of realistic simulated data sets. The data-set length, observing schedule, and noise levels were chosen to emulate the NANOGrav 15 yr data set. Simulated signals from millions of binaries drawn from models based on the Illustris cosmological hydrodynamical simulation were added to the data. We find that the standard statistical methods perform remarkably well on these simulated data sets, even though their fundamental assumptions are not strictly met. They are able to achieve a confident detection of the background. However, even for a fixed set of astrophysical parameters, different realizations of the universe result in a large variance in the significance and recovered parameters of the background. We also find that the presence of loud individual binaries can bias the spectral recovery of the background if we do not account for them