Spinal release of tumour necrosis factor activates c-Jun N-terminal kinase and mediates inflammation-induced hypersensitivity.

BackgroundMounting evidence points to individual contributions of tumour necrosis factor-alpha (TNF) and the c-Jun N-terminal kinase (JNK) pathway to the induction and maintenance of various pain states. Here we explore the role of spinal TNF and JNK in carrageenan-induced hypersensitivity. As links between TNF and JNK have been demonstrated in vitro, we investigated if TNF regulates spinal JNK activity in vivo.MethodsTNF levels in lumbar cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay, spinal TNF gene expression by real-time polymerase chain reaction and TNF protein expression, JNK and c-Jun phosphorylation by western blotting. The role of spinal TNF and JNK in inflammation-induced mechanical and thermal hypersensitivity was assessed by injecting the TNF inhibitor etanercept and the JNK inhibitors SP600125 and JIP-1 intrathecally (i.t.). TNF-mediated regulation of JNK activity was examined by assessing the effect of i.t. etanercept on inflammation-induced spinal JNK activity.ResultsTNF levels were increased in CSF and spinal cord following carrageenan-induced inflammation. While JNK phosphorylation followed the same temporal pattern as TNF, c-jun was only activated at later time points. Intrathecal injection of TNF and JNK inhibitors attenuated carrageenan-induced mechanical and thermal hypersensitivity. TNF stimulation induced JNK phosphorylation in cultured spinal astrocytes and blocking the spinal actions of TNF in vivo by i.t. injection of etanercept reduced inflammation-induced spinal JNK activity.ConclusionsHere we show that spinal JNK activity is dependent on TNF and that both TNF and the JNK signalling pathways modulate pain-like behaviour induced by peripheral inflammation

Gaze and viewing angle influence visual stabilization of upright posture

Focusing gaze on a target helps stabilize upright posture. We investigated how this visual stabilization can be affected by observing a target presented under different gaze and viewing angles. In a series of 10-second trials, participants (N = 20, 29.3 ± 9 years of age) stood on a force plate and fixed their gaze on a figure presented on a screen at a distance of 1 m. The figure changed position (gaze angle: eye level (0°), 25° up or down), vertical body orientation (viewing angle: at eye level but rotated 25° as if leaning toward or away from the participant), or both (gaze and viewing angle: 25° up or down with the rotation equivalent of a natural visual perspective). Amplitude of participants’ sagittal displacement, surface area, and angular position of the center of gravity (COG) were compared. Results showed decreased COG velocity and amplitude for up and down gaze angles. Changes in viewing angles resulted in altered body alignment and increased amplitude of COG displacement. No significant changes in postural stability were observed when both gaze and viewing angles were altered. Results suggest that both the gaze angle and viewing perspective may be essential variables of the visuomotor system modulating postural responses

Orbital Migration of Interacting Stellar Mass Black Holes in Disks around Supermassive Black Holes

The merger rate of stellar-mass black hole binaries (sBHBs) inferred by the Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO) suggests the need for an efficient source of sBHB formation. Active galactic nucleus (AGN) disks are a promising location for the formation of these sBHBs, as well as binaries of other compact objects, because of powerful torques exerted by the gas disk. These gas torques cause orbiting compact objects to migrate towards regions in the disk where inward and outward torques cancel, known as migration traps. We simulate the migration of stellar mass black holes in an example of a model AGN disk, using an augmented N-body code that includes analytic approximations to migration torques, stochastic gravitational forces exerted by turbulent density fluctuations in the disk, and inclination and eccentricity dampening produced by passages through the gas disk, in addition to the standard gravitational forces between objects. We find that sBHBs form rapidly in our model disk as stellar-mass black holes migrate towards the migration trap. These sBHBs are likely to subsequently merge on short time-scales. The process continues, leading to the build-up of a population of over-massive stellar-mass black holes. The formation of sBHBs in AGN disks could contribute significantly to the sBHB merger rate inferred by LIGO.Comment: 18 pages, 13 figures, Accepted to Ap

Galaxy Zoo and SPARCFIRE: constraints on spiral arm formation mechanisms from spiral arm number and pitch angles

In this paper, we study the morphological properties of spiral galaxies, including measurements of spiral arm number and pitch angle. Using Galaxy Zoo 2, a stellar mass-complete sample of 6222 SDSS spiral galaxies is selected. We use the machine vision algorithm sparcfire to identify spiral arm features and measure their associated geometries. A support vector machine classifier is employed to identify reliable spiral features, with which we are able to estimate pitch angles for half of our sample. We use these machine measurements to calibrate visual estimates of arm tightness, and hence estimate pitch angles for our entire sample. The properties of spiral arms are compared with respect to various galaxy properties. The star formation properties of galaxies vary significantly with arm number, but not pitch angle. We find that galaxies hosting strong bars have spiral arms substantially (4°-6°) looser than unbarred galaxies. Accounting for this, spiral arms associated with many-armed structures are looser (by 2°) than those in two-armed galaxies. In contrast to this average trend, galaxies with greater bulge-to-total stellar mass ratios display both fewer and looser spiral arms. This effect is primarily driven by the galaxy disc, such that galaxies with more massive discs contain more spiral arms with tighter pitch angles. This implies that galaxy central mass concentration is not the dominant cause of pitch angle and arm number variations between galaxies, which in turn suggests that not all spiral arms are governed by classical density waves or modal theories

A comparison of statistical hadronization models

We investigate the sensitivity of fits of hadron spectra produced in heavy ion collisions to the choice of statistical hadronization model. We start by giving an overview of statistical model ambiguities, and what they tell us about freeze-out dynamics. We then use Montecarlo generated data to determine sensitivity to model choice. We fit the statistical hadronization models under consideration to RHIC data, and find that a comparison $\chi^2$ fits can shed light on some presently contentious questions.Comment: Proceedings for SQM2003 [7th Int. Conf. on Strangeness in Quark Matter (Atlantic Beach, NC, USA, Mar 12-17, 2003)], to be published in Journal of Physics G (Typos corrected, reference added

Space-time analysis of reaction at RHIC

Space-time information about the Au-Au collisions produced at RHIC are key tools to understand the evolution of the system and especially assess the presence of collective behaviors. Using a parameterization of the system's final state relying on collective expansion, we show that pion source radii can be tied together with transverse mass spectra and elliptic flow within the same framework. The consistency between these different measures provide a solid ground to understand the characteristics of collective flow and especially the possible peculiar behavior of particles such as Xi, Omega or phi. The validity of the short time scales that are extracted from fits to the pion source size is also addressed. The wealth of new data that will soon be available from Au-Au collisions at sqrt{s_{NN}} = 200 GeV, will provide a stringet test of the space-time analysis framework developped in these proceedings.Comment: Invited talk given at the SQM2003 conference (March 2003), to be published in Journal of Physics G. 10 pages, 3 figure

Multistate Survey of American Dog Ticks \u3ci\u3e(Dermacentor variabilis)\u3c/i\u3e for \u3ci\u3eRickettsia\u3c/i\u3e Species

Dermacentor variabilis, a common human-biting tick found throughout the eastern half and along the west coast of the United States, is a vector of multiple bacterial pathogens. Historically, D. variabilis has been considered a primary vector of Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever. A total of 883 adult D. variabilis, collected between 2012 and 2017 from various locations in 12 states across the United States, were screened for rickettsial DNA. Tick extracts were evaluated using three real-time PCR assays; an R. rickettsii-specific assay, a Rickettsia bellii-specific assay, and a Rickettsia genus-specific assay. Sequencing of ompA gene amplicons generated using a seminested PCR assay was used to determine the rickettsial species present in positive samples not already identified by species-specific real-time assays. A total of 87 (9.9%) tick extracts contained R. bellii DNA and 203 (23%) contained DNA of other rickettsial species, including 47 (5.3%) with Rickettsia montanensis, 11 (1.2%) with Rickettsia amblyommatis, 2 (0.2%) with Rickettsia rhipicephali, and 3 (0.3%) with Rickettsia parkeri. Only 1 (0.1%) tick extract contained DNA of R. rickettsii. These data support multiple other contemporary studies that indicate infrequent detection of R. rickettsii in D. variabilis in North America

Ethanol Distribution, Dispensing, and Use: Analysis of a Portion of the Biomass-to-Biofuels Supply Chain Using System Dynamics

The Energy Independence and Security Act of 2007 targets use of 36 billion gallons of biofuels per year by 2022. Achieving this may require substantial changes to current transportation fuel systems for distribution, dispensing, and use in vehicles. The U.S. Department of Energy and the National Renewable Energy Laboratory designed a system dynamics approach to help focus government action by determining what supply chain changes would have the greatest potential to accelerate biofuels deployment. The National Renewable Energy Laboratory developed the Biomass Scenario Model, a system dynamics model which represents the primary system effects and dependencies in the biomass-to-biofuels supply chain. The model provides a framework for developing scenarios and conducting biofuels policy analysis. This paper focuses on the downstream portion of the supply chain–represented in the distribution logistics, dispensing station, and fuel utilization, and vehicle modules of the Biomass Scenario Model. This model initially focused on ethanol, but has since been expanded to include other biofuels. Some portions of this system are represented dynamically with major interactions and feedbacks, especially those related to a dispensing station owner’s decision whether to offer ethanol fuel and a consumer’s choice whether to purchase that fuel. Other portions of the system are modeled with little or no dynamics; the vehicle choices of consumers are represented as discrete scenarios. This paper explores conditions needed to sustain an ethanol fuel market and identifies implications of these findings for program and policy goals. A large, economically sustainable ethanol fuel market (or other biofuel market) requires low end-user fuel price relative to gasoline and sufficient producer payment, which are difficult to achieve simultaneously. Other requirements (different for ethanol vs. other biofuel markets) include the need for infrastructure for distribution and dispensing and widespread use of high ethanol blends in flexible-fuel vehicles

Distinct Mechanisms for Induction and Tolerance Regulate the Immediate Early Genes Encoding Interleukin 1β and Tumor Necrosis Factor α

Interleukin-1β and Tumor Necrosis Factor α play related, but distinct, roles in immunity and disease. Our study revealed major mechanistic distinctions in the Toll-like receptor (TLR) signaling-dependent induction for the rapidly expressed genes (IL1B and TNF) coding for these two cytokines. Prior to induction, TNF exhibited pre-bound TATA Binding Protein (TBP) and paused RNA Polymerase II (Pol II), hallmarks of poised immediate-early (IE) genes. In contrast, unstimulated IL1B displayed very low levels of both TBP and paused Pol II, requiring the lineage-specific Spi-1/PU.1 (Spi1) transcription factor as an anchor for induction-dependent interaction with two TLR-activated transcription factors, C/EBPβ and NF-κB. Activation and DNA binding of these two pre-expressed factors resulted in de novo recruitment of TBP and Pol II to IL1B in concert with a permissive state for elongation mediated by the recruitment of elongation factor P-TEFb. This Spi1-dependent mechanism for IL1B transcription, which is unique for a rapidly-induced/poised IE gene, was more dependent upon P-TEFb than was the case for the TNF gene. Furthermore, the dependence on phosphoinositide 3-kinase for P-TEFb recruitment to IL1B paralleled a greater sensitivity to the metabolic state of the cell and a lower sensitivity to the phenomenon of endotoxin tolerance than was evident for TNF. Such differences in induction mechanisms argue against the prevailing paradigm that all IE genes possess paused Pol II and may further delineate the specific roles played by each of these rapidly expressed immune modulators. © 2013 Adamik et al