Mrgprd Enhances Excitability in Specific Populations of Cutaneous Murine Polymodal Nociceptors

The Mas-related G protein-coupled receptor D (Mrgprd) is selectively expressed in nonpeptidergic nociceptors that innervate the outer layers of mammalian skin. The function of Mrgprd in nociceptive neurons and the physiologically relevant somatosensory stimuli that activate Mrgprd^-expressing (Mrgprd^+) neurons are currently unknown. To address these issues, we studied three Mrgprd knock-in mouse lines using an ex vivo somatosensory preparation to examine the role of the Mrgprd receptor and Mrgprd+ afferents in cutaneous somatosensation. In mouse hairy skin, Mrgprd, as marked by expression of green fluorescent protein reporters, was expressed predominantly in the population of nonpeptidergic, TRPV1-negative, C-polymodal nociceptors. In mice lacking Mrgprd, this population of nociceptors exhibited decreased sensitivity to cold, heat, and mechanical stimuli. Additionally, in vitro patch-clamp studies were performed on cultured dorsal root ganglion neurons from Mrgprd^(–/–) and Mrgprd^(+/–) mice. These studies revealed a higher rheobase in neurons from Mrgprd^(–/–) mice than from Mrgprd^(+/–) mice. Furthermore, the application of the Mrgprd ligand β-alanine significantly reduced the rheobase and increased the firing rate in neurons from Mrgprd^(+/–) mice but was without effect in neurons from Mrgprd^(–/–) mice. Our results demonstrate that Mrgprd influences the excitability of polymodal nonpeptidergic nociceptors to mechanical and thermal stimuli

Oxygen isotopic ratios in cool R Coronae Borealis stars

We investigate the relationship between R Coronae Borealis (RCB) stars and hydrogen-deficient carbon (HdC) stars by measuring precise 16O/18O ratios for five cool RCB stars. The 16O/18O ratios are derived by spectrum synthesis from high-resolution (R=50,000) K-band spectra. Lower limits to the 16O/17O and 14N/15}N ratios as well as Na and S abundances (when possible) are also given. RCB stars in our sample generally display less 18O than HdC stars - the derived 16O/18O ratios range from 3 to 20. The only exception is the RCB star WX CrA, which seems to be a HdC-like star with 16O/18O=0.3. Our result of a higher 16O/18O ratio for the RCB stars must be accounted for by a theory of the formation and evolution of HdC and RCB stars. We speculate that a late dredge-up of products of He-burning, principally 12C and 16O, may convert a 18O-rich HdC star into a 18O-poor RCB star as the H-deficient star begins its final evolution from a cool supergiant to the top of the white dwarf cooling track.Comment: Accepted for publication in the Astrophysical Journal; 21 pages, 3 Tables, 11 Figure

Quiescent H2 Emission From Pre-Main Sequence Stars in Chamaeleon I

We report the discovery of quiescent emission from molecular hydrogen gas located in the circumstellar disks of six pre-main sequence stars, including two weak-line T Tauri stars (TTS), and one Herbig AeBe star, in the Chamaeleon I star forming region. For two of these stars, we also place upper limits on the 2->1 S(1)/1->0 S(1) line ratios of 0.4 and 0.5. Of the 11 pre-main sequence sources now known to be sources of quiescent near-infrared hydrogen emission, four possess transitional disks, which suggests that detectable levels of H$_2$ emission and the presence of inner disk holes are correlated. These H$_2$ detections demonstrate that these inner holes are not completely devoid of gas, in agreement with the presence of observable accretion signatures for all four of these stars and the recent detections of [Ne II] emission from three of them. The overlap in [Ne II] and H$_2$ detections hints at a possible correlation between these two features and suggests a shared excitation mechanism of high energy photons. Our models, combined with the kinematic information from the H$_2$ lines, locate the bulk of the emitting gas at a few tens of AU from the stars. We also find a correlation between H$_2$ detections and those targets which possess the largest H$\alpha$ equivalent widths, suggesting a link between accretion activity and quiescent H$_2$ emission. We conclude that quiescent H$_2$ emission from relatively hot gas within the disks of TTS is most likely related to on-going accretion activity, the production of UV photons and/or X-rays, and the evolutionary status of the dust grain populations in the inner disks.Comment: 12 pages, emulateapj, Accepted by Ap

Everolimus dosing recommendations for tuberous sclerosis complex–associated refractory seizures

ObjectiveThe present analysis examined the exposure-response relationship by means of the predose everolimus concentration (C-min) and the seizure response in patients with tuberous sclerosis complex-associated seizures in the EXIST-3 study. Recommendations have been made for the target C-min range of everolimus for therapeutic drug monitoring (TDM) and the doses necessary to achieve this target C-min

Low-load resistance exercise completed to volitional failure decreases pain perception post-exercise in females and males

Exercise-induced hypoalgesia (EIH) is the acute pain reduction post-exercise. Typically, high-intensity and/or long-duration exercise is required to elicit EIH. Alternatively, low-load resistance exercise with blood flow restriction (LL+BFR) may elicit EIH. However, there is conflicting evidence regarding the necessary repetitions and volume load. This study evaluated EIH after 75 repetitions (1×30, 3×15) (BFR-75) and four sets to volitional failure (BFR-F) protocols. Twenty-six participants completed unilateral knee extensions at 30% of maximal strength using a BFR-75 and BFR-F protocol. Pain pressure threshold (PPT) of the rectus femoris was assessed before and after exercise. Repetitions completed, volume load, occlusion time, and PPT were analyzed. Participants completed more repetitions (91.4±30.5), volume load (5,204.9±2,367.0 Nm), and had a longer occlusion time (345.8±76.2 seconds) during BFR-F compared to BFR-75 (73.2±3.7 repetitions, 4,451.1±1,498.1 Nm, 300.5±52.2 seconds, respectively). Collapsed across sex, PPT increased from pre- (3.24±1.91 kgf) to post-exercise (3.76±2.27 kgf) for BFR-F but not BFR-75 (3.51±1.67 to 3.68±2.04 kgf). The results indicated that BFR-F, but not for BFR-75, elicited EIH, as assessed by an increase in PPT. Lower loads used during LL+BFR may be a clinically relevant alternative to high-intensity and/or long-duration exercise in populations that may not tolerate high-intensity or prolonged exercise to induce EIH

Families index theory for Overlap lattice Dirac operator. I

The index bundle of the Overlap lattice Dirac operator over the orbit space of lattice gauge fields is introduced and studied. Obstructions to the vanishing of gauge anomalies in the Overlap formulation of lattice chiral gauge theory have a natural description in this context. Our main result is a formula for the topological charge (integrated Chern character) of the index bundle over even-dimensional spheres in the orbit space. It reduces under suitable conditions to the topological charge of the usual (continuum) index bundle in the classical continuum limit (this is announced and sketched here; the details will be given in a forthcoming paper). Thus we see that topology of the index bundle of the Dirac operator over the gauge field orbit space can be captured in a finite-dimensional lattice setting.Comment: Latex, 23 pages. v4: minor improvements, results unchanged; to appear in Nucl.Phys.

The fall and rise of V854 Centauri: long-term ultraviolet spectroscopy of a highly-active R Coronae Borealis star

We examine long-term low-dispersion IUE, SWP and LWP spectroscopy of the R Coronae Borealis (RCB) star V854 Cen, obtained across the deep 1991, 1992-1993 and 1994 declines. We also report the optical light curve for the star in the interval 1987-1998, including multi-color photometry obtained during 1989-1998. Analysis of the UV emission line spectra indicates most lines decay during the deep declines on characteristic timescales comparable to that reported for optical features. Fe, Mg and neutral C lines decay on timescales of typically 50-100 d. Other lines, notably ionized C lines, decay on longer timescales (> 200 d) or appear to be unaffected by the declines. The general nature of the UV emission lines and other UV features during the declines is consistent with the E1/E2/BL line-region model developed from the behavior of optical spectral features during declines. However, the detailed line-behavior indicates large intrinsic variability between decline events inconsistent with the simple E1/E2/BL model. Limited temporal coverage prevents detailed examination of the geometry of the emission line region or the obscuring dust. We also report the first detection of the transition-region line C IV 1550 in the spectrum of an RCB star.Comment: AJ in press (June), 7 figures, 4 table