Human visceral nociception: findings from translational studies in human tissue.

Peripheral sensitization of nociceptors during disease has long been recognized as a leading cause of inflammatory pain. However, a growing body of data generated over the last decade has led to the increased understanding that peripheral sensitization is also an important mechanism driving abdominal pain in highly prevalent functional bowel disorders, in particular, irritable bowel syndrome (IBS). As such, the development of drugs that target pain-sensing nerves innervating the bowel has the potential to be a successful analgesic strategy for the treatment of abdominal pain in both organic and functional gastrointestinal diseases. Despite the success of recent peripherally restricted approaches for the treatment of IBS, not all drugs that have shown efficacy in animal models of visceral pain have reduced pain end points in clinical trials of IBS patients, suggesting innate differences in the mechanisms of pain processing between rodents and humans and, in particular, how we model disease states. To address this gap in our understanding of peripheral nociception from the viscera and the body in general, several groups have developed experimental systems to study nociception in isolated human tissue and neurons, the findings of which we discuss in this review. Studies of human tissue identify a repertoire of human primary afferent subtypes comparable to rodent models including a nociceptor population, the targeting of which will shape future analgesic development efforts. Detailed mechanistic studies in human sensory neurons combined with unbiased RNA-sequencing approaches have revealed fundamental differences in not only receptor/channel expression but also peripheral pain pathways.Non

The responses of the four main substitution mechanisms of H in olivine to H2O activity at 1050 °C and 3 GPa

The water solubility in olivine (CH2O) has been investigated at 1050 °C and 3 GPa as a function of water activity (aH2O) at subsolidus conditions in the piston-cylinder apparatus, with aH2O varied using H2O–NaCl fluids. Four sets of experiments were conducted to constrain the effect of aH2O on the four main substitution mechanisms. The experiments were designed to grow olivine in situ and thus achieve global equilibrium (G-type), as opposed to hydroxylating olivine with a pre-existing point-defect structure and impurity content (M-type). Olivine grains from the experiments were analysed with polarised and unpolarised FTIR spectroscopy, and where necessary, the spectra have been deconvoluted to quantify the contribution of each substitution mechanism. Olivine buffered with magnesiowüstite produced absorbance bands at high wavenumbers ranging from 3566 to 3612 cm−1. About 50% of the total absorbance was found parallel to the a-axis, 30% parallel to the b-axis and 20% parallel to the c-axis. The total absorbance and hence water concentration in olivine follows the relationship of CH2O∝aH2O2, indicating that the investigated defect must involve four H atoms substituting for one Si atom (labelled as [Si]). Forsterite buffered with enstatite produced an absorbance band exclusively aligned parallel the c-axis at 3160 cm−1. The band position, polarisation and observed CH2O∝aH2O are consistent with two H substituting for one Mg (labelled as [Mg]). Ti-doped, enstatite-buffered olivine displays absorption bands, and polarisation typical of Ti-clinohumite point defects where two H on the Si-site are charge-balanced by one Ti on a Mg-site (labelled as [Ti]). This is further supported by CH2O∝aH2O and a 1:1 relationship of molar H2O and TiO2 in these experiments. Sc-doped, enstatite-buffered experiments display a main absorption band at 3355 cm−1 with CH2O∝aH2O0.5 and a positive correlation of Sc and H, indicating the coupled substitution of a trivalent cation plus a H for two Mg (labelled as [triv]). Our data demonstrate that extreme care has to be taken when inferences from experiments conducted at aH2O=1 are applied to the mantle, where in most cases, a low aH2O persists. In particular, the higher exponent of the [Si] substitution mechanism means that the contribution of this hydrous defect to total water content will decrease more rapidly with decreasing aH2O than the contributions of the other substitution mechanisms. The experiments confirm previous results that the [Mg] mechanism holds an almost negligible amount of water under nearly all T-P-fO2-fH2O conditions that may be anticipated in nature. However, the small amounts of H2O we find in substituting by this mechanism are similar in the experiments on forsterite doped with either Sc or Ti to those in the undoped forsterite at equivalent aH2O (all buffered by enstatite), confirming the assumption that, thermodynamically, CH2O substituting by each mechanism does not depend on the water concentration that substitutes by other mechanisms.We gratefully acknowledge the Australian Research Council (ARC) support through DP110103134 to JH and HON, and FL130100066 to HON, which partly supported PT during the final stages of this project. RS acknowledges an Australian Postgraduate Award

Predicting facebook users online privacy protection: Risk, trust, norm focus theory, and the theory of planned behavior

Journal ArticleThis is an Accepted Manuscript of an article published by Taylor & Francis in The Journal of Social Psychology on 21 April 2014, available online: http://wwww.tandfonline.com/10.1080/00224545.2014.914881The present research adopts an extended theory of the planned behavior model that included descriptive norms, risk, and trust to investigate online privacy protection in Facebook users. Facebook users (N = 119) completed a questionnaire assessing their attitude, subjective injunctive norm, subjective descriptive norm, perceived behavioral control, implicit perceived risk, trust of other Facebook users, and intentions toward protecting their privacy online. Behavior was measured indirectly 2 weeks after the study. The data show partial support for the theory of planned behavior and strong support for the independence of subjective injunctive and descriptive norms. Risk also uniquely predicted intentions over and above the theory of planned behavior, but there were no unique effects of trust on intentions, nor of risk or trust on behavior. Implications are discussed. © Copyright © Taylor & Francis Group, LLC

SN 2011hw: Helium-Rich Circumstellar Gas and the Luminous Blue Variable to Wolf-Rayet Transition in Supernova Progenitors

We present optical photometry and spectroscopy of the peculiar Type IIn/Ibn supernova SN2011hw. Its light curve exhibits a slower decline rate than normal SNeIbc, with a peak absolute magnitude of -19.5 (unfiltered) and a secondary peak of -18.3 mag (R). Spectra of SN2011hw are unusual compared to normal SN types, most closely resembling the spectra of SNeIbn. We center our analysis on comparing SN 2011hw to the well-studied TypeIbn SN2006jc. While the two SNe have many important similarities, the differences are quite telling: compared to SN2006jc, SN2011hw has weaker HeI and CaII lines and relatively stronger H lines, its light curve has a higher luminosity and slower decline rate, and emission lines associated with the progenitor's CSM are narrower. One can reproduce the unusual continuum shape of SN2011hw with equal contributions of a 6000K blackbody and a spectrum of SN2006jc. We attribute this emission component and many other differences between the two SNe to extra opacity from a small amount of additional H in SN2011hw, analogous to the small H mass that makes SNeIIb differ from SNeIb. Slower speeds in the CSM and elevated H content suggest a connection between the progenitor of SN2011hw and the class of Ofpe/WN9 stars, which have been associated with LBVs in their hot quiescent phases between outbursts, and are H-poor - but not H-free like classical Wolf-Rayet (WR) stars. We conclude that the similarities and differences between SN2011hw and SN2006jc can be largely understood if their progenitors exploded at different points in the transitional evolution from an LBV to a WR star.Comment: 11 pages, 7 figures, submitted to MNRA

WR 110: A Single Wolf-Rayet Star With Corotating Interaction Regions In Its Wind?

A 30-day contiguous photometric run with the MOST satellite on the WN5-6b star WR 110 (HD 165688) reveals a fundamental periodicity of P = 4.08 +/- 0.55 days along with a number of harmonics at periods P/n, with n ~ 2,3,4,5 and 6, and a few other possible stray periodicities and/or stochastic variability on timescales longer than about a day. Spectroscopic RV studies fail to reveal any plausible companion with a period in this range. Therefore, we conjecture that the observed light-curve cusps of amplitude ~ 0.01 mag that recur at a 4.08 day timescale may arise in the inner parts, or at the base of, a corotating interaction region (CIR) seen in emission as it rotates around with the star at constant angular velocity. The hard X-ray component seen in WR 110 could then be a result of a high velocity component of the CIR shock interacting with the ambient wind at several stellar radii. Given that most hot, luminous stars showing CIRs have two CIR arms, it is possible that either the fundamental period is 8.2 days or, more likely in the case of WR 110, there is indeed a second weaker CIR arm for P = 4.08 days, that occurs ~ two thirds of a rotation period after the main CIR. If this interpretation is correct, WR 110 therefore joins the ranks with three other single WR stars, all WN, with confirmed CIR rotation periods (WR 1, WR 6, and WR 134), albeit with WR 110 having by far the lowest amplitude photometric modulation. This illustrates the power of being able to secure intense, continuous high-precision photometry from space-based platforms such as MOST. It also opens the door to revealing low-amplitude photometric variations in other WN stars, where previous attempts have failed. If all WN stars have CIRs at some level, this could be important for revealing sources of magnetism or pulsation in addition to rotation periods.Comment: 25 pages, 8 figures, 2 tables, accepted in Ap

LIPOGENESIS IN ADIPOSE TISSUE FROM OVARIECTOMIZED AND INTACT HEIFERS IMMUNIZED AGAINST ESTRADIOL AND(OR) IMPLANTED WITH TRENBOLONE ACETATE

Forty-two heifers were allotted randomly to six treatment groups: 1) intact controls, 2) intact heifers implanted with trenbolone acetate, 3) ovariectomized heifers, 4) ovariectomized heifers implanted with trenbolone acetate, 5) intact heifers immunized against estradiol and 6) intact heifers immunized against estradiol and implanted with trenbolone acetate. Blood titers of estradiol-17β were increased over lO0-fold in heifers immunized against estradiol in Freund\u27s complete adjuvant or saline:squalene/arlacel containing Mycobacterium. Lipogenic enzyme activities and acetate incorporation into fatty acids were increased in subcutaneous adipose tissue obtained at slaughter from heifers receiving immunization or the combination of immunization and trenbolone acetate. The increased lipogenic capacity was not reflected in either cell diameter or cells per gram adipose tissue. Ovariectomy in combination with trenbolone acetate caused the lowest activities for all enzymes measured. This treatments also caused the greatest decrease in cell diameter, which resulted in the largest number of cells per gram of adipose tissue. Trenbotone acetate alone had no detectable effect on lipogenesis in the intact heifer, but the combination of ovariectomy and trenbolone acetate caused substantial decreases in enzyme activities, in most cases a significant decrease as compared with ovariectomized heifers. The data suggest that trenbolone acetate is able to depress lipogenesis only when not competing with the effects of circulating estradiol

LIPOGENESIS IN ADIPOSE TISSUE FROM OVARIECTOMIZED AND INTACT HEIFERS IMMUNIZED AGAINST ESTRADIOL AND(OR) IMPLANTED WITH TRENBOLONE ACETATE

Forty-two heifers were allotted randomly to six treatment groups: 1) intact controls, 2) intact heifers implanted with trenbolone acetate, 3) ovariectomized heifers, 4) ovariectomized heifers implanted with trenbolone acetate, 5) intact heifers immunized against estradiol and 6) intact heifers immunized against estradiol and implanted with trenbolone acetate. Blood titers of estradiol-17β were increased over lO0-fold in heifers immunized against estradiol in Freund\u27s complete adjuvant or saline:squalene/arlacel containing Mycobacterium. Lipogenic enzyme activities and acetate incorporation into fatty acids were increased in subcutaneous adipose tissue obtained at slaughter from heifers receiving immunization or the combination of immunization and trenbolone acetate. The increased lipogenic capacity was not reflected in either cell diameter or cells per gram adipose tissue. Ovariectomy in combination with trenbolone acetate caused the lowest activities for all enzymes measured. This treatments also caused the greatest decrease in cell diameter, which resulted in the largest number of cells per gram of adipose tissue. Trenbotone acetate alone had no detectable effect on lipogenesis in the intact heifer, but the combination of ovariectomy and trenbolone acetate caused substantial decreases in enzyme activities, in most cases a significant decrease as compared with ovariectomized heifers. The data suggest that trenbolone acetate is able to depress lipogenesis only when not competing with the effects of circulating estradiol

Genomic imprinting variations in the mouse type 3 deiodinase gene between tissues and brain regions.

The Dio3 gene, which encodes for the type 3 deiodinase (D3), controls thyroid hormone (TH) availability. The lack of D3 in mice results in tissue overexposure to TH and a broad neuroendocrine phenotype. Dio3 is an imprinted gene, preferentially expressed from the paternally inherited allele in the mouse fetus. However, heterozygous mice with paternal inheritance of the inactivating Dio3 mutation exhibit an attenuated phenotype when compared with that of Dio3 null mice. To investigate this milder phenotype, the allelic expression of Dio3 was evaluated in different mouse tissues. Preferential allelic expression of Dio3 from the paternal allele was observed in fetal tissues and neonatal brain regions, whereas the biallelic Dio3 expression occurred in the developing eye, testes, and cerebellum and in the postnatal brain neocortex, which expresses a larger Dio3 mRNA transcript. The newborn hypothalamus manifests the highest degree of Dio3 expression from the paternal allele, compared with other brain regions, and preferential allelic expression of Dio3 in the brain relaxed in late neonatal life. A methylation analysis of two regulatory regions of the Dio3 imprinted domain revealed modest but significant differences between tissues, but these did not consistently correlate with the observed patterns of Dio3 allelic expression. Deletion of the Dio3 gene and promoter did not result in significant changes in the tissue-specific patterns of Dio3 allelic expression. These results suggest the existence of unidentified epigenetic determinants of tissue-specific Dio3 imprinting. The resulting variation in the Dio3 allelic expression between tissues likely explains the phenotypic variation that results from paternal Dio3 haploinsufficiency.This is the final version of the article. It is available from the Endocrine Society in Molecular Endocrinology here: http://press.endocrine.org/doi/pdf/10.1210/me.2014-1210

Shear turbulence in the high-wind Southern Ocean using direct measurements

Author Posting. © American Meteorological Society, 2022. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 52(10), (2022): 2325–2341, https://doi.org/10.1175/jpo-d-21-0015.1.The ocean surface boundary layer is a gateway of energy transfer into the ocean. Wind-driven shear and meteorologically forced convection inject turbulent kinetic energy into the surface boundary layer, mixing the upper ocean and transforming its density structure. In the absence of direct observations or the capability to resolve subgrid-scale 3D turbulence in operational ocean models, the oceanography community relies on surface boundary layer similarity scalings (BLS) of shear and convective turbulence to represent this mixing. Despite their importance, near-surface mixing processes (and ubiquitous BLS representations of these processes) have been undersampled in high-energy forcing regimes such as the Southern Ocean. With the maturing of autonomous sampling platforms, there is now an opportunity to collect high-resolution spatial and temporal measurements in the full range of forcing conditions. Here, we characterize near-surface turbulence under strong wind forcing using the first long-duration glider microstructure survey of the Southern Ocean. We leverage these data to show that the measured turbulence is significantly higher than standard shear-convective BLS in the shallower parts of the surface boundary layer and lower than standard shear-convective BLS in the deeper parts of the surface boundary layer; the latter of which is not easily explained by present wave-effect literature. Consistent with the CBLAST (Coupled Boundary Layers and Air Sea Transfer) low winds experiment, this bias has the largest magnitude and spread in the shallowest 10% of the actively mixing layer under low-wind and breaking wave conditions, when relatively low levels of turbulent kinetic energy (TKE) in surface regime are easily biased by wave events.This paper is VIMS Contribution 4103. Computational resources were provided by the VIMS Ocean-Atmosphere and Climate Change Research Fund. AUSSOM was supported by the OCE Division of the National Science Foundation (1558639)